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Chronic Kidney Disease:

Chronic Kidney Disease:

End-stage renal disease (ESRD) results when the kidneys can no longer function well enough to sustain life. It is estimated that this occurs when the glomerular filtration rate (GFR) falls to between 10 and 15 mL/min.

Among African Americans, the incidence of ESRD is at least 4 times higher than among whites (Figure 1). In this article, we discuss possible explanations for the disproportionate burden of ESRD on the African American community. We also present practical tips, tailored specifically to the needs of African Americans, on how to detect renal insufficiency earlier, how to slow the progression of the disease, and when-and how-to work with specialists to provide optimal care for patients with chronic and end-stage kidney disease.

EPIDEMIOLOGY

At present, ESRD develops in more than 100,000 Americans each year, and more than 450,000 persons are currently receiving renal replacement therapy for ESRD.1 In addition, it is estimated that for every patient with ESRD, another 25 have abnormally elevated serum creatinine levels. Thus, approximately 5.6% of Americans have some degree of renal insufficiency.2

ESRD and chronic kidney disease (CKD) represent a substantial financial burden. ESRD accounts for annual Medicare expenditures of nearly $18 billion.1

The incidence of ESRD among African Americans is 995 per million; for the past decade, the rate has increased each year by 6% or 7% from the rate of the previous decade.3,4 Although they represent only 13% of the US population, African Americans account for more than 30% of patients with ESRD who are receiving dialysis and for 18% of patients who receive kidney transplants.1 In addition, ESRD develops in African Americans at a younger age (average age at onset, 57 years) than in whites (average age at onset, 64 years) or in Asians (average age at onset, 61 years). The incidence is also higher in each decade of life among African Americans than among other racial groups.

POSSIBLE CAUSES OF INCREASED INCIDENCE OF ESRD

Together, diabetes and hypertension are thought to account for almost 75% of ESRD (Figure 2). The higher prevalence of hypertension and diabetes in African Americans is responsible for some of the increased incidence of ESRD in these patients; however, it does not explain all of the disparity (Figure 3).3,5,6

Perneger and colleagues7 have estimated that 33% of the excess risk of ESRD seen in African Americans can be explained by lower socioeconomic status and limited access to health care. The association between renal failure and lower levels of education and income is strong. Persons with less education and lower income levels are less likely to receive adequate medical care and are less like- ly to be able to afford medications. As a result, their medical conditions are often suboptimally treated and disease progression is less frequently detected.

RISK FACTORS AND THEIR MANAGEMENT

Prominent among risk factors for the precipitation or progression of CKD in African Americans are hypertension and diabetes. Early and better treatment of these conditions could translate into very large decreases in the incidence of CKD.

Hypertension. Even high-normal blood pressure (BP) has been shown to be associated with a 90% increased risk of ESRD compared with optimally controlled BP (less than 120/80 mm Hg).8

Prevalence and severity. The prevalence of hypertension among African Americans aged 18 to 74 years is approximately 30% (compared with 23% among whites).9High BP develops 10 years earlier in African Americans than it does in whites, and African Americans are 7 times more likely to have severe elevations in BP than are whites. In addition, for any given BP elevation, kidney damage is likely to be considerably more severe in African Americans than in whites.4,10 Theories to account for the racial difference abound; one is that African Americans have a heightened response to a sodium load and intrinsic impairment in their ability to excrete sodium.11

Rates of control. Of African Americans aged 18 to 74 years who have hypertension, BP is controlled (less than 140/90 mm Hg) in only 26%.9 Even among African Americans who take antihypertensive medication, the condition is controlled in only 48%.9

Although approximately 75% of hypertensive Americans with elevated serum creatinine levels receive antihypertensive medications, a substantial fraction (approximately 50%) of this group is treated suboptimally.1 In one recent study, hypertensive African American patients with renal insufficiency were prescribed a mean of 2.4 medications; however, BP was less than 140/90 mm Hg in only 20% and less than 130/85 mm Hg in just 11.2%.12

BP goals. The action shown to be most important in slowing the progression of renal failure is BP reduction. The following BP targets are currently recommended:

  • Lower than 140/90 mm Hg for nondiabetic patients with uncomplicated hypertension.13
  • 130/80 mm Hg for patients with microalbuminuria; diabetes; or history of a cardiovascular event, stroke, or transient ischemic attack; or who are at high risk for coronary heart disease.14
  • 125/75 mm Hg for patients with proteinuria of 1 g/d or more.

