38: Chronic Kidney Disease

Chronic kidney disease (CKD) is defined as the presence of reduced glomerular filtration rate (GFR) or evidence of kidney damage for at least 3 months, which becomes increasingly common at older ages. In older populations, GFR should be estimated using a prediction equation. CKD stage should be assigned based on the level of kidney function. The vast majority of older adults with CKD will die without progressing to end-stage renal disease (ESRD); however, even mild-to-moderate CKD is associated with functional decline, cognitive impairment, frailty, and complex comorbidity.

The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) disease-specific guidelines have been established to direct the evaluation and management of patients with CKD; however, because of the substantial heterogeneity in life expectancy, functional status and health priorities among older adults with CKD, an individualized, patient-centered approach might be helpful. Special considerations must be made when treating CKD-related comorbidities and complications. Among older adults with advanced CKD, a shared decision-making approach should be used to facilitate decisions about dialysis. Geriatric assessment may be helpful to identify older adults who are vulnerable to functional decline and poor outcomes after initiation of dialysis. Palliative and supportive care should be offered to those who experience a high symptom burden regardless of disease stage and dialysis decision.

The NKF/KDOQI Clinical Practice Guidelines provide standardized terminology for the evaluation and stratification of CKD. Based on these guidelines, CKD is defined as the presence of reduced GFR or evidence of kidney damage for at least 3 months. Kidney damage is defined as pathologic abnormalities or markers of damage, most frequently identified by albuminuria. This CKD definition is based on GFR and kidney damage, regardless of the underlying kidney disease etiology.

Among older adults, serum creatinine is a poor marker of kidney function. However, because measuring GFR is not clinically feasible, GFR should be estimated using prediction equations based on the serum creatinine and other factors affecting creatinine production including age, race and gender. Multiple estimating formulas are available (see www.kidney.org/professionals/kdoqi/gfr_calculator.cfm) including the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Although there is no consensus on which formula should be used for older adults, the CKD-EPI equation may be superior, especially among patients with normal GFR.

After estimating GFR, CKD stage should be assigned based on the level of kidney function. The stages range from 1 to 5, with a higher stage indicating more severe CKD (Figure 38–1). The guidelines include a clinical action plan based on the CKD stage. In early stages, the focus is on diagnosis of CKD, treatment of comorbid conditions, and slowing CKD progression. In later stages, guidelines recommend preparation and initiation of renal replacement therapy.

Although age-specific cutpoints for CKD staging have been proposed, current recommendations do not support age-specific cutpoints. A revised staging system that incorporates level of GFR and urinary albumin-to-creatinine ratio (ACR: normal <30, high 30–300, and very high >300 mg/g) has also been proposed.

The prevalence and incidence of CKD increases markedly with age. In a large analysis of data from a U.S. population-based study of more than 30,000 participants, the prevalence of CKD defined as an eGFR <60 mL/min/1.73 m² was 1%, 10%, 27%, and 51% among those <60, 60–69, 70–79, and ≥80 years old, respectively. The prevalence of albuminuria defined as an ACR ≥30 mg/g was 7%, 14%, 21%, and 33% among those <60, 60–69, 70–79 and ≥80 years old, respectively.

Among older adults, CKD is associated with adverse health outcomes, including mortality, cardiovascular disease (CVD), and ESRD. The natural history of CKD has traditionally been described as a progressive decline in kidney function with an expectation that a significant proportion of these patients will develop ESRD and require renal replacement therapy. Accordingly, a priority of CKD management is to identify and treat patients with early stage CKD to slow disease progression. However, more than 95% of older adults with CKD die without progressing to ESRD. Although the risk of ESRD may decrease with age, even mild-to-moderate CKD is associated with functional decline, cognitive impairment, and frailty.

Common Risk Factors

Risk factors for new-onset CKD include older age, obesity, smoking history, diabetes, and hypertension. Other important risk factors include history of CVD, family history of CKD or ESRD, history of urinary tract infection or urinary obstruction, and systemic illnesses that may affect the kidney (eg, systemic lupus erythematosus, multiple myeloma).

Screening for Chronic Kidney Disease

Because of the age-related decline in kidney function, poor correlation between eGFR and pathologic findings on kidney biopsy, and concerns about the validity of GFR estimating equations in older populations, using eGFR to screen all older adults for CKD is not recommended. For an older patient, reduced eGFR (<60 mL/min/1.73 m²) should be interpreted in the context of the medical history and other lab abnormalities (eg, history of diabetic retinopathy, rate of eGFR decline, presence of elevated ACR) before a diagnosis of CKD is made.

