MANAGERIAL. Potential Application of the National Kidney Foundation s Chronic Kidney Disease Guidelines in a Managed Care Setting

Transcription

1 Potential Application of the National Kidney Foundation s Chronic Kidney Disease Guidelines in a Managed Care Setting Micah L. Thorp, DO, MPH; and Loris Eastman, RN, CNN Chronic kidney disease (CKD) is a public health problem in the United States with rising incidence and prevalence. The disease may progress to end-stage renal disease, which is associated with significant morbidity and mortality. The National Kidney Foundation recently established clinical practice guidelines to aid in the identification and stratification of CKD. Central to these guidelines is the use of glomerular filtration rate estimation equations. Integrated healthcare systems can use the guidelines to identify patients with CKD early in its course. Early identification allows for timely nephrology referral, institution of measures to slow the progression of CKD, and treatment of CKD-specific complications. Administration of these efforts early in the course of CKD improves subsequent morbidity and mortality of affected patients. By identifying CKD early in its course, patients can be referred to a coordinated case management team that can help administer care. The team can follow up a patient from the early diagnosis of CKD to end-stage renal disease and renal replacement therapy. Finally, continuous quality improvement can be instituted to assist in improving patient care. (Am J Manag Care. 2004;10: ) For editorial comment, please see page 413. More than 19 million Americans have chronic kidney disease (CKD). 1 Adverse outcomes and conditions are associated with CKD, including coronary heart disease, 2 congestive heart failure, 3 and premature death. 4 Patients who survive the conditions associated with CKD develop end-stage renal disease (ESRD) and require dialysis or transplantation. The US Renal Data System 5 estimated in a 2002 report that there are more than persons with ESRD in the United States and that the rate of ESRD is increasing 5% to 6% per year. Several risk factors predispose patients to CKD, including diabetes mellitus, hypertension, and age. With rising rates of diabetes mellitus and hypertension in an aging population, it is projected that the prevalence of CKD will continue to increase. 5 Little is known about the progression of CKD to ESRD. The estimated 19 million persons in the United States who have CKD is a significantly larger population than the with ESRD. The large number of patients with CKD relative to the smaller number with ESRD has led some to conclude that many patients with CKD die before ESRD or never progress. 6 Common diseases associated with CKD (ie, diabetes mellitus and cardiac disease) are associated with high mortality rates, which may explain some of the apparent lack of CKD progression. The concept that diseases causing CKD lead to death before ESRD remains a theory, as the natural history of CKD remains unknown. Although little is known about the progression of CKD in the aggregate, progression and treatment of specific kidney diseases causing CKD are well understood. Most notably, diabetic nephropathy, the underlying etiology of nearly 40% of cases of ESRD, 5 can be ameliorated with the use of angiotension-converting enzyme inhibitors, 7 aggressive glycemic control, 8 and appropriate management of hypertension. 9 Early identification of CKD among diabetic patients, combined with these interventions, has been shown to decrease the rate of progression of diabetic nephropathy (and thus ESRD). 10 Similar approaches to the management of nondiabetic kidney diseases have been shown to slow the progression of CKD to ESRD as well. 11 In addition to slowing the course of CKD, treatment of its many adverse effects (eg, anemia, hyperparathyroidism, etc) is important in ensuring quality patient care. 12 The appropriate addition of erythropoietin therapy, 13 management of calcium and phosphorous, 14 and timely referral to a nephrologist 15 are some of the important measures that improve outcomes among patients with CKD. With little understood about the progression of CKD, many patients with CKD may not survive long enough to develop ESRD. Therefore, interventions to improve the health of patients with CKD may improve patient outcomes before the development of ESRD and thus From the Lake Road Nephrology Center, Kaiser Kidney Program, Kaiser Permanente Northwest, Milwaukie, Ore. Address correspondence to: Micah L. Thorp, DO, MPH, Lake Road Nephrology Center, Kaiser Kidney Program, Kaiser Permanente Northwest, 6902 SE Lake Road, Milwaukie, OR micahthorp@comcast.net. VOL. 10, NO. 7 THE AMERICAN JOURNAL OF MANAGED CARE 417

