Chapter 5: Nephrology

A 49-year-old, female with a 5-year history of diabetes mellitus type 2, presents for an initial visit. She has no known complications of diabetes. She takes metformin, glyburide, and aspirin. On examination, you find a pleasant, obese female in no distress. Her blood pressure is 136/86 mm Hg. As you discuss monitoring her diabetes, you recommend screening for early kidney disease.

Question 5.1.1 Which of the following approaches is the recommended way to screen for diabetic kidney disease?

A) Obtain a 24-hour urine collection for albumin now and again in 3 years.

B) Obtain a spot urine albumin every year.

C) Obtain a spot urine albumin/creatinine ratio every year.

D) Obtain a urinalysis every year.

E) Obtain a serum creatinine every year.

Answer 5.1.1 The correct answer is "C." Moderately increased albuminuria (previously known by the misnomer "microalbuminuria") is a marker for increased risk of future kidney disease in diabetic patients. The best test to evaluate for moderately increased albuminuria is the urine albumin/creatinine ratio. Its advantages include ease of use, relatively low cost, and good correlation with 24-hour urine collections. Some of you may have chosen "B." A "spot microalbumin" (now a spot albumin) is a common but less accurate way to provide screening and may still be in use in some areas. As a practical matter, many physicians use urine albumin alone as a method of screening, but this method does not allow for corrections for variations in urine volume and dilution. A random spot urine albumin/creatinine ratio is normally less than 30 mg/g. Values above 30 mg/g are consistent with 24-hour measures showing abnormal amounts of albumin. Answers "D" and "E" offer measures of kidney function that simply are not sensitive enough to use for screening purposes.

Question 5.1.2 Her albumin/creatinine ratio is 42 mg/g. The next step to confirm moderately increased albuminuria is:

A) Repeat urine albumin/creatinine ratio.

B) Urine dipstick for protein.

C) 24-hour urine collection for total protein excretion.

D) Serum creatinine.

E) Referral to a nephrologist.

Answer 5.1.2 The correct answer is "A." Verification by repeat urine albumin/creatinine ratio is sufficient for a diagnosis of moderately increased albuminuria, so 24-hour urine collections need not be performed for confirmation. Of note, the diagnosis of moderately increased albuminuria requires 2 of 3 urine specimens showing >30 mg/g albumin/creatinine over a 6-month period. Since protein excretion must exceed 300 to 500 mg/day for a urine dipstick to detect proteinuria, urinalysis ("B") is not sensitive enough to be diagnostic. Serum creatinine elevation may be a marker for diabetic kidney disease, but it would develop late in the process. Nephrology referral is premature—you went to medical school; you can do this!

Question 5.1.3 Which of the following can cause a false-negative albumin/creatinine ratio?

A) Vigorous exercise.

B) Fever.

C) Cachexia.

D) Poor glycemic control.

E) Large muscle mass.

Answer 5.1.3 The correct answer is "E." Patients with a large muscle mass have a high rate of creatinine excretion, which may result in a falsely negative albumin/creatinine ratio (as the urine creatinine goes up, the ratio obviously goes down). Cachectic patients have the opposite problem, with low amounts of creatinine excretion, resulting in false-positive albumin/creatinine ratio. Fever, vigorous exercise, heart failure, and poor glycemic control can cause transient increases in albuminuria, potentially resulting in false-positive albumin/creatinine ratios.

Your patient's other laboratory studies reveal the following: hemoglobin A_1c 6.4%, serum creatinine 1.4 mg/dL, and normal electrolytes. A month later, your patient returns. Her blood pressure is 138/84 mm Hg. Her urine albumin/creatinine remains elevated on a second measurement. According to an eye examination yesterday, she has nonproliferative diabetic retinopathy.

Question 5.1.4 Because your patient has type 2 diabetes mellitus and moderately increased albuminuria, you realize that her likelihood of progressing to overt nephropathy is:

A) Almost zero.

B) About half that of a similar patient with type 1 diabetes.

C) Nearly equal to that of a similar patient with type 1 diabetes.

D) More than twice that of a similar patient with type 1 diabetes.

E) Absolutely certain (100% chance).

Answer 5.1.4 The correct answer is "C." Although earlier studies showed a greater progression to overt nephropathy in type 1 diabetics, more recent studies demonstrate a nearly equal rate of progression in types 1 and 2. About 20% to 40% of Caucasian patients with diabetes type 2 and moderately increased albuminuria will progress to diabetic nephropathy. The rate of progression to nephropathy in non-Caucasian populations is even higher.

Question 5.1.5 What is the most appropriate next step in the evaluation and management of this patient's moderately increased albuminuria?

A) Start an angiotensin-converting enzyme (ACE) inhibitor.

B) Start an angiotensin receptor blocker (ARB).

C) Order renal ultrasound with Doppler of the renal arteries.

D) Start insulin.

E) Order a 24-hour urine collection for total protein.

Answer 5.1.5 The correct answer is "A." ACE inhibitors should be the first-choice drugs unless there is a contraindication to their use. "B," an ARB, should be second-line choice in the event that the patient cannot tolerate an ACE inhibitor. "C," a renal ultrasound, is not indicated at this point in time. "D" is also incorrect. Your patient already has good glucose control (HbA_1c of 6.4%). As previously stated, a 24-hour urine collection is not necessary for diagnosis.

The patient has a full urinalysis to rule out renal inflammation (e.g., nephritis) and overt proteinuria (nephrotic syndrome). The urinalysis is entirely negative.

Question 5.1.6 What further investigations must your patient undergo to eliminate other potential causes of proteinuria?

A) Renal biopsy.

B) Renal ultrasound with Doppler of the renal arteries.

C) ANA, ESR, CRP.

D) All of the above.

E) None of the above.

Answer 5.1.6 The correct answer is "E." No further evaluation is necessary in this patient with moderately increased albuminuria. The combination of diabetic retinopathy (a marker for diabetic renal disease), hypertension (BP >140/90 mm Hg in a diabetic patient), and abnormal protein in the urine as measured by the urine albumin/creatinine ratio is sufficient to make the diagnosis of early diabetic nephropathy. Renal biopsy is quite invasive and unlikely to change management. ANA, ESR, CRP, and ultrasound are unlikely to offer new information. If things change (e.g., nephritic urine and gross proteinuria), further evaluation may be indicated.

You continue to follow this patient for several years. She ultimately is admitted for chest pain, rules out for myocardial infarction, but has a positive stress test. She will need to have a cardiac catheterization. Her creatinine is now 1.5 mg/dL, and her glomerular filtration rate is in the range of stage 3 chronic kidney disease.

Question 5.1.7 In addition to holding her metformin, which of the following interventions would be most likely to reduce her risk of developing contrast-induced nephropathy?

A) N-acetylcysteine and IV saline.

B) N-acetylcysteine and mannitol.

C) IV saline.

D) Sodium bicarbonate and mannitol.

E) Mannitol and IV saline.

Answer 5.1.7 The correct answer is "C." For patients at risk of contrast-induced nephropathy, contrast studies should be avoided if possible (see helpful tip below). If a contrast study must be done, stop aggravating medications like nonsteroidal anti-inflammatory drugs (NSAIDs-–this patient shouldn't be on these anyway since she has CKD!). Hydration, usually with IV saline, should be given if there are no contraindications (e.g., heart failure). Nonionic lower osmolality (or even iso-osmolar) contrast agents should be used, and we recommend discussing these cases individually with your radiologist, cardiologist or whomever is performing the procedure.

Sodium bicarbonate and N-acetylcysteine do not have good evidence for effectiveness, but they also do not appear to do harm. Sodium bicarbonate (isotonic sodium bicarbonate solution at 3 mL/kg for 1 hour before the procedure and continue at 1 mL/kg for 6 hours after the procedure) can be used as current evidence indicates that it has similar efficacy to IV saline. N-acetylcysteine needs to be started the day before the procedure and the evidence is conflicting. The diuretics (mannitol, furosemide, etc.) may be associated with an increased risk of nephropathy, and mannitol in particular has an undesirable side effect profile.

Upon cardiac catheterization, she is found to have several lesions. She undergoes coronary artery bypass grafting and is discharged. Her creatinine remains stable at 1.5 mg/dL.

A few months later, she presents with gradually increasing dyspnea and cough. Her urine output is reported to be normal. Her vitals show temperature 37°C, pulse 76 bpm, respiratory rate 24, and blood pressure 92/46 mm Hg. You note crackles at both lung bases. Her heart rhythm is regular and an S4 is audible. She has JVD of 9 cm and 2+ pitting pretibial edema.

The ECG shows sinus tachycardia but no evidence of potassium toxicity (peaked T-waves). Laboratory results: troponin-T and CK normal, BUN 70 mg/dL, Cr 2.0 mg/dL (her baseline was 1.5 mg/dL), Na 128 mEq/L, K 5.5 mEq/L (reference range 3.5–5.0), HCO₃ 19 mEq/L, WBC 14,500 per mm³, remainder of the CBC is normal. Urinalysis shows protein and glucose and a specific gravity >1.030, but there are few cells and no casts. Cultures and a chest x-ray are pending.

Question 5.1.8 You suspect that her elevated creatinine is primarily due to which of the following processes?

A) Adverse toxic effects of drugs on the kidney.

B) Heart failure or other prerenal cause of renal failure such as dehydration.

C) Sudden progression of diabetic nephropathy.

D) Urinary obstruction.

