Primary Care Considerations for the Older Adult with Chronic Kidney Disease
Upon completion of this educational activity, participants should be able to:
1. Define chronic kidney disease and be familiar with its classification.
2. Recognize the high prevalence of chronic kidney disease in older adults.
3. Identify key management aspects to preventing the progression of chronic kidney disease in older adults.
4. Identify important therapeutic targets in the management of chronic kidney disease and its complications.
5. Identify appropriate indications for early nephrology referral in older patients with chronic kidney disease.
Chronic kidney disease (CKD) is a common and frequently progressive condition associated with significant morbidity and mortality. The incidence and prevalence of CKD continues to rise in the United States, particularly in the elderly population. Early stages of CKD are usually clinically silent, while more advanced stages are manifested by nonspecific symptoms and a variety of biochemical abnormalities. Care of older patients with CKD therefore requires a high degree of awareness and knowledge of the many different manifestations. In this article, we will review primary care aspects for the management of patients with CKD, with emphasis on issues pertinent to the geriatric population.
In 2002, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) released guidelines to standardize the definition of CKD and its stages.1 Chronic kidney disease is defined as the presence of structural or functional kidney damage for greater than 3 months and is classified according to the severity of decline in glomerular filtration rate (GFR; Table I). An analysis of the most recent National Health And Nutrition Examination Survey (NHANES) data estimated the prevalence of CKD stages 1 through 4 to be 13.1% of the general adult U.S. population, or greater than 26 million people.2 The prevalence of all stages of CKD increases with age. Compared to a prevalence of less than 1% in patients age 20-39 years, nearly 40% of patients over the age of 70 years have CKD stage 3 or 4.2 Thus, CKD is an important consideration for anyone caring for older adults.
Several factors contribute to the increasing prevalence of CKD with aging, including the natural decline in renal function seen with aging itself. Risk factors for CKD such as hypertension and atherosclerotic disease also increase with age. While a comprehensive review of the approach to CKD evaluation is beyond the scope of this article, initial work-up should minimally include a urinalysis and renal imaging. In general, renal ultrasound is preferred as an initial imaging modality for its ability to accurately assess renal size, to rule out obstructive nephropathy, and for its noninvasive nature. Specifically in the older adult we also recommend evaluation for occult multiple myeloma, as upwards of 50% of myeloma patients have renal involvement, and renal dysfunction may be the presenting manifestation.3 For a more comprehensive discussion on CKD evaluation, the reader is referred to KDOQI guidelines.1 The role and timing of nephrology referral is discussed below.
Preventing CKD Progression
A primary goal of CKD management is to delay or prevent progression toward end-stage renal disease. Achievement of this goal is most likely to occur with interventions during the early stages of CKD when significant residual renal function remains. To help identify at-risk patients, many laboratories now routinely report estimated GFR values along with serum creatinine measurements. The most commonly used formula to derive these values is the Modification of Diet in Renal Disease (MDRD) formula.4 Although the original MDRD trial did not include patients over the age of 70 years, subsequent studies have demonstrated the validity of this formula in geriatric populations.5,6 Despite routine estimated GFR reporting, however, studies suggest that there remains underrecognition of early stages of CKD, highlighting the need for increased awareness.7,8
Delay in progression of CKD can be accomplished through aggressive modification of risk factors, most notably strict blood pressure control. Both the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)9 and KDOQI guidelines10 recommend a target blood pressure of less than 130/80 mm Hg in patients with CKD. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are considered first-line drugs due to their demonstrated superior efficacy in delaying progression of CKD when compared to other classes of antihypertensive agents.11-13 The reno-protective benefit of ACE inhibitors has been demonstrated even in patients with advanced CKD (estimated GFR < 30 mL/ min/1.73m2),14 a group in whom ACE inhibitors and ARBs are often incorrectly assumed to be contraindicated. Compared head-to-head, ACE inhibitors and ARBs appear to provide equivalent efficacy,15,16 and literature suggests that combination use is safe and may provide synergistic renal benefits.17,18 Of note, since none of the large clinical trials enrolled patients over age 70 years, there remains a paucity of data to guide CKD management specifically among older adults. Nonetheless, with initiation at low doses and gentle titration, ACE inhibitors and ARBs are generally well-tolerated even in the frail elderly and should be considered a cornerstone of CKD management.
In patients with diabetes mellitus, strict glycemic control (targeting hemoglobin A1C < 7%) has been shown to decrease the likelihood of developing microvascular complications and, in patients with established nephropathy, slowing the rate of CKD progression.19 Patients with diabetes should be screened annually for the development of microalbuminuria (urine microalbumin:creatinine ratio of > 30 mg/g), and identified patients should be treated with an ACE inhibitor or ARB, even if normotensive.19,20 The benefit of using these agents prophylactically in nonalbuminuric and normotensive diabetic patients remains uncertain.