2 Figure. An Approach to Identification and Referral of Patients With Chronic Kidney Disease Within an Integrated Healthcare System Using Laboratory Data, Calculate Modification of Diet in Renal Disease Glomerular Filtration Rate (GFR) for All Creatinine Levels Witin Patient Population Stratify Patients into National Kidney Foundation Stages Review Patients in Stages 3, 4, and 5 Not Yet Seen by a Nephrologist Inform Primary Care Physician that Patient Has Decreased GFR and May Benefit from Nephrology Referral increase the number of patients with ESRD. Conversely, earlier intervention among patients may slow or halt progression and decrease the number of patients with ESRD. In either case, intervention at an early stage seems appropriate. The National Kidney Foundation (NKF) has established clinical practice guidelines that define and stratify CKD based on the glomerular filtration rate (GFR). 16 The guidelines have been developed to help physicians identify CKD among individual patients and subsequently manage its many complications. The use of the NKF guidelines is, however, not limited to management of individual patients. The guidelines offer a significant opportunity to manage populations of patients, especially within large integrated healthcare systems. The use of patient demographic information, laboratory findings, patient education, and comprehensive supportive services can maximize the effect of these guidelines within a large population. The resulting effect of population-based CKD management may help curtail the epidemic of CKD and ever-growing numbers of patients requiring renal replacement therapy. This article will discuss the potential roles the NKF guidelines can play in the population-based management of CKD within integrated healthcare systems. Identifying Patients With CKD A central feature of the NKF guidelines is the use of the GFR to identify and stratify CKD. The GFR is considered the best means of assessing total kidney function. 17 Although other means of evaluating kidney function are often used (eg, serum creatinine and creatinine clearance), they are less reflective of functional nephron capacity than the GFR. Serum creatinine and creatinine clearance levels are problematic because they overestimate the GFR (because of secreted creatinine) at low levels. 18 The GFR is difficult and expensive to measure directly. Although GFR measurements using iothalamate or inulin are accurate, the are also cumbersome and expensive. Many physicians do not regularly use GFR estimation equations unless they suspect a patient has decreased renal function. As a result, patients with relatively normal serum creatinines but decreased GFRs may remain undiagnosed. The NKF recommends that laboratories reporting serum creatinine levels, when possible, calculate a GFR estimation equation. 19 Most such equations rely on a combination of laboratory and demographic information. For example, a commonly used GFR estimation equation was derived for the Modification of Diet in Renal Disease Study. 20 In its simplest form, it requires serum creatinine level, age, sex, and whether or not the patient is African American. Greater precision can be achieved by adding variables that include serum albumin and blood urea nitrogen levels. A benefit of using GFR estimation equations is a more accurate assessment of kidney function at low levels. 20 With such a calculation already made, physicians would be less likely to overestimate renal function among patients with a seemingly normal serum creatinine and a low GFR. A problem with some GFR estimation equations is the uncertainty of an estimated GFR (egfr) when the true GFR is greater than about 60 ml/min per 1.73 m 2. The previously mentioned Modification of Diet in Renal Disease equation is an example. As the study 20 examined patients with decreased GFRs, the Modification of Diet in Renal Disease estimation equation was not thoroughly assessed among patients with normal renal function. As a result, a patient with normal kidney function may appear to have decreased function. To address this problem, the National Kidney Disease Education Program 21 has recommended that values greater than 60 ml/min per 1.73 m 2 be reported simply as above 60 ml/min per1.73 m 2, without being specific. This approach would seem reasonable when considering the NKF definition of CKD. The diagnostic criteria define CKD as a GFR greater than 60 ml/min per 1.73 m 2 and the presence of radiological, serological, or urinary evidence, while a lower GFR is CKD without other crite- 418 THE AMERICAN JOURNAL OF MANAGED CARE JULY 2004

