Antioxidants for adults with chronic kidney disease.

Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012. To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients. We searched the Cochrane Kidney and Transplant Register of Studies until 15 November 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We included all randomised controlled trials investigating the use of antioxidants, compared with placebo, usual or standard care, no treatment, or other antioxidants, for adults with CKD on cardiovascular and kidney endpoints. Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using random effects models and expressed as risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We included 95 studies (10,468 randomised patients) that evaluated antioxidant therapy in adults with non-dialysis-dependent CKD (31 studies, 5342 patients), dialysis-dependent CKD (41 studies, 3444 patients) and kidney transplant recipients (21 studies, 1529 patients). Two studies enrolled dialysis and non-dialysis patients (153 patients). Twenty-one studies assessed the effects of vitamin antioxidants, and 74 assessed the effects of non-vitamin antioxidants. Overall, the quality of included studies was moderate to low or very low due to unclear or high risk of bias for randomisation, allocation concealment, blinding, and loss to follow-up. Compared with placebo, usual care, or no treatment, antioxidant therapy may have little or no effect on cardiovascular death (8 studies, 3813 patients: RR 0.94, 95% CI 0.64 to 1.40; I² = 33%; low certainty of evidence) and probably has little to no effect on death (any cause) (45 studies, 7530 patients: RR 0.95, 95% CI 0.82 to 1.11; I² = 0%; moderate certainty of evidence), CVD (16 studies, 4768 patients: RR 0.79, 95% CI 0.63 to 0.99; I² = 23%; moderate certainty of evidence), or loss of kidney transplant (graft loss) (11 studies, 1053 patients: RR 0.88, 95% CI 0.67 to 1.17; I² = 0%; moderate certainty of evidence). Compared with placebo, usual care, or no treatment, antioxidants had little to no effect on the slope of urinary albumin/creatinine ratio (change in UACR) (7 studies, 1286 patients: MD -0.04 mg/mmol, 95% CI -0.55 to 0.47; I² = 37%; very low certainty of evidence) but the evidence is very uncertain. Antioxidants probably reduced the progression to kidney failure (10 studies, 3201 patients: RR 0.65, 95% CI 0.41 to 1.02; I² = 41%; moderate certainty of evidence), may improve the slope of estimated glomerular filtration rate (change in eGFR) (28 studies, 4128 patients: MD 3.65 mL/min/1.73 m², 95% CI 2.81 to 4.50; I² = 99%; low certainty of evidence), but had uncertain effects on the slope of serum creatinine (change in SCr) (16 studies, 3180 patients: MD -13.35 µmol/L, 95% CI -23.49 to -3.23; I² = 98%; very low certainty of evidence). Possible safety concerns are an observed increase in the risk of infection (14 studies, 3697 patients: RR 1.30, 95% CI 1.14 to 1.50; I² = 3%; moderate certainty of evidence) and heart failure (6 studies, 3733 patients: RR 1.40, 95% CI 1.11 to 1.75; I² = 0; moderate certainty of evidence) among antioxidant users. Results of studies with a low risk of bias or longer follow-ups generally were comparable to the main analyses. We found no evidence that antioxidants reduced death or improved kidney transplant outcomes or proteinuria in patients with CKD. Antioxidants likely reduce cardiovascular events and progression to kidney failure and may improve kidney function. Possible concerns are an increased risk of infections and heart failure among antioxidant users. However, most studies were of suboptimal quality and had limited follow-up, and few included people undergoing dialysis or kidney transplant recipients. Furthermore, the large heterogeneity in interventions hampers drawing conclusions on the efficacy and safety of individual agents.

Colombijn JM ，Hooft L ，Jun M ，Webster AC ，Bots ML ，Verhaar MC ，Vernooij RW ... -  《Cochrane Database of Systematic Reviews》

HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis.

