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The objective was to systematically review and synthesize evidence regarding benefits and harms of screening for and monitoring and treatment of chronic kidney disease (CKD) stages 1–3.
The data sources were MEDLINE® and Cochrane Database of Systematic Reviews electronic databases, hand searches of references from relevant systematic reviews and eligible trials, and references from expert consultants.
We screened abstracts and full text articles of identified references for eligibility and reviewed randomized controlled trials (RCTs) for evidence on benefits and harms of CKD treatments. We reviewed RCTs and observational studies for evidence regarding possible benefits and harms of CKD screening or monitoring. For all included RCTs, data were extracted, quality was rated, and strength of evidence was graded. Evidence on the benefits and harms of CKD treatments was quantitatively synthesized when possible. Additional evidence on CKD screening and monitoring was qualitatively described.
We found no RCTs of CKD screening or monitoring. In treatment RCTs, several interventions significantly reduced clinical events. In patients with proteinuria, nearly all with diabetes and hypertension, angiotensin converting enzyme inhibitors (ACEIs) (relative risk [RR], 0.60, 95 percent confidence interval [CI], 0.43 to 0.83) and angiotensin receptor blockers (ARBs) (RR 0.77, 95 percent CI, 0.66 to 0.90) significantly reduced risk of end-stage renal disease (ESRD) versus placebo. In patients with microalbuminuria who had cardiovascular disease or diabetes with other cardiovascular risk factors, ACEI treatment reduced mortality risk (RR 0.79, 95 percent CI, 0.66 to 0.96) versus placebo. In individuals with hyperlipidemia and impaired estimated glomerular filtration rate (eGFR) or creatinine clearance, HMG CoA-reductase inhibitors (statins) reduced risk of mortality (RR 0.80, 95 percent CI, 0.68 to 0.95), myocardial infarction (MI), and stroke compared with placebo. However, limited data addressed whether these effects differed between patients with and without CKD or as a function of CKD severity. In RCTs that directly compared different treatments, including high dose versus low dose, combination versus monotherapy, and strict versus standard control, it was unclear whether intensification of treatment improves clinical outcomes. Reporting of study withdrawals and adverse events was limited. Based on treatment RCT findings and additional indirect data, including high CKD prevalence, low CKD recognition and limited CKD monitoring in usual care, uncertain sensitivity of screening and monitoring measures for CKD, and insufficient evidence on CKD screening and monitoring harms, the overall benefits of CKD screening and monitoring are unclear. The likelihood of benefit, if present, appears to be greater in specific subgroups. For example, individuals not being treated with ACEIs or ARBs who have cardiovascular disease or diabetes combined with other cardiovascular risk factors may benefit from screening for albuminuria. Individuals not being treated with a statin who have hyperlipidemia and no cardiovascular disease may benefit from screening for impaired eGFR. Younger patients, and those without diabetes, hypertension, cardiovascular disease, or obesity, are the least likely to benefit from CKD screening. Individuals with impaired eGFR and at high risk for cardiovascular complications who are not being treated with ACEIs or ARBs may benefit from monitoring for incident albuminuria.
No trials directly show a benefit for CKD screening or monitoring. The likelihood of benefit, if present, appears to be greater in specific subgroups. Screening and monitoring harms are poorly described. In selected CKD patients, ACEI or ARB treatment reduces ESRD risk, ACEI treatment reduces mortality risk, and statin treatment reduces risk of mortality, MI, and stroke. Many of these patients may already warrant treatment with these therapies regardless of CKD status. Many knowledge gaps remain, and additional research should increase understanding regarding optimal approaches to CKD screening, monitoring, and treatment.