Chronic Kidney Disease

• Objective: To review clinical guideline recommendations for the identification and management of chronic kidney disease (CKD). • Methods: Qualitative assessment of the literature and review of current management guidelines. • Results: The incidence and prevalence of CKD is rising rapidly. Mortality rates are still unacceptably high despite improved technical and medical knowledge in the care of patients with end-stage renal disease (CKD stage 5). Efforts to decrease the morbidity and mortality observed with end-stage renal disease have focused on improving care in the earlier stages of kidney disease. These efforts seek greater involvement from primary care physicians, who have a critical role to play in early identification, treatment, and appropriate referral of patients with CKD. Multiple clinical practice guidelines are available to guide primary care physicians in identifying patients with CKD and in initiating therapy, which includes treatment of the primary disease and comorbid conditions, interventions to prevent progression of kidney disease and complications of CKD, and interventions to maintain a good quality of life. Collaboration with a nephrologist is best initiated no later than stage 3 of CKD. • Conclusion: Early recognition of CKD along with timely initiation of comprehensive treatment and collaboration with a nephrologist will provide optimal care for patients with CKD. The prevalence of chronic kidney disease (CKD) in the United States has reached epidemic proportions [1–4]. Data presented in the National Kidney Foundation’s (NKF’s) Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines estimate that over 20 million adult Americans have some degree of CKD and an additional 20 million have risk factors for developing CKD [5]. End-stage renal disease (ESRD) is the final stage in the continuum of CKD. According to the U.S. Renal Data Systems, more than 412,215 patients were receiving renal replacement therapy for ESRD as of December 2001 [6]. This number is projected to increase to more than 660,000 by 2010 [6]. Incident rates adjusted for age show that patients over age 65 years are the fastest growing cohort of new ESRD patients [6]. In 2000, the average yearly cost of treatment for each patient with ESRD was approximately $68,000 [7]. Despite improvements in dialysis and transplantation medicine over the past 40 years, mortality rates in ESRD remain in the 20% to 25% range [6]. Recent efforts to decrease ESRD morbidity and mortality have focused on identifying patients at earlier stages of CKD and providing interventions to delay the progression of kidney disease [5,8–14]. These efforts require greater involvement from the primary care physician, who can play a critical role through early recognition and treatment of patients with CKD as well as informed collaboration with a nephrologist once a referral is made. Current treatment guidelines that support the primary care physician in providing care to patients with CKD are available from the NKF and the Renal Physicians Association (RPA). NKF and RPA guidelines are the most widely used in the United States, and more than a dozen sets of guidelines from these organizations provide extensive information in multiple areas. However, the application of these guidelines in clinical practice can be limited by their length (each approximately 200 pages) and complexity. In this article, we present a distillation of NKF and RPA guideline recommendations on the identification and management of CKD. Screening and Classification The K/DOQI guidelines define chronic kidney disease as a persistent reduction in kidney function (ie, glomerular filtration rate [GFR] < 60 mL/min/1.73 m2) for more than 3 months or evidence of kidney damage with or without reduction in GFR for more than 3 months [5]. Kidney damage is identified as structural or functional abnormalities of the kidneys (eg, with radiologic imaging) or abnormal composition of blood or urine. It has been suggested that all patients with CKD be From the Division of Nephrology, Department of Medicine, University of Virginia Health System, Charlottesville, VA. diagnosed as such and terms like “insufficiency,” “chronic renal failure,” and “renal dysfunction” be avoided [5]. Screening for CKD is done with measurement of blood pressure and serum glucose, urinalysis (including microscopy), measurement of albumin-to-creatinine ratio in a spot urine sample (proteinuria), and estimation of the GFR. These tests are readily available, relatively inexpensive, and already performed widely in primary care physicians’ offices. Patients with one or more risk factors for CKD (Table 1) should be screened at least once every year. Diabetics, patients with family history of kidney disease, African Americans, and hypertensive patients are at particularly high risk [15]. Timely identification of CKD is inevitably linked to the clinical methods of measuring or monitoring renal function. Despite its widespread use for the past decades, serum creatinine concentration alone is an inadequate indicator of renal function, especially in the elderly. Inulin clearance is the gold standard for measuring GFR, but this method is seldom used in clinical practice because it is cumbersome and costly [16]. Clearance of endogenous creatinine (24-hour urine collection) has been used, but this method frequently overestimates GFR and is becoming obsolete based on studies that have shown that various prediction equations are convenient and more accurate for assessing GFR [17,18]. The most popular prediction equations are the MDRD formula (adults < 70 years) (from the Modification of Diet in Renal Disease trial), the Cockcroft-Gault formula (all adults), and the Schwartz formula (children) [19–21] (Figure 1). The prediction equations are readily available on personal digital assistant software and on various sites on the internet [22,23]. A national effort is underway to have clinical laboratories routinely report estimated GFRs [22]. This improvement has been implemented successfully at our center. Once patients with CKD are identified, the extent of their disease is classified based on estimated GFRs using the K/DOQI staging system (Table 2) [5]. The clinical course of CKD is variable and dependent on concurrent comorbidities and the stage of CKD. Across all stages, patients are more likely to die of cardiovascular disease than to progress to ESRD [24]. For patients who survive, those in stages 4 and 5 are very likely to progress to ESRD [19]. Presently, there is less information available in the literature about the clinical course of patients in earlier stages (stage 3 and below). The ongoing Chronic Renal Insufficiency Cohort study is likely to provide valuable information about the course of early CKD and the relationship with cardiovascular disease in the near future [25].