3 Using CKD Guidelines ria. 22 Therefore, patients with radiological, serological, or urinary evidence of CKD have CKD regardless of the GFR and (at least in theory) should be diagnosed based on other findings. Application of the NKF definition of CKD and use of the Modification of Diet in Renal Disease estimation equations allow for an automated system of CKD identification. When a patient has his or her serum creatinine level checked, demographic information can be obtained and entered into the laboratory computer reporting system. When the serum value is obtained, an egfr can be automatically calculated and reported. To ensure that patients with acute renal insufficiency or failure are not diagnosed with CKD, the NKF criteria for the diagnosis require measurement of at least 2 egfrs 3 months apart. 22 Therefore, laboratory reporting of egfrs is only the first step in establishing a diagnosis. Healthcare systems with electronic medical records that integrate laboratory information may be able to automate the identification of CKD by using multiple egfrs, calculating the interval, and reporting to physicians whether a specific patient meets the criteria for the diagnosis of CKD. Healthcare systems that do not integrate laboratory data with an electronic medical record may be limited in their ability to take this second step and automatically identify patients with CKD on the basis of laboratory values. Such systems may instead rely on physician recognition of CKD. CKD Stratification and Population Management Once a GFR has been established, the NKF guidelines recommend stratifying patients into 1 of 5 stages: stage 1 (GFR, 90 ml/min per 1.73 m 2 ), stage 2 (GFR, ml/min), stage 3 (GFR, ml/min), stage 4 (GFR, ml/min), and stage 5 (GFR, <15 ml/min) Additional criteria for patients in stages 1 and 2 include kidney damage for longer than 3 months manifest by pathological abnormalities or markers of kidney damage in blood or urine samples or on imaging tests. Markers of kidney damage include proteinuria, abnormalities of the urinary sediment, or abnormal radiological findings. Identifying patients with stage 1 or 2 CKD requires more than a GFR estimation. The most common radiological, serological, or urinary evidence of CKD in most populations is proteinuria. As proteinuria is often transient, multiple measurements may be required. 25 Three approaches commonly used to identify proteinuria include measurement of the protein-creatinine ratio on a random urine sample, protein measurement from a 24-hour urine collection, or protein identified by urine dipstick. The ratio from a spot urine sample is the most easily obtained and is less frequently associated with collection error. A ratio greater than 200 mg/g is considered an elevated level of proteinuria on a random urine sample. Elevations of proteinuria due to transient conditions (exercise, urinary tract infections, etc) make it necessary to confirm an initial test result with repeated measures. There are few guidelines regarding how often proteinuria needs to be detected before it is recognized as a chronic problem (and thus providing for the diagnosis of CKD). One guideline has been suggested by the American Diabetes Association for assistance in identifying microalbuminuria among diabetic patients with potential renal disease. The guideline suggests that 2 of 3 test results for microalbumin need to be positive during 3 to 6 months to suggest a patient has diabetes mellitus with renal disease. 26 The NKF recommends that patients with positive findings on 2 or more quantitative tests 1 to 2 weeks apart be diagnosed with chronic proteinuria. 25 Healthcare systems with integrated electronic medical record and laboratory computer systems may be able to establish protocols to ensure that patients with proteinuria (or albuminuria) on a single sample undergo the appropriate repeat testing. Computerized systems can flag physicians regarding the need for possible follow-up testing once a positive result has been obtained. A final benefit of laboratory identification of CKD is the potential creation of an automated surveillance system reporting lists of patients with CKD at various stages to a centralized monitor (perhaps a nephrologist or nephrology oversight group) that can review individual cases, alert primary care physicians, or directly refer patients to a nephrologist. A surveillance system that monitors laboratory results and cross-checks with patient records to ensure that patients who have CKD are receiving appropriate treatment and referral can prevent patients from being overlooked who may benefit from specific intervention. Such a system may rely on monitoring GFRs of patients. Those in stages 3, 4, or 5 who have not yet seen a nephrologist can be contacted through their primary care physician and advised that they should see a nephrologist. In addition, patients who may benefit from early interventions, including the use of angiotension-converting enzyme (ACE) inhibitors, lipid-lowering agents, or tight diabetes mellitus control can be identified early in the course of their disease. The NKF recommends that the management of patients with CKD in stages 1 or 2 should focus on determination of a diagnosis and developing a treatment plan that includes comorbid conditions and the underlying cause of kidney disease. 25 Comorbid conditions often associated with CKD include hypertension, diabetes mellitus, and hypercholesterolemia. 27 Slowing VOL. 10, NO. 7 THE AMERICAN JOURNAL OF MANAGED CARE 419

