REVIEW CME EDUCATIONAL OBJECTIVE: Readers will optimize the care of their patients who have chronic kidney disease CREDIT ANKIT SAKHUJA, MD JENNIFER HYLAND, RN, MSN, CNP JAMES F. SIMON, MD Division of Nephrology and Hyperten- Department of Nephrology and Hypertension, Program Director, Nephrology Fellowship, Department sion, Mayo Clinic, Rochester, MN Glickman Urological and Kidney Institute, of Nephrology and Hypertension, Glickman Urological Cleveland Clinic and Kidney Institute, Cleveland Clinic; Assistant Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH Managing advanced chronic kidney disease: A primary care guide ABSTRACT ccountable-care organizations are be- A coming more prominent in the United Chronic kidney disease (CKD) is a common disorder that States, and therefore health care systems in the requires close collaboration between the primary care near future will be reimbursed on the basis of physician and nephrologist. Most aspects of early CKD their ability to care for patient populations rath- can be managed in the primary care setting with ne- er than individual patients. As a result, primary phrology input. As the disease progresses, many aspects care physicians will need to be well versed in the of care should be transitioned to the nephrologist, espe- care of patients with common chronic diseases cially as the patient nears end-stage renal disease, when such as chronic kidney disease (CKD). By one dialysis and transplantation must be addressed. estimate, patients with CKD constitute 14% of the US population age 20 and older, or more KEY POINTS than 31 million people.1 An earlier article in this journal reviewed Steps to stabilize renal function include blood pressure how to identify patients with CKD and how and diabetes control. to interpret the estimated glomerular filtration rate (GFR).2 This article examines the care of Patients have a very high risk of cardiovascular disease, patients with advanced CKD, how to manage and one should try to reduce modifiable risk factors their health risks, and how to optimize their such as hypertension (which is also a risk factor for the care by coordinating with nephrologists. progression of CKD) and hyperlipidemia. ■ GOALS OF CKD CARE In addition to controlling blood pressure, angiotensin-con- CKD is defined either as renal damage (which verting enzyme inhibitors and angiotensin receptor block- is most commonly manifested by proteinuria, ers reduce proteinuria, a risk factor for progression of CKD. but which may include pathologic changes on biopsy or other markers of damage on se- rum, urine, or imaging studies), or as a GFR Patients with CKD develop secondary hyperparathyroid- less than 60 mL/min/1.73 m2 for at least 3 3 ism, hyperphosphatemia, and, in advanced CKD, hypo- months. It is divided into five stages (TABLE 1). calcemia, all leading to disorders of bone mineral metab- Since most patients with CKD never reach olism. Low vitamin D levels should be raised with supple- end-stage renal disease, much of their care is ments, and high phosphorus levels should be lowered aimed at slowing the progression of renal dys- with dietary restriction and phosphate binders. function and addressing medical issues that arise as a result of CKD. To these ends, it is important to detect CKD early and refer these patients to a nephrology team in a timely manner. Their care doi:10.3949/ccjm.81a.13046 can be separated into several important tasks: CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 81 • NUMBER 5 MAY 2014 289 Downloaded from www.ccjm.org on September 23, 2021. For personal use only. All other uses require permission. ADVANCED KIDNEY DISEASE Studies discussed in this article shown to go longer without CKD progression than those referred in later stages.4 Early refer- AASK—African American Study of Kidney Disease and Hypertension40 ral to a nephrologist has also been associated 5 ACCORD— Action to Control Cardiovascular Risk in Diabetes37 with a decreased mortality rate. The studies that found these trends, however, were limited 78 CHOIR—Correction of Hemoglobin and Outcomes in Renal Insufficiency by the fact that patients with stage 3 CKD are CREATE —Cardiovascular Reduction Early Anemia Treatment Epoetin79 less likely to progress to end-stage renal dis- ease or to die of cardiovascular disease than HOPE —Heart Outcomes Prevention Evaluation16 patients with stage 4 or 5 CKD. IDEAL—Initiating Dialysis Early and Late99 Once stage 4 CKD develops, the nephrolo- IDNT—Irbesartan Diabetic Nephropathy Trial46 gist should take a more active role in the care plan. In this stage, cardiovascular risk rises, 17 PREVEND—Prevention of Renal and Vascular End-stage Disease and the risk of developing end-stage renal dis- SHARP—Study of Heart and Renal Protection28 ease rises dramatically.6 With comprehensive care in a CKD clinic, even patients with ad- TREAT—Trial to Reduce Cardiovascular Events With Aranesp Therapy80 vanced CKD are more