Cardiovascular disease is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), and the absolute risk of cardiovascular events is similar to people with coronary artery disease. This is an update of a review first published in 2009 and updated in 2014, which included 50 studies (45,285 participants). To evaluate the benefits and harms of statins compared with placebo, no treatment, standard care or another statin in adults with CKD not requiring dialysis. We searched the Cochrane Kidney and Transplant Register of Studies up to 4 October 2023. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. An updated search will be undertaken every three months. Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on death, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD (estimated glomerular filtration rate (eGFR) 90 to 15 mL/min/1.73 m2) were included. Two or more authors independently extracted data and assessed the study risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes and risk ratios (RR) for dichotomous benefits and harms with 95% confidence intervals (CI). The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We included 63 studies (50,725 randomised participants); of these, 53 studies (42,752 participants) compared statins with placebo or no treatment. The median duration of follow-up was 12 months (range 2 to 64.8 months), the median dosage of statin was equivalent to 20 mg/day of simvastatin, and participants had a median eGFR of 55 mL/min/1.73 m2. Ten studies (7973 participants) compared two different statin regimens. We were able to meta-analyse 43 studies (41,273 participants). Most studies had limited reporting and hence exhibited unclear risk of bias in most domains. Compared with placebo or standard of care, statins prevent major cardiovascular events (14 studies, 36,156 participants: RR 0.72, 95% CI 0.66 to 0.79; I2 = 39%; high certainty evidence), death (13 studies, 34,978 participants: RR 0.83, 95% CI 0.73 to 0.96; I² = 53%; high certainty evidence), cardiovascular death (8 studies, 19,112 participants: RR 0.77, 95% CI 0.69 to 0.87; I² = 0%; high certainty evidence) and myocardial infarction (10 studies, 9475 participants: RR 0.55, 95% CI 0.42 to 0.73; I² = 0%; moderate certainty evidence). There were too few events to determine if statins made a difference in hospitalisation due to heart failure. Statins probably make little or no difference to stroke (7 studies, 9115 participants: RR 0.64, 95% CI 0.37 to 1.08; I² = 39%; moderate certainty evidence) and kidney failure (3 studies, 6704 participants: RR 0.98, 95% CI 0.91 to 1.05; I² = 0%; moderate certainty evidence) in people with CKD not requiring dialysis. Potential harms from statins were limited by a lack of systematic reporting. Statins compared to placebo may have little or no effect on elevated liver enzymes (7 studies, 7991 participants: RR 0.76, 95% CI 0.39 to 1.50; I² = 0%; low certainty evidence), withdrawal due to adverse events (13 studies, 4219 participants: RR 1.16, 95% CI 0.84 to 1.60; I² = 37%; low certainty evidence), and cancer (2 studies, 5581 participants: RR 1.03, 95% CI 0.82 to 1.30; I² = 0%; low certainty evidence). However, few studies reported rhabdomyolysis or elevated creatinine kinase; hence, we are unable to determine the effect due to very low certainty evidence. Statins reduce the risk of death, major cardiovascular events, and myocardial infarction in people with CKD who did not have cardiovascular disease at baseline (primary prevention). There was insufficient data to determine the benefits and harms of the type of statin therapy. Statins reduce death and major cardiovascular events by about 20% and probably make no difference to stroke or kidney failure in people with CKD not requiring dialysis. However, due to limited reporting, the effect of statins on elevated creatinine kinase or rhabdomyolysis is unclear. Statins have an important role in the primary prevention of cardiovascular events and death in people who have CKD and do not require dialysis. Editorial note: This is a living systematic review. We will search for new evidence every three months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Tunnicliffe DJ ，Palmer SC ，Cashmore BA ，Saglimbene VM ，Krishnasamy R ，Lambert K ，Johnson DW ，Craig JC ，Strippoli GF ... -  《Cochrane Database of Systematic Reviews》

Peritoneal dialysis versus haemodialysis for people commencing dialysis.