4 the progression of CKD includes controlling diabetes mellitus, 8 treatment of hypertension, 28 and use of an ACE inhibitor 11 or angiotension receptor blocker. 29 As CKD advances to GFRs less than 60 ml/min per 1.73 m 2, the NKF recommends additional focus on the specific complications of CKD (ie, development of bone disease, anemia, and protein malnutrition). 16 Anemia develops among patients with CKD because of a relative deficiency of erythropoietin. It is recommended that patients with stage 3 CKD have hemoglobin levels checked and, if less than 12.5 g/dl, undergo an evaluation of their anemia. 24 If the workup is unremarkable and the patient is not iron deficient, treatment with erythropoietin is undertaken. Bone disease occurs as a result of vitamin D deficiency and hyperparathyroidism. Bone disease in CKD may manifest as high-turnover bone disease with high parathyroid hormone levels or as low-turnover bone disease with low or normal parathyroid hormone levels. 14 It is recommended that patients with GFRs less than 60 ml/min per 1.73 m 2 be evaluated for bone disease with longitudinal measurements of parathyroid hormone, phosphorus, and ionized calcium levels. 30 Treatment of bone disease involves vitamin D replacement or use of phosphate binders. Protein malnutrition is common among dialysis patients and those with CKD. Patients with CKD with protein malnutrition have greater morbidity and mortality than those who do not. 31 To prevent protein malnutrition, early and ongoing dietary assessments, usually conducted by a dietician, are necessary. Complicating treatment of protein malnutrition are continued questions regarding potential benefits of a low protein diet during early CKD. The results of the Modification of Diet in Renal Disease Study 32 (which studied whether low protein diets slow the rate of progression of CKD) were inconclusive, further fueling the controversy. As a result, the NKF has recommended that patients with a GFR less than 25 ml/min per 1.73 m 2 consume 0.60 g/kg of body weight per day of protein, but does not make recommendations for patients with higher GFRs. As the recommended dietary allowance of protein for adults with a normal GFR is 0.75 g/kg per day, it seems reasonable that patients with GFRs of 25 ml/min or higher consume this amount. 33 Patients with stage 4 CKD (GFR, ml/min per 1.73 m 2 ) should begin the preparing for renal replacement therapy. At this point, patients should see or have seen a nephrologist, been educated regarding renal replacement options, and (if hemodialysis is likely to be administered) have a dialysis access graft placed. Patients with stage 5 CKD (GFR, <15 ml/min per 1.73 m 2 ) should receive renal replacement therapy as determined by their nephrologist. Nephrology Referral Timely referral to a nephrologist is correlated with improved morbidity and mortality after the initiation of dialysis. 34 Ensuring appropriate referral to a nephrologist can be accomplished within health systems that have integrated laboratory, primary care, and specialty services (Figure). Application of the NKF guidelines to a system that is programmed to automatically stage CKD can determine which patients are more likely to need a nephrology referral. An integrated healthcare system, particularly one with an electronic medical record (one that contains laboratory, radiological, pharmacy, and medical history information) can help to further determine which patients should be closely monitored and which can be followed up less frequently. Once patients who need to be seen by a nephrologist have been referred, case management can be an important means of further managing a population of patients with CKD. Case management allows for coordination of CKD- and ESRD-specific issues. Coordinated Care Management Patients with CKD have specific problems that require therapy from nurses and physicians with special knowledge of kidney disease. The development of a multidisciplinary care management group within large healthcare systems is helpful in administering quality care among patients with CKD and ESRD. Elements of a care management team often include a nurse care manager, social worker, vascular access coordinator, and dietician. Care should begin before ESRD and be maintained from the time of diagnosis of CKD through renal replacement therapy (dialysis or transplantation). At least 1 study 35 has shown that patients seen by such a team before initiation of dialysis had fewer cerebrovascular events, decreased hospital days, and reduced overall mortality compared with those not followed up before dialysis. Patient education is an important part of care management and should be initiated early in the course of CKD. Patients involved in predialysis education had a slower rate of decline in renal function than those not exposed to an educational system. 36 Patient education may take place in the form of a group class, individual meetings with members of the care management team, mailings, videos, and so on. The focus of education should include an understanding of kidney function, modification of diet and lifestyle to slow disease progression, coping skills, and participation in healthcare discussions. Educational activities should be 420 THE AMERICAN JOURNAL OF MANAGED CARE JULY 2004

