The kidneys are responsible for several vital homeostatic processes, including the excretion of nitrogenous waste products, the regulation of fluid volume and electrolytes, acid–base balance, and the production of hormones important for blood pressure regulation, erythropoiesis, and bone metabolism. They are frequently affected by disease, both acute (occurring over days to weeks) and chronic (occurring over months to years). Acute kidney injury (AKI), formerly known as acute renal failure, has become an increasingly common cause of hospitalization, with an incidence of 5% to 7% among hospitalized patients. Chronic kidney disease (CKD) reportedly affects 13% of adults in the United States, and is associated with significant morbidity, mortality, and expense. The recent advent of automatic reporting of estimated glomerular filtration rate (eGFR) with serum creatinine by hospital laboratories has resulted in more patients being identified as having impaired renal function. In order to provide the highest level of care for patients presenting with acute or CKD, the clinician should have a strong understanding of the fundamental issues relevant to their evaluation and management.
EVALUATION OF THE RENAL PATIENT
HISTORY AND PHYSICAL EXAMINATION
The evaluation of the patient with kidney disease begins with a thorough history and physical examination. The clinician should identify whether the renal disease is acute or chronic. If the patient’s previous medical records are available, this can be determined by quickly reviewing prior laboratory testing, with particular attention given to serum creatinine, blood urea nitrogen, and urinalyses. Patients who present with AKI should be questioned about recent symptoms (eg, vomiting, diarrhea, edema, difficulty voiding, decreased appetite, weight changes) and events (eg, changes in oral intake, new medications, nonsteroidal anti-inflammatory drug [NSAID] use, intravenous contrast administration, recent colonoscopy) that may help narrow the differential diagnosis of AKI. Symptoms such as fever, rashes, arthralgias, epistaxis, and hemoptysis suggest an underlying inflammatory condition such as vasculitis. For patients who develop AKI during their hospitalization, recent hospital events—including episodes of hypotension, recent diagnostic and therapeutic procedures, and initiation of new medications—should be reviewed. All patients presenting with AKI or CKD should be questioned about symptoms associated with uremia, including fatigue, nausea, vomiting, pruritus, metallic taste, lethargy, and confusion, since these symptoms may indicate the need for dialysis.
Patients should be asked whether they have a prior history of kidney disease or other relevant systemic diseases, such as diabetes and hypertension. In patients with CKD, who may or may not be presenting with an acute kidney-related problem, the clinician should establish the chronicity, severity, and cause of the underlying kidney disease. In patients with end-stage renal disease (ESRD), information about the patient’s nephrologist, outpatient dialysis unit, and regular dialysis schedule (including the timing of the last dialysis session) should be obtained and conveyed to the clinicians and other health care providers who will be facilitating the patient’s dialysis during the hospitalization. The clinician should also obtain a complete and current list of the patient’s medications, including prescription medications as well as all over-the-counter medications, herbal remedies, and supplements. A family history of kidney disease or other systemic illnesses should also be documented.
The physical examination starts with a review of the patient’s vital signs. While fever should always raise suspicion for an infection, particularly in dialysis patients or immunosuppressed patients, it can also be observed in the setting of acute glomerulonephritis, vasculitis, and allergic interstitial nephritis. Blood pressure may be elevated (eg, in acute nephritic syndrome, malignant hypertension, scleroderma, long-standing kidney disease), normal, or low (eg, in volume depletion, sepsis, cirrhosis, heart failure). Fluid intake and output should be reviewed to help determine volume status and the need for fluid repletion, diuresis, or dialysis.
Key aspects of the exam include the bedside determination of volume status and a search for physical signs associated with specific kidney diseases and uremia. Assessment of volume status is essential for the diagnosis and management of most renal diseases. In prerenal acute kidney injury, the presence of hypervolemia (eg, elevated jugular venous pressure, pulmonary congestion, peripheral edema) suggests decreased renal perfusion from congestive heart failure or cirrhosis, whereas hypovolemia (postural pulse increase >30 beats/min, severe postural dizziness, dry axilla or mucous membranes) would be more consistent with volume depletion from bleeding or gastrointestinal losses. To best assess the jugular venous pulsation, the patient should be reclined with the head elevated at 30° to 45°, and the elevation of the right internal jugular vein above the sternal angle should be measured. Certain physical findings are associated with specific renal diseases (Table 61-1). Palpable purpura may be observed in vasculitic processes such as granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis), microscopic polyangiitis, Churg-Strauss syndrome, or Henoch-Schönlein purpura. Abdominal bruits with refractory hypertension and progressive renal failure are suggestive of renovascular disease. Funduscopic examination can reveal arteriolar narrowing, hemorrhages, exudates, or papilledema—findings consistent with chronic hypertension.
TABLE 61-1History and Physical Examination Findings in Renal Disease ||Download (.pdf) TABLE 61-1 History and Physical Examination Findings in Renal Disease
|Renal Disease ||History ||Physical Exam Findings |
|Prerenal acute kidney injury || |
Volume depletion (hemorrhage, vomiting, diarrhea, diuretics, burns)
Medications (NSAIDs, ACE inhibitors/ARBs, cyclosporine, tacrolimus)
Orthostatic hypotension, dry mucous membranes and axillae
Elevated JVP, +S3, lung rales, edema (heart failure)
Jaundice, ascites, edema (cirrhosis)
Intrarenal acute kidney injury
Gross hematuria or cola-colored urine
Cough and hemoptysis (Goodpasture syndrome)
Epistaxis, sinusitis, hemoptysis, arthralgias, (Wegener, Churg-Strauss)
Rash, arthralgias (systemic lupus erythematosus)
Recent respiratory infection (postinfectious glomerulonephritis, IgA nephropathy)
Fever, arthralgias, rash
Medications (NSAIDs, antibiotics)
Episode of hypotension
Medications (aminoglycosides, amphotericin B, cisplatin)
Trauma, muscle necrosis (rhabdomyolysis)
History of multiple myeloma
History of atherosclerosis
Recent vascular intervention
Flank pain (renal vein thrombosis)
Fever, palpable purpura, arthritis (vasculitis)
Saddle-nose deformity (Wegener)
Oral ulcers, rash, arthritis, pericardial rub (SLE)
Fever, skin rash
Warm (early sepsis) or cold extremities (late sepsis)
Livedo reticularis, ischemic extremities
|Postrenal acute kidney injury || |
Urinary urgency, hesitancy, oliguria or anuria
Flank pain, renal colic
History of nephrolithiasis
Medications (acyclovir, indinavir, anticholinergics)
|Nephrotic syndrome || || |
|Uremia || |
Fatigue, lethargy, confusion, seizures
Anorexia, nausea, vomiting
Pruritus, metallic taste, bleeding
Pericardial or pleural friction rub
Dry and atrophic skin, pallor, hyperpigmentation, ecchymoses, uremic frost
Key aspects of the physical examination include:
Determination of the patient’s volume status;
Identification of physical manifestations that suggest specific renal disease conditions;
Search for signs of uremia.
The physical findings of uremia are highly variable. Uremic pericarditis or pleuritis may be present, as manifested by a pericardial or pleural friction rub, respectively. The pericardial friction rub classically has three components, one systolic and two diastolic, and a scratchy or grating quality. Skin and nail changes may include uremic frost (the fine residue of excreted urea on the surface of the skin), skin hyperpigmentation, or half-and-half nails (sharp demarcation between proximal and distal nail halves). Patients with fluid retention may have pulmonary congestion or peripheral edema. Neurological findings include confusion, coma, asterixis, and sensory deficits. The presence of these physical findings, especially the pericardial friction rub and neurological abnormalities, may indicate the need for dialysis.
Serum electrolytes are essential to the evaluation of the patient with acute and chronic renal disease. Both hyponatremia and hypernatremia may be seen in patients with kidney disease. Impaired renal function decreases renal potassium excretion, and may lead to potentially life-threatening hyperkalemia in oliguric or anuric patients. The serum potassium concentration may not be an accurate indicator of total body potassium stores, since most of the total body potassium is confined to the intracellular fluid compartment. For example, in diabetic ketoacidosis, patients frequently have elevated serum potassium levels despite diminished total body potassium stores. Serum chloride and bicarbonate levels are useful in the assessment of volume and acid–base status. The serum anion gap, used in the assessment of metabolic acidosis, can be calculated from serum sodium, chloride, and bicarbonate concentrations (AG = Na+ – [Cl– + HCO3–]). Serum calcium, phosphorus, and magnesium levels yield important information about renal tubular function and bone mineral metabolism. Hyperphosphatemia and hypocalcemia are common in patients with acute and chronic renal disease, and contribute to the development of secondary hyperparathyroidism.
Blood urea nitrogen and creatinine
Blood urea nitrogen (BUN) and creatinine are nitrogenous end products of metabolism that rise in the setting of renal disease. Urea is formed from ammonia derived from protein breakdown, while creatinine is a byproduct of muscle creatine metabolism. Urea and creatinine are freely filtered by the kidneys but handled differently in the tubular system. Urea is partly reabsorbed in the proximal tubule and inner medullary collecting duct, while creatinine is secreted to a small extent by the tubules. Despite these confounding effects of tubular handling, BUN and creatinine are still the most commonly used biomarkers of renal function. Neither test is ideal for the early detection of renal disease. Elevated serum BUN is sometimes attributable to nonrenal factors, such as high-protein intake, upper gastrointestinal tract bleeding, and high catabolism states, such as fever, corticosteroids, and burns. Serum creatinine may also be affected by many factors, including muscle mass and medications that impair tubular creatinine secretion, such as trimethoprim and cimetidine. Though BUN and creatinine are the traditional primary biomarkers of renal injury, their use may decrease in the future in favor of more sensitive and specific biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin C.