E) Urinary tract infection.

Answer 5.1.8 The correct answer is "B." Your patient has clinical evidence of heart failure (HF), including edema and rales. With a BUN/Cr ratio greater than 20 and an elevated urine-specific gravity, she appears to have a prerenal azotemia, likely secondary to insufficient cardiac output. Drugs ("A") may play a role in her dehydration, but the BUN/Cr ratio of >20 argues against a renal cause of her elevated creatinine. Therefore, the most likely culprit is HF. Diabetes should not cause a sudden worsening of renal disease. Although it has not been eliminated as a cause, urinary obstruction ("D") is not likely since she has good urine output. Answer "E" is incorrect since the urinalysis does not support diagnosis of infection, and CHF explains the overall clinical picture much better.

Question 5.1.9 Given her diabetes and renal disease, which of the following is the most likely cause of her hyperkalemia?

A) Renal tubular acidosis (RTA) type 1.

B) RTA type 2.

C) RTA type 3.

D) RTA type 4.

E) RTA type 5.

Answer 5.1.9 The correct answer is "D." RTA type 4 is due to aldosterone deficiency or resistance to the activity of aldosterone. The most common cause of RTA type 4 is hyporeninemic hypoaldosteronism, which is often seen in diabetic nephropathy. The disorder is recognized by hyperkalemia and mild acidosis. RTA types 1 and 2 usually are hypokalemic and these forms of RTA are not associated with diabetes. RTA type 3 is a rare autosomal-recessive disorder. RTA type 5 does not exist.

Question 5.1.10 In an effort to reduce her serum potassium level (not temporize), you should do which of the following?

A) Temporarily hold her furosemide and ACE inhibitor.

B) Increase her furosemide and temporarily hold her ACE inhibitor.

C) Administer IV calcium gluconate.

D) Bolus IV normal saline 1 to 2 L.

E) Give albuterol by nebulizer.

Answer 5.1.10 The correct answer is "B." Ah, test-taking—clearly not real life! The best answer here is to increase renal clearance of potassium with furosemide while holding the ACEI. Because ACE inhibitors can increase serum potassium, you should stop hers. "But what about her heart failure?" you ask. Well, good question. Given that her potassium is only slightly elevated, the ACEI could be continued while monitoring her serum potassium. "A" is incorrect; stopping the furosemide may lead to worsening HF symptoms and worsening hyperkalemia. In hyperkalemia, calcium gluconate ("C") is used to protect cardiac conduction, but it is not effective for reducing potassium concentrations. A bolus of normal saline ("D") is contraindicated in a patient with an acute HF exacerbation. Albuterol ("E") is a temporizing measure, reducing serum potassium by forcing potassium into the intracellular space.

Question 5.1.11 Because her creatinine clearance is low (and she is in HF) you should also discontinue:

A) Insulin.

B) Metoprolol.

C) Metformin.

D) Aspirin.

E) Simvastatin.

Answer 5.1.11 The correct answer is "C." Your patient's creatinine increased from 1.5 to 2.0 mg/dL, corresponding to a 33% reduction in creatinine clearance—a rough measurement of glomerular filtration rate (GFR). When creatinine clearance decreases, patients on metformin are at higher risk of developing the rare adverse effect of lactic acidosis. There is some evidence that patients with mild HF or slight elevations in creatinine can safely take the drug, but stopping metformin in renal failure continues to be the standard of care.

You administer intravenous furosemide. The night after admission she starts vomiting, and your partner inserts a nasogastric tube, which is inadvertently left to continuous suction overnight (don't do this … there is almost no indication for an NG tube—especially on continuous suction). The next morning, your patient's laboratory results are as follows: BUN 49 mg/dL, Cr 2.0 mg/dL, Na 132 mEq/L, K 3.5 mEq/L, and HCO₃ 35 mEq/L (normal 23–29 mEq/L).

Question 5.1.12 On the basis of history and laboratory data provided, you strongly suspect:

A) Metabolic acidosis.

B) Respiratory acidosis.

C) Metabolic alkalosis.

D) Respiratory alkalosis.

Answer 5.1.12 The correct answer is "C." Loss of gastric acid, through emesis or gastric suction, can result in a metabolic alkalosis. Although no pH is available to confirm alkalosis, you are able to infer the diagnosis based on the elevation in serum HCO₃.

Your patient recovers surprisingly well from her heart failure. Her creatinine returns to baseline (1.5 mg/dL). You try to re-challenge the patient with an ACE inhibitor. However, her hyperkalemia recurs and she is unable to tolerate either ACEI or ARB. With beta-blocker and loop diuretic therapy, her average blood pressure is 130/80 mm Hg. At a follow-up visit, you find no signs or symptoms of HF.

Question 5.1.13 You want to lower your patient's risk of progressing to end-stage renal disease. To reduce proteinuria, which of the following strategies is best?

A) Add isosorbide dinitrate.

B) Add a nondihydropyridine calcium channel blocker (e.g., diltiazem, verapamil).

C) Add a dihydropyridine calcium channel blocker (e.g., amlodipine, nifedipine).

D) Restrict protein in the diet.

E) Aim for a higher A1C target, around 8%.

Answer 5.1.13 The correct answer is "B." Nondihydropyridine calcium channel blockers reduce protein excretion in diabetic patients with nephropathy and slow down the progression of renal disease—but not to the degree of ACE inhibitors. "A," a long-acting nitrate, would be effective for angina and will lower blood pressure but does not demonstrate an effect on diabetic nephropathy. The dihydropyridine calcium channel blockers ("C") do not slow down progression to nephropathy to the same degree as some other antihypertensive drugs. The effect of protein restriction ("D") on nephropathy is controversial and not clearly beneficial; therefore, more effective therapies should be initiated first. Finally, "E" is incorrect since better glycemic control is associated with renal protection.

Over the next year, your patient experiences increasing difficulties with glycemic control. Despite your efforts, her proteinuria and serum creatinine increase. As you discuss referral to a nephrologist, she asks about dialysis.

Question 5.1.14 Which of the following is NOT an indication for dialysis?

A) Severe hyperkalemia due to renal failure.

B) Accelerated hypertension.

C) Malnutrition.

D) Persistent nausea and vomiting despite treatment.

E) Bleeding secondary to uremia.

Answer 5.1.14 The correct answer is "C." In chronic renal failure due to any cause, absolute clinical indications for initiating dialysis include: persistent nausea and vomiting, pericarditis, fluid overload, uremic encephalopathy, accelerated hypertension, bleeding due to uremia, serum creatinine greater than 12 mg/dL, and severe electrolyte abnormalities that cannot be otherwise handled. These are potentially life-threatening situations that must be dealt with acutely. Malnutrition is a relative indication that occurs more indolently.

Objectives: Did you learn to…

• Screen for moderately increased albuminuria in diabetic patients?

• Evaluate and treat moderately increased albuminuria and overt proteinuria in diabetic patients?

• Identify prerenal acute kidney injury?

• Describe the features of RTA type 4?

• Identify gastric suctioning as a cause of metabolic alkalosis in the hospital?

• Discuss when to initiate dialysis in a patient with chronic renal failure?

A 49-year-old African-American female with diabetes mellitus type 2, hypertension and hyperlipidemia returns for a follow-up visit. She's had diabetes for 15 years, and her control has been variable over that time. Now, her glycosylated hemoglobin is 8%. She has developed moderately increased albuminuria and diabetic retinopathy. You point out that her renal function has progressively declined, which alarms her since her mother is on hemodialysis. Her creatinine was 1.2 mg/dL 3 years ago, and now it is 1.9 mg/dL. Her GFR is 36 mL/min/1.73 m². She weighs 100 kg, and her blood pressure is 120/76 mm Hg.

Question 5.2.1 Which of the following is the most appropriate description of her renal function?

A) Stage 1 chronic kidney disease (CKD).

B) Stage 2 CKD.

C) Stage 3 CKD.

D) Stage 4 CKD.

E) Stage 5 CKD.

Answer 5.2.1 The correct answer is "C." She has stage 3 CKD. Table 5-1 defines the various stages of CKD. Not all patients will progress through all of the stages of CKD. On the basis of age alone, many elderly patients may be classified as having stage 1 or 2 CKD, and they may never progress. Knowledge of a patient's CKD stage is useful in determining how to treat, what drugs to avoid, etc.

You increase the patient's insulin and lisinopril doses, confirm that she is taking aspirin, and convince her to quit smoking (you are very persuasive—not to mention good looking and strong … and humble!). One month later, your patient returns with typical symptoms of a urinary tract infection (UTI) without systemic symptoms (e.g., fever, nausea). Her urine culture grows Escherichia coli resistant to trimethoprim/sulfamethoxazole but susceptible to all other antibiotics tested.

Question 5.2.2 The most appropriate antibiotic regimen for this patient's UTI is:

A) Ciprofloxacin 250 mg PO every other day for two doses.

B) Ciprofloxacin 250 mg PO once.

C) Ciprofloxacin 250 mg PO BID for 3 days.

D) Levofloxacin 750 mg PO daily for 7 days.

Answer 5.2.2 The correct answer is "C." This patient's GFR is 36 mL/min/1.73 m² and her creatinine clearance is 56 mL/min (using the Cockcroft–Gault equation given earlier). Therefore, the usual ciprofloxacin dose of 250 mg PO BID for UTI is safe and appropriate. Less frequent dosing may be required for a lesser GFR or creatinine clearance. The important thing here is to recall that CKD may require dosage adjustments for many medications. Numerous drugs are renally cleared, so it's always prudent to know the GFR or creatinine clearance and check for dosage adjustments before prescribing.