Medical History and Physical Exam

Evaluation of CKD includes a thorough medical history, physical exam, and specific laboratory measures. The goal of this evaluation is to identify the underlying cause or causes, as multifactorial disease is common among older adults. A further goal is to identify CKD-related complications.

The medical history should include information on diabetes, hypertension, CVD, lower urinary tract disease and an evaluation for symptoms suggestive of vasculitis. Patients should be asked if they have a family history of CKD or ESRD. Typically, symptoms related to CKD do not occur until disease is advanced (eGFR <15 mL/min/1.73 m²) and include sleep disturbance, decreased attentiveness, nausea, vomiting, weight change, dyspnea, lower-extremity edema, fatigue, muscle cramps, peripheral neuropathy, and pruritus. A review of medications should also be performed to assess for medications that may be exacerbating kidney injury, such as nonsteroidal antiinflammatory drugs (NSAIDs), or medications that may be contraindicated or require dose reductions in CKD, such as hypoglycemic agents, oral and intravenous antimicrobials, antihypertensive agents, and opioids. Several resources are available to further assist in medication dosing and management for patients with CKD.

Because of the disproportionately higher rates of geriatric syndromes among older adults with CKD, comprehensive geriatric assessment for functional status, cognition, depression, and impaired mobility should be considered in this population.

The physical exam should include vital signs, orthostatic blood pressure and pulse, evaluation of volume status, and evaluation of skin and extremities.

Lab Evaluation

Diagnostic testing should include urinalysis and random ACR. Twenty-four-hour urine collections for protein and creatinine clearance can be considered, but may be difficult for older adults. Blood work includes sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, calcium, phosphorus, albumin, total protein, lipid profile, and complete blood count with differential. Additional tests may be indicated if the differential diagnosis includes causes other than diabetes or hypertension.

Evaluation for Underlying Causes

Prior to attributing reduced eGFR to CKD, an evaluation for reversible conditions causing acute kidney injury (AKI) should be considered. In addition, a rapid reduction in eGFR in a patient with known CKD should be considered AKI and evaluated promptly (see Figure 38–1).

Hypertension and diabetes are the 2 most common causes of CKD. However, multiple factors may contribute to the risk for CKD in the older population, including renal vascular disease, chronic urinary obstruction, systemic vasculitis, multiple myeloma, or intrinsic kidney disorders such as glomerulonephritis or nephrotic syndrome. High levels of proteinuria, abnormal urinary sediment with red or white blood cells, or rapidly progressive loss of kidney function should prompt work-up for causes other than diabetes or hypertension.

CKD-related complications include fluid and electrolyte abnormalities, bone and mineral disease, anemia and poor nutrition. Many of these complications can be treated by a primary care physician, but as kidney disease progresses and complications become more complex, referral to a nephrologist may be helpful. There are also special considerations for treating CKD-related complications among older adults (Table 38–1).

In the Primary Care Setting

Because of the large number of older adults with mild-to-moderate CKD, care for these patients is often provided by the primary care physician. Routine treatment of CKD in the primary care setting includes monitoring of kidney function, managing CKD-related complications, treating CVD risk factors, preventing additional kidney injury, and promoting general health.

Medical optimization of hypertension and diabetes may improve kidney function and prevent progression of kidney disease (see Table 38–1). Preferred medications for blood pressure control in patients with CKD include diuretics, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and β blockers. Achieving blood pressure and hemoglobin A1c goals often requires multiple medications and the benefits of aggressive medical treatments to reach recommended targets should be considered in the context of the patient’s health goals and balanced against the risks of treatment, particularly in frail older patients.

Proteinuria is an independent risk factor for progression of kidney disease as well as for mortality. ACEIs or ARBs are recommended as first-line treatment for proteinuria. However, older adults are underrepresented in the clinical trials used to develop CKD guidelines and evidence on the benefits of ACEIs and ARBs in this population is limited. Furthermore many older adults with reduced eGFR do not have proteinuria and the effectiveness of angiotensin blockade in these patients is limited. Finally, older adults are at risk for adverse drug events, therefore after initiation or dose increase of an ACEI or ARB, the serum creatinine and potassium should be measured.

In addition to treatment of high blood pressure and hyperglycemia, optimization of other risk factors to prevent CKD progression include smoking cessation and avoidance of nephrotoxins and additional kidney injury. However, there is limited evidence of the effectiveness of these interventions specifically among older adults with CKD.