Peritoneal dialysis (PD) and haemodialysis (HD) are two possible modalities for people with kidney failure commencing dialysis. Only a few randomised controlled trials (RCTs) have evaluated PD versus HD. The benefits and harms of the two modalities remain uncertain. This review includes both RCTs and non-randomised studies of interventions (NRSIs). To evaluate the benefits and harms of PD, compared to HD, in people with kidney failure initiating dialysis. We searched the Cochrane Kidney and Transplant Register of Studies from 2000 to June 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. MEDLINE and EMBASE were searched for NRSIs from 2000 until 28 March 2023. RCTs and NRSIs evaluating PD compared to HD in people initiating dialysis were eligible. Two investigators independently assessed if the studies were eligible and then extracted data. Risk of bias was assessed using standard Cochrane methods, and relevant outcomes were extracted for each report. The primary outcome was residual kidney function (RKF). Secondary outcomes included all-cause, cardiovascular and infection-related death, infection, cardiovascular disease, hospitalisation, technique survival, life participation and fatigue. A total of 153 reports of 84 studies (2 RCTs, 82 NRSIs) were included. Studies varied widely in design (small single-centre studies to international registry analyses) and in the included populations (broad inclusion criteria versus restricted to more specific participants). Additionally, treatment delivery (e.g. automated versus continuous ambulatory PD, HD with catheter versus arteriovenous fistula or graft, in-centre versus home HD) and duration of follow-up varied widely. The two included RCTs were deemed to be at high risk of bias in terms of blinding participants and personnel and blinding outcome assessment for outcomes pertaining to quality of life. However, most other criteria were assessed as low risk of bias for both studies. Although the risk of bias (Newcastle-Ottawa Scale) was generally low for most NRSIs, studies were at risk of selection bias and residual confounding due to the constraints of the observational study design. In children, there may be little or no difference between HD and PD on all-cause death (6 studies, 5752 participants: RR 0.81, 95% CI 0.62 to 1.07; I2 = 28%; low certainty) and cardiovascular death (3 studies, 7073 participants: RR 1.23, 95% CI 0.58 to 2.59; I2 = 29%; low certainty), and was unclear for infection-related death (4 studies, 7451 participants: RR 0.98, 95% CI 0.39 to 2.46; I2 = 56%; very low certainty). In adults, compared with HD, PD had an uncertain effect on RKF (mL/min/1.73 m2) at six months (2 studies, 146 participants: MD 0.90, 95% CI 0.23 to 3.60; I2 = 82%; very low certainty), 12 months (3 studies, 606 participants: MD 1.21, 95% CI -0.01 to 2.43; I2 = 81%; very low certainty) and 24 months (3 studies, 334 participants: MD 0.71, 95% CI -0.02 to 