You assume the UTI cleared because you do not hear from her for a few months. Then her sister brings her in for an acute illness including nausea, emesis, confusion and generalized weakness. These symptoms began yesterday. The only other thing new with her health is heartburn which she has been self-treating with increasingly larger amounts of Tums^® (calcium carbonate), taking "handfuls" over the last few days. Her laboratory results now include creatinine 2.5 mg/dL, calcium 14 mg/dL (normal range 8.9–10.5 mg/dL), and HCO₃ 37 mEq/L (normal 22–28 mEq/L).

Question 5.2.3 The most appropriate treatment for her now includes:

A) Hydrochlorothiazide (HCTZ).

B) Furosemide.

C) Normal saline IV.

D) A and C.

E) B and C.

Answer 5.2.3 The correct answer is "C." Your patient is now presenting with a classic case of milk-alkali syndrome. The diagnosis should be recognized by the triad of hypercalcemia, metabolic alkalosis, and renal insufficiency in combination with the history of typical symptoms (described in the case) and excessive calcium carbonate ingestion. Treatment includes removal of the offending agent and treatment of the hypercalcemia with IV saline (to improve renal perfusion and metabolic alkalosis). "A," thiazide diuretics, results in reabsorption of calcium—the opposite of what you want to achieve in a patient with hypercalcemia. "B," furosemide, has fallen out of favor and requires the establishment of euvolemia first. Even then you need 10 L of saline per day with 100 mg of IV furosemide every 1 to 2 hours. This is usually impractical and hasn't been shown to add anything.

You get the patient through her episode of hypercalcemia and advise her to lay off the calcium-based antacids, favoring an H₂-antagonist instead. As your patient's renal disease progresses over the years, you find that she has become anemic with a hemoglobin of 9.9 g/dL. She takes a multivitamin. Her iron studies are consistent with anemia of chronic disease and her screening colonoscopy last year was normal. The anemia is normocytic and normochromic.

Question 5.2.4 If you were to treat her with an erythropoietic agent (e.g., erythropoietin or darbepoetin), her target hemoglobin would be:

A) 9 to 10 g/dL.

B) 10 to 11 g/dL.

C) 13 to 14 g/dL.

D) >15 g/dL.

Answer 5.2.4 The correct answer is "B." For patients with CKD and anemia of chronic disease (when other causes of anemia have been ruled out and/or treated), erythropoietic agents should NOT be used to achieve "near normal" hemoglobin levels. Target levels are determined on an individual basis but in general will be about 10 to 11 g/dL. Higher hemoglobin levels—in particular, attempts to "normalize" the hemoglobin concentration—are associated with a greater risk of adverse events, including increased risk of mortality, need for dialysis, heart failure, graft thrombosis, uncontrolled hypertension, etc. These findings are consistent with a similar finding in cancer patients (JAMA. 2010;303(9):857–864; N Engl J Med. 2009;361:2019–2032). If the patient is an appropriate candidate, the initial erythropoietin dose is approximately 50 to 100 units/kg per week. Because of the need to preserve veins for future hemodialysis access, we recommend that erythropoietin be administered subcutaneously. The FDA suggests withholding erythropoietin for hemoglobin >12 g/dL or if the hemoglobin increases by >1 g/dL in any 2-week period.

Objectives: Did you learn to…

• Stage CKD?

• Adjust medication doses based on renal function?

• Recognize and treat milk-alkali syndrome?

• Recognize appropriate targets for the treatment with erythropoietic agents?

A 55-year-old male presents to your office for evaluation of blood in his urine. It turns out that he had a life insurance physical and the urinalysis showed 2+ blood on urine dipstick and 2 RBC/hpf. The remainder of the urinalysis and microscopic examination was normal.

Question 5.3.1 After an appropriate history and physical examination, your first step in the evaluation of this urine abnormality is to:

A) Repeat the urinalysis and microscopic examination.

B) Obtain urine for culture.

C) Order a renal ultrasound.

D) Order a CT scan of the abdomen.

E) Order an intravenous pyelogram (IVP).

Answer 5.3.1 The correct answer is "A." According to the urinalysis, there is a small amount of blood in your patient's urine, but the number of RBCs is actually normal (<3 RBC/hpf). Your first step should be to repeat the urinalysis and urine microscopic examination to determine if this patient actually meets the criteria for microscopic hematuria (≥3 RBC/hpf on two of the three properly collected urine specimens, according to the American Urological Association). A urine culture may prove useful later in the evaluation process but is not necessary now. Likewise, ordering imaging studies is premature because the diagnosis of microscopic hematuria has not been made.

Further history reveals that he smokes one to two packs of cigarettes per day. He has a normal blood pressure and the remainder of the physical examination is unrevealing. On two urine samples, you find microscopic hematuria, with a positive dipstick and 5 RBC/hpf. The rest of the urinalysis is normal, and there are no red cell casts.

Question 5.3.2 In your evaluation of this patient, you include all of the following tests EXCEPT:

A) Urine cytology.

B) CBC.

C) Serum creatinine.

D) CT scan of the abdomen and pelvis with particular note of the kidneys.

E) Renal biopsy.

Answer 5.3.2 The correct answer is "E." In most cases of microscopic hematuria, renal biopsy is not indicated. However, if an intrinsic renal cause of hematuria is suspected, renal biopsy may prove necessary. Intrinsic renal disease is more likely if there is proteinuria, hypertension, elevated serum creatinine, or an active urinary sediment (e.g., nephritic, dysmorphic red cells, red cell casts).

There is no completely standardized evaluation of microscopic hematuria, and recommendations vary depending on the author. However, the recommendations always include serum creatinine and usually include CBC, coagulation studies, and serum chemistries. Depending on the patient's age, further studies may be indicated. For patients older than 40 years, you should consider studies to evaluate for urinary tract cancers. Urine cytology has low sensitivity but high specificity for bladder cancer and may be quite useful in conjunction with cystoscopy. Imaging of the urinary system is an absolute requirement in the work-up of microscopic hematuria in older patients (generally, those over age 40 years). CT scan appears to have the greatest sensitivity for detecting masses, but ultrasound, IVP, or the combination of the two may also be employed. Cystoscopy should be considered if the CT scan is normal since CT is poor at visualizing bladder abnormalities. See Table 5-2 for a suggested work-up for microscopic hematuria.

Question 5.3.3 The US Preventive Services Task Force recommends which of the following screening strategies for detecting microscopic hematuria?

A) Annual urinalysis after age 50.

B) Urinalysis every 2 years after age 50.

C) Annual urinalysis after age 65.

D) Annual urinalysis in all high-risk patients older than 65 years.

E) No screening at any age.

Answer 5.3.3 The correct answer is "E." The USPSTF recommends against routine screening for microscopic hematuria to detect urinary tract cancers. In one-time urine specimens in healthy adults, the presence of abnormal numbers of RBCs (≥3 RBCs/hpf) can be as high as 39%. In up to 70% of patients, even after imaging of the upper and lower urinary tract, the source of microscopic hematuria cannot be found. In a low-risk population, the false-positive rate of microscopic hematuria found on urinalysis would be unacceptably high. Also, there is no evidence that early detection of urinary tract cancers through screening urinalysis improves prognosis.

Your patient returns to discuss his laboratory and radiology results. His serum creatinine is 1.1 mg/dL, and his CBC, chemistries, and coagulation studies are normal. His urine cytology was negative, as was cystoscopy performed by your friendly neighborhood urologist. CT scan of the abdomen and pelvis reveals normal size kidneys and no masses, but three stones, measuring 2 to 3 mm in diameter, are noted in the left renal pelvis. There does not appear to be any obstruction. Your patient denies any history of renal colic.

Question 5.3.4 Regarding the finding of stones in the left renal pelvis, which of the following interventions is warranted at this time?

A) Observation.

B) Lithotripsy.

C) Ureteral stent placement.

D) Ketorolac and fluids by IV.

E) Prophylactic nephrectomy.

Answer 5.3.4 The correct answer is "A." The incidental finding of stones during the evaluation of microscopic hematuria is common. The stones may be the reason for your patient's hematuria. Since the stones are small, they may pass without intervention. Most stones less than 5 mm in diameter will pass spontaneously. No further intervention is warranted in asymptomatic patients. "D" is of particular note. Ketorolac and other NSAIDs are effective in treating the pain of urolithiasis. However, fluid is not helpful in treating acute ureteral colic (unless the patient is dehydrated). Fluid does nothing to "push" the stone out: fluid increases pain and the body simply shifts the excess fluid to the nonobstructed kidney.

Your patient does well for a year. When you see him next, he presents to your office as a late afternoon add-on and complains of severe abdominal pain that woke him from sleep at 3 AM. He describes the pain as "sharp" or "crampy," occurring in his left lower quadrant and radiating to the left testicle. Although the pain has waxed and waned, it has never resolved completely. He is also nauseated and has been vomiting. On examination, he is afebrile and tachycardic and has a blood pressure of 110/56 mm Hg. He appears uncomfortable and is writhing in pain. There is left lower quadrant, flank, and costovertebral angle tenderness.

Question 5.3.5 Your next action is to:

A) Prescribe oral ibuprofen and morphine and arrange follow-up tomorrow.