Estimated glomerular filtration rate
All patients with kidney disease, both acute and chronic, should have their kidney function assessed by estimation of the glomerular filtration rate (GFR). GFR may be estimated by measuring serum creatinine, calculating the creatinine clearance, or using estimation equations such as the Cockcroft-Gault formula, the Modification of Diet in Renal Disease (MDRD) equation, or the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. The normal GFR in a healthy adult is >90 mL/min. GFR decreases with age, at a rate of approximately 1 mL/min/y after age 35. Elderly patients may also have lower-creatinine levels due to decreased muscle mass. Measurement of serum creatinine is the most frequently used surrogate for GFR. As serum creatinine concentrations are affected by muscle mass, dietary protein intake, and certain medications, it is not the most accurate method of estimating GFR. The Cockcroft-Gault, MDRD, and CKD-EPI equations take into account serum creatinine, as well as other defined factors such as age, race, gender, and weight. They were designed to estimate GFR in patients with established CKD, and are most useful for this purpose. While the performance of these equations has been evaluated in a variety of different racial and ethnic populations with and without kidney disease, they should still be interpreted with caution in specific patient populations that have yet to be well validated, including individuals with normal or near-normal renal function, children, and elderly individuals. The CKD-EPI equation may be superior to the MDRD equation in estimating GFR in patients with normal or mildly impaired (GFR >60 mL/min/1.73 m2) renal function. Serum creatinine and the estimation equations should only be used to approximate GFR in patients with stable kidney function (unchanging serum creatinine). If the clinician is uncertain about the accuracy of GFR estimation, a 24-hour urine collection can be performed to calculate creatinine clearance.
Serum creatinine and the estimation equations should only be used to approximate GFR in patients with stable kidney function (unchanging serum creatinine).
The examination of the urinary sediment by microscopy can provide useful diagnostic information about both acute and chronic kidney disease.
Urine particles lyse easily after collection, and therefore urine samples should be examined within 2 to 4 hours of acquisition.
The pathognomonic finding of ATN on urinary sediment is the presence of coarse muddy brown granular casts, which represent extensive renal tubular epithelial cell injury.
In acute kidney injury, a fractional excretion of sodium (FENa) in combination with clinical history and other lab tests may help differentiate between prerenal etiologies and acute tubular necrosis (ATN).
While a FENa of <1% in the setting of AKI is generally thought to indicate prerenal azotemia, it can also be seen in contrast-induced nephropathy, rhabdomyolysis, acute glomerulonephritis, hepatorenal syndrome, early urinary obstruction, acute interstitial nephritis, and even ATN.
A FENa may be difficult to interpret in the setting of diuretic therapy.
If the patient has a nonanion gap metabolic acidosis, the urine anion gap (UAG) may help differentiate between gastrointestinal losses of bicarbonate (eg, diarrhea) and renal tubular acidosis. It is calculated as follows: (urine Na+ + urine K+) – urine Cl–.
Proteinuria, a hallmark of kidney damage, is most frequently detected qualitatively by urine dipstick, which grades proteinuria on a scale of concentration: trace, 1+ (30 mg/dL), 2+ (100 mg/dL), 3+ (300 mg/dL). Normal urine may test slightly positive if very concentrated. The urine dipstick is only capable of detecting urinary albumin, which is the most abundant protein seen with glomerular proteinuria. The presence of other proteins, such as immunoglobulin light chains, will not be detected by dipstick alone. Proteinuria by dipstick should prompt a more accurate quantification. This is done either by measuring the urine protein and urine creatinine concentrations in a random urine sample to determine the urine protein-to-creatinine ratio, or by a 24-hour urine collection for protein and creatinine excretion rate.
In the absence of gross bleeding, hematuria is most commonly discovered on a urine dipstick (which detects the pseudoperoxidase activity of hemoglobin) or urinalysis. False-positive dipstick results are seen in the setting of hemoglobinuria, myoglobinuria, menstrual blood in the urine, vigorous exercise, and concentrated urine. If significant proteinuria or renal dysfunction is also present, the kidney should be considered the source of hematuria until proven otherwise, and a renal biopsy should be considered to establish a diagnosis. Microscopic hematuria in the absence of proteinuria and renal dysfunction is known as isolated hematuria.
The differential diagnosis of isolated microscopic hematuria can be divided into renal (glomerular) or extrarenal (nonglomerular) processes. Immunoglobulin A (IgA) nephropathy, thin basement membrane disease, and Alport syndrome are three of the more common causes of glomerular hematuria. Common etiologies of nonglomerular hematuria include urinary tract infections, kidney stones, urinary tract tumors, trauma, bladder polyps, polycystic kidney disease, medullary cystic disease, and metabolic abnormalities such as hypercalciuria and hyperuricosuria. Hematuria associated with exercise, especially running, is usually a benign condition in which the blood source is likely the renal pelvis.
Hematuria from the glomerulus may or may not be associated with flank pain, while ureteral conditions that obstruct the urinary tract and cause bleeding can produce severe pain and renal colic. Other causes of hematuria are usually painless. In extrarenal hematuria, the red blood cells typically appear normal on urinary sediment, round and uniform, whereas in glomerular hematuria, the red blood cells may appear dysmorphic due to distortion from the passage through the glomerular filtration barrier. Imaging studies are indicated to search for structural causes of hematuria. Detection of persistent extrarenal hematuria should prompt further workup and urologic consultation to identify the source of bleeding. In older individuals, bladder cancer should be considered. In isolated glomerular hematuria, a renal biopsy is not typically indicated, since the pathologic diagnosis rarely has any effect on the management or outcome.
The examination of the urinary sediment by microscopy can provide useful diagnostic information about both acute and CKD. Urine particles lyse easily after collection, and therefore urine samples should be examined within 2 to 4 hours of acquisition. White blood cells (pyuria), when greater than 2 per high-power field, can be observed with upper or lower-urinary tract infections, contamination from genital secretions, or renal inflammation, as in interstitial nephritis or acute glomerulonephritis.
Urinary casts are cylindrical aggregates of protein and/or cells that form in the lumen of the distal convoluted tubule or collecting duct. Hyaline casts, the most common type of cast, are acellular and consist primarily of Tamm-Horsfall mucoprotein produced by tubular epithelial cells. They can be seen in the setting of dehydration or vigorous exercise in normal patients who produce concentrated urine, but can be seen in patients with proteinuria. Granular casts, the second most common type of cast, are usually formed from degenerating cellular casts or protein-containing lysosomes, and can appear fine or coarse in texture. Muddy brown granular casts contain degenerating tubular epithelial cells, and are commonly seen in acute tubular injury. Fatty casts are hyaline casts that contain lipid droplets and can be observed in patients with diseases causing lipiduria, such as nephrotic syndrome. The approach to hematuria is described above. When red blood cells leak through the glomerular filtration barrier, they can form red blood cell casts in the tubular lumen, a finding that is consistent with acute glomerulonephritis. White blood cell casts indicate renal inflammation or infection, and can be seen in acute glomerulonephritis, interstitial nephritis, and acute pyelonephritis. Red blood cell casts and white blood cell casts are always pathologic, and should prompt further evaluation of the patient for the clinical entities already mentioned.
Measurements of urinary sodium, potassium, chloride, and creatinine can be useful in the evaluation of a number of renal conditions. In acute kidney injury, the fractional excretion of sodium (FENa), combined with clinical history and other lab tests, may help differentiate between prerenal etiologies and acute tubular necrosis (ATN). The FENa can be calculated by the following formula: (urine Na+ × plasma creatinine)/(plasma Na+ × urine creatinine) × 100. A FENa < 1% is commonly seen in prerenal causes of oliguria, and a FENa > 2% is usually indicative of ATN. However, a FENa < % 1 can also be seen in contrast-induced nephropathy, rhabdomyolysis, acute glomerulonephritis, hepatorenal syndrome, early urinary obstruction, acute interstitial nephritis, and even ATN. Furthermore, a FENa may be difficult to interpret in the setting of a patient taking diuretics. In such cases, calculating the fractional excretion of urea (FEUrea) may help to differentiate prerenal AKI (FEUrea < 35%) from ATN (FEUrea 50%-65%).
In nonanion gap metabolic acidosis, one can calculate a urine anion gap (UAG) to help differentiate between gastrointestinal losses of bicarbonate (eg, diarrhea) and renal tubular acidosis using the following formula: (urine Na+ + urine K+) – urine Cl–. A negative UAG is consistent with gastrointestinal losses, whereas a positive UAG is frequently seen with renal tubular acidosis.
Serum enzyme levels should be interpreted cautiously in patients with impaired renal function. Cardiac enzymes, including cardiac troponin T (cTnT), cardiac troponin I (cTnI), and the muscle/brain (MB) isoenzyme of creatine kinase (CK-MB), are often elevated in acute or chronic kidney disease, even in the absence of acute myocardial injury. A large percentage of false-positive elevations in cTnT and CK-MB are seen in patients with ESRD when these markers are used to diagnose acute myocardial infarction (MI). The use of cTnI is less likely to be associated with false-positive elevations. Serial measurements of cTnI are currently the most specific marker of myocardial damage in patients with renal failure and suspected acute MI.