Intense medical optimization of multiple conditions in geriatric patients often requires polypharmacy and should be considered in the context of the patient’s preferences and health care goals. In older adults with CKD, complex comorbidity and geriatric syndromes are common, signs and symptoms often do not reflect a single underlying pathophysiologic process, there can be substantial heterogeneity in life expectancy, functional status and health priorities, and information on the safety and efficacy of interventions is lacking. For all these reasons, an individualized, patient-centered approach to CKD management for geriatric patients may be useful (see Figure 38–1).

Referral

The NKF/KDOQI guidelines recommend referral of patients with CKD Stage 4 (eGFR <30 mL/min/1.73 m²) to a nephrologist for comanagement (see Figure 38–1). Indications for earlier nephrology referral include an unexplained, rapid decline in kidney function, the presence of active urinary sediment, proteinuria without underlying diabetes, or for patients with possible underlying systemic diseases such as multiple myeloma, hepatitis, or HIV. Additionally, patients with significant metabolic derangements may benefit from earlier evaluation and management by a nephrologist. Patients with gross hematuria or microscopic hematuria with a negative nephrologic work-up or with risk factors for bladder cancer should be considered for urologic referral.

Dialysis

Older adults represent the fastest growing group with ESRD. Decisions about whether or not to start dialysis can be challenging. While it is ideal to make decisions about dialysis initiation well in advance of a patient’s reaching ESRD, because of the difficulty in predicting CKD progression and the competing risk for death this is often not possible. Qualitative research in this area suggests that uncertainty about the expected course of CKD appears to be an important concern among both patients and nephrologists. Because of this uncertainty, nephrologists have also reported avoiding discussions with patients about the future and prognosis.

Overall, progression to ESRD carries a poor prognosis. The benefits of dialysis in geriatric patients are less-well-studied and highly variable, depending on the patient’s baseline functional status and other medical conditions. Among patients 80–84 years old initiating dialysis, the average life expectancy was 16 months; however, survival ranged from as short as 5 months to as long as 36 months (interquartile range). Older adults starting dialysis are at increased risk for persistent functional decline, increased hospitalizations and are more likely to die in the hospital than at home. In one study of patients ≥80 years of age, within 6 months of initiating dialysis over 30% had a decline in functional ability and required increased caregiver support or nursing home care. Factors associated with death within one year of initiating dialysis in octogenarian patients were poor nutritional status, late referral to a nephrologist, and functional dependence.

A shared decision-making approach that includes the patient, their family and caregivers along with the nephrologist and primary care physician should be used. It may be helpful to elicit the patient and family’s values, preferences and health goals and then use these to guide the decision making discussion. Because of the likelihood of functional decline after dialysis initiation, geriatric assessment before initiation of dialysis that includes measures such as gait speed, functional assessment for basic and instrumental activities of daily living and cognitive testing may be helpful to identify those at highest risk for poor outcomes.

Withdrawal of Dialysis

Particularly for older adults with multimorbidity and geriatric syndromes, any early benefit of dialysis may quickly become a burden to the patient and family or may fail to improve symptoms that were attributed to ESRD, such as cognitive deficits. Withdrawal of dialysis is best done with the support of hospice or palliative care, as patients are likely to live for several days after stopping dialysis and have high symptom burden.

Kidney Transplant

Transplant is the best option for long-term renal replacement therapy. Advanced age alone should not be a contraindication to consideration for transplantation; several studies have demonstrated comparable outcomes among younger and older transplant patients. However, potential candidates must be selected carefully because of the competing risk of death and high complexity of post-transplant care. Predictive models may help determine which older patients may be appropriate for consideration.

Palliative and Supportive Care

Regardless of whether patients decide to pursue or forgo dialysis, patients with advanced CKD experience a high symptom burden and palliative and supportive care that addresses physical, emotional, and social suffering should be considered. For patients not on dialysis, fluid overload can be managed with diuretics if the patient still produces urine. Uremia commonly manifests as nausea, and can be managed with antiemetics. Hyperkalemia can be managed to some extent with diuretics and potassium excreting agents such as Kayexalate (sodium polystyrene sulfonate). The improvement of metabolic parameters achieved with these therapies must be balanced with the burden of treatment (eg, urinary incontinence, diarrhea). Patients with ESRD often report symptom burdens and reductions in quality of life similar to patients with terminal malignancy. Pain is a common symptom and should be treated aggressively; however, caution is needed when using renally cleared opioids such as morphine. Patients nearing the end of life may benefit from hospice or palliative care referral.