    Multiple agents are often needed to meet these goals.

    Lifestyle modification and BP reduction. In patients with a high-normal BP (130 to 139/85 to 89 mm Hg), effective nonpharmacologic interventions include:

  • Smoking cessation.
  • Weight loss.
  • Reduction of sodium intake (to less than 100 mEq/d).
  • Reduction of alcohol intake (to no more than 1 to 2 drinks per day).
  • Increased physical activity (30 to 45 minutes of aerobic activity on most days).15

    Potassium supplementation or a diet rich in potassium has been shown to reduce systolic BP in African American adults by about 6.9 mm Hg and diastolic BP by about 2.5 mm Hg.16 The DASH (Dietary Approaches to Stop Hypertension) diet (Table 1), which incorporates foods rich in potassium and fiber, is an inexpensive and effective way to decrease BP.17,18

    Moderate dietary protein restriction may retard the rate of renal function decline; however, the magnitude of the effect is relatively weak.19 Hence, protein restriction may be helpful in conjunction with other interventions but not as the principal therapy.

    Diabetes.In the United States, diabetes is arguably the most substantive risk factor for the development of CKD.20 Most of the excess ESRD attributed to diabetes occurs in patients with type 2 rather than type 1 diabetes.

    During the past decade, type 2 diabetes has increased in both incidence and prevalence in African Americans. Currently, the prevalence of diabetes is 8.2% in African Americans and 4.8% in whites.21 Krop and colleagues22 found that the decline in renal function in African Americans with diabetes was 3 times greater than that observed in whites with diabetes. Lower socioeconomic status, poor health behaviors, and inadequate glucose and BP control accounted for 82% of the observed disparity.21

    Poor glucose control is a strong predictor of the development of diabetic nephropathy.23 However, tight glucose control is most important in early renal disease, when the creatinine level is normal or near normal; once overt diabetic nephropathy is established, glucose control has little effect on the rate of decline of the GFR.24 It is argued that BP control is more important than glycemic control in established diabetic nephropathy; this position is the basis for the recommendation that BP be aggressively controlled-to less than 130/80 mm Hg-in patients with diabetes.25

    ACE inhibitor therapy for hypertension and diabetes.Patients with diabetes in whommicroalbuminuria has progressed to macroalbuminuria (300 mg/24h or more) are likely to develop ESRD over a period of years. Antihypertensive therapy with angiotensin-converting enzyme (ACE) inhibitors has been shown to decrease proteinuria and slow progression of CKD to frank ESRD.26 In the African American Study of Kidney Disease and Hypertension (AASK), ramipril reduced clinical events by 46% compared with the calcium channel blocker, amlodipine. In addition, ramipril was more effective at helping preserve kidney function than either amlodipine or metoprolol.27

    Although prior studies have shown that ACE-inhibitor monotherapy in African Americans produces less reduction in BP than that observed in whites, more recent work has suggested that suboptimal dosing of ACE inhibitors may account for this response.28 It is also thought that high sodium intake in salt-sensitive African Americans may impair the ability of ACE inhibitors to work effectively.28

    EARLY DETECTION OF CHRONIC KIDNEY DISEASE

    Renal insufficiency often goes undetected because it is asymptomatic in its early stage, when serum creatinine levels are elevated. The GFR is one of the best indicators of kidney function. CKD has been defined by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative Work Group as being either kidney damage or a GFR of less than 60 mL/min/1.73 m2 for at least 3 months (Table 2).

    Patients with diabetes, hypertension, or a family history of kidney disease are at higher risk for CKD. Regularly measure serum creatinine levels and check for urinary protein in such patients. However, measurement of serum creatinine levels is a poor predictor of true GFR because the results may be influenced by assay techniques, endogenous and exogenous substances, renal tubular handling of creatinine, and other factors (Table 3). For example, older persons with low muscle mass, whose GFR is in the 30 to 80 mL/min range, often have a serum creatinine level within the laboratory's normal range. Thus, their kidney disease may go unrecognized.

    To minimize these influences, use a GFR estimation equation (Table 4) instead of simply the serum creatinine level to assess GFR. In particular, the MDRD (Modifications of Diet in Renal Diseases) study equation29 and the Cockcroft-Gault equation30 have been shown to be valid.