1.48; I2 = 72%; very low certainty). PD had uncertain effects on residual urine volume at 12 months (3 studies, 253 participants: MD 344.10 mL/day, 95% CI 168.70 to 519.49; I2 = 69%; very low certainty). PD may reduce the risk of RKF loss (3 studies, 2834 participants: RR 0.55, 95% CI 0.44 to 0.68; I2 = 17%; low certainty). Compared with HD, PD had uncertain effects on all-cause death (42 studies, 700,093 participants: RR 0.87, 95% CI 0.77 to 0.98; I2 = 99%; very low certainty). In an analysis restricted to RCTs, PD may reduce the risk of all-cause death (2 studies, 1120 participants: RR 0.53, 95% CI 0.32 to 0.86; I2 = 0%; moderate certainty). PD had uncertain effects on both cardiovascular (21 studies, 68,492 participants: RR 0.96, 95% CI 0.78 to 1.19; I2 = 92%) and infection-related death (17 studies, 116,333 participants: RR 0.90, 95% CI 0.57 to 1.42; I2 = 98%) (both very low certainty). Compared with HD, PD had uncertain effects on the number of patients experiencing bacteraemia/bloodstream infection (2 studies, 2582 participants: RR 0.34, 95% CI 0.10 to 1.18; I2 = 68%) and the number of patients experiencing infection episodes (3 studies, 277 participants: RR 1.23, 95% CI 0.93 to 1.62; I2 = 20%) (both very low certainty). PD may reduce the number of bacteraemia/bloodstream infection episodes (2 studies, 2637 participants: RR 0.44, 95% CI 0.27 to 0.71; I2 = 24%; low certainty). Compared with HD; It is uncertain whether PD reduces the risk of acute myocardial infarction (4 studies, 110,850 participants: RR 0.90, 95% CI 0.74 to 1.10; I2 = 55%), coronary artery disease (3 studies, 5826 participants: RR 0.95, 95% CI 0.46 to 1.97; I2 = 62%); ischaemic heart disease (2 studies, 58,374 participants: RR 0.86, 95% CI 0.57 to 1.28; I2 = 95%), congestive heart failure (3 studies, 49,511 participants: RR 1.10, 95% CI 0.54 to 2.21; I2 = 89%) and stroke (4 studies, 102,542 participants: RR 0.94, 95% CI 0.90 to 0.99; I2 = 0%) because of low to very low certainty evidence. Compared with HD, PD had uncertain effects on the number of patients experiencing hospitalisation (4 studies, 3282 participants: RR 0.90, 95% CI 0.62 to 1.30; I2 = 97%) and all-cause hospitalisation events (4 studies, 42,582 participants: RR 1.02, 95% CI 0.81 to 1.29; I2 = 91%) (very low certainty). None of the included studies reported specifically on life participation or fatigue. However, two studies evaluated employment. Compared with HD, PD had uncertain effects on employment at one year (2 studies, 593 participants: RR 0.83, 95% CI 0.20 to 3.43; I2 = 97%; very low certainty). The comparative effectiveness of PD and HD on the preservation of RKF, all-cause and cause-specific death risk, the incidence of bacteraemia, other vascular complications (e.g. stroke, cardiovascular events) and patient-reported outcomes (e.g. life participation and fatigue) are uncertain, based on data obtained mostly from NRSIs, as only two RCTs were included.