Liver and pancreatic enzymes can also be affected in patients with renal failure. Serum aminotransferase levels are frequently found to be in the lower range of normal values in patients with CKD and ESRD. In the absence of liver disease, gammaglutamyl transpeptidase (GGT) levels are most often normal, but may be elevated in a small percentage of patients. Serum alkaline phosphatase levels are often elevated in dialysis patients, usually from coexisting bone disease. An isolated elevation in serum alkaline phosphatase may not correlate well with hepatobiliary disease in ESRD patients; however, if a chronically elevated alkaline phosphatase level is accompanied by an elevation in serum GGT or 5′-nucleotidase, one should be more suspicious of an obstructive or infiltrative hepatobiliary process.
Serum levels of both amylase and lipase can be elevated in patients with CKD and ESRD, even when acute pancreatitis is not present. The levels of these enzymes in ESRD patients are commonly threefold to fivefold higher than baseline, but are typically less than three times the upper limit of normal. The elevations are due primarily to decreased renal clearance, though in the case of serum lipase, the use of heparin during hemodialysis has also been found to contribute to elevated levels.
Ultrasonography is a safe, noninvasive, rapid, and inexpensive diagnostic imaging modality used to study the kidneys. Ultrasonography requires neither ionizing radiation nor a potentially toxic intravenous contrast agent, which makes it a safe initial imaging study, especially for patients with known renal insufficiency. Renal ultrasonography can provide valuable information about kidney size, shape, and gross appearance. Normal adult kidneys are approximately 9 to 13 cm (4-5 in) in length and 5 to 7.5 cm (2-3 in) wide, and should not differ by much more than 1 cm. With chronic injury, the renal parenchyma is replaced with fibrotic tissue and the renal cortex becomes thinner, causing diseased kidneys to shrink. In patients with kidney disease of uncertain duration, the finding of smaller kidneys on ultrasonography suggests longstanding renal disease. Enlarged kidneys may be seen in autosomal dominant polycystic kidney disease, urinary tract obstruction, HIV nephropathy, early diabetic nephropathy, and infiltrative diseases such as amyloidosis or myeloma. Asymmetric kidneys may indicate unilateral kidney disease, and the clinician must determine whether the smaller or larger kidney is abnormal. Increased renal echogenicity is common and nonspecific finding, usually denoting medical renal disease. Renal ultrasonography can also identify the presence of renal cysts, stones, or masses. In patients presenting with acute kidney injury, renal ultrasonography can identify obstructive uropathy, which usually manifests as hydronephrosis, although false-negative results can be seen in patients with early obstruction (<3-4 days), volume depletion, or obstruction due to retroperitoneal fibrosis or compression by retroperitoneal or intraparenchymal tumor or blood.
Doppler ultrasonography can provide information about the presence and flow of blood through the vessels of the kidney. High-velocity or disorganized flow patterns can be seen in patients with hemodynamically significant renal artery stenosis. Elevated vascular resistive indices (>0.80) in a stenotic kidney are suggestive of severe parenchymal disease and a low likelihood of response to revascularization. Given the enhanced toxicities of iodinated contrast agents or gadolinium in renal disease, Doppler ultrasonography has become widely used as the initial imaging study to evaluate renal artery stenosis. The sensitivity of Doppler ultrasonography is highly operator dependent, and can be affected by patient anatomy.
In the evaluation of the patient with suspected renal colic, noncontrast helical CT scanning is currently the gold standard for diagnosing nephrolithiasis and can detect essentially all kidney stones, with the exception of indinavir stones. Noncontrast CT can also detect ureteric obstruction in acute kidney injury, which is particularly helpful when intravenous (IV) contrast should be avoided due to nephrotoxicity.
The drawback to the use of iodinated contrast agents is potential nephrotoxicity, especially in patients with preexisting renal impairment, diabetes, heart failure, or hypovolemia (see below). In patients with ESRD who have residual renal function, administration of contrast dye can induce further tubular damage and lead to loss of the remaining renal function. As preservation of residual renal function in patients with ESRD has been shown to correlate with improved survival even after the initiation of dialysis, the use of contrast in these patients should be avoided if possible. When the risk of nephrotoxicity is not prohibitive, IV iodinated contrast is useful for imaging of the renal parenchyma, facilitating the evaluation and detection of renal mass lesions such as renal cell carcinoma. CT angiography can be used to diagnose suspected renal artery stenosis or aneurysms. CT urography allows imaging of the collecting system and can identify filling defects such as stones, blood clots, and tumors.
Magnetic resonance imaging
The primary role of renal magnetic resonance imaging (MRI) is the evaluation of renal masses. MRI can effectively differentiate benign versus malignant lesions in the kidney, especially when CT scanning with intravenous iodinated contrast is contraindicated or if ultrasonographic and CT scans are nondiagnostic. MR angiography (MRA), which involves the administration of intravenous gadolinium, has become the modality of choice in the evaluation of renovascular disease. According to one meta-analysis, gadolinium-enhanced MRA had a reported sensitivity of 97% and specificity of 85% for the detection of renal artery stenosis. However, the use of gadolinium-based contrast agents in moderate to severe CKD has been associated with the development of nephrogenic systemic fibrosis (NSF), with debilitating fibrosis of the skin, joints, eyes, and other internal organs. Patients with an estimated GFR <30 mL/min or requiring dialysis should not be given gadolinium-based contrast agents. In these patients, Doppler ultrasonography is a safer alternative.
Radionuclide studies may be used to obtain functional information about the kidneys. Static radionuclide scans employ a radiolabeled tracer (eg, technetium 99m-DMSA) that binds to renal parenchymal cells, but is not excreted into the tubules. These studies are useful in quantifying the functional cortical tissue of each kidney and determining the percentage contribution of each kidney to total renal function. Dynamic radionuclide scans use tracers (eg, technetium 99m-DTPA, technetium 99m-MAG3) that are taken up by nephrons and then excreted into the collecting system. A diuretic such as furosemide is often administered just prior to injection of the tracer to ensure high levels of diuresis during the study. Dynamic scans can be used to evaluate potential renal tract obstructions as well as the response to treatment of the obstruction.
Acute kidney injury (AKI), formerly termed acute renal failure, is a sudden and sustained decline in renal function with the failure to excrete metabolic waste, maintain fluid and electrolyte balance, and regulate acid–base homeostasis. AKI is an increasingly common cause of hospitalization, with 1% of all patients reported to have AKI upon admission to the hospital and 2% to 5% of inpatients subsequently developing AKI during their hospitalization. In spite of advances in intensive care and dialysis support over the last 50 years, the overall mortality rate of AKI remains high, ranging from 20% to 90% depending on illness severity and medical setting. The role of the hospitalist is to diagnose common causes of AKI, to identify and treat reversible factors, to recognize when dialysis is required, and to know when to consult a nephrologist.
Two classification systems, the RIFLE and AKIN criteria, have defined and stratified AKI by stages of severity based on graded increases in serum creatinine and periods of decreased urine output (Table 61-2). The more recent AKIN criteria have proposed a definition for AKI that incorporates the prognostic significance associated with small changes in serum creatinine. The diagnosis of AKI can be established by (1) an abrupt (within 48 hours) absolute increase in serum creatinine of ≥0.3 mg/dL from baseline, (2) a percentage increase in serum creatinine of ≥50%, or (3) oliguria of ≤0.5 mL/kg/h for > 6 hours. Although both the RIFLE and AKIN classification systems have been validated in a variety of clinical settings, their utility at this time appears to be greater for research use than for the bedside.
TABLE 61-2Definitions and Classification Systems for Acute Kidney Injury ||Download (.pdf) TABLE 61-2 Definitions and Classification Systems for Acute Kidney Injury
|RIFLE Stages ||AKIN Stages ||RIFLE Increase in Serum Creatinine ||AKIN Increase in Serum Creatinine ||RIFLE and AKIN Urine Output |
|Risk (R) ||1 ||≥150%-200% ||≥0.3 mg/dL or ≥150%-200% ||<0.5 mL/kg/h × >6 h |
|Injury (I) ||2 ||>200%-300% ||>200%-300% ||<0.5 mL/kg/h × >12 h |
|Failure (F) ||3 ||>300% ||>300% or acute renal replacement therapy ||<0.3 mL/kg/h × ≥24 h |
|Loss (L) ||Complete loss of kidney function for >4 wk |
|End-stage kidney disease (E) ||Need for renal replacement therapy for >3 mo |
AKI can be divided into three diagnostic categories based on the anatomic location of injury: prerenal, intrarenal, and postrenal (Table 61-3). It can be further subdivided into oliguric (urine output < 400 mL/d) and nonoliguric (urine output > 400 mL/d), with patients producing less than 100 mL urine/d considered to be anuric. These distinctions are important, given that epidemiological studies have found that oliguria in the setting of AKI is an independent predictor of mortality. Oliguric AKI is more characteristic of prerenal etiologies and urinary obstruction, while nonoliguric AKI is commonly seen in intrarenal AKI. Anuria is uncommon and is usually associated with complete urinary tract obstruction, bilateral renal infarction, renal vein thrombosis, cortical necrosis, or high-grade ischemic acute tubular necrosis.