likely to have a stabili- zation of renal function.7 Kinchen et al8 found that patients referred to a nephrologist within • Identify the cause of CKD, if possible; ad- 4 months of starting dialysis had a lower sur- dress potentially reversible causes such as vival rate than those referred earlier. There- obstruction or medication-related causes. fore, if a nephrologist was not involved in the If a primarily glomerular process (marked patient’s care prior to stage 4, then a referral by heavy proteinuria and dysmorphic red must be made. blood cells and red blood cell casts in the Recommendation. Patients with stage 3 urine sediment) or interstitial nephritis CKD can be referred for an initial evaluation (manifested by white blood cells in the and development of a treatment plan, but most Most patients urine) is suspected, refer to a nephrologist of the responsibility for their care can remain early. with the primary care provider. Once stage 4 with CKD • Provide treatment to correct the specific CKD develops, the nephrologist should as- never reach cause (if one is present) or slow the dete- sume an increasing role. However, if glomeru- rioration of renal function. lar disease is suspected, we recommend referral end-stage • Address cardiovascular risk factors. to a nephrologist regardless of the estimated renal disease • Address metabolic abnormalities related GFR. to CKD. • If the CKD is advanced, educate the pa- ■ ELEVATED CARDIOVASCULAR RISK tient about end-stage renal disease and its Patients with stage 3 CKD are 20 times more treatment options, and guide the patient likely to die of a cardiovascular event than to through the transition to end-stage renal 6 disease. reach end-stage renal disease. This increased risk does not quite reach the status of a car- diovascular disease risk equivalent, as does ■ WHEN SHOULD A NEPHROLOGIST 9,10 BE CONSULTED? diabetes, but cardiovascular risk reduction should be a primary focus of care for the CKD The ideal timing of referral to a nephrologist is patient. not well defined and depends on the comfort The cardiovascular risk in part is at- level of the primary care provider. tributed to a high prevalence of traditional Treatments to slow the progression of CKD cardiovascular risk factors, including diabe- and decrease cardiovascular risk should begin tes mellitus, hypertension, and hyperlipid- early in CKD (ie, in stage 3) and can be man- emia.11,12 About two-thirds of CKD patients aged by the primary care provider with guid- have metabolic syndrome, which is a risk fac- ance from a nephrologist. Patients referred tor for cardiovascular disease and is associ- to a nephrologist while in stage 3 have been ated with more rapid progression of CKD.13 290 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 81 • NUMBER 5 MAY 2014 Downloaded from www.ccjm.org on September 23, 2021. For personal use only. All other uses require permission. SAKHUJA AND COLLEAGUES TABLE 1 Stages of chronic kidney disease Glomerular filtration rate (GFR) Stage Description (mL/min/1.73 m2) 1 Kidney damage with normal or increased GFR ≥ 90 2 Kidney damage with mild decrease in GFR 60–89 3 Moderately decreased GFR 30–59 4 Severely decreased GFR 15–29 5 Kidney failure < 15 (or dialysis) Chronic kidney disease is defined as either kidney damage or GFR < 60 mL/min/1.73 2m for ≥ 3 months. Kidney damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. NATIONAL KIDNEY FOUNDATION, INC. KDOQI CLINICAL PRACTICE GUIDELINES FOR CHRONIC KIDNEY DISEASE: EVALUATION, CLASSIFICATION, AND STRATIFICATION. HTTP://WWW.KIDNEY.ORG/PROFESSIONALS/KDOQI/GUIDELINES_CKD/P4_CLASS_G1.HTM. ACCESSED MARCH 5, 2014. REPRINTED WITH PERMISSION FROM THE NATIONAL KIDNEY FOUNDATION, INC. In addition, renal dysfunction, proteinuria, with various stages of CKD, including ad- and hyperphosphatemia are also risk factors vanced CKD, had fewer major vascular 14–19 for cardiovascular disease. events if they received the combination of The risk of death from a cardiovascular low-dose simvastatin (Zocor) and ezetimibe event increases as kidney function declines, (Zetia). However, the evidence does not sug- with reported 5-year death rates of 19.5% in gest that statin therapy slows the progression Patients in stage 2, 24.3% in stage 3, and 45.7% in stage of CKD.28–31 stage 3 CKD 4 CKD. However, imbalance between mor- Recommendation. Manage hyperlipidemia are roughly tality risk and progression to end-stage renal aggressively using statin therapy with or with- 20 disease may be age-dependent. Younger pa- out ezetimibe, with a target low-density lipo- 20 times more tients (age 45 and younger) are more likely protein cholesterol level below 100 mg/dL.32 likely to die of to progress to end-stage renal disease, where- as in older patients (over age 65), the rela- Manage other cardiovascular risk factors a cardiovascular tive risk of dying of cardiovascular disease is Because hypertension and proteinuria are risk event than higher.