Ethier I ，Hayat A ，Pei J ，Hawley CM ，Johnson DW ，Francis RS ，Wong G ，Craig JC ，Viecelli AK ，Htay H ，Ng S ，Leibowitz S ，Cho Y ... -  《Cochrane Database of Systematic Reviews》

Interventions for BK virus infection in kidney transplant recipients.

BK virus-associated nephropathy (BKVAN), caused by infection with or reactivation of BK virus, remains a challenge in kidney transplantation. Screening is recommended for all kidney transplant recipients. For those with clinically significant infection, reduction of immunosuppression is the cornerstone of management. There is no specific antiviral or immunomodulatory therapy sufficiently effective for routine use. This review aimed to examine the benefits and harms of interventions for BK virus infection in kidney transplant recipients. We searched the Cochrane Kidney and Transplant Register of Studies up to 5 September 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. All randomised controlled trials (RCTs) and cohort studies investigating any intervention for the treatment or prevention of BKVAN for kidney transplant recipients. Two authors independently assessed the study quality and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Twelve RCTs (2669 randomised participants) were included. Six studies were undertaken in single centres, and six were multicentre studies; two of these were international studies. The ages of those participating ranged from 44 to 57 years. The length of follow-up ranged from three months to five years. All studies included people with a kidney transplant, and three studies included people with signs of BK viraemia. Studies were heterogeneous in terms of the type of interventions and outcomes assessed. The overall risk of bias was low or unclear. Intensive screening for the early detection of BK viraemia or BK viruria prevents graft loss (1 study, 908 participants: RR 0.00, 95% CI 0.00 to 0.05) and decreases the presence of decoy cells and viraemia at 12 months (1 study, 908 participants: RR 0.06, 95% CI 0.03 to 0.11) compared to routine care (high certainty evidence). No other outcomes were reported. Compared to placebo, fluoroquinolones may slightly reduce the risk of graft loss (3 studies, 393 participants: RR 0.37, CI 0.09 to 1.57; I2 = 0%; low certainty evidence), probably makes little or no difference to donor-specific antibodies (DSA), may make little or no difference to BK viraemia and death, had uncertain effects on BKVAN and malignancy, but may increase the risk of tendonitis (2 studies, 193 participants: RR 5.66, CI 1.02 to 31.32; I2 = 0%; low certainty evidence). Compared to tacrolimus (TAC), cyclosporin (CSA) probably makes little or no difference to graft loss and death, may make little or no difference to BKVAN and malignancy, but probably decreases BK viraemia (2 studies, 263 participants: RR 0.61, 95% CI 0.26 to 1.41; I2 = 38%) and probably reduces the risk of new-onset diabetes after transplantation (1 study, 200 participants: RR 0.41, 95% CI 0.12 to 1.35) (both moderate certainty evidence). Compared to azathioprine, mycophenolate mofetil (MMF) probably makes little or no difference to graft loss and BK viraemia but probably reduces the risk of death (1 study, 133 participants: RR 0.43, 95% CI 0.16 to 1.16) and malignancy (1 study, 199 participants: RR 0.43, 95% CI 0.16 to 1.16) (both moderate certainty evidence). Compared to mycophenolate sodium (MPS), CSA has uncertain effects on graft loss and death, may make little or no difference to BK viraemia, but may reduce BKVAN (1 study, 224 participants: RR 0.06, 95% CI 0.00 to 1.20; low certainty evidence). Compared to immunosuppression dose reduction, MMF or TAC conversion to everolimus or sirolimus may make little or no difference to graft loss, BK viraemia or BKVAN (low certainty evidence). TAC conversion to sirolimus probably results in more people having a reduced BK viral load (< 600 copies/mL) than immunosuppression reduction (1 study, 30 participants: RR 1.31, 95% CI 0.90 to 1.89; moderate certainty evidence). Compared to MPS, everolimus had uncertain effects on graft loss and BK viraemia, may reduce BKVAN (1 study, 135 participants: 0.06, 95% CI 0.00 to 1.11) and may increase the risk of death (1 study, 135 participants: RR 3.71, 95% CI 0.20 to 67.35) (both low certainty evidence). Compared to CSA, everolimus may make little or no difference to BK viraemia, has uncertain effects on graft loss and BKVAN, but may increase the risk of death (1 study, 185 participants: RR 3.71, 95% CI 0.42 to 32.55; low certainty evidence). Compared to immunosuppression reduction, the leflunomide derivative FK778 may make little or no difference to graft loss, probably results in a greater reduction in plasma BK viral load (1 study, 44 participants: -0.60 copies/µL, 95% CI -1.22 to 0.02; moderate certainty evidence), but had uncertain effects on BKVAN and malignancy. Aggravated hypertension may be increased with KF778 (1 study, 46 participants: RR 8.23, 95% CI 0.50 to 135.40; low certainty evidence). There were no deaths in either group. Intense monitoring early after transplantation for BK viruria and BK viraemia is effective in improving BK virus infection outcomes as it helps with early detection of the infection and allows for a timely reduction in immunosuppression reduction. There is insufficient evidence to support any other intervention for BK virus infection in kidney transplant recipients.

Wajih Z ，Karpe KM ，Walters GD 《Cochrane Database of Systematic Reviews》

Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease.