TABLE 61-3Etiologies of Acute Kidney Injury ||Download (.pdf) TABLE 61-3 Etiologies of Acute Kidney Injury
|Prerenal ||Postrenal |
ANCA-associated vasculitis (granulomatosis with angiitis, microscopic polyangiitis, Churg-Strauss syndrome)
Anti-GBM disease (Goodpasture syndrome)
Immune complex disease (lupus nephritis, poststreptococcal glomerulonephritis, cryoglobulinemia, IgA nephropathy)
Drug-induced (NSAIDs, penicillin analogues and cephalosporins, rifampin, sulfa drugs)
Autoimmune (SLE, Sjögren syndrome)
Infections (legionella, leptospirosis, cytomegalovirus, streptococci)
• Nephrotoxic acute tubular necrosis
Cast nephropathy (myeloma kidney)
Iodinated contrast agents
Pigment nephropathy (hemoglobin, myoglobin)
• Large vessel
• Small vessel
Prerenal AKI is defined as a reduction in GFR caused by hypoperfusion of the kidney. In most cases of prerenal AKI, the kidneys are morphologically normal. Prerenal AKI can be divided into conditions that cause volume depletion and conditions that induce renal vasoconstriction. True volume depletion may result from hemorrhage or gastrointestinal, urinary, or cutaneous fluid losses. Effective volume depletion refers to decreased effective circulating volume in the setting of normovolemia or hypervolemia, and can result from marked vasodilatation as seen in the setting of sepsis, heart failure, cirrhosis, and third-spacing. Renal vasoconstriction is most often caused by medications, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), NSAIDs, intravenous iodinated contrast agents, and the immunosuppressant drugs cyclosporine and tacrolimus.
Patients with prerenal AKI usually present with an elevated BUN and creatinine, and the ratio of BUN to creatinine is classically greater than 20:1. Urinalysis often reveals an elevated specific gravity without significant hematuria or proteinuria. The urinary sediment is typically bland but may show hyaline casts. The kidneys, in an appropriate response to the reduction in renal perfusion, maximize sodium and water reabsorption. Urine sodium is typically low, and the FENa and urea are <1% and <35%, respectively. Patients with prerenal AKI often respond favorably to volume resuscitation and discontinuation of any offending therapeutic agents.
In all cases of intrarenal AKI, the primary abnormality is within the kidney. Intrarenal AKI can be subdivided into four anatomic categories: glomerular disease, interstitial disease, tubular disease, and vascular disease. As in prerenal AKI, patients generally present with an elevated BUN and creatinine, though the ratio is usually normal (<20:1). The FENa may be variable and cannot reliably distinguish between the different causes of intrarenal AKI. The urinalysis is frequently abnormal, and findings on the urinary sediment can provide clues to the location of the kidney injury. In some patients, the clinical presentation and laboratory evaluation are insufficient to establish a diagnosis, and a percutaneous renal biopsy may be indicated to better guide management.
The most common cause of intrarenal AKI is ATN, which is responsible for most cases of AKI in hospitalized patients. ATN may be caused by either ischemic or nephrotoxic injury. Ischemic ATN is often associated with periods of prolonged hypotension and markedly reduced renal perfusion, which can be seen in the setting of heart failure, sepsis, or cardiac surgery. Nephrotoxic ATN can be caused by either endogenous (eg, heme pigments) or exogenous toxins (eg, aminoglycoside antibiotics, amphotericin B, cisplatin, and iodinated contrast agents). While many patients typically experience an oliguric phase (onset within 24 hours of the renal insult and duration of 1-3 weeks) followed by a diuretic phase (increase in urine output that is indicative of renal recovery), some patients remain nonoliguric throughout. The pathognomonic finding on urinary sediment is the presence of coarse muddy brown granular casts, which represent extensive renal tubular epithelial cell injury. Due to impaired tubular sodium reabsorption, the urine sodium is >40 mEq/L and the FENa is usually >2%. Both ischemic and nephrotoxic ATN resolve in most cases, but dialysis is sometimes required when renal injury is severe. A recently reported cause of renal injury is the use of sodium phosphate salts for bowel cleansing prior to colonoscopy, with phosphate precipitation in the kidney in volume-depleted patients or those with CKD.
The glomerular type of AKI involves acute inflammation of the glomeruli or glomerular vessels. Acute glomerulonephritis can be either renal-limited or associated with systemic illnesses such as infections, such as poststreptococcal glomerulonephritis, autoimmune disorders such as systemic lupus erythematosus, or vasculitides such as granulomatosis with angiitis. The urinalysis is always abnormal and classically reveals evidence of damage to the glomerular filtration barrier, with proteinuria, dysmorphic red blood cells, and red blood cell casts. Urine sodium and FENa may be low. The workup of acute glomerulonephritis should include serologic tests such as complement levels, antistreptococcal antibodies, antibodies against hepatitis B and C, antinuclear antibodies, antineutrophil cytoplasmic antibodies, antiglomerular basement membrane antibodies, and cryoglobulins. Definitive diagnosis usually requires a renal biopsy.
Acute interstitial nephritis (AIN) is defined as inflammation of the renal interstitium that results in AKI. AIN is most often caused by medications, such as antibiotics, NSAIDs, anticonvulsants, and proton pump inhibitors, but can also be associated with infections and autoimmune diseases. Classic symptoms include fever, rash, and arthralgias. However, the classic triad of fever, maculopapular erythematous rash, and eosinophilia is observed in only 10% of cases of AIN. Laboratory testing may reveal a FENa >1%, but this is not always reliable. Urinalysis may show mild proteinuria (<1 g/d), and the urinary sediment may reveal red blood cells, white blood cells, and white blood cell casts. Occasionally, urine eosinophils are observed with a Wright or Hansen stain, but this finding is neither highly sensitive nor specific for the diagnosis of AIN and can be seen in other inflammatory conditions. Definitive diagnosis can be established with a renal biopsy. Treatment of AIN is primarily the identification and cessation of the offending agent.
AKI can also be caused by acute vascular disease affecting either the large or the small renal blood vessels. Large-vessel diseases involve the renal arteries and veins and include bilateral renal artery stenosis, renal thromboembolism, renal artery dissection, and renal vein thrombosis. As a general rule, large-vessel disease must be bilateral in order to cause AKI, with the exception of unilateral disease in the patient with a solitary kidney. Patients may present with symptoms of renal infarction, complaining of acute flank pain and hematuria. Small-vessel diseases that can cause AKI include malignant hypertension, scleroderma renal crisis, and cholesterol atheroembolic disease. Patients with cholesterol atheroembolic disease often have a history of recent aortic instrumentation or surgical intervention or anticoagulation. Physical exam may reveal livedo reticularis on the skin overlying the lower extremities, toe or foot discoloration, or Hollenhorst plaques in the retina. The urinalysis in vascular AKI typically shows microscopic hematuria with or without proteinuria. Eosinophilia, eosinophiluria, and hypocomplementemia can also be seen in cholesterol atheroembolic disease. Imaging (eg, CT, MRI, or radionuclide studies) is often required to confirm the diagnosis of large-vessel disease.
In all patients presenting with AKI, urinary tract obstruction must be ruled out early, since timely intervention often improves or fully restores renal function. Obstruction to the flow of urine commonly occurs at the level of the prostate, particularly in adult men, but can occur at any location along the urinary tract. Upper urinary tract obstruction (ie, at the level of the ureters or renal pelvis) must be bilateral in order to cause AKI; the sole exception is unilateral obstruction in the patient with a solitary kidney. Common causes of postrenal AKI include hypertrophy or cancer of the prostate, obstructing kidney stones, urothelial tumors, and retroperitoneal fibrosis or malignancies. Patients with bilateral obstruction may present with oliguria (partial obstruction), polyuria (a sign of associated nephrogenic diabetes insipidus), or anuria (complete obstruction), and may report symptoms of flank pain, abdominal pain, renal colic, or hematuria. Ultrasonographic imaging usually reveals hydronephrosis, though this may be absent in retroperitoneal or infiltrative diseases that encase the ureters or kidneys. CT and dynamic radionuclide studies can also be used to diagnose urinary obstruction. Treatment of postrenal AKI focuses on relief of the obstruction.
Management of AKI should be focused on treating and reversing the specific cause of injury. Patients with prerenal AKI, for example, should be given volume resuscitation to restore euvolemia. In postrenal AKI due to urinary obstruction, relief of the obstruction can improve and in many cases fully restore renal function. Currently, there are no effective pharmacologic therapies for the treatment of AKI, and treatment focuses more on supportive management. Basic principles of management in AKI include:
Optimization of volume status and hemodynamic parameters. Daily weights and intake and output should be monitored closely. Medications that can compromise renal perfusion, including ACE inhibitors, ARBs, NSAIDs, and calcineurin inhibitors, should be discontinued. Patients who are hypovolemic should be given volume accordingly, with either crystalloids, colloids, or blood products. With few exceptions, such as the setting of cirrhosis, the use of colloids has not been proven to be more beneficial than crystalloids in AKI. Vasopressors or inotropes should be considered in patients who remain hypotensive despite volume resuscitation. In patients who are hypervolemic, the role of diuretics in the treatment of AKI is controversial. Although loop diuretics may be useful to treat volume overload in an oliguric patient, conversion of oliguric to nonoliguric AKI with diuretics has not been shown to improve survival or shorten the time to renal recovery. At high doses, loop diuretics may also lead to ototoxicity. Therefore, these medications should be used judiciously in patients with AKI.
Close monitoring and management of renal function, acid–base status, and serum electrolytes. Serum BUN, creatinine, and electrolytes should be monitored daily. If hyperkalemia is present, medical treatment should be initiated, such as intravenous calcium gluconate, insulin, inhaled albuterol, and sodium polystyrene sulfonate (kayexalate). Specific treatment depends on the severity, urine output, and ECG abnormalities; dialysis may be necessary if electrocardiographic abnormalities are present. Potassium intake via diet, medications, and intravenous fluids should also be eliminated. Hyperphosphatemia can be treated with oral phosphorus binders such as calcium acetate, calcium carbonate, sevelamer hydrochloride, and sevelamer carbonate. Aluminum hydroxide is highly effective at lowering phosphorus levels in severe cases, but its use should be limited to no more than 1 to 2 weeks due to the potential for aluminum toxicity. If acidemia is present, patients can be treated with intravenous fluids containing sodium bicarbonate.