    PREVENTION AND MONITORING OF COMORBID DISEASE IN PATIENTS WITH CKD

    Prevention is an important component of primary care for patients with chronic renal insufficiency in whom ESRD has not yet developed. African Americans, in particular, may be less likely to receive appropriate preventive care. A study of Medicare patients in New Jersey showed that African Americans with chronic renal insufficiency were less likely to be examined for diabetic retinopathy than their white counterparts.31

    Because patients with CKD are at increased risk for death from cardiovascular causes, it is important to initiate and continue routine screening for cardiovascular risk factors and to ask about smoking. In addition to being a risk factor for cardiovascular and pulmonary diseases, smoking has been identified as a potential risk factor for hypertensive renal disease and other microvascular kidney abnormalities.32

    Table 5 lists additional preventive health care measures that are important for patients with CKD.

    WHEN TO REFER

    Patients with chronic renal insufficiency often present for dialysis with anemia, left ventricular hypertrophy, or congestive heart failure. This need not be the case. Timely and appropriate input by specialists can make a difference in the care and health of such patients. Early referral to a nephrologist allows for clinically significant anemia (hemoglobin level of less than 10 mg/dL or hematocrit less than 30%) to be treated adequately with recombinant human erythropoietin and iron. (Red blood cell indexes should be monitored every 1 to 2 weeks at the beginning of erythropoietin therapy and every 4 to 12 weeks thereafter. Patients should reach a hematocrit goal of between 33% and 36% after 2 to 4 months of treatment.33)

    Early referral also increases the likelihood that permanent vascular access will be established at the initiation of dialysis.34 Moreover, it can ensure that patients have ample opportunity to make informed choices about treatment. Finally, early referral is associated with a lower risk of death than late referral.

    African American men and women are more likely to be referred to a specialist late in the course of their disease (less than 4 months before beginning dialysis).35,36 Current practice guidelines for the treatment of CKD recommend that patients with a GFR less than 30 mL/min/1.73 m2 be referred to a nephrologist.37 Referral to a nephrologist is also needed when a specific treatable cause is possible, when chronic renal insufficiency is rapidly progressive, or when therapeutic goals cannot be met.

    Comanagement and good communication between the primary care clinician and the nephrologist can ensure timely interventions to retard progression of the disease (Table 6). Finally, it is important that discussions between the physician and the patient about options for ESRD treatment be initiated early to help prepare the patient for the inevitable lifestyle changes and to facilitate psychological acceptance of his or her condition (see Table 6). The National Kidney Disease Education Program established by the NIH,38 which focuses on high-risk African Americans, and the Kidney Disease Outcomes Quality Initiative (KDOQI) established by the National Kidney Foundation39 can help primary care physicians make appropriate treatment decisions regarding the care of patients with CKD.

    RACIAL DIFFERENCES IN RENAL REPLACEMENT THERAPY

    Studies show that African Americans and the poor of all races are as likely as whites to receive renal replacement therapy of some kind; this is probably attributable to the fact that Medicare covers ESRD treatment.40,41

    Renal transplantation. In the 1970s, dialysis was viewed as the optimal treatment of patients with chron- ic kidney failure. However, with the emergence of more powerful immunosuppressive regimens, renal transplantation has become the optimal therapy because it not only improves survival but also quality of life.42 It is also less costly than dialysis in the long run.

    Although they represent 37% of the US dialysis population, African Americans receive only 25% of cadaveric kidneys and 14% of kidneys originating from live donors.2 One study found that among patients considered to be appropriate candidates for transplantation, African Americans were less likely than whites to be referred for evaluation, to be placed on the waiting list, or to undergo transplantation.43 The difference in rates of referral and of placement on the waiting list remained significant even after adjustment for the fact that African Americans are less likely than whites to prefer transplantation.44

    Several practical issues make it difficult to find suitable matches for African American transplant patients. These include:

  • Lack of African American live donors.
  • Significantly greater anti-major histocompatibility complex (MHC) reactivity than in comparable whites.
  • Weight of the MHC matching in the United Network of Organ Sharing allocation algorithms.
  • Difficulty in completing the transplant referral process.45

    Dialysis. Studies have shown that African Americans are less than half as likely as whites to receive peritoneal dialysis (rather than hemodialysis). However, African Americans who progress to ESRD and undergo hemodialysis live longer than similarly treated whites. This survival advantage is seen even though African American patients who receive hemodialysis have more anemia, more hypertension, poorer vascular access, less adequate dialysis, and less compliance than white patients who receive hemodialysis. The reasons for this are poorly understood and cannot be explained simply by the younger age of African Americans on initiation of dialysis therapy.

  • References

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