B) Give IM ketorolac and arrange follow-up tomorrow.

C) Bolus 1 L IV saline, administer IV ceftriaxone, and arrange follow-up tomorrow.

D) Send him to the emergency department (ED) for pain management, fluids, and possible admission.

Answer 5.3.5 The correct answer is "D." In a patient with known kidney stones presenting with classic findings of urolithiasis, the most likely diagnosis is renal colic due to stones. This patient is nauseated and vomiting frequently and may not do well at home overnight. He is unlikely to tolerate oral medications and could become dehydrated. In addition, we don't have a urinalysis, and a postobstructive UTI is an indication for admission and possibly stenting. For these reasons, the most appropriate action is aggressive pain management, which can be accomplished in the ED. If the patient is unable to keep down oral pain medications after treatment in the ED, admission to the hospital is warranted. Narcotic analgesics, IV NSAIDs (e.g., ketorolac), and IV fluids to maintain euvolemia are all appropriate. The role of antibiotics will depend on urinalysis findings, but most cases of acute renal colic do not require antibiotics.

You admit the patient to the ED; start IV saline to maintain hydration; and administer narcotics, NSAIDs (ketorolac) and antiemetics. CT scan shows a 5-mm stone in the proximal ureter. There is no hydronephrosis. Serum electrolytes, BUN, creatinine, and CBC are all normal. Urinalysis reveals 2+ blood, 1+ leukocyte esterase, trace protein, pH 6, specific gravity 1.025, 20 RBC/hpf, few calcium oxalate crystals, and otherwise normal.

Question 5.3.6 Which of the following is the most appropriate management at this point in time?

A) Add antibiotics to the current therapy.

B) Continue the current therapy and observe.

C) Refer for extracorporeal shock wave lithotripsy.

D) Refer for endoscopic lithotripsy.

Answer 5.3.6 The correct answer is "B." There is no reason to change management at this point in time. Many 5-mm stones will pass spontaneously. Although leukocyte esterase is detected on the urine dipstick, there is no compelling evidence of infection (e.g., fever, elevated WBC count, and WBCs on microscopic examination), so antibiotics are not necessary. But culturing the urine would be prudent.

Question 5.3.7 Your patient—a man possessing incredible foresight—asks how he can avoid kidney stones in the future. Which of the following tests will be most useful in determining the treatments that may prevent future stone formation?

A) Urine culture.

B) Stone recovery and analysis.

C) Urinary calcium excretion.

D) Urinary oxalate excretion.

E) Serum uric acid.

Answer 5.3.7 The correct answer is "B." The prevention of further stone formation is aided by knowledge of the stone type. You should always attempt to recover the stone and send it for analysis—unless the patient is a well-known stone former and the composition of his or her stones is already known. The other studies listed may have value. Struvite stones form during bacterial infections of the urinary tract and a urine culture ("A") will help direct therapy when these stones are identified. Calcium oxalate stones are the most common and 24-hour urine collection to determine calcium and oxalate excretion ("C") can lead to diagnoses of metabolic disturbances (hyperoxaluria and hypercalciuria). Patients with uric acid stones ("D") should be evaluated for symptoms of gout and undergo serum uric acid measurements.

Your patient passes the stone, his pain completely resolves, and he is discharged from the hospital within 24 hours of his admission. The stone is pure calcium oxalate. Studies of his 24-hour urine collection are pending.

Question 5.3.8 In order to reduce his risk of forming more stones, you tell him to incorporate all of the following lifestyle changes EXCEPT:

A) Restrict calcium intake.

B) Restrict oxalate intake (e.g., leafy green vegetables, chocolate).

C) Increase daily water intake.

D) Add a glass of orange juice daily.

E) Reduce meat and fish consumption.

Answer 5.3.8 The correct answer is "A." To prevent recurrent urolithiasis, restricted calcium intake was encouraged in the past. Now, moderate calcium intake (1 g/day) is recognized as beneficial and should be encouraged. Patients should take calcium with meals, which will bind oxalate and prevent its absorption. A low-calcium diet actually leads to an increased risk of urolithiasis. Increase in urine oxalate greatly increases the risk of stone formation. Restriction of oxalate ("B") in the diet may help to reduce the risk of recurrent urolithiasis. Foods high in oxalate include spinach, rhubarb, nuts, and legumes. Unfortunately, oxalate is also the end product of numerous metabolic pathways, and significant reduction in urinary oxalate levels often proves difficult (good news for you rhubarb fans! We like rhubarb pie and chocolate … say, I feel a stone coming on).

Increased fluid intake ("C") to achieve a urine volume >2 L/day reduces stone formation. Water and citrus juices ("D") are traditionally recommended (hypocitraturia is associated with stone formation), but most fluids consumed are associated with a positive effect, including drinks with caffeine.

Red meat, fish, and poultry ("E") are sources of purine, which is metabolized to uric acid. A uric acid crystal can form a pure uric acid stone or serve as a nidus for calcium stone formation. Therefore, a general recommendation to avoid recurrent urolithiasis is to reduce purines (e.g., meat) in the diet.

Question 5.3.9 Your patient is wondering if he should have his urolithiasis worked up to determine an etiology. All of the following are reasons to pursue a further evaluation in this patient EXCEPT:

A) A strong family history of stones.

B) African ancestry.

C) Chronic diarrhea.

D) Hypertension.

E) Bariatric surgery.

Answer 5.3.9 The correct answer is "D." Simply having hypertension is not a reason to work-up a patient for renal stones. All of the other choices are correct. Of note is "B." Patients of African ancestry are less likely to have stones. Therefore, the work-up is more likely to reveal a pathologic process in these patients. "C" and "E" are also of note. Anything that can cause malabsorption including bowel surgery, history of inflammatory bowel disease, etc., can increase the risk of stones. Thus, evaluation is indicated in these patients.

Because of his strong family history, you decide to proceed with evaluation. Results of your patient's 24-hour urine have returned and are as follows (normal values):

• Volume 1.6 L.

• pH 6.5.

• Creatinine clearance normal.

• Calcium 410 mg (reference range 100–300 mg).

• Uric acid 410 mEq (reference range 250–750 mEq).

• Oxalate 42 mg (reference range 7–44 mg).

• Citrate 560 mg (reference range 100–800 mg).

• Magnesium 3.1 mEq (reference range 3–5 mEq).

Question 5.3.10 Which of the following medications is most likely to reduce his risk of developing kidney stones in the future?

A) Allopurinol.

B) Potassium citrate.

C) Hydrochlorothiazide.

D) Sodium bicarbonate.

E) Furosemide.

Answer 5.3.10 The correct answer is "C." According to the 24-hour urine studies, your patient has hypercalciuria, sub-optimal urine volumes (the goal for urine output in urolithiasis should be 2 L/day or more), and no other abnormalities. Patients with urolithiasis and hypercalciuria benefit from the long-term treatment with thiazide diuretics, such as hydrochlorothiazide, which decrease calcium excretion and therefore stone formation. Furosemide increases calcium excretion and has the potential to increase stone formation.

Even though it seems counterintuitive, patients with calcium stones and hyperuricosuria may benefit from allopurinol. It is thought that hyperuricosuria predisposes to calcium stones. Also, allopurinol is useful in the treatment of patients with uric acid stones. Patients with uric acid stones and hyperuricosuria may benefit from alkalinization of the urine with sodium bicarbonate or potassium citrate. In general, dietary citrate should be maximized. Oral potassium citrate is indicated for patients with hypocitraturia.

The patient is wondering whether he can expect to get another stone.

Question 5.3.11 All of the following are true EXCEPT:

A) The peak incidence of kidney stones occurs at age 30.

B) Kidney stones are more common in men than in women.

C) The rate of a second kidney stone is 60% to 80%.

D) Only people who become dehydrated can expect to have a second stone.

E) Living in a hot climate can predispose to a second stone.

Answer 5.3.11 The correct answer is "D." While dehydration predisposes patients to a second stone (and thus "E"), maintaining optimal hydration lowers the risk but is not a foolproof remedy. Kidney stones are more common in men and have a peak incidence at age 30. About 60% to 80% of patients with a kidney stone will suffer a recurrence.

Question 5.3.12 Which of these patients with urolithiasis requires hospitalization?

A) A patient with a high-grade obstruction.

B) A patient with intractable pain or vomiting.

C) A patient with an associated urinary tract infection.

D) A patient with a solitary kidney or transplanted kidney.

E) All of the above.

Answer 5.3.12 The correct answer is "E." All of the patients listed above should be admitted. Obviously, patients having uncontrollable pain or vomiting will do poorly as outpatients. Urolithiasis with a coexistent UTI is a significant problem due to the risk of abscess formation, bacteremia, and renal parenchymal destruction. These patients require IV antibiotics and immediate urologic consultation, particularly in the presence of comorbidity. Patients with solitary or transplanted kidneys or in whom the diagnosis of renal colic is unclear should be admitted for monitoring of renal function and further evaluation.

Objectives: Did you learn to…

• Define microscopic hematuria?

• Evaluate a patient with microscopic hematuria based on risk and differential diagnosis?

• Describe the difficulties inherent in employing urine studies to screen for urinary tract cancers?

• Evaluate a patient with urolithiasis?

• Identify causes of urolithiasis based on the characteristics of the stone?

• Manage a patient with symptomatic urolithiasis?

• Use strategies to prevent stone formation based on the characteristics of the stone?