Appropriate adjustment of medication dosing. All medications should be dosed to reflect the level of renal impairment, based on estimated GFR, or the need for dialysis (Table 61-4). Since eGFR can only be calculated when the serum creatinine is stable, a GFR of <10 should be assumed for patients whose serum creatinine is acutely increasing. Narcotics may accumulate in patients with renal impairment and should be used with great caution.
Avoidance of nephrotoxins. Medications that are nephrotoxic, such as NSAIDs and aminoglycosides, should not be given to patients with AKI. ACE inhibitors or ARBs taken on a chronic basis for hypertension or cardiovascular disease should be stopped until renal function has recovered. Intravenous iodinated contrast agents and gadolinium-containing agents should be avoided.
Management of uremic bleeding. Patients with severe AKI and uremia may develop bleeding diatheses due to uremic platelet dysfunction. This can be treated with synthetic arginine vasopressin analogues (eg, intravenous DDAVP 0.3 mcg/kg × 1-2 doses). Hemodialysis is the definitive treatment, and should be performed in cases of severe bleeding.
Nutritional support. Malnutrition is highly prevalent in patients with AKI. It is associated with higher risks of in-hospital mortality, nosocomial complications, and prolonged hospitalization. Appropriate nutritional is thus essential to the management of AKI, and consultation with an experienced dietitian may be beneficial. Hyperkalemia and hyperphosphatemia are common in patients with AKI, and a diet that is low in potassium and phosphorus should be instituted. Critically ill patients with AKI are in a highly catabolic state and at high risk for severe protein energy wasting. Nutritional support, parenteral or enteral, is frequently required in order to ensure adequate delivery of protein and energy, prevent further metabolic derangements and complications, improve wound healing, bolster the immune system, and decrease mortality.
TABLE 61-4Dosing Adjustments for Commonly Prescribed Medications in Patients with Impaired Renal Function ||Download (.pdf) TABLE 61-4 Dosing Adjustments for Commonly Prescribed Medications in Patients with Impaired Renal Function
|Drug ||Usual Dose ||GFR > 50 mL/min/1.73 m2 ||GFR 10-50 mL/min/1.73 m2 ||GFR < 10 mL/min/1.73 m2 |
|Acyclovir (oral) ||200-800 mg every 4-12 h ||100% ||100% ||200 mg every 12 h |
|Allopurinol ||300 mg daily ||75% ||50% ||25% |
|1.5-3 g IV every 6-8 h ||100% ||1.5-3 g IV every 12 h (GFR 15-29) ||1.5-3g IV every 24 h (GFR 5-14) |
|Cefazolin (Ancef) ||500 mg-1.5 g every 8 h ||100% ||Every 12 h ||50% every 24-48 h |
|Ceftazidime (Fortaz) ||1-2 g every 8-12 h ||100% ||Every 12-24 h ||Every 24-48 h |
|Ceftriaxone (Rocephin) ||1-2 g every 24 h ||No adjustment needed || || |
|Ciprofloxacin ||400 mg IV or 500-750 mg orally every 12 h ||100% ||50%-75% ||50% |
|Enoxaparin (Lovenox) || |
Prophylaxis: 30 mg SC every 12 h
DVT treatment: 1 mg/kg SC every 12 h or 1.5 mg/kg SC once daily
|Usual dosage || |
30 mg SC daily (GFR < 30)
1 mg/kg SC every 24 h (GFR < 30)
|Fluconazole (Diflucan) ||200-400 mg every 24 h ||100% ||50% ||50% |
|Gabapentin (Neurontin) ||300-600 mg three times daily ||Usual dosage || |
400-1400 mg/d (divided twice daily) (GFR 30-59)
200-700 mg/d (GFR 15-29)
100-300 mg daily
|Levetiracetam (Keppra) ||500-1500 mg every 12 h ||Usual dosage || |
250-750 mg every 12 h (GFR 30-50)
250-500 mg every 12 h (GFR < 30)
Hemodialysis: 500-1000 mg every 24 h, supplemental dose of 250-500 mg recommended after dialysis
|Levofloxacin (Levaquin) ||250-750 mg orally/IV daily ||Usage dosage ||500 mg initial dose, then 250 mg every 24 h ||500 mg initial dose, then 250 mg every 48 h |
|Metformin (Glucophage) ||500-1000 mg twice daily || |
Contraindicated in men with serum creatinine >1.5 mg/dL and women with serum creatinine >1.4 mg/dL or patients with GFR <60
Should be temporarily discontinued 24-48 h prior to administration of any radiocontrast agents and not restarted for 48 h afterward due to the risk of developing lactic acidosis
|Metoclopramide (Reglan) ||10-15 mg three to four times daily ||Usual dosage ||50% ||25% |
|Piperacillin/Tazobactam (Zosyn) ||3.375 g IV every 6-8 h ||100% || |
2.25 g IV every 6 h (GFR 20-40)
2.25 g IV every 8 h (GFR < 20)
|2.25 g IV every 8 h |
|Simvastatin (Zocor) ||10-80 mg daily ||Usual dosage ||Usual dosage ||Start at 5 mg daily |
|Vancomycin ||1 g IV every 12 h ||1 g IV every 12 h || |
Start with 1 g IV every 12 h (GFR 40-60)
Start with 1g IV every 24 h (GFR < 40)
Determine dose by serum level monitoring
It should be noted that, in spite of the available treatment modalities and advances in dialysis technology, mortality in patients with AKI remains high, with a rate of approximately 50% to 80% in critically ill patients.
When to consult a nephrologist
There are a number of common clinical scenarios that are considered nephrologic emergencies, and immediate evaluation by a nephrologist should be requested.
Indications for emergent nephrology consultation include:
Volume overload in an oliguric or anuric patient
Hyperkalemia with serum potassium >5.5 to 6 mEq/L and/or associated with changes on the electrocardiogram and other electrolyte abnormalities, especially in an oligoanuric patient
Toxic overdoses that can be treated with hemodialysis, including ethylene glycol, methanol, and lithium
Symptomatic or severe hyponatremia
Rapidly progressive glomerulonephritis
Microangiopathic hemolytic anemias, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome
Indications for renal biopsy
Percutaneous renal biopsy can be instrumental to the diagnosis of AKI. This procedure is typically performed under ultrasonographic guidance with local anesthesia, although CT-guided biopsy is an alternative in morbidly obese patients. In the setting of AKI, a renal biopsy may be most helpful either when the diagnosis of acute glomerulonephritis is suspected or when the cause of renal failure is unknown. Other common indications for performing a renal biopsy include unexplained glomerular hematuria, significant proteinuria, and nephrotic syndrome. Absolute contraindications to percutaneous renal biopsy include uncontrolled moderate to severe hypertension, uncontrolled bleeding diathesis or severe anemia, an uncooperative patient, and a solitary functional kidney. Relative contraindications include anatomic abnormalities of the kidney that may increase the risk of the procedure, skin infection overlying the biopsy site, active renal or perinephric infection, hydronephrosis, and the presence of multiple renal cysts or a renal tumor. The most common complication following percutaneous renal biopsy is bleeding, which usually occurs within 12 to 24 hours postbiopsy. Other complications include pain, gross hematuria, and infection.
Chronic warfarin anticoagulation is not a contraindication to renal biopsy. However, the need and urgency for biopsy must be weighed against the risk of thrombosis if anticoagulation is stopped. In patients chronically taking aspirin or other antithrombotic agents, these medications should be held as soon as it is known that a biopsy will be performed (ideally 1-2 weeks prior to the procedure) and should not be resumed until 1 to 2 weeks after the procedure. Heparin should be stopped at least 6 hours prior to the biopsy, and held for at least 12 to 24 hours postbiopsy.
Dialysis is initiated to prevent and treat the life-threatening complications and uremic symptoms associated with severe AKI. Generally accepted indications to start dialysis in the setting of AKI include (1) severe metabolic acidosis; (2) hyperkalemia, especially if electrocardiographic abnormalities are present; (3) volume overload refractory to the use of diuretics; and (4) uremic signs and symptoms, such as pericarditis, altered mental status, or seizures. The optimal timing of dialysis initiation has not been well established. Although a few retrospective and nonrandomized trials have found that earlier initiation of dialysis may improve survival, these results have yet to be tested in a large prospective randomized clinical trial.
Postoperative renal failure
Postoperative AKI resulting in oliguria and an elevated serum creatinine is one of the most common and serious complications of surgery, representing 18% to 47% of all cases of hospital-acquired AKI. It is associated with a higher risk for serious infections and sepsis, greater costs of hospitalization, and increased mortality following both cardiac and noncardiac surgery. Up to 30% of patients undergoing cardiovascular and thoracic surgeries develop postoperative AKI, and up to 7% of these patients need renal replacement therapy. Furthermore, postoperative AKI that requires dialysis carries an in-hospital mortality rate of 60% to 80%.
The most common cause of postoperative AKI is ischemic ATN resulting from decreased renal perfusion during surgery. Common surgical scenarios for the development of ATN include supra- or infrarenal aortic cross-clamping in vascular surgery and cardiopulmonary bypass during cardiac surgery. Risk factors for the development of postoperative AKI include preexisting renal dysfunction, diabetes mellitus, advanced age (>65), major vascular surgery, cardiopulmonary bypass times greater than 3 hours, and recent exposure to nephrotoxic agents including contrast dyes, NSAIDs, and aminoglycosides. Patients may present postoperatively with either an acute elevation in serum creatinine or reduced urine output.