Cardiovascular Morbidity and Mortality
Numerous studies have demonstrated that CKD is an independent risk factor for cardiovascular mortality, with an inverse relationship between risk and GFR level.21,22 Statistically, patients with CKD are more likely to die from cardiac disease than to progress to end-stage renal failure.23,24 Therefore, an important component of CKD management is aggressive modification of cardiovascular risk factors such as hypertension, diabetes mellitus, and hyperlipidemia. Aggressive management of each of these factors will also help delay CKD progression.
The benefits of lipid-lowering therapy using statins in the geriatric population (including octogenarians) has been confirmed in numerous clinical trials, for both primary and secondary prevention of cardiovascular events.25-27 Based on these studies, the most recent update of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines recommends treating older adults (age > 70 yr) the same as the general population, including intensive lipid-lowering therapy in those at increased risk.28 The ATP III guidelines do not specifically note CKD as a major risk factor in determining low-density lipoprotein (LDL) target, as there has been little clinical investigation done within this population. However, given the overwhelming risk for cardiovascular events, the NKF KDOQI guidelines view patients with CKD as a high-risk group, and therefore suggest an LDL target of < 100 mg/dL.29 Moreover, there is a growing body of literature to suggest that statin therapy may slow progression of CKD,30,31 although these results need to be confirmed in large clinical trials.
Drug Therapy Considerations
Drug prescribing in the geriatric population is complicated by the high prevalence of CKD and resultant need for dosage adjustments. Failure to adjust for reduced renal function can lead to significant toxicity; conversely, underprescribing of appropriate drugs in patients with CKD has also been observed.32 Therefore, both awareness of CKD and knowledge of appropriate dosage adjustments are essential. A comprehensive review of this topic is beyond the scope of this article, and the reader is referred to a recent review by Munar and Singh,33 as well as to the reference book Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children34 (Table II). Below we offer several examples of drug dosage and interaction using scenarios commonly encountered in geriatric practice.
Nonsteroidal anti-inflammatory drug (NSAID) use is very common in the elderly and can contribute to both acute and chronic renal insufficiency.35 Furthermore, NSAIDs may exacerbate hyperkalemia, a potentially serious occurrence in patients with advanced CKD. For this reason, we strongly suggest avoiding NSAIDs and using acetaminophen as the first-line analgesic in patients with CKD. An exception is daily aspirin use for cardioprotective effects.
Diabetic agents should be used with caution in patients with CKD stage 3 and beyond. Metformin is contraindicated when the GFR falls below 50 mL/min/1.73m2 due to the risk of lactic acidosis, although some have advocated continuing this medicine with close monitoring. The sulfonylurea drugs glyburide and chlorpropamide are both renally cleared, and their use in patients with CKD can result in severe hypoglycemia. Conversely, glipizide is primarily hepatically metabolized and should be considered the sulfonylurea of choice in patients with CKD. Similarly, the thiazolidinediones (pioglitazone, rosiglitazone) undergo hepatic metabolism and can be used safely in CKD.
Many older adults also take over-the-counter supplements or herbal remedies. Since “natural” remedies are not subject to Food and Drug Administration regulation, it is incumbent upon practitioners to be aware of potential side effects of commonly ingested substances. In particular, several substances warrant close observation in patients with CKD. Aristocholic acid was previously a common ingredient in Chinese remedies promoted for weight loss and was found to be associated with interstitial nephritis leading to end-stage renal disease.36 Noni juice is promoted for general well-being but can be dangerous in patients with CKD due to its very high potassium content.37 Juniper berry, used for dyspepsia, has been associated with worsening renal insufficiency. Licorice root is advocated for upper-respiratory symptoms and can exacerbate hypertension and fluid retention.
Anemia is a common complication of CKD, usually developing when GFR falls below 60 mL/min/1.73m2 . The prevalence of anemia increases significantly with more advanced renal insufficiency and is present in more than 40% of patients with CKD stage 4.38 Therefore, among patients with known CKD stage 3 or higher, hemoglobin should be checked at least annually. The anemia of CKD results from a relative deficiency in renal erythropoietin production and remains a diagnosis of exclusion. Particularly in the geriatric population, other causes of anemia such as iron deficiency or hematologic disorders (eg, multiple myeloma, myelodysplastic syndromes) must be excluded.
Once the diagnosis of renal anemia is established, the mainstay of management is erythropoietin replacement therapy. Current guidelines recommend a target hemoglobin level of 11 g/dL to 12 g/dL.39 This target is supported by randomized clinical trials that have failed to show any survival benefit from higher hemoglobin targets (eg, 13 g/dL to 15 g/dL range). Furthermore, there is accumulating evidence to suggest that higher hemoglobin targets are actually associated with an increase in cardiovascular events40 and mortality.41 Nevertheless, other studies have suggested that normalization of hemoglobin confers quality- of-life benefits such as improved mental health and physical well-being.42,43 These factors are of particular importance in the geriatric population at risk of functional decline. Hemoglobin targets may need to be individualized in this group.
