Chronic Kidney Disease
Chronic kidney disease (CKD) is an important source of long-term morbidity and mortality. It has been estimated that CKD affects more than 20 million people in the United States. Given that most patients are asymptomatic until the disease has significantly progressed, they remain unaware of the condition. Thus, it is essential to have clinical practice guidelines aimed at early detection, evaluation, diagnosis, and treatment of this condition. This chapter reviews the medical management of patients with CKD, emphasizing measures aimed at slowing disease progression and treatment of its common complications. Methods used for estimating the level of renal function are presented elsewhere in this section (“Kidney Function Assessment: Creatinine-Based Estimation Equations”).
DEFINITION AND STAGING
CKD is an irreversible, progressive reduction in renal function. The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines define CKD as sustained kidney damage indicated by the presence of structural or functional abnormalities (e.g., microalbuminuria/proteinuria, hematuria, histologic or imaging abnormalities), and/or reduced glomerular filtration rate (GFR) to less than 60 mL/min/1.73 m2 for at least 3 months. Based on GFR estimation, the National Kidney Foundation has classified CKD into five stages (Table 1).1
EVALUATION AND TREATMENT
Once the presence of CKD and the disease stage have been established, the K/DOQI recommends following a stage-specific clinical action plan (see Table 1). During stages 1 and 2, the focus should be on treating comorbid conditions, addressing reduction of cardiovascular risk factors. and instituting measures to slow the progression of kidney disease. During these early stages, aggressive blood pressure control is the mainstay of therapy. In stage 3, in addition to continuing with the measures described, the focus shifts to evaluating and treating complications of CKD, such as anemia and the effects of abnormal mineral metabolism on bone and overall health. By stage 4, preparations for renal replacement therapy (dialysis, transplantation, or both) should begin. When stage 5 is reached, or when symptoms of the uremic syndrome ensue, renal replacement therapy is started.
SLOWING DISEASE PROGRESSION
Given the progressive nature of most forms of CKD, with a continued decrease in the GFR over time, it is important to address factors known to contribute to loss of renal function. Primary renoprotective strategies for limiting the progression of CKD are presented in Table 2.
Table 2 Renoprotective Strategies for Slowing Progression of Chronic Kidney Disease
| Parameter | Goal | Intervention |
|---|---|---|
| Blood pressure control (mm Hg) | <130/80 if proteinuria <1 g/day; <125/75 if proteinuria >1 g/day | ACE inhibitors, ARBs, sodium, restriction, diuretics |
| Reduction in proteinuria | <0.5 g/day | ACE inhibitors, ARBs |
| Glycemic control | HgbA1c< 7% | Dietary counseling, oral hypoglycemic agents, insulin |
| Dietary protein restriction | 0.6-0.8 g/kg/day | Dietary counseling |
| Lipid lowering | LDL <100 mg/dL | Dietary counseling, statins |
| Lifestyle modifications | Smoking cessation, achieving ideal body weight, regularly exercising | Counseling, exercise program |
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; LDL, low-density lipoprotein.
Hypertension
The progression of CKD is strongly linked to hypertension control. A number of studies have shown that for diabetic and nondiabetic kidney disease, elevated blood pressure is associated with a faster decline in GFR. The Modification of Diet in Renal Disease (MDRD) study has shown that control of hypertension is even more important in patients with proteinuria higher than 1 g/day, because lowering blood pressure to a target of 125/75 mm Hg in these patients achieves a greater decrease in the rate of decline of GFR than in patients with less proteinuria.2 For patients with proteinuria higher than 3 g/day, the impact of blood pressure lowering was even greater. The MDRD study also showed that hypertensive African Americans have faster progression of CKD compared with their white counterparts. However, reduction of blood pressure to lower than 125/75 mm Hg reduced the rate of decline by 50% in this group.
Dietary Protein Restriction
Extensive studies of chronic renal failure in animal models have shown that reduced dietary protein is associated with a reduction in glomerular hyperfiltration and slows the progression of renal disease. Although animal models of disease and treatment do not always apply to humans, a number of human studies in nondiabetic and diabetic renal disease have tested whether dietary protein restriction ameliorates the rate of progression of disease. The MDRD study was the largest controlled multicenter trial to compare usual protein intake (1 g/kg/day) with low (0.6 g/kg/day) and very low (0.28 g/kg/day) protein intake in nondiabetic patients.2 Although the primary outcome was inconclusive, several subanalyses have suggested that a prescribed dietary protein intake of 0.6 g/kg/day as compared with 1 g/kg/day reduces the rate of progression by about 28%, the same benefit seen in achieving the low blood pressure goal. A meta-analysis of five of the best studies of both diabetic and nondiabetic renal disease has suggested that a small reduction in rate of progression occurs with dietary protein restriction. In an analysis of the MDRD data, Locatelli and Del Vecchio have found that adherence to a low (0.6 g/kg/day) versus a usual (1 g/kg/d) protein diet for 9 years would delay the need for renal replacement therapy by approximately 1 year.3 The difficulty of achieving consistent dietary protein restriction, however, makes the application of this intervention unwieldy and prone to failure, especially in diabetic patients. Compliance in the MDRD was successful but required intensive regular interaction by dietitians.
Summary
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