A number of principles can guide the evaluation and management of postoperative AKI:
Identification of inciting factors. Perioperative records and flowsheets should be thoroughly reviewed for evidence of hypotension, significant intraoperative or postoperative fluid losses (eg, blood and intravascular fluid losses, insensible losses, drainage losses, and third-spaced fluid losses), and the administration of potentially nephrotoxic agents (eg, NSAIDs for pain control or hydroxyethyl starches used for volume resuscitation).
Hemodynamic monitoring. Patients should have close perioperative hemodynamic monitoring, and if necessary, invasive monitoring with intra-arterial, central venous, or pulmonary arterial catheters.
Maintenance of adequate renal perfusion. Though no optimal mean arterial pressure (MAP) has been established to ensure adequate renal perfusion, maintaining a MAP of at least >65 mm Hg and preferably >75 to 80 mm Hg is recommended.
Optimization of volume status. Intravenous fluid hydration should be administered to optimize renal perfusion in patients with volume depletion or hemodynamic instability. Patients who develop oliguria are often hypovolemic and should be given a fluid challenge. If they respond favorably with an improvement in urine output or hemodynamic parameters, more fluid challenges can be attempted.
Avoidance of nephrotoxic agents. Concomitant use of nephrotoxic medications is a risk factor for the development of postoperative AKI. If iodinated contrast agents must be used for diagnostic or therapeutic purposes, the smallest amount of nonionic iso-osmolar volume of contrast should be used. Other drugs such as NSAIDs, aminoglycosides, and amphotericin B should be avoided if possible. Patients who take ACE inhibitors or ARBs on a chronic basis should discontinue these medications prior to surgery, since chronic ACE inhibition reportedly increases the risk of postoperative AKI.
Pharmacologic agents. Several agents, including dopamine, fenoldapam, atrial natriuretic peptide, mannitol, calcium-channel blockers, and loop diuretics, have been tested for their ability to prevent postoperative AKI. The results of these studies are inconclusive, and there is insufficient evidence to recommend their use at this time.
Hepatorenal syndrome (HRS) is a functional form of AKI that occurs primarily in patients with cirrhosis and ascites. The pathophysiology of HRS is thought to be due to nitric oxide–induced vasodilation of the splanchnic circulation, leading to marked intrarenal arterial vasoconstriction and a reduction in GFR. There are two types of HRS: type 1 HRS is the rapidly progressive form of the disease characterized by a doubling of the initial serum creatinine level to greater than 2.5 mg/dL over a period of less than 2 weeks. The prognosis of patients with type 1 HRS without liver transplantation is generally very poor. Type 2 HRS is a more moderate form of renal failure characterized by serum creatinine levels between 1.5 and 2.5 mg/dL and associated with a more indolent course and improved survival compared to type 1 HRS. Both type 1 and type 2 HRS can occur spontaneously or develop after a precipitating event, most commonly a bacterial infection such as spontaneous bacterial peritonitis (SBP). Diagnostic criteria for HRS were recently revised by the International Ascites Club (IAC) in 2015, taking into account newer definitions of AKI, and now include the following: (1) cirrhosis with ascites; (2) increase in serum creatinine of ≥0.3 mg/dL within 48 hours, or ≥50% increase in serum creatinine from baseline, known or presumed to have occurred within the past 7 days; (3) no response after two consecutive days with diuretic withdrawal and volume expansion with albumin 1 g/kg body weight; (4) absence of shock; (5) no current or recent treatment with nephrotoxic drugs; and (6) no macroscopic signs of structural kidney injury (proteinuria >500 mg/d, microhematuria with >50 red blood cells per high-power field, and/or abnormal renal ultrasonography). With proper medical treatment, HRS is potentially reversible. Type 1 HRS can be treated with vasoconstrictors (eg, terlipressin, midodrine in combination with octreotide, norepinephrine) combined with albumin. Transjugular intrahepatic portal shunt (TIPS) may be considered in patients with type 1 HRS with either partial response (decrease in serum creatinine to ≥0.3 mg/dL above the baseline value) or no response (no regression in AKI) to medication. There is currently no definitive evidence demonstrating a benefit to using vasoconstrictors in patients with type 2 HRS. In patients being treated for SBP, prophylaxis with albumin is indicated, as this has been shown in one randomized clinical trial to lower the incidence of HRS by 66%, with significant reductions in 30-day mortality rates. The suggested dose of albumin is 1.5 mg/kg body weight on the first day, followed by 1 mg/kg body weight on the third day. Liver transplantation remains the treatment of choice for both type 1 and type 2 HRS.
Contrast-induced nephropathy is one of the most common causes of AKI in the hospital setting, with incidence rates ranging from <5% to >30%. Contrast-induced AKI is commonly defined as an increase in serum creatinine (either an absolute increase of 0.5 mg/dL or a 25% increase from baseline) within the first 24 hours after contrast exposure. The mechanism of injury involves renal vasoconstriction, impaired vasodilation, medullary hypoxia, and direct tubular cell damage. Preexisting renal impairment (eGFR < 60 mL/min) and diabetes mellitus are the most important risk factors for contrast-induced AKI, though heart failure, hypovolemia, nephrotoxic drugs, and hemodynamic instability are also significant risk factors.
A number of preventive strategies have been studied in patients at risk for contrast-induced AKI:
Type of contrast agent. The choice of contrast agent is important, since higher-osmolar agents are associated with greater nephrotoxicity. In high-risk patients, nonionic iso-osmolar (eg, iodixanol) and low-osmolar (eg, iohexol, ioversol, iopamidol) contrast agents have been shown to have lower nephrotoxicity.
Volume expansion. Intravenous hydration is clearly beneficial in the prevention of contrast-induced AKI, though the optimal hydration fluid has yet to be determined. The current evidence indicates that isotonic fluids (either normal saline or sodium bicarbonate) are more protective than half-normal saline. Although initial clinical trials showed a benefit to using sodium bicarbonate over normal saline, more recent evidence has not confirmed these findings. The rate and timing of hydration are also unclear. If using normal saline, one possible regimen is 1 mL/kg for 6 to 12 hours before the procedure, followed by 1 mL/kg for 6 to 12 hours after the procedure. Alternatively, if using isotonic sodium bicarbonate (three 50 mL ampules each containing 50 mEq of sodium bicarbonate in 850 mL of 5% dextrose in water), one possible regimen is a bolus of 3 mL/kg for 1 hour prior to the procedure, followed by an infusion of 1 mL/kg for 6 hours after the procedure.
N-Acetylcysteine. Though frequently used in the prevention of contrast-induced AKI, N-acetylcysteine has had inconsistent results in most clinical studies and meta-analyses. While some trials have reported significant protection, others have shown less substantial or even insignificant benefits. Given its relatively benign side effect profile and low cost, however, N-acetylcysteine is still often recommended as an adjunctive agent to IV hydration. In at-risk patients, it can be administered as 600 or 1200 mg orally twice daily on the day before and the day of the procedure.
Diuretics. The use of diuretics, particularly mannitol and furosemide, has not shown any benefit and may actually be harmful to patients.
Hemodialysis/hemofiltration. Although iodinated contrast agents are removable by dialysis, there is currently no definitive evidence to suggest that prophylactic hemodialysis or hemofiltration reduces the incidence of contrast-induced AKI.
Therapeutic agents frequently cause AKI in the hospital setting. The clinician should suspect drug toxicity when there is an acute rise in serum creatinine associated with the recent administration of a drug. As with AKI, drug nephrotoxicity can be divided into prerenal, intrarenal, and postrenal mechanisms. The most common mechanisms involve direct renal tubular injury resulting in ATN or renal interstitial inflammation leading to AIN. Other forms of injury include tubular obstruction due to drug precipitation, alterations in intrarenal blood flow, and, less commonly, glomerular disease. Drugs that are commonly associated with nephrotoxicity and their primary mechanisms of toxicity are listed in Table 61-5.
TABLE 61-5Nephrotoxic Drugs in Acute Kidney Injury
Drug-induced ATN is seen with the administration of medications that are excreted primarily by the kidneys, including aminoglycoside antibiotics, amphotericin B, and cisplatin. Aminoglycosides, commonly prescribed for the treatment of Gram-negative bacterial infections, cause dose-dependent ATN with a frequency ranging from 10% to 20%. Neomycin causes the greatest nephrotoxicity; gentamicin, tobramycin, and amikacin cause intermediate nephrotoxicity; and streptomycin causes the least nephrotoxicity. It should be recognized that aminoglycoside toxicity may follow oral administration of neomycin in cirrhotics, joint lavage after orthopedic procedures, and skin applications in burn patients. ATN typically develops 5 to 10 days after initiation of aminoglycoside treatment, and is generally nonoliguric. The kidney injury is usually reversible with withdrawal of the drug, but renal replacement therapy may be necessary in some cases.
AIN accounts for 3% to 15% of all drug-induced AKI. The most common offending agents include NSAIDs, penicillins, cephalosporins, sulfonamides, rifampin, ciprofloxacin, and proton-pump inhibitors. While the onset of drug-induced AIN has been reported as early as a few days after a secondary exposure to a medication, it usually occurs 7 to 14 days and as late as weeks to months after a primary exposure. AIN is typically reversible with withdrawal of the drug, though renal recovery may take weeks to months. Treatment of AIN with steroids has an unclear benefit, though some case series suggest that a short course of prednisone (1 mg/kg/d for up to 4 weeks) may increase the rate of recovery.