Guidelines suggest that adults with diabetes and kidney disease receive treatment with angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). This is an update of a Cochrane review published in 2006. We compared the efficacy and safety of ACEi and ARB therapy (either as monotherapy or in combination) on cardiovascular and kidney outcomes in adults with diabetes and kidney disease. We searched the Cochrane Kidney and Transplants Register of Studies to 17 March 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We included studies evaluating ACEi or ARB alone or in combination, compared to each other, placebo or no treatment in people with diabetes and kidney disease. Two authors independently assessed the risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. One hundred and nine studies (28,341 randomised participants) were eligible for inclusion. Overall, the risk of bias was high. Compared to placebo or no treatment, ACEi may make little or no difference to all-cause death (24 studies, 7413 participants: RR 0.91, 95% CI 0.73 to 1.15; I2 = 23%; low certainty) and with similar withdrawals from treatment (7 studies, 5306 participants: RR 1.03, 95% CI 0.90 to 1.19; I2 = 0%; low certainty). ACEi may prevent kidney failure (8 studies, 6643 participants: RR 0.61, 95% CI 0.39 to 0.94; I2 = 0%; low certainty). Compared to placebo or no treatment, ARB may make little or no difference to all-cause death (11 studies, 4260 participants: RR 0.99, 95% CI 0.85 to 1.16; I2 = 0%; low certainty). ARB have uncertain effects on withdrawal from treatment (3 studies, 721 participants: RR 0.85, 95% CI 0.58 to 1.26; I2 = 2%; low certainty) and cardiovascular death (6 studies, 878 participants: RR 3.36, 95% CI 0.93 to 12.07; low certainty). ARB may prevent kidney failure (3 studies, 3227 participants: RR 0.82, 95% CI 0.72 to 0.94; I2 = 0%; low certainty), doubling of serum creatinine (SCr) (4 studies, 3280 participants: RR 0.84, 95% CI 0.72 to 0.97; I2 = 32%; low certainty), and the progression from microalbuminuria to macroalbuminuria (5 studies, 815 participants: RR 0.44, 95% CI 0.23 to 0.85; I2 = 74%; low certainty). Compared to ACEi, ARB had uncertain effects on all-cause death (15 studies, 1739 participants: RR 1.13, 95% CI 0.68 to 1.88; I2 = 0%; low certainty), withdrawal from treatment (6 studies, 612 participants: RR 0.91, 95% CI 0.65 to 1.28; I2 = 0%; low certainty), cardiovascular death (13 studies, 1606 participants: RR 1.15, 95% CI 0.45 to 2.98; I2 = 0%; low certainty), kidney failure (3 studies, 837 participants: RR 0.56, 95% CI 0.29 to 1.07; I2 = 0%; low certainty), and doubling of SCr (2 studies, 767 participants: RR 0.88, 95% CI 0.52 to 1.48; I2 = 0%; low certainty). Compared to ACEi plus ARB, ACEi alone has uncertain effects on all-cause death (6 studies, 1166 participants: RR 1.08, 95% CI 0.49 to 2.40; I2 = 20%; low certainty), withdrawal from treatment (2 studies, 172 participants: RR 0.78, 95% CI 0.33 to 1.86; I2 = 0%; low certainty), cardiovascular death (4 studies, 994 participants: RR 3.02, 95% CI 0.61 to 14.85; low certainty), kidney failure (3 studies, 880 participants: RR 1.36, 95% CI 0.79 to 2.32; I2 = 0%; low certainty), and doubling of SCr (2 studies, 813 participants: RR 1.14, 95% CI 0.70 to 1.85; I2 = 0%; low certainty). Compared to ACEi plus ARB, ARB alone has uncertain effects on all-cause death (7 studies, 2607 participants: RR 1.02, 95% CI 0.76 to 1.37; I2 = 0%; low certainty), withdrawn from treatment (3 studies, 1615 participants: RR 0.81, 95% CI 0.53 to 1.24; I2 = 0%; low certainty), cardiovascular death (4 studies, 992 participants: RR 3.03, 95% CI 0.62 to 14.93; low certainty), kidney failure (4 studies, 2321 participants: RR 1.15, 95% CI 0.67 to 1.95; I2 = 29%; low certainty), and doubling of SCr (3 studies, 2252 participants: RR 1.18, 95% CI 0.85 to 1.64; I2 = 0%; low certainty). Comparative effects of different ACEi or ARB and low-dose versus high-dose ARB were rarely evaluated. No study compared different doses of ACEi. Adverse events of ACEi and ARB were rarely reported. ACEi or ARB may make little or no difference to all-cause and cardiovascular death compared to placebo or no treatment in people with diabetes and kidney disease but may prevent kidney failure. ARB may prevent the doubling of SCr and the progression from microalbuminuria to macroalbuminuria compared with a placebo or no treatment. Despite the international guidelines suggesting not combining ACEi and ARB treatment, the effects of ACEi or ARB monotherapy compared to dual therapy have not been adequately assessed. The limited data availability and the low quality of the included studies prevented the assessment of the benefits and harms of ACEi or ARB in people with diabetes and kidney disease. Low and very low certainty evidence indicates that it is possible that further studies might provide different results.

Natale P ，Palmer SC ，Navaneethan SD ，Craig JC ，Strippoli GF ... -  《Cochrane Database of Systematic Reviews》