A 19-year-old female presents to your office concerned about protein in her urine. As a college student, she has a part-time job in a medical laboratory. She "repurposed" a few urine dipsticks from the laboratory—you know, "just checking her urine"—and found that she had 2+ protein on her dipstick. She has no urinary symptoms and denies fever, weight changes and edema. She is afebrile with a blood pressure of 118/68 mm Hg. Examination is otherwise unremarkable. Repeat urinalysis in the office confirms 2+ protein, specific gravity 1.020, pH 6.5, and no blood. The urine microscopic examination is normal.

Question 5.4.1 Which of the following is the most appropriate next action in evaluating this patient?

A) Repeat urinalysis and urine culture.

B) Ultrasound of the kidneys.

C) 24-hour urine collection for protein and creatinine.

D) Random urine protein/creatinine ratio.

Answer 5.4.1 The correct answer is "D." Did you go for "C"? A random urine is much easier than collecting a 24-hour urine and correlates well with 24-hour collections. You could ask the patient to collect urine for 24 hours for protein and creatinine measurements, but why? Who wants to lug around a jug of their own urine all day? What will she tell her friends and co-workers?

Your patient already has protein on urinalysis twice. Another urinalysis ("A") will not help to determine if this is truly a worrisome finding or not. There is no evidence of a UTI (no leukocyte esterase, nitrites, etc., and no symptoms); thus, culture would be very low yield. There is no indication for renal ultrasound ("B") at this point.

Question 5.4.2 Which type(s) of protein are detected on a urine dipstick?

A) Albumin.

B) Amino acids.

C) Immunoglobulin light chains.

D) A and B.

E) A and C.

Answer 5.4.2 The correct answer is "A." The urine dipstick only detects large–molecular-weight proteins—generally this means albumin. Amino acids are not detected. Immunoglobulin light chains, such as Bence Jones proteins, are also not detected on urine dipstick.

Her urine protein/creatinine ratio is equivalent to 1 g of urine protein per day. Creatinine clearance is normal. Serum creatinine, BUN, albumin, glucose, and electrolytes are normal.

Question 5.4.3 Which of the following is the best next step in your evaluation and management?

A) Start her on a low-protein diet.

B) Order CT scan of abdomen and pelvis.

C) Measure recumbent urine protein level.

D) Refer for renal biopsy.

Answer 5.4.3 The correct answer is "C." Proteinuria may be either transient or persistent. Transient proteinuria is often due to fever, exercise, or other causes and is not associated with significant kidney disease. Transient proteinuria is found in 7% of women and 4% of men. It often resolves spontaneously, and subsequent urine tests will probably be negative. However, at this point you don't know if this case will be transient or persistent proteinuria.

Orthostatic proteinuria is a common type of transient proteinuria seen in young, healthy persons. Up to 5% of adolescents have orthostatic proteinuria, and young adults may present with it as well. Protein is spilled in the urine when the patient is upright, but not when recumbent. There are two ways to determine recumbent urine protein: an easy way and a hard way. The easy way is to have the patient void before going to bed, stay supine all night (8 hours), and collect urine immediately upon waking. This urine is checked for protein/creatinine ratio. Another urine sample must be checked for protein/creatinine ratio after the patient has been upright. If the upright is abnormal and the recumbent is normal, you have diagnosed orthostatic proteinuria (and impressed your colleagues). The "hard way" involves splitting a 24-hour urine collection—two jugs of urine and the required arithmetic. Orthostatic proteinuria is a benign condition that usually resolves as the patient ages, requiring no additional evaluation.

A finding of 1 g of protein in a 24-hour urine collection is abnormal (normal <0.15 g/day), but it does not yet reach the nephrotic range (>3 g/day). Regardless, a low-protein diet ("A") is not helpful. CT scan of the abdomen and pelvis ("B") is unlikely to add any new information. Referring for renal biopsy ("D") is premature.

The patient collects urine in upright and recumbent positions, and both have abnormal amounts of protein. You refer the patient to a nephrologist who recommends follow-up rather than biopsy. Annual follow-up will include blood pressure, serum creatinine, and spot urine protein/creatinine ratio.

Question 5.4.4 In order to prevent worsening proteinuria, the nephrologist also recommends which of the following medications?

A) Amlodipine.

B) Diltiazem.

C) Furosemide.

D) Benazepril.

E) Aspirin.

Answer 5.4.4 The correct answer is "D." Patients with proteinuria tend to respond well to ACE inhibitors. ACE inhibitors have been shown to reduce proteinuria by 35% to 40%. This effect is true in nondiabetic patients with proteinuria as well as in diabetic patients. ACE inhibitors appear to be superior to other antihypertensives, including calcium channel blockers ("A" and "B"). Furosemide ("C") would be indicated if your patient develops edema, but loop diuretics should not be used primarily for the treatment of hypertension or proteinuria. Aspirin ("E") may be indicated for protection against coronary artery disease in patients with risk factors, including CKD, but it is not a primary treatment of proteinuria or hypertension. Remember that NSAIDs can adversely affect renal function.

Unfortunately, over the next few years, your patient develops hypertension. You maximize the dose of benazepril and need to add another drug to control her pressure. Her proteinuria increases to 3.5 g/day, and her plasma creatinine increases to 2 mg/dL. She develops edema, and her serum albumin is 2.8 g/dL. The urine shows only protein and no inflammatory components.

Question 5.4.5 This patient's current clinical condition is most appropriately described as:

A) Hypertensive nephropathy.

B) Acute renal failure.

C) Focal nephritic glomerulonephritis.

D) Nephrotic syndrome.

E) Floating kidney.

Answer 5.4.5 The correct answer is "D." While identifying no specific disease state, the term nephrotic syndrome refers to a constellation of signs and laboratory abnormalities. A number of diseases may lead to nephrotic syndrome (keep reading for more on this). When urine protein exceeds 3 g/day, it is often referred to as "nephrotic range" proteinuria. Complete nephrotic syndrome is characterized by nephrotic range proteinuria, edema, hypertension, hypoalbuminemia, and hyperlipidemia (Table 5-3).

Question 5.4.6 Which of the following findings in urine sediment is associated with nephrotic syndrome?

A) Red cell casts.

B) White cell casts.

C) Oval fat bodies.

D) Uric acid crystals.

E) Granular casts.

Answer 5.4.6 The correct answer is "C." Urine sediment in nephrotic syndrome is typically bland. There is little cellular matter. Oval fat bodies and fatty casts occur in the urine of patients with heavy proteinuria and hyperlipidemia. Fat bodies reflect the increased permeability of the glomeruli and suggest some type of glomerular disease (including nephrotic syndrome) albeit not necessarily active disease. However, fat can also be seen in patients with polycystic kidney disease and fat embolism syndrome.

Red cell casts ("A"), the hallmark of glomerulonephritis, are absent in nephrotic urine. White cell casts ("B") are associated with interstitial nephritis and pyelonephritis. Uric acid crystals ("D") are sometimes seen in gout, hyperuricemia and urate stone disease. Granular casts ("E") are not specific to any particular pathologic process and may be found in acute tubular necrosis, glomerulonephritis, and other renal diseases. See Table 5-4 for more details on urine sediment.

Question 5.4.7 Nephrotic syndrome is not a specific disease entity but can be the end result of a number of processes. Which of the following cause(s) nephrotic syndrome?

A) Diabetes.

B) Minimal change disease.

C) Amyloidosis.

D) Systemic lupus erythematosus.

E) All of the above.

Answer 5.4.7 The correct answer is "E." All of the above can be a cause of nephrotic syndrome. Remember that many causes of nephrotic syndrome can present initially with nephritic urine. Causes of nephrotic syndrome are summarized in Table 5-5.

Question 5.4.8 Which of the following tests is NOT indicated in most patients with nephrotic syndrome?

A) Hepatitis B and C serology.

B) ANA.

C) Serum and urine protein electrophoresis.

D) Antistreptococcal antibodies (e.g., ASO titer).

E) CA-125 antigen.

Answer 5.4.8 The correct answer is "E." Evaluation for cancer should be done if there is a specific reason to believe the patient has a malignancy (weight loss, mass on examination, etc.). CA-125 is a marker for ovarian cancer (among others … colon, pancreatic, etc.) and need not be done routinely. Plus, it's not a useful screening test for ovarian cancer. In addition to a thorough history and physical routine evaluation of patients with nephrotic syndrome (and nephritis and glomerulonephritis) include the following:

• Hepatitis B and C serology.

• ANA.

• Serum and urine protein electrophoresis.

• ASO titer.

• Cryoglobulins.

• Serum complement levels.

• ANCA.

• Serum calcium (to rule out sarcoid).

• Antiglomerular basement membrane antibodies.

Use clinical judgment to guide your work-up. However, this evaluation will find the cause of most cases of nephritis/nephrotic syndrome.

The diagnosis in your patient is unclear despite the work-up noted above. It is time to consider a renal biopsy.

Question 5.4.9 Absolute contraindications to renal biopsy include which of the following?

A) Hypertension.

B) Use of warfarin or other anticoagulant for atrial fibrillation.

C) Pyelonephritis.

D) Solitary renal cyst.

E) All of the above.