Drug-induced urinary obstruction generally results from the precipitation of drugs within the renal tubules or ureters. Crystal-induced AKI and nephrolithiasis may occur with acyclovir and indinavir. Certain analgesics containing aspirin, phenacetin, and caffeine may cause renal papillary necrosis, and with sloughing of the necrotic tissue that may lead to acute ureteral obstruction. Patients with drug-induced urinary obstruction may present with symptoms of renal colic and acute urinary tract obstruction. Management involves hydration, pain control, and discontinuation of the medication, although invasive removal of the stones may be required in severe cases.
A number of medications are known to modulate renal hemodynamics and cause a prerenal type of AKI. When renal perfusion is decreased, regulation of GFR involves vasodilation of the afferent arteriole and vasoconstriction of the efferent arteriole. Drugs that inhibit these compensatory mechanisms further impair renal perfusion and lead to AKI. These agents include NSAIDs, ACE inhibitors, ARBs, cyclosporine, tacrolimus, and iodinated contrast agents. NSAIDs inhibit the production of prostaglandins, which mediate afferent arteriolar vasodilation. In patients with normal renal function, this effect is largely inconsequential, but in those whose baseline renal perfusion is already impaired (eg, patients with heart failure or volume depletion), it can significantly reduce intrarenal blood flow and renal function. In contrast, ACE inhibitors and ARBs selectively block angiotensin II-mediated vasoconstriction of the efferent arteriole. An increase in serum creatinine of up to 30% is acceptable with ACE inhibitors and ARBs, given the proven long-term renal protective effects of these medications, but more significant loss of renal function may be observed in patients with decreased renal perfusion or renovascular disease. Cyclosporine and tacrolimus, calcineurin inhibitors widely used as immunosuppressants, cause intense afferent and efferent arteriolar vasoconstriction. Most patients taking these medications experience a reduction in GFR within weeks to months of starting therapy. As this effect is generally reversible and thought to be dose related, cyclosporine-, or tacrolimus-induced AKI can usually be managed with dose reduction.
Several agents used to treat cancer are toxic to the kidneys and may cause AKI. Intravascular volume depletion, simultaneous administration of other nephrotoxic drugs or iodinated contrast agents, urinary tract obstruction, and underlying renal disease increase the risk of chemotherapy-induced nephrotoxicity. Cisplatin can cause dose-related acute tubular necrosis and significant hypomagnesemia due to renal magnesium wasting. AKI may be reversible, though the repeated administration of cisplatin may lead to chronic and irreversible kidney damage. Aggressive hydration with intravenous fluids, particularly isotonic normal saline, can increase urine volume and flow and reduce the risk of cisplatin toxicity. Newer-generation platinum compounds such as carboplatin and oxaliplatin are generally less nephrotoxic, but may also cause acute tubular injury.
Methotrexate is not nephrotoxic at low doses (<0.5-1.0 g/m2) but may have nephrotoxicity at higher doses (1-15 g/m2). Methotrexate may precipitate in the tubules, causing direct tubular injury and urinary obstruction. Prophylaxis with intravenous fluid administration and urinary alkalinization reduces the potential for toxicity. Dosing must be adjusted in patients with preexisting renal impairment.
Alkylating agents such as cyclophosphamide and ifosfamide are known to cause hemorrhagic cystitis and hyponatremia. Ifosfamide is more nephrotoxic than cyclophosphamide, and can cause significant proximal tubular dysfunction, leading to a Fanconi-like syndrome with renal tubular acidosis and hypophosphatemia, and as well as distal nephron toxicity resulting in nephrogenic diabetes insipidus. Interleukin-2, often used to treat renal cell carcinoma and metastatic melanoma, can cause reversible AKI by inducing a capillary leak syndrome that leads to interstitial edema and volume depletion. Treatment is focused on restoring intravascular volume and stabilizing hemodynamic parameters. Table 61-6 lists several chemotherapeutic agents that commonly cause nephrotoxicity.
TABLE 61-6Chemotherapeutic Agents and Mechanisms of Toxicity ||Download (.pdf) TABLE 61-6 Chemotherapeutic Agents and Mechanisms of Toxicity
|Chemotherapeutic Agent ||Mechanism of Toxicity |
Tubular injury, renal magnesium wasting
Hemorrhagic cystitis, hyponatremia
Proximal tubular dysfunction
Biological response modifiers
Cardiorenal syndrome (CRS) describes a set of acute or chronic conditions involving the heart and the kidney in which dysfunction of one organ leads to dysfunction of the other. Though it was previously thought that primary cardiac disease gave rise to renal dysfunction, evidence now suggests that renal impairment can also lead to cardiac dysfunction. A recently proposed classification system divides CRS into five subtypes: (1) type 1 CRS (acute worsening of cardiac function leads to acute kidney injury), (2) type 2 CRS (chronic abnormalities in cardiac function lead to CKD), (3) type 3 CRS (acute worsening of renal function causes acute cardiac dysfunction), (4) type 4 CRS (CKD contributes to decreased cardiac function, ventricular hypertrophy, diastolic dysfunction, and increased risk of adverse cardiovascular events), and (5) type 5 CRS (a systemic condition causes both cardiac and renal dysfunction). Type 1 CRS, which is a common occurrence, is most relevant to the discussion of AKI. Patients with type 1 CRS present with acute heart failure that leads to the development of AKI, due to a reduction in renal perfusion. AKI tends to be more severe in patients with acute heart failure with systolic dysfunction compared to those with diastolic dysfunction. The early diagnosis of type 1 CRS is difficult, since at the time when an elevation in serum creatinine is detected, kidney injury has already occurred, and little can be done therapeutically. Often, patients with type 1 CRS develop a decreased responsiveness to diuretic therapy, and the use of higher doses or combinations of diuretics can worsen the AKI. Patients with volume overload who are refractory to diuretics may need fluid removal through ultrafiltration.
Potent vasodilating medications used in heart disease, such as hydralazine and calcium channel blockers, may manifest as edema, decreased urinary salt and water excretion, azotemia, and diuretic resistance. This syndrome occurs primarily in the patient with CKD or renovascular disease and can be thought of as a renal “steal” syndrome. Many drugs used in a cardiac setting are excreted by the kidney and may reach toxic systemic levels in renal disease. These include digoxin, procainamide, and morphine. Blood pressure reduction may have paradoxical effects on cardiac and renal function. For many reasons, management of patients with CRS is challenging, and involvement of a multidisciplinary team consisting of nephrologists, cardiologists, critical care physicians, and cardiac surgeons is recommended.
Rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis (RPGN) is characterized by the acute onset of glomerular inflammation and progressive loss of renal function over a short period of time (days to weeks to months). Crescent formation within injured glomeruli is one of the pathologic hallmarks of this disease process. Patients may present with hypertension, azotemia, oliguria, proteinuria, and edema. The urinary sediment is typically active, with dysmorphic red blood cells and red blood cell casts. RPGN is classified into three categories based on the cellular mechanism and immunofluorescence pattern: type 1 (anti-GBM disease, linear pattern of IgG staining), type 2 (immune complex disease, granular pattern of IgG staining), and type 3 (pauci-immune disease, little or no immunofluorescent staining). Serological tests (eg, anti-GBM antibody, antineutrophil cytoplasmic antibodies [ANCAs], antinuclear antibody [ANA], complement levels) should be ordered, though definitive diagnosis frequently requires renal biopsy. The diagnosis of RPGN should be considered a nephrologic emergency, and a nephrology consultation should be requested immediately to assist with renal biopsy and initiate appropriate treatment.
CKD affects approximately 13% of all adults in the United States. The Kidney Disease Outcomes Quality Initiative (K/DOQI) program defines CKD in adults as either (1) evidence of structural or functional kidney abnormalities, such as albuminuria, abnormal urinalyses, abnormal renal imaging, with or without decreased glomerular filtration rate (GFR); or (2) decreased GFR persisting for more than 3 months. The National Kidney Foundation has stratified CKD into five stages of severity (Table 61-7). CKD and ESRD are associated with significant complications, including anemia, hypertension, bone disease, and acid–base and electrolyte disturbances, all of which are frequently encountered in the hospital setting.
TABLE 61-7Staging of Chronic Kidney Disease ||Download (.pdf) TABLE 61-7 Staging of Chronic Kidney Disease
|Stage ||Description ||GFR (mL/min/1.73 m2) |
|1 ||Kidney damage with normal or ↑ GFR ||≥90 |
|2 ||Kidney damage with mild ↓ GFR ||60-89 |
|3 ||Moderate ↓ GFR ||30-59 |
|4 ||Severe ↓ GFR ||15-30 |
|5 ||Kidney failure ||<15 or dialysis |
GENERAL INPATIENT MANAGEMENT
The management of a hospitalized patient with CKD or ESRD should be guided by a number of important general principles. First, the patient’s nephrologist and dialysis unit, if applicable, should be contacted upon admission and discharge. This promotes communication and facilitates continuity of care, often providing the hospitalist with the most current patient information, including patient history, medication regimen, vascular access history, and baseline parameters such as blood pressure and estimated dry weight. Second, admission orders should take into account the special needs of patients with CKD and ESRD. Vital signs should include regular blood pressure measurements, daily weights, and accurate measurements of intake and output. Unnecessary phlebotomy should be avoided, particularly in patients with anemia, and routine blood tests in dialysis patients can often be drawn at their dialysis sessions just prior to initiation. Third, all measures should be taken to protect the vascular access of ESRD patients who are receiving hemodialysis. Blood pressures and blood draws should be performed in the arm contralateral to the one with the vascular access. If blood must be drawn from the ipsilateral arm, it should be taken from the most distal vein possible, preferably from the dorsum of the hand. Given their increased risk of infection, hemodialysis catheters should be reserved for dialysis use only, and under no circumstances with the exception of life-threatening emergencies should a dialysis catheter be accessed for other purposes.
