Managing advanced chronic kidney disease: A primary care guide

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ABSTRACTChronic kidney disease (CKD) is a common disorder that requires close collaboration between the primary care physician and nephrologist. Most aspects of early CKD can be managed in the primary care setting with nephrology input. As the disease progresses, many aspects of care should be transitioned to the nephrologist, especially as the patient nears end-stage renal disease, when dialysis and transplantation must be addressed.


  • Steps to stabilize renal function include blood pressure and diabetes control.
  • Patients have a very high risk of cardiovascular disease, and one should try to reduce modifiable risk factors such as hypertension (which is also a risk factor for the progression of CKD) and hyperlipidemia.
  • In addition to controlling blood pressure, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers reduce proteinuria, a risk factor for progression of CKD.
  • Patients with CKD develop secondary hyperparathyroidism, hyperphosphatemia, and, in advanced CKD, hypocalcemia, all leading to disorders of bone mineral metabolism. Low vitamin D levels should be raised with supplements, and high phosphorus levels should be lowered with dietary restriction and phosphate binders.



Accountable-care organizations are becoming more prominent in the United States, and therefore health care systems in the near future will be reimbursed on the basis of their ability to care for patient populations rather than individual patients. As a result, primary care physicians will need to be well versed in the care of patients with common chronic diseases such as chronic kidney disease (CKD). By one estimate, patients with CKD constitute 14% of the US population age 20 and older, or more than 31 million people.1

An earlier article in this journal reviewed how to identify patients with CKD and how to interpret the estimated glomerular filtration rate (GFR).2 This article examines the care of patients with advanced CKD, how to manage their health risks, and how to optimize their care by coordinating with nephrologists.


CKD is defined either as renal damage (which is most commonly manifested by proteinuria, but which may include pathologic changes on biopsy or other markers of damage on serum, urine, or imaging studies), or as a GFR less than 60 mL/min/1.73 m2 for at least 3 months.3 It is divided into five stages (Table 1).

Since most patients with CKD never reach end-stage renal disease, much of their care is aimed at slowing the progression of renal dysfunction 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 can be separated into several important tasks:

  • Identify the cause of CKD, if possible; address potentially reversible causes such as obstruction or medication-related causes. If a primarily glomerular process (marked by heavy proteinuria and dysmorphic red blood cells and red blood cell casts in the urine sediment) or interstitial nephritis (manifested by white blood cells in the urine) is suspected, refer to a nephrologist early.
  • Provide treatment to correct the specific cause (if one is present) or slow the deterioration of renal function.
  • Address cardiovascular risk factors.
  • Address metabolic abnormalities related to CKD.
  • If the CKD is advanced, educate the patient about end-stage renal disease and its treatment options, and guide the patient through the transition to end-stage renal disease.


The ideal timing of referral to a nephrologist is not well defined and depends on the comfort level of the primary care provider.

Treatments to slow the progression of CKD and decrease cardiovascular risk should begin early in CKD (ie, in stage 3) and can be managed by the primary care provider with guidance from a nephrologist. Patients referred to a nephrologist while in stage 3 have been shown to go longer without CKD progression than those referred in later stages.4 Early referral to a nephrologist has also been associated with a decreased mortality rate.5 The studies that found these trends, however, were limited by the fact that patients with stage 3 CKD are less likely to progress to end-stage renal disease or to die of cardiovascular disease than patients with stage 4 or 5 CKD.

Once stage 4 CKD develops, the nephrologist should take a more active role in the care plan. In this stage, cardiovascular risk rises, and the risk of developing end-stage renal disease rises dramatically.6 With comprehensive care in a CKD clinic, even patients with advanced CKD are more likely to have a stabilization of renal function.7 Kinchen et al8 found that patients referred to a nephrologist within 4 months of starting dialysis had a lower survival rate than those referred earlier. Therefore, if a nephrologist was not involved in the patient’s care prior to stage 4, then a referral must be made.

Recommendation. Patients with stage 3 CKD can be referred for an initial evaluation and development of a treatment plan, but most of the responsibility for their care can remain with the primary care provider. Once stage 4 CKD develops, the nephrologist should assume an increasing role. However, if glomerular disease is suspected, we recommend referral to a nephrologist regardless of the estimated GFR.


Patients with stage 3 CKD are 20 times more likely to die of a cardiovascular event than to reach end-stage renal disease.6 This increased risk does not quite reach the status of a cardiovascular disease risk equivalent, as does diabetes,9,10 but cardiovascular risk reduction should be a primary focus of care for the CKD patient.

The cardiovascular risk in part is attributed to a high prevalence of traditional cardiovascular risk factors, including diabetes mellitus, hypertension, and hyperlipidemia.11,12 About two-thirds of CKD patients have metabolic syndrome, which is a risk factor for cardiovascular disease and is associated with more rapid progression of CKD.13 In addition, renal dysfunction, proteinuria, and hyperphosphatemia are also risk factors for cardiovascular disease.14–19

The risk of death from a cardiovascular event increases as kidney function declines, with reported 5-year death rates of 19.5% in stage 2, 24.3% in stage 3, and 45.7% in stage 4 CKD. However, imbalance between mortality risk and progression to end-stage renal disease may be age-dependent.20 Younger patients (age 45 and younger) are more likely to progress to end-stage renal disease, whereas in older patients (over age 65), the relative risk of dying of cardiovascular disease is higher.


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