5 Using CKD Guidelines started early and continued throughout the course of the patient s illness. As CKD progresses, specific information should be presented about the different dialysis options available, dialysis access placement, transplantation, and decisions to forgo renal replacement therapy. Referral for education is an excellent point at which to begin case management of patients with CKD. Within the multidisciplinary team, individual team members should address specific issues. A social worker assists in finding placement for dialysis treatment, helps to arrange transportation, and provides support during the transition to dialysis. Efforts to facilitate dialysis in a manner that allows patients to continue to work are a part of dialysis planning. The renal nutritionist may begin monitoring laboratory results to manage bone disease and promote dietary compliance and diabetes mellitus management in the face of changing renal function. Nurse managers can assist with vascular access placement, transplant workup, and erythropoietin administration. The period immediately preceding and immediately following the initiation of dialysis is often stressful for patients and requires close monitoring. The benefits of patient management early in the course of CKD often manifest at the time of dialysis initiation. A well-prepared patient, with the support of a multidisciplinary team, can undergo an easier transition to dialysis. Once a patient starts dialysis, many of the functions of the multidisciplinary team are continued within the dialysis unit. Integrated healthcare systems that have their own dialysis units may continue to use the same team to manage patient populations before and after development of ESRD. Those systems that contract with outside dialysis units to provide dialysis for patients with ESRD need to consider the role of ongoing care management once the patient is receiving similar services through the dialysis unit. The continuation of some services may be appropriate (such as dialysis access and transplant coordination), while others may be duplicative. Continuous Quality Improvement The NKF guidelines can be applied to continuous quality improvement within an integrated healthcare system. Specific outcome measurements for each stage of CKD and ESRD can be measured and followed up. Identifying problems within individual dialysis units or among elements of care management should allow systems to improve population health and ultimately decrease the morbidity of patients with CKD. Efforts to slow the progression of CKD among patients with specific kidney diseases, such as diabetic nephropathy, might also benefit from the NKF guidelines. By following up the progression of CKD among specific populations, healthcare systems can ensure that important interventions (eg, the use of ACE inhibitors among patients with diabetic nephropathy) are administered to a maximum number of patients within the population. Other continuous quality improvement targets include preparation for dialysis or transplantation, beginning when the egfr falls below 30 ml/min per 1.73 m 2. This includes dialysis access placement, which (for hemodialysis patients) ideally involves placement of an arteriovenous fistula, an access requiring up to 4 months to mature. Arteriovenous fistulas are the least likely form of dialysis access to be associated with complications and are thus preferred. The NKF Kidney Dialysis Outcomes Quality Initiative suggests a target goal of 50% of new kidney failure patients having an arteriovenous fistula placed before starting hemodialysis. 37 Conclusions The NKF guidelines for the identification, evaluation, and management of CKD provide integrated healthcare systems an opportunity to more efficiently and precisely manage patients with the disease. Patients with CKD can be identified using automated calculations of GFRs based on laboratory and demographic information. Once identified, patients may be stratified using the NKF criteria and appropriate intervention undertaken. Integrated healthcare systems can use the NKF criteria to automate the identification and referral of patients with CKD. As CKD progresses, coordinated care management should be instituted and continued as the disease progresses to ESRD. Finally, continuous quality improvement can be facilitated by data collection. REFERENCES 1. Jones CA, McQuillan GM, Kusek JW, et al. Serum creatinine levels in the US population: Third National Health and Nutrition Examination Survey [published correction appears in Am J Kidney Dis. 2000;35:178]. Am J Kidney Dis. 1998;32: Culleton BF, Larson MG, Wilson PW, Evans JC, Parfrey PS, Levy D. Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. Kidney Int. 1999;56: McCullough PA. Scope of cardiovascular complications in patients with kidney disease. Ethn Dis. 2002;12:S Drey N, Roderick P, Mullee M, Rogerson M. A population-based study of the incidence and outcomes of diagnosed chronic kidney disease. Am J Kidney Dis. 2003;42: US Renal Data System. USRDS 2002 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Keith D, Nichols G, Gullion C, Brown J, Smith D. Mortality of chronic kidney disease (CKD) in a large HMO population [abstract]. J Am Soc Nephrol. 2002;13:620A. Abstract SU-P EUCLID Study Group. Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. Lancet. 1997;349: VOL. 10, NO. 7 THE AMERICAN JOURNAL OF MANAGED CARE 421