Answer 5.4.9 The correct answer is "C." The presence of renal or perirenal infection is a contraindication to renal biopsy. None of the others are absolute contraindications. However, uncontrollable hypertension, irreversible coagulopathy, multiple bilateral cysts, hydronephrosis, small kidneys (indicative of chronic, irreversible disease), known renal tumor, and lack of consent are all contraindications to renal biopsy. Simply being on warfarin or another anticoagulant, which can be stopped or reversed, is not a contraindication to biopsy.

Question 5.4.10 Which of the following is an indication for renal biopsy?

A) Persistent hematuria in a patient with normal renal function and an otherwise negative work-up.

B) Persistent low-grade proteinuria (1–2 g/day range) with normal blood pressure and creatinine.

C) Suspected case of IgA nephropathy.

D) Nephrotic syndrome likely from diabetes mellitus.

E) Persistent low-grade proteinuria with elevated blood pressure and/or elevated creatinine.

Answer 5.4.10 The correct answer is "E." Patients with low-grade proteinuria and elevated serum creatinine and/or hypertension should have a renal biopsy in order to determine the etiology of their disease. Indications for biopsy are listed in Table 5-6.

Objectives: Did you learn to…

• Evaluate and follow a healthy-appearing patient with proteinuria?

• Define and diagnose orthostatic proteinuria and understand its significance?

• Manage a patient with progressive proteinuria?

• Define and evaluate nephrotic syndrome?

• Identify causes of nephrotic syndrome?

While covering the ED, a 62-year-old female you have known for several years presents with her husband. She appears lethargic and is unable to give a coherent history. Her husband tells you that she began having stomach pain, nausea, and diarrhea 2 days ago. Although she has not been vomiting, she has been unable to drink or eat much due to nausea. She takes furosemide for edema and albuterol/ipratropium (Combivent) for chronic obstructive pulmonary disease (COPD). She smokes a pack of cigarettes per day.

On physical examination, her respiratory rate is 30, pulse 104 bpm, blood pressure 112/64 mm Hg, and temperature 37.9°C. She is somnolent and disoriented (maybe she's post-call?). Oral mucosa is dry. Lung examination demonstrates diminished air movement bilaterally. Her abdomen is diffusely tender, but there is no rebound. Rectal examination is negative for occult blood.

The first laboratory test you have available is a room air arterial blood gas (although venous would have been fine, right?): pH 7.12, PaCO₂ 33 mm Hg, PaO₂ 80 mm Hg, HCO₃ 10 mEq/L, and oxygen saturation 92%.

Question 5.5.1 This blood gas is most consistent with which of the following processes?

A) Compensated metabolic acidosis.

B) Compensated respiratory acidosis.

C) Poorly compensated metabolic acidosis.

D) Poorly compensated respiratory acidosis.

E) Pure respiratory alkalosis.

Answer 5.5.1 The correct answer is "C." This patient is clearly acidotic, as her pH is well below the normal range of 7.35 to 7.45. So, obviously, whatever she has, it will be poorly compensated, ruling out "A" and "B." Based on the bicarbonate (HCO₃) level and the history of gastrointestinal losses due to diarrhea, you would suspect a metabolic acidosis. In order to have appropriate respiratory compensation, the PaCO₂ should fall 12 points for every 10-point drop in the HCO₃ below the normal level (normal HCO₃ is around 24 mEq/L).

In this case, the HCO₃ is 10 mEq/L (14 points below normal); therefore, the PaCO₂ is expected to drop by about (1.2 × 14 = 16.8) or approximately 17. However, the PaCO₂ is not 23 mm Hg; it is 33 mm Hg (close to the normal range of 35–45). The patient's PaCO₂ is too high to appropriately compensate for her metabolic acidosis, and she thus has a poorly compensated metabolic acidosis.

There is another way to do this:

The pH should change by 0.08 for every 10 change in CO₂. So, if a patient's CO₂ is 50, the pH should be 7.32 if it is an uncompensated respiratory acidosis. If they are more acidotic (e.g., 7.24), they have a mixed respiratory and metabolic acidosis. If they are less acidotic (e.g., 7.39), they have a compensated respiratory acidosis.

While you are providing supportive care, the patient's laboratory results are completed: Na 134 mEq/L, K 2.1 mEq/L, Cl 112 mEq/L, HCO₃ 10 mEq/L, BUN 29 mg/dL, Cr 1.1 mg/dL, Ca 9.1 mg/dL; CBC: WBC 16,100 cells/mm³, Hgb 13.9 g/dL, platelets 167,000 cells/mm³; urinalysis: specific gravity 1.030, remainder normal. Troponin-T, CK, and liver enzymes are normal.

Question 5.5.2 All of the following may be contributing to hypokalemia in this patient EXCEPT:

A) Hypomagnesemia.

B) Furosemide.

C) Acidosis.

D) Beta-agonists such as albuterol.

E) Diarrhea.

Answer 5.5.2 The correct answer is "C." Acidosis should cause a spurious elevation in potassium—not hypokalemia. Magnesium ("A") depletion promotes potassium loss. Thus, hypomagnesemia can contribute to hypokalemia. "B," furosemide and other loop diuretics, causes renal potassium wasting. "D," beta-agonists shift potassium into cells thereby lowering the serum potassium. Diarrhea ("E") causes direct gastrointestinal losses of potassium.

Other causes of hypokalemia include thiazide diuretics, metabolic alkalosis (often from protracted emesis—although this represents a shift of potassium intracellularly and not a true hypokalemia), hyperaldosteronism, and RTA types 1 and 2.

Question 5.5.3 Since your administration likes to keep the hospital at 99% capacity, there are currently no cardiac-monitored beds available for this patient. The most appropriate initial therapy to correct her hypokalemia (2.1 mEq/L) is to give your patient:

A) KCl 40 mEq orally.

B) KCl 80 mEq orally.

C) KCL 20 mEq per hour IV.

D) KCl 20 mEq push IV.

E) KCl 60 mEq per hour IV.

Answer 5.5.3 The correct answer is "C." Remember that this patient is nauseated and lethargic and has been unable to eat. Thus, oral potassium replacement is not going to work. Couple this with the fact that she is profoundly hypokalemic, and IV replacement becomes the treatment of choice. One should not give more than 20 mEq KCl IV per hour without a cardiac monitor. It should be given through a large bore peripheral IV or a central line due to venous irritation. If you chose "D," you just failed your test. IV push KCl is fatal.

Most commonly, the chloride salt of potassium (KCl) is administered to replete potassium stores. In the conscious patient with a functional gastrointestinal tract, oral KCl should be administered. Oral and intravenous bioavailability is very similar, but oral doses greater than 40 to 60 mEq may not be well tolerated.

Question 5.5.4 In addition to KCl repletion, which of the following interventions do you initiate now in an attempt to correct the acidosis?

A) Bolus normal saline.

B) Sodium bicarbonate.

C) Bolus 5% dextrose.

D) Intubation and mechanical ventilation.

Answer 5.5.4 The correct answer is "A." On the basis of history, physical examination, and BUN/creatinine ratio, your patient is dehydrated. The first step is to correct the dehydration with intravenous fluids. Normal saline is preferred over dextrose ("C"), which might lead to further hyponatremia and hypokalemia. In addition, dextrose will not stay intravascular and will actually precipitate a diuresis by making the serum hypotonic. "B" is incorrect. There is no evidence that bicarbonate improves outcomes in metabolic acidosis. The best initial approach is to correct the underlying problem. In most cases, volume replacement will lead to improvement in acidosis without needing to resort to bicarbonate. Although she is oxygenating well now, if your patient's respiratory condition deteriorates, she may require intubation ("D") and ventilator settings could be adjusted to aid in correcting the acid/base disorder.

Objectives: Did you learn to…

• Define acidosis and distinguish compensated from poorly compensated acidosis?

• Discuss causes of hypokalemia?

• Manage a patient with metabolic acidosis and hypokalemia?

The primary mechanism by which renal failure occurs in rhabdomyolysis is:

A) Glomerular destruction.

B) Acute tubular necrosis (ATN).

C) Interstitial nephritis.

D) None of the above.

The correct answer is "B." Myoglobin deposits in the renal tubules, causing local damage and ischemia, which results in acute tubular necrosis. Findings in the urinary sediment that support acute tubular necrosis include renal tubular epithelial cells and dark brown casts of granular material ("muddy" brown casts).

Which of the following is/are associated with autosomal dominant polycystic kidney disease (ADPKD)?

A) Liver cysts.

B) Cerebral aneurysms.

C) Colonic diverticula.

D) Cardiac valvular disease.

E) All of the above.

The correct answer is "E." All of the above are associated with polycystic kidney disease. Of particular importance is the possibility of cerebral aneurysms (5–20%) leading to subarachnoid hemorrhage. However, aneurysm rupture remains fairly rare (but does seem to run in families—and seems to result in a really bad day for your patient). Currently, screening for subarachnoid aneurysms in asymptomatic patients with ADPKD is not recommended.

ADPKD occurs in 1 in every 400 to 2,000 live births and is, as the name implies, autosomal dominant. Common extrarenal manifestations of ADPKD include cerebral aneurysms, hepatic cysts, cardiac valve disease, colonic diverticula, and abdominal and inguinal hernias.

A 79-year-old female nursing home resident with moderate dementia presents for worsening confusion over the last 2 days. She just finished antibiotics for a urinary tract infection. Her temperature is 38.1°C, pulse 110 bpm, respiratory rate 18 breaths/minute, and blood pressure 118/60 mm Hg. She is disoriented and lethargic. Examination of the heart, lungs, and abdomen is unremarkable.

