JAMA Guideline Synopsis: Chronic Kidney Disease Screening

Summary of the Clinical Problem

Chronic kidney disease (CKD) is an important health issue associated with increased morbidity, mortality and health care costs. CKD is defined by greater than three months of decreased kidney function identified by a reduced estimated glomerular filtration rate (eGFR) <60mL/min/1.73m2 or by blood or urine markers of kidney damage regardless of eGFR.¹ Using this definition, about which there remains some controversy, over 14% of the US population has CKD and 6% have CKD Stage 3 or higher.^2,3 Stage 3 CKD confers a greater risk of CKD-related complications and progression to end stage renal disease (ESRD).³ Because CKD has a long asymptomatic phase, there are acceptable screening tests, and the health consequences associated with the disease are high, it is a disease that is amenable to screening. Furthermore, the impact of a screening is potentially great as only 10% of individuals with CKD are aware of their diagnosis and intervention proven to reduce the risk of CKD progression exist.⁴

Characteristics of the Guideline Source

The American College of Physicians (ACP) commissioned an independent multidisciplinary group to conduct a systematic review of the published literature on chronic kidney disease screening from 1985–2011.⁵ The evidence review sought to answer questions related to whether: 1) CKD screening improves clinical outcomes and 2) what harms result from systematic screening. Further, it sought to determine whether (in adults with CKD Stages 1 to 3: 3) monitoring for worsening kidney function or kidney damage improves clinical outcomes, 4) harms result from this monitoring, 5) treatment improves clinical outcomes, and 6) what harms, if any, result from this treatment.⁵ The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, chronic heart failure, composite vascular outcomes, composite renal outcomes, end-stage renal disease, quality of life, physical function, and activities of daily living. The ACP panel publically reported disclosures regarding potential financial, professional, and intellectual conflicts of interest.

Evidence Base

The guideline committee found no randomized controlled trials (RCTs) of CKD screening or monitoring. Benefits were therefore based on treatment trials that included patients with diabetes and/or hypertension. Potential harms included misclassification due to false-positive results, psychological effects of being labeled with CKD, medication adverse events, and increased health care costs.

The committee examined whether there were valid, reliable, and clinically available tests to screen for CKD and to monitor CKD progression for patients with CKD Stage 1–3 are valid and reliable. The tests for CKD screening are blood testing for serum creatinine to estimate GFR or urine testing for protein (microalbuminuria or macroalbuminuria). The guideline committee determined that no studies have evaluated the sensitivity and specificity of point-in-time CKD screening, using an estimated GFR and/or albuminuria, to detect CKD (defined by chronicity of ≥3 months). They also determined that there is no standardized method of collection and measurement of urinary albumin and creatinine and they had concerns both about the reliability of the tests, and intra-individual variability based on body position, activity and temperature.⁶

Furthermore, the committee explored whether early identification of CKD in the general population would change management. Again, available evidence concerns individuals with CKD and hypertension or diabetes. Evidence supports blood pressure and glycemic control reducing the risk and progression of CKD.^7,8 In addition, RCT evidence demonstrates that for individuals with Stage 1–3 CKD and concomitant hypertension or diabetes, renin-angiotension blockade using angiotensin converting enzyme inhibitor and angiotension II-receptor blocker significantly reduced progression to ESRD. Moderate quality evidence shows that ACE-inhibitors reduced the risk for end-stage renal disease (ESRD) (relative risk [RR], 0.65 [95% CI, 0.49 to 0.88]) compared with placebo in patients with stage 1 to 3 CKD.⁵ Similarly, high-quality evidence demonstrated that ARBs reduced the risk for ESRD in patients with stage 1 to 3 CKD (RR, 0.77 [CI, 0.66 to 0.90]) compared with placebo. Low quality evidence shows no additional benefit for ACE and ARB combination therapy compared to either treatment alone. Nearly all of the individuals in these had diabetes and hypertension. For individuals without proteinuria, there was insufficient evidence of benefit from ACE or ARBs. In addition, there was no demonstrated clinical benefit for tight blood pressure control, a low protein diet or strict glycemic control.

Discussion

The ACP guideline recommends against screening asymptomatic adults. This recommendation stands at odds with that from the American Society of Nephrology who “strongly recommends regular screening for kidney disease regardless of risk factors.”⁹ The ACP guideline was intended to provide guidance for clinicians caring for patients who are asymptomatic (as are most patients with CKD) and without known CKD risk factors. For those patients, the ACP guideline argues, the current literature lacks evidence in support of CKD screening.

The ACP guideline provides less guidance on which groups of patients physicians should be screening. Many patients seen in a clinician’s office have CKD risk factors such as a family history of kidney failure, diabetes, hypertension, older age, or obesity. The ACP contends that there is insufficient evidence to evaluate the benefits and harms of screening for CKD in asymptomatic adults with CKD risk factors. However, selective screening is supported by the National Kidney Foundation (NKF), the Renal Physicians Association (RPA), and the American Diabetes Association (ADA). The ADA supports screening in individuals with diabetes, and both the NKF and RPA support screening for individuals with diabetes and hypertension. The NKF and RPA further recommend screening in other risk groups included African-Americans and at-risk ethnic groups, those age 60 and older, and those with a family history of kidney failure.¹⁰

Areas in Need of Future Study or Ongoing Research

Practicing clinicians may continue to face difficult decisions regarding screening until further research is completed. To date, there are no randomized clinical trials that assess the benefits or harms for CKD screening in asymptomatic individuals. Studies are needed to quantify both benefits and harms of screening, in addition to evaluating screening measures e.g. eGFR, microalbuminuria, macroalbuminuria, and target groups (e.g. older age, obese, cardiovascular disease, and specific racial/ethnic groups). Similarly, there have been no randomized trials that address the clinical benefits or harms of monitoring for CKD progression. Trials can help to establish both clinically effective monitoring tests and monitoring intervals. Finally, in order for population-based screening to be worthwhile, effective treatments to slow CKD progression are needed for individuals with early CKD without hypertension or diabetes.