6 8. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development of long-term complications of insulin-dependent diabetes mellitus. N Engl J Med. 1993;329: Parving HH, Anderson AR, Smidt UM. Early aggressive antihypertensive treatment reduces rate of decline of kidney function in diabetic nephropathy. Lancet. 1983;1: Bakris GL, Williams M, Dworkin L, et al, National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000;36: Ruggenenti P, Remuzzi G. Angiotension-converting enzyme inhibitor therapy for nondiabetic progressive renal disease. Curr Opin Nephrol Hypertens. 1997;6: Barrett BJ. Applying multiple interventions in chronic kidney disease. Semin Dial. 2003;16: McGonigle RJ, Wallin JD, Shadduck RK, Fisher JW. Erythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency. Kidney Int. 1984;25: Sherrard DJ, Hercz G, Pei Y, et al. The spectrum of bone disease in end-stage renal failure: an evolving disorder. Kidney Int. 1993;43: Kinchen KS, Sadler J, Fink N, et al. The timing of specialist evaluation in chronic kidney disease and mortality. Ann Intern Med. 2002;137: National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: evaluation, classification, and stratification: part 1: executive summary. Am J Kidney Dis. 2002;39(suppl 1):S17-S Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification [published correction appears in Ann Intern Med. 2003;139:605]. Ann Intern Med. 2003;139: Shemesh O, Golbetz H, Kriss JP, Myers BD. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int. 1985;28: National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: evaluation, classification, and stratification: part 5: evaluation of laboratory measurements for clinical assessment of kidney disease. Estimation of GFR. Am J Kidney Dis. 2002;39(suppl 1):S76-S Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D, Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130: National Kidney Disease Education Program. Meeting on creatinine assay and reporting of estimated GFR Available at: Accessed May 10, National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Part 4-Definition and Classification of Chronic Kidney Disease. Am J Kidney Dis. 2002;39(suppl 1):S46-S National Kidney Foundation Web site. Available at: Accessed May 10, National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Guideline 8-Association of level of GFR with Anemia. Am J Kidney Dis. 2002;39(suppl 1):S120-S National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Guideline 5-Assessment of Proteinuria. Am J Kidney Dis. 2002;39(suppl 1):S93-S102. [ 26. Molitch ME, DeFronzo RA, Franz MJ, Keane WF, Mogensen CE, Parving HH. Diabetic nephropathy. Diabetes Care. 2003;26(suppl 1):S94-S Lam KSL, Cheng IKP, Janus ED, Pang RWC. Cholesterol-lowering therapy may retard the progression of diabetic nephropathy. Diabetologia. 1995;38: Walker WG. Hypertension-related renal injury: a major contributor to endstage renal disease. Am J Kidney Dis. 1993;22: Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345: National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Guideline 10-Association of level of GFR with Bone Disease and Disorders of Calcium and Phosphate Metabolism. Am J Kidney Dis. 2002;39(suppl 1):S143-S Holland D, Lam M. Predictors of hospitalization and death amongst predialysis patients: a retrospective study. Nephrol Dial Transplant. 2000;15: Levey AS, Greene T, Beck GJ, et al, Modification of Diet in Renal Disease Study Group. Dietary protein restriction and the progression of chronic renal disease: what have all the results of the MDRD Study shown? J Am Soc Nephrol. 1999;10: National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Guideline 9-Association of GFR with Nutritional Status. Am J Kidney Dis. 2002;39(suppl 1):S128-S Stack AG. Impact of timing of nephrology referral and pre-esrd care on mortality risk among new ESRD patients in the United States. Am J Kidney Dis. 2003;41: Jungers P, Nguyen KT, Massey ZA, Man NK. Incidence of atherosclerotic cardiovascular events in patients with chronic anemia: epidemiologic studies in Ile de France. Nephrologie. 1998;19: Binik YM, Devins GM, Barre PE, et al. Live and learn: patient education delays the need to initiate renal replacement therapy in end-stage renal disease. J Nerv Ment Dis. 1993;181: National Kidney Foundation. III. NKF K/DOQI Clinical Practice Guidelines for Vascular Access: update Am J Kidney Dis. 2001;37(suppl 1):S137-S THE AMERICAN JOURNAL OF MANAGED CARE JULY 2004