Laboratory studies are as follows: Na 165 mEq/L, K 4.6 mEq/L, Cl 118 mEq/L, HCO₃ 28 mEq/L, BUN 31 mg/dL, Cr 1.1 mg/dL. Urine specific gravity is >1.030 and urine osmolality is 700 mmol/kg (elevated, reflecting reabsorption of free water). Her CBC is normal.

Initial treatment for this patient should be:

A) Normal saline IV bolus.

B) Dextrose 5% IV bolus.

C) Sterile water IV bolus.

D) Loop diuretics.

E) DDAVP.

The correct answer is "A." Demented or delirious patients with an acute febrile illness may not be able to consume enough free water to avoid hypernatremia. Several mechanisms may be at work: free water loss due to illness, impaired thirst, and inability to respond to thirst due to cognitive or physical impairments.

Just as with hyponatremia, the hypernatremic patient should not be corrected too quickly. Sudden changes in plasma sodium may result in cerebral edema. Although there are no standardized guidelines to direct the correction of hypernatremia, most authorities recommend a maximal correction of 0.5 to 1 mEq/L/hr. In this patient who appears hypovolemic, the primary concern is to give volume. The administration of normal saline will allow you to administer volume while lowering her plasma sodium. Dextrose 5% solution will likely lower the sodium too quickly. Sterile water should never be administered IV because it will cause massive local hemolysis.

"E" is incorrect. This patient's kidney function is appropriate for her hypernatremia. She is concentrating her urine, as evidenced by her high urine specific gravity and urine osmolality. Therefore, she does not have diabetes insipidus, which is characterized by large volumes of dilute urine. DDAVP is an appropriate treatment for central diabetes insipidus. See Table 5-7 for more on causes of hypernatremia.

A surgical colleague asks you to consult on a patient because of increasing creatinine (yes, we know this will never happen with a surgeon—just consider this a thought experiment). A 63-year-old woman was admitted for an elective cholecystectomy. She is on postoperative day 3 and has fever and delirium. Her current medications are morphine, cefotetan, and acetaminophen as needed. She takes nothing by mouth, but has intravenous fluids (5% dextrose/0.45% saline) running at 100 cc/hr … continuously … since surgery. Plasma studies from the day of surgery and this morning are available:

Question 5.6.1 The BUN/Cr ratio on the day of consultation suggests that:

A) She is dehydrated.

B) She has a prerenal cause of her increased creatinine, such as hypoperfusion.

C) Intrinsic kidney disease is more likely than a prerenal cause of her increased creatinine.

D) None of the above.

Answer 5.6.1 The correct answer is "C." A BUN/Cr ratio <20 generally indicates an intrinsic renal cause of renal failure (increasing Cr) while a BUN/Cr ratio >20 indicates a prerenal cause such as hypoperfusion (e.g., CHF, dehydration). In this patient, the BUN/Cr ratio is 15, suggesting intrinsic renal disease.

Question 5.6.2 Which of the following is the most appropriate first step in determining the nature of this patient's elevated creatinine?

A) Give a trial bolus of normal saline.

B) CT scan of the abdomen.

C) Determine volume of urine output.

D) Obtain urine for culture.

E) Give a trial dose of furosemide.

Answer 5.6.2 The correct answer is "C." Currently, all you know about this patient's kidney function is that it has declined since her admission and that it is not likely from a prerenal cause. It is important to know if this patient is oliguric/anuric or has adequate urine output. This is important because it can affect the treatment. For example, oliguric or anuric patients may become volume overloaded easily in response to IV fluids. Although hospital measurements of intake and output are often plagued by errors, you should start this evaluation by analyzing the patient's urine output, as well as fluid intake. Urine culture and CT scan may eventually play a role in your evaluation. The decision to give fluids or diuretics cannot be made until more information is gathered.

Vital signs, intake, and output have been recorded by the nurses for each shift since admission and are provided in Table 5-8.

Question 5.6.3 You have now determined that your patient has become oliguric. Which of the following is most likely to help you narrow the differential diagnosis of renal failure?

A) Calculation of creatinine clearance.

B) Arterial blood gases.

C) CT scan of the abdomen.

D) Fractional excretion of sodium (FENa).

E) Furosemide challenge.

Answer 5.6.3 The correct answer is "D." In this patient, you know that her BUN/Cr ratio is <20, pointing you toward intrinsic renal disease. But this ratio is not specific enough to rely upon. In oliguric renal failure, the FENa is a useful tool to help differentiate prerenal causes of renal failure from intrinsic renal causes. If the FENa is less than 1%, the kidney is functioning appropriately to conserve sodium and water to better perfuse the kidney, and a prerenal cause of failure is more likely such as hypoperfusion from shock, dehydration, heart failure, etc. If the FENa is greater than 1%, salt and water losses are excessive, suggesting intrinsic kidney dysfunction. This calculation is most meaningful in oliguric renal failure (urine output <400 cc/day), but can also be used with any acute kidney injury in order to help determine the possible underlying cause. Also, FENa may be inaccurate in the elderly, patients receiving diuretics, and in chronic renal failure. The equation used to calculate FENa is:

On examination, you find a mildly disoriented female in no acute distress. She has lower extremity and sacral edema. You obtain urine studies, showing a specific gravity of 1.020, pH 6, 3 RBCs/hpf, 2 WBCs/hpf, and muddy brown granular casts. The urine creatinine is 6.5 mg/dL and the urine sodium is 45 mEq/L. You calculate the FENa at >1%.

Question 5.6.4 Given the clinical course and urine findings, which of the following is the best diagnosis?

A) Acute tubular necrosis (ATN).

B) Acute interstitial nephritis (AIN).

C) Vasculitis.

D) Heart failure (HF).

E) Lactic acidosis.

Answer 5.6.4 The correct answer is "A." ATN is a major cause of acute kidney injury in hospitalized patients. ATN is the result of toxic and/or ischemic effects on the kidney tubules. Metabolic derangements in ATN include progressive hyponatremia, hyperkalemia, and metabolic acidosis with a high anion gap, all of which are present in this case. Typically patients with ATN have a FENa >1% (or FEUrea >50%) and a urine sodium >40 mEq/L (Remember, the functioning kidney should be retaining sodium to increase its perfusion with extrinsic AKI). This is not happening here. So it is an intrinsic renal problem. In this case, FENa is 9.9%. In addition, "muddy" brown casts (renal tubular cell casts) are often found in the urinary sediment of patients with ATN. All of these findings point to ATN as the cause of renal failure in this patient.

Question 5.6.5 Based on the available data (including the vital signs in Table 5-8 and urine values), you suspect that ATN in this patient is the result of:

A) Acetaminophen.

B) Hypotension.

C) Intrinsic renal infection.

D) Cefotetan.

E) Any of the above is equally likely.

Answer 5.6.5 The correct answer is "B." As you review the vital signs, intake, and output, you will notice that the patient had a hypotensive period associated with tachycardia and fever (day 2, shifts 1 and 2). She then developed progressively lower urine output despite stable IV intake. It is likely that she has had an ischemic insult to her kidneys as a result of hypotension and decreased perfusion. While many medications can cause ATN, cefotetan and acetaminophen are relatively safe. More often, cephalosporins cause acute interstitial nephritis (fever, +/– rash, white cell casts, and eosinophils in the urine and perhaps in the peripheral blood).

When you go to check on the patient later in the afternoon, she has become more tachypneic and has rales on examination.

Question 5.6.6 Which of the following recommendations do you make for this patient's continuing care?

A) Administer dopamine.

B) Increase IV fluids to 200 cc/hr, using 5% dextrose/0.45% saline.

C) Hemodialysis.

D) Administer hydrochlorothiazide.

E) Administer furosemide.

Answer 5.6.6 The correct answer is "E." The treatment of acute renal failure due to ATN is largely supportive. In this oliguric patient with signs of volume overload, a trial of a loop diuretic is appropriate. Intravenous furosemide dosed at 20 to 100 mg every 6 to 12 hours is a reasonable way to start. Of note, furosemide will often improve the symptoms of volume overload even if there is no diuresis; it has some direct vasodilating affect which decreases pulmonary artery pressure. "A," dopamine, is not effective in the treatment of ATN (it is not "renal sparing" and does not increase GFR). "B," more fluid, is clearly not indicated in this patient who is already fluid overloaded. Why not dialysis you ask ("C")? Early dialysis in ATN is associated with greater mortality and increased kidney damage from hypotension, infection, and complement activation in the kidney. "D," HCTZ, is less likely than furosemide to achieve a good diuretic effect in the setting of a low GFR.

Your patient has very little response to furosemide, but you match her input and output and she has enough insensible loss to resolve her rales. She begins to eat, and you monitor her fluid intake carefully. You match her fluid intake with output, giving normal saline to match her urine output and suspected insensible losses. You treat her hyperkalemia with sodium polystyrene sulfonate without sorbitol (Kayexalate), which is effective. Her BUN and creatinine continue to rise over the next two days and reach 60 and 4 mg/dL, respectively. The plasma HCO₃ is 18 mEq/L.

Question 5.6.7 You now recommend:

A) Hemodialysis.

B) Sodium bicarbonate.

C) Strict protein restriction.

D) Continuing to match intake and output.

E) All of the above.

