The strength of the evidence (high, moderate, low, or insufficient evidence to determine benefits or risks) and strength of recommendations (strong, weak) are defined at the end of the "Major Recommendations" field.
Recommendation 1: The American College of Physicians (ACP) recommends against screening for chronic kidney disease (CKD) in asymptomatic adults without risk factors for CKD. (Grade: weak recommendation; low-quality evidence)
Screening is recommended when it improves important clinical outcomes while limiting harms for screened individuals. Screening for CKD does not meet these generally accepted criteria for population-based screening. Although prevalence increases with age, CKD has a relatively low prevalence in the general population without risk factors. The accuracy of available screening measures for CKD or its progression is uncertain. No available evidence evaluates the sensitivity and specificity of various screening tests in the general population. Albuminuria and serum creatinine-derived estimated glomerular filtration rate (GFR) are widely available in primary care settings, with a high sensitivity and high specificity for 1-time measures of renal damage or dysfunction, but the risk for false-positive results is also very high.
There was no evidence evaluating the benefits of early treatment in patients identified by screening. In contrast, harms, including false-positive results, disease labeling, and unnecessary testing and treatment, are associated with the screening. Given the potential harms of screening for stage 1 to 3 CKD and unknown benefits, current evidence does not support screening for stage 1 to 3 CKD in adults without risk factors.
Recommendation 2: ACP recommends against testing for proteinuria in adults with or without diabetes who are currently taking an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II–receptor blocker (ARB). (Grade: weak recommendation; low-quality evidence)
Evidence suggests that treatment with ACE inhibitors (moderate-quality evidence) or ARBs (high-quality evidence) reduces the risk for end-stage renal disease (ESRD). Whether there are additional benefits of testing patients who are already taking ACE inhibitors or ARBs for proteinuria is unknown. Proteinuria is an intermediate marker; there is no evidence that monitoring proteinuria levels in patients taking ACE inhibitors or ARBs is beneficial or that reduced proteinuria levels translate into improved outcomes for patients with CKD.
Recommendation 3: ACP recommends that clinicians select pharmacologic therapy that includes either an ACE inhibitor (moderate-quality evidence) or an ARB (high-quality evidence) in patients with hypertension and stage 1 to 3 chronic kidney disease. (Grade: strong recommendation)
Evidence showed that treatment with ACE inhibitors (moderate-quality) or ARBs (high-quality) reduces the risk for ESRD in patients with stage 1 to 3 CKD. These medications also reduced composite renal outcomes, the risk for doubling of serum creatinine, and the progression from microalbuminuria to macroalbuminuria. Head-to-head trials revealed no difference in outcomes with ACE inhibitors or ARBs. The harms of ACE inhibitors include cough, angioedema, hyperkalemia, rash, loss of taste, and leukopenia. The harms of ARBs include hyperkalemia, angioedema, and dizziness.
The current evidence did not show any benefit of combination therapy with an ACE inhibitor plus an ARB compared with monotherapy with ACE inhibitors or ARBs. In addition, the risk for adverse effects significantly increased with ACE inhibitor plus ARB combination therapy, including cough, hyperkalemia, hypotension, and acute kidney failure requiring dialysis.
Evidence revealed no difference in ESRD or mortality between strict blood pressure control (128 to 133/75 to 81 mm Hg) and standard control (134 to 141/81 to 87 mm Hg).
Recommendation 4: ACP recommends that clinicians choose statin therapy to manage elevated low-density lipoprotein in patients with stage 1 to 3 chronic kidney disease. (Grade: strong recommendation; moderate-quality evidence)
High-quality evidence showed that statins reduced the risk for all-cause mortality. Evidence also showed that statins lower the risk for myocardial infarction (MI), stroke, and most cardiovascular outcomes in patients with stage 1 to 3 CKD. Patients included in the studies had mean low-density lipoprotein levels of 142 mg/dL (range, 109 to 192 mg/dL).
Two recently published systematic reviews not included in the Agency for Healthcare Research and Quality (AHRQ) report also showed benefits of lipid lowering therapy or statin therapy in patients with CKD. One study showed that statin therapy decreased mortality and cardiovascular events in patients with stage 1 to 3 CKD, and the other study showed that lipid-lowering therapy (including statins) decreased cardiac death and atherosclerosis-mediated cardiovascular events in patients with CKD. Low-quality evidence showed no effect on the risk for ESRD in patients with stage 1 to 3 CKD.
Grading of Quality of Evidence
High-Quality Evidence: Evidence is considered high quality when it is obtained from 1 or more well-designed and well-executed randomized, controlled trials (RCTs) that yield consistent and directly applicable results. This also means that further research is very unlikely to change confidence in the estimate of effect.
Moderate-Quality Evidence: Evidence is considered moderate quality when it is obtained from RCTs with important limitations—for example, biased assessment of the treatment effect, large loss to follow-up, lack of blinding, unexplained heterogeneity (even if it is generated from rigorous RCTs), indirect evidence originating from similar (but not identical) populations of interest, and RCTs with a very small number of participants or observed events. In addition, evidence from well-designed controlled trials without randomization, well-designed cohort or case–control analytic studies, and multiple time series with or without intervention are in this category. Moderate-quality evidence also means that further research will probably have an important effect on confidence in the estimate of effect and may change the estimate.
Low-Quality Evidence: Evidence obtained from observational studies would typically be rated as low quality because of the risk for bias. Low-quality evidence means that further research is very likely to have an important effect on confidence in the estimate of effect and will probably change the estimate. However, the quality of evidence may be rated as moderate or even high, depending on circumstances under which evidence is obtained from observational studies. Factors that may contribute to upgrading the quality of evidence include a large magnitude of the observed effect, a dose–response association, or the presence of an observed effect when all plausible confounders would decrease the observed effect.
Insufficient Evidence to Determine Net Benefits or Risks: When the evidence is insufficient to determine for or against routinely providing a service, the recommendation is graded as "insufficient evidence to determine net benefits or risks." Evidence may be conflicting, of poor quality, or lacking, and hence the balance of benefits and harms cannot be determined. Any estimate of effect that is very uncertain as evidence is either unavailable or does not permit a conclusion.
|The American College of Physicians Guideline Grading System*
|Quality of Evidence
||Strength of Recommendation
||Benefits Clearly Outweigh Risks and Burden or Risks and Burden Clearly Outweigh Benefits
||Benefits Finely Balanced with Risks and Burden
|Insufficient evidence to determine net benefits or risks
*Adopted from the classification developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group.