Metabolic Bone Disease
Bone health is an especially important consideration in the elderly due to the prevalence of osteoporosis and the high associated morbidity and mortality from complications such as hip fracture. Further complicating this issue in patients with CKD is secondary hyperparathyroidism, which develops as GFR falls below 60 mL/min/1.73m2 and contributes to disordered bone mineral metabolism and fracture risk.44 Current KDOQI guidelines suggest checking a parathyroid hormone (PTH) level when a patient’s GFR falls below 60 mL/min/1.73m2, with supplemental vitamin D therapy prescribed to maintain PTH levels in the normal or modestly elevated range for patients with CKD stage 3 and 4.45 Care must be taken not to oversuppress PTH, as this can result in low-turnover bone disease, which is also associated with a higher fracture risk.46
Hyperphosphatemia is an independent risk factor for mortality among dialysis patients47 and represents an important target for CKD management. Phosphorus retention begins as early as CKD stage 2 and contributes to the pathogenesis of secondary hyperparathyroidism, although overt hyperphosphatemia (level > 4.6 mg/dL) rarely occurs before GFR declines below 30 mL/min/1.73m2.38 Dietary phosphorus restriction to 1000 mg per day is the first step in management and contributes to lowering PTH levels.45 Nutrition consultation is a critical aspect of dietary modification, and it is essential that the person who prepares meals and/or does the grocery shopping be involved in the educational process. When dietary changes alone are inadequate, the prescription of oral phosphate binders with meals and snacks is an effective option. Either calcium acetate or calcium carbonate is a reasonable initial choice among patients with low or normal calcium levels. However, because some calcium absorption does occur and may contribute to worsening vascular calcification and even mortality,48 non-calcium–containing binders such as sevelamer hydrochloride or lanthanum carbonate should be considered in patients with higher calcium levels.
Another contributor to bone risk in patients with CKD is the development of metabolic acidosis as a result of the kidney’s inability to excrete the obligate daily acid load produced from protein metabolism. Metabolic acidosis leads to bone buffering and results in osteopenia, and bicarbonate supplementation is indicated to maintain a serum total CO2 level greater than or equal to 22 mEq/L.45 Sodium-containing bicarbonate preparations must be used with caution because of the risk of exacerbating hypertension.
With progressive CKD, a discussion regarding choice of renal replacement therapy becomes necessary. Patients over the age of 70 years are often considered unsuitable candidates for renal transplantation. Similarly, peritoneal dialysis demands a great deal of patient involvement and/or caregiver support, and few elderly patients choose this modality. Therefore the primary options for the majority of older adults with CKD approaching renal failure are hemodialysis or palliative care without dialysis.
There is no defined age cut-off for offering hemodialysis, and in our own practice we have had numerous highly functioning octogenarians maintained on hemodialysis with an excellent quality of life. Yet, clearly, not every patient with CKD is an appropriate candidate for dialysis. Examples of such patients include those with poor functional status or advanced dementia. Low functional status at dialysis initiation is a predictor of mortality, and at least one study suggests that dialysis therapy does not prolong survival in this population but contributes to the “unnecessary medicalisation of death.”49 As with other terminal conditions, advanced patient and family education is vital in arriving at an informed decision not to pursue renal replacement therapy. Often, there are misconceptions regarding what dialysis therapy entails, as well as what dialysis can offer. Such advanced discussions also allow for appropriate palliative care planning.
A traditional view in nephrology has been that death from progressive uremia is a relatively painless process, particularly in comparison to other terminal conditions such as cancer; however, recent studies challenge this view. A survey of patients with end-stage renal disease who chose not to pursue renal replacement therapy showed a high prevalence and degree of symptomatology, including pain in over 50%.50 A recent review further highlights the current lack of expertise in palliative care of patients with CKD and emphasizes the need for further research.51
Timing of Nephrology Referral
Optimal management of patients with CKD involves close cooperation between nephrologists and primary care physicians. In early stages of CKD, nephrologists can help to define goals in risk factor modification. In later stages, nephrologists often assume responsibility for aspects of CKD care such as erythropoietin therapy for anemia, preparations for dialysis, and referral for transplantation.
We strongly advocate for early nephrology referral to help modify risk factors for CKD progression and to allow adequate time to prepare for renal replacement therapy. Indeed, studies have demonstrated that early nephrology referral (at least 3-6 mo before initiation of dialysis) has been associated with higher vascular access rates,52 lower mortality on dialysis,53 and higher transplantation rates.54 As discussed in the previous section, nephrology involvement may also facilitate discussions on palliative approaches and allow for an informed decision not to pursue renal replacement therapy when appropriate.
Given the high prevalence of CKD, it is impractical to refer all patients for evaluation by a nephrologist. Indeed, many patients with mild CKD experience a stable course and do not require intervention. Table III provides guidelines that may help primary care physicians triage those patients who should be referred early in their course, regardless of patient age.
Chronic kidney disease is highly prevalent in the geriatric population and is associated with significant morbidity and mortality. Primary care physicians should be familiar with common management issues such as anemia, metabolic bone disease, medication management, and cardiovascular risk factor modification among patients with CKD (Tables II and IV). Early referral to nephrology is critical in allowing adequate time to prepare for renal replacement therapy and to assist in palliative care discussions when appropriate. Future research should be directed at evaluating the optimal management of geriatric patients as they approach end-stage renal failure, particularly in terms of palliative care needs.