Answer 5.6.7 The correct answer is "D." At this point, there is no reason to change your therapeutic approach. In particular, hemodialysis is not necessary. Indications for hemodialysis in this patient might include symptomatic uremia (e.g., coma, pericarditis), severe hyperkalemia or acidosis unresponsive to other therapies, and complications of volume overload (e.g., pulmonary edema). Dialysis is actually associated with worse outcomes and prolonged renal disease (complement fixation in the kidney produces additional injury, episodic hypotension from dialysis increases kidney injury). Sodium bicarbonate is used orally in patients with significant chronic acidosis in end-stage renal disease, but many patients can tolerate the temporary mild acidosis associated with acute kidney injury. Dramatic protein restriction will probably help to control uremia, but lower BUN should not be your primary goal. Your patient is recovering from surgery and was probably septic. She requires good nutrition to continue to heal.

Question 5.6.8 In patients with acute tubular necrosis, the most common cause of death is:

A) Hemorrhage.

B) Adverse event of hemodialysis.

C) Infection.

D) Transfusion reaction.

E) Heart failure secondary to fluid overload.

Answer 5.6.8 The correct answer is "C." In patients with ATN who die, infection is the usual culprit. It is critical to avoid sepsis in these patients. Also, serious infection resulting in sepsis is a common cause of ATN. It's the circle of life … or death, in this instance.

Ten days after her surgery, your patient's urine output increases markedly. Her BUN and creatinine return to their premorbid levels. The National Kidney Foundation makes you an honorary nephrologist and awards you the Bronze Nephron.

Objectives: Did you learn to…

• Evaluate a hospitalized patient for acute kidney injury?

• Use urine studies, including urine sodium and FENa, to assist in the diagnosis of acute kidney injury?

• Identify acute tubular necrosis?

• Describe common causes of acute tubular necrosis, its treatment, and its prognosis?

While on call, you admit a 75-year-old female for confusion. One month ago, she started HCTZ for hypertension. Her medications include HCTZ 25 mg daily, levothyroxine 125 mcg daily, aspirin 81 mg daily, sertraline (Zoloft) 50 mg daily, and atorvastatin (Lipitor) 40 mg daily. She has a 50-pack-year history of tobacco use and continues to smoke.

On examination, you find an irritable, confused female in no acute distress. Her admission vitals: BP 100/60 mm Hg, P 120 bpm, RR 12 breaths/minute, T 36.1°C, weight 50 kg. Her oral mucosa is dry and she has poor skin turgor. She has clear lungs, an S4 on heart examination, and no edema. Her neurological examination is nonfocal.

Laboratory results: Na 110 mEq/L (low), K 3.0 mEq/L (low), Cl 70 mEq/L (low), HCO₃ 33 mEq/L (high), BUN 30 mg/dL, Cr 1.0 mg/dL, glucose 110 mg/dL. Plasma osmolality 220 mOsm/L (normal 270–299 mOsm/L).

Question 5.7.1 Which of the following statements is true regarding the etiology of her hyponatremia?

A) She has pseudohyponatremia.

B) She has isovolemic hyponatremia.

C) She has hypovolemic hyponatremia.

D) She has hypervolemic hyponatremia.

Answer 5.7.1 The correct answer is "C." The definition of hyponatremia is a plasma sodium concentration below 135 mEq/L. The evaluation of hyponatremia begins with the determination of the validity of the plasma sodium measurement. First question: is this pseudohyponatremia ("A")? Look at the measured serum osmolality. If it is low (as it is here), the patient does not have pseudohyponatremia. Pseudohyponatremia is caused by either hyperlipidemia or hyperproteinemia decreasing the water content of plasma. This distinction was more important in the past; newer laboratory techniques compensate for pseudohyponatremia.

Hyperglycemia and severe uremia can cause hyponatremia (not called "pseudohyponatremia" for reasons that the editors don't fully understand). In an instance where a patient's measured sodium concentration is hyponatremic and his glucose is 800 mg/dL, the measured serum osmolality may be normal or elevated (due to the elevated glucose, which "counts" as osmoles) and should be compared to the calculated osmolality using the equation:

If the calculated osmolality approximates the measured osmolality, then much of the "hyponatremia" will autocorrect when the hyperglycemia is corrected. Therefore, you would not want to aggressively correct the serum sodium concentration without consideration of the patient's hyperglycemia. When in doubt, frequent sodium monitoring is advisable.

The next step in the evaluation of hyponatremia is to determine the patient's volume status. This patient has no signs of volume overload, such as edema or crackles, making hypervolemia unlikely. She is tachycardic with a low blood pressure, dry mucous membranes, and a BUN/Cr ratio greater than 20, suggesting she is hypovolemic. Most likely, she has a hypovolemic hyponatremia.

Question 5.7.2 What further information will help you narrow the differential diagnosis of hyponatremia in this patient?

A) FENa.

B) Urine osmolality and urine sodium concentration.

C) Urine creatinine concentration.

D) Urine potassium and calcium concentration.

Answer 5.7.2 The correct answer is "B." Urine osmolality can be used to distinguish between impaired water excretion caused by SIADH (syndrome of inappropriate secretion of anti-diuretic hormone), and pathologic water intake (polydipsia). In SIADH, the urine will be inappropriately concentrated with urine osmoles of >100 mosmol/kg (the patient is unable to retain sodium). FENa is discussed earlier; although the word "sodium" is in it, FENa is not helpful for discovering the etiology of hyponatremia. Concentration of potassium and calcium is not likely to add any useful information.

You order urine studies. Urinalysis: specific gravity 1.025, pH 5.0, trace protein, 0 to 1 RBC/hpf, 0 to 1 WBC/hpf, otherwise negative. Spot urine Na 70 mEq/L (elevated) and urine osmolality = 700 mmol/kg (elevated).

Question 5.7.3 Given the patient's history, urine studies, and hypovolemic status, what is the most likely diagnosis?

A) Syndrome of inappropriate secretion of anti-diuretic hormone (SIADH).

B) Heart failure (HF).

C) Diuretic-induced hyponatremia.

D) Hyponatremia due to reset osmostat.

E) Potato chip deficiency (hypopringlism).

Answer 5.7.3 The correct answer is "C." In order to be useful in the diagnosis of hyponatremia, urine studies must be viewed in the context of volume status, plasma osmolality, and electrolyte levels. This patient's laboratory results are consistent with SIADH. However, patients with SIADH should be euvolemic or slightly hypervolemic. Thus, her laboratory results and clinical picture are most consistent with diuretic-induced hyponatremia. Note that she also has a contraction alkalosis (low chloride, elevated bicarbonate).

The appropriate response of the kidney to hypoosmolality is to make maximally dilute urine (retain sodium to correct the hypoosmolality). Thus, the urine should have a specific gravity less than 1.005 and osmolality less than 100 mmol/kg.

Inappropriately concentrated urine (osmolality >100 mmol/kg) occurs when there is limited excretion of fluid and may be observed in SIADH, HF, cirrhosis, and renal failure. This is also reflected in the urine sodium. If the kidneys respond to hyponatremia as expected, urine sodium concentration should be low, typically less than 20 mmol/L and often less than 10 mmol/L (the kidneys are attempting to retain sodium to increase the serum osmolarity). In the setting of hypovolemia, if the urine sodium concentration is inappropriately high, something is inappropriately spurring the kidney to excrete sodium (e.g., diuretic use, hypoaldosteronism). In this patient, the elevated urine sodium is likely due to the diuretic. Diuretic use is the most common cause of hypovolemic hypoosmolality, and thiazides are more commonly associated with hyponatremia than are loop diuretics (furosemide, etc.). Your patient is hypovolemic and hyponatremic, with a high urine sodium concentration and the history of diuretic use: most likely, her hyponatremia is diuretic induced.

"D," a reset osmostat, requires special mention. A reset osmostat, which is responsible for 20% to 30% of hyponatremia, occurs when the patient's body "adapts" to hyponatremia and gives up trying to correct the problem: the kidneys just throw in the towel. Patients with a reset osmostat will present like SIADH (hyponatremia, euvolemia or slight hypervolemia, and inappropriately concentrated urine) but will be resistant to treatment. If a patient with apparent SIADH does not respond to the usual treatment, consider a reset osmostat. Since patients with a reset osmostat generally have mild hyponatremia (125–130 mg/dL) and are generally asymptomatic, trying to correct the sodium by limiting water intake is unnecessary and futile.

Question 5.7.4 In addition to discontinuing her diuretic, which of the following approaches is the best initial therapy for her hyponatremia?

A) Saline 0.9% 1 L bolus followed by 150 cc/hr.

B) Fluid restriction to 1,500 cc/day.

C) Saline 3% 100 cc/hr for 24 hours.

D) Saline 0.45% 100 cc/hr for 24 hours.

E) Saline 3% at 60 cc/hr and furosemide 40 mg IV.

Answer 5.7.4 The correct answer is "A." This patient is hypotensive and tachycardic and thus needs volume somewhat quickly to address her abnormal vital signs. If this patient was not hemodynamically compromised, you could forgo the fluid bolus. Excessively rapid correction of hyponatremia may lead to pontine myelinolysis.

Sodium concentrations less than 120 mEq/L are considered severe hyponatremia. Patients with acute, severe hyponatremia are almost always symptomatic as a result of the low sodium. By definition, acute hyponatremia has been present for 48 hours or less and chronic hyponatremia for more than 48 hours. As previously discussed, your patient's hyponatremia is due to a diuretic, which she started 1 month ago. Therefore, her hyponatremia is more likely to be chronic.