Patients with CKD frequently have altered drug metabolism due to changes in glomerular flow and filtration, tubular reabsorption and secretion, and renal bioactivation and metabolism. In addition, other factors such as drug absorption, bioavailability, distribution volume, and protein binding may also be altered and can influence the handling of medications. Inappropriate dosing can result in either drug toxicity or ineffectiveness. On hospital admission, the complete medication list should be carefully reviewed, and particular attention should be given to medications that produce long-lasting active metabolites in the setting of reduced renal clearance. All medications, especially those that are initiated during the hospitalization, should be appropriately dosed according to a patient’s reduction in GFR.
Nutrition is a vital part of the care of the hospitalized CKD patient. If available in the hospital, a registered renal dietitian can be of tremendous value in providing dietary recommendations during the hospitalization as well as in counseling patients on healthy eating habits following discharge. According to the K/DOQI guidelines, patients with CKD stages 1 to 4 should be on a low-sodium (<2000 mg/d) diet, and potassium and phosphorus intake should be adjusted according to lab values. Provided that urine output is normal, there is no restriction on the amount of fluid in these patients’ diets. Patients with ESRD should be placed on a diet that is low in potassium (2000–3000 mg/d), low in phosphorus (800-1000 mg/d), and low in sodium (<2000 mg/d). Fluid intake should be limited to 1.5 to 2 liters daily to prevent large increases in interdialytic weight gain. Certain water-soluble vitamins are lost during hemodialysis and can be replaced with a daily multivitamin such as Diatx ZN (Pamlab, LLC), Dialyvite 3000 (Hillestad Pharmaceuticals), Nephplex Rx (Nephro-Tech, Inc.), Nephrocaps (Fleming Company), and Nephro-Vite Rx (Watson).
An estimated 50% to 75% of patients with a GFR <60 mL/min/1.73 m2 (CKD stages 3-5) have hypertension, and as renal function declines, hypertension becomes increasingly prevalent. Given the higher risk of cardiovascular morbidity and mortality associated with hypertension and CKD, the National Kidney Foundation Clinical Practice Guidelines for Hypertension recommend that in all patients with hypertension and CKD, blood pressure should be targeted to a systolic value of <130 mm Hg and a diastolic value of <80 mm Hg to decrease the risk of cardiovascular events and delay the progression of CKD. ACE inhibitors and ARBs should be considered as first-line therapy for hypertension in CKD, given their antiproteinuric effects and long-term renoprotective effects. Diuretics, particularly loop diuretics, can be particularly useful in optimizing blood pressure. Loop diuretic doses should be titrated upward as tolerated until normalization of blood pressure is achieved or the patient develops symptoms or signs of overly aggressive diuresis (eg, lightheadedness, hypotension, rising BUN and creatinine). The effectiveness of thiazide diuretics decreases in patients with a GFR <30 mL/min; however, these medications can be used synergistically with loop diuretics to improve diuresis in patients with refractory edema. Patients with ESRD on hemodialysis should have their morning doses of blood pressure medications held on dialysis days to prevent intradialytic hypotension and facilitate volume removal during dialysis.
Normocytic, normochromic anemia is a common complication of CKD and ESRD. It is primarily due to a deficiency in erythropoietin production by the kidneys, though other contributing factors may include iron deficiency, shortened red blood cell survival, uremic inhibitors of erythropoiesis, hemolysis, bleeding, loss of blood in hemodialysis circuits, and repeated blood draws. Anemia becomes more common as GFR decreases to <60 mL/min/1.73 m2. Treatment of anemia in CKD patients improves quality of life and decreases mortality. The K/DOQI guidelines recommend that the hemoglobin target in dialysis and nondialysis patients with CKD is generally in the range of 11.0 to 12.0 g/dL. Treatment with an erythropoiesis-stimulating agent such as erythropoietin or darbepoietin alfa reduces the need for frequent blood transfusions and is recommended in anemic CKD patients. In nondialysis patients, levels above this target should be avoided, due to recent evidence demonstrating that these levels are associated with adverse cardiovascular outcomes. Therefore, the hemoglobin target in dialysis and nondialysis patients with CKD should not be >13.0 g/dL.
To ensure that anemic patients will respond to treatment with erythropoietin or darbepoietin, iron stores should be monitored regularly via the serum ferritin concentration, serum iron concentration, and total iron binding capacity. Iron deficiency in patients with CKD is defined as transferrin saturation (TSAT) <20% or serum ferritin <100 ng/mL. Patients who meet either of these criteria should be given iron supplementation, either orally (eg, ferrous sulfate 325 mg three times daily) or intravenously (eg, iron sucrose, iron gluconate) to maintain a TSAT >20% to 25% and serum ferritin between 200 and 500 ng/mL.
Renal phosphorus excretion is decreased in patients with CKD and can result in elevated serum phosphorus levels and lower serum calcium levels due to increased binding of phosphorus. Serum calcium and phosphorus levels should be followed regularly in the inpatient setting. Patients with CKD or ESRD with hyperphosphatemia should be placed on low-phosphorus diets (<800-1000 mg/d) and counseled to limit their intake of foods that are high in phosphorus, such as dairy products, meats, dried beans and peas, and cola drinks. Hyperphosphatemia that cannot be adequately controlled by dietary modification alone should be treated with oral phosphorus-binding agents. Oral aluminum hydroxide, historically the first agent made available to treat hyperphosphatemia, is rarely used these days because of its long-term risk of aluminum toxicity and osteomalacia. It has been largely replaced by the calcium-containing (calcium acetate, calcium carbonate, and calcium citrate) and non–calcium-containing phosphorus binders (sevelamer hydrochloride, sevelamer carbonate, and lanthanum carbonate). When administered with meals, these medications inhibit the gastrointestinal absorption of phosphorus; thus they are not effective at lowering serum phosphorus levels in patients not receiving any dietary intake. Calcium acetate has been demonstrated in a number of studies to be more cost-effective than sevelamer. However, in patients who develop extraskeletal calcifications or recurrent hypercalcemia from calcium-containing phosphorus binders, sevelamer and lanthanum are suitable, though more expensive, alternatives. Calcium-containing phosphorus binders and sevelamer or lanthanum can also be used in combination to treat hyperphosphatemia that is difficult to control with a single agent. Sevelamer hydrochloride has been associated with metabolic acidosis; in these patients, substituting with sevelamer carbonate may be of benefit, as this formulation does not decrease serum bicarbonate levels.
Acid–base and electrolytes
Patients with CKD may have a metabolic acidosis due to impaired acid secretion. Sodium bicarbonate should be administered to patients with serum bicarbonate concentrations <22 mEq/L to prevent the complications of chronic metabolic acidosis, specifically bone disease and loss of lean body mass due to increased breakdown of skeletal muscle. Sodium bicarbonate can be given as oral tablets (650 mg [7 mEq] twice daily with meals) or alternatively in the form of baking soda (1/2 to 1 teaspoon dissolved in water or juice twice daily with meals). Patients may experience some abdominal bloating with bicarbonate treatment. Citrate salts should not be used as alkalinizing agents in CKD, as they may increase aluminum absorption.
Electrolyte disorders are also common in patients with CKD and ESRD. When GFR decreases to <15 to 20 mL/min, renal potassium excretion is impaired and hyperkalemia may occur. In patients who still produce adequate urine output, acute hyperkalemia can usually be managed medically with calcium gluconate (if electrocardiographic changes are present), insulin, inhaled albuterol, potassium-binding resins (eg, sodium polystyrene sulfonate), and loop diuretics. Patients with ESRD and oliguria or anuria will often require dialysis therapy to treat hyperkalemia. Chronic management of hyperkalemia involves dietary potassium restriction. Loop diuretics and potassium-binding resins are usually not necessary but can be useful for long-term control. If resins are used, it should be noted that they can result in hypocalcemia, sodium overload, and malabsorption of other medications. When given as a retention enema, they can cause colonic ulceration. These resins should not be given with aluminum hydroxide gels. Hypokalemia is less common in patients with CKD but can be caused by low-potassium intake, diuretic use, or gastrointestinal losses.
The ability of the kidney to properly concentrate or dilute urine is reduced as renal function is progressively lost, and both hyponatremia and hypernatremia are common in patients with CKD. Hyponatremia may be due to impaired free water clearance or volume depletion through renal or extrarenal sodium losses. A careful assessment of volume status can guide appropriate treatment. Patients who are euvolemic or hypervolemic will usually benefit from free water restriction and occasionally diuretics, whereas patients who are hypovolemic may require administration of intravenous normal saline. Hypernatremia maybe due to impaired water intake, in patients with poor thirst mechanisms or decreased access to water, or excessive renal or extrarenal water losses. Hypernatremia may also accompany recovery from AKI, during the osmotic diuresis of high levels of urea. Patients should be given free water, either orally or intravenously, to correct the water deficit.
The management of a hospitalized patient with CKD or ESRD should be guided by the following general principles
The patient’s nephrologist and dialysis unit, if applicable, should be contacted upon admission and discharge.
Admission orders should take into account the special needs of patients with CKD and ESRD.
All measures should be taken to protect the vascular access of ESRD patients who are receiving hemodialysis.
All medications, especially those that are initiated during the hospitalization, should be appropriately dosed according to a patient’s reduction in GFR.
In ESRD patients with little or no urine production, oral fluid intake should be closely monitored and restricted to 1 to 1.5 L/d. Large interdialytic weight gains (>4-5 kg) due to liberal fluid consumption or administration of intravenous fluids and medications can make volume removal during dialysis more difficult.
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