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Modifiable Lifestyle Factors for Primary Prevention of CKD: A Systematic Review and Meta-Analysis.
Kelly, JT, Su, G, Zhang, L, Qin, X, Marshall, S, González-Ortiz, A, Clase, CM, Campbell, KL, Xu, H, Carrero, JJ
Journal of the American Society of Nephrology : JASN. 2021;(1):239-253
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Abstract
BACKGROUND Despite increasing incidence of CKD, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist. METHODS To evaluate the consistency of evidence associating modifiable lifestyle factors and CKD incidence, we searched MEDLINE, Embase, CINAHL, and references from eligible studies from database inception through June 2019. We included cohort studies of adults without CKD at baseline that reported lifestyle exposures (diet, physical activity, alcohol consumption, and tobacco smoking). The primary outcome was incident CKD (eGFR<60 ml/min per 1.73 m2). Secondary outcomes included other CKD surrogate measures (RRT, GFR decline, and albuminuria). RESULTS We identified 104 studies of 2,755,719 participants with generally a low risk of bias. Higher dietary potassium intake associated with significantly decreased odds of CKD (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.65 to 0.94), as did higher vegetable intake (OR, 0.79; 95% CI, 0.70 to 0.90); higher salt intake associated with significantly increased odds of CKD (OR, 1.21; 95% CI, 1.06 to 1.38). Being physically active versus sedentary associated with lower odds of CKD (OR, 0.82; 95% CI, 0.69 to 0.98). Current and former smokers had significantly increased odds of CKD compared with never smokers (OR, 1.18; 95% CI, 1.10 to 1.27). Compared with no consumption, moderate consumption of alcohol associated with reduced risk of CKD (relative risk, 0.86; 95% CI, 0.79 to 0.93). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for secondary outcomes were consistent with the primary finding. CONCLUSIONS These findings identify modifiable lifestyle factors that consistently predict the incidence of CKD in the community and may inform both public health recommendations and clinical practice.
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Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease.
Chung, EY, Ruospo, M, Natale, P, Bolignano, D, Navaneethan, SD, Palmer, SC, Strippoli, GF
The Cochrane database of systematic reviews. 2020;(10):CD007004
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Abstract
BACKGROUND Treatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a Cochrane review first published in 2009 and updated in 2014. OBJECTIVES To evaluate the effects of aldosterone antagonists (selective (eplerenone), non-selective (spironolactone or canrenone), or non-steroidal mineralocorticoid antagonists (finerenone)) in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including kidney failure (previously know as end-stage kidney disease (ESKD)), major cardiovascular events, and death (any cause); kidney function (proteinuria, estimated glomerular filtration rate (eGFR), and doubling of serum creatinine); blood pressure; and adverse events (including hyperkalaemia, acute kidney injury, and gynaecomastia). SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 13 January 2020 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 Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA We included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists in combination with ACEi or ARB (or both) to other anti-hypertensive strategies or placebo in participants with proteinuric CKD. DATA COLLECTION AND ANALYSIS Two authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used together with their 95% confidence interval (CI). Risk of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE. MAIN RESULTS Forty-four studies (5745 participants) were included. Risk of bias in the evaluated methodological domains were unclear or high risk in most studies. Adequate random sequence generation was present in 12 studies, allocation concealment in five studies, blinding of participant and investigators in 18 studies, blinding of outcome assessment in 15 studies, and complete outcome reporting in 24 studies. All studies comparing aldosterone antagonists to placebo or standard care were used in addition to an ACEi or ARB (or both). None of the studies were powered to detect differences in patient-level outcomes including kidney failure, major cardiovascular events or death. Aldosterone antagonists had uncertain effects on kidney failure (2 studies, 84 participants: RR 3.00, 95% CI 0.33 to 27.65, I² = 0%; very low certainty evidence), death (3 studies, 421 participants: RR 0.58, 95% CI 0.10 to 3.50, I² = 0%; low certainty evidence), and cardiovascular events (3 studies, 1067 participants: RR 0.95, 95% CI 0.26 to 3.56; I² = 42%; low certainty evidence) compared to placebo or standard care. Aldosterone antagonists may reduce protein excretion (14 studies, 1193 participants: SMD -0.51, 95% CI -0.82 to -0.20, I² = 82%; very low certainty evidence), eGFR (13 studies, 1165 participants, MD -3.00 mL/min/1.73 m², 95% CI -5.51 to -0.49, I² = 0%, low certainty evidence) and systolic blood pressure (14 studies, 911 participants: MD -4.98 mmHg, 95% CI -8.22 to -1.75, I² = 87%; very low certainty evidence) compared to placebo or standard care. Aldosterone antagonists probably increase the risk of hyperkalaemia (17 studies, 3001 participants: RR 2.17, 95% CI 1.47 to 3.22, I² = 0%; moderate certainty evidence), acute kidney injury (5 studies, 1446 participants: RR 2.04, 95% CI 1.05 to 3.97, I² = 0%; moderate certainty evidence), and gynaecomastia (4 studies, 281 participants: RR 5.14, 95% CI 1.14 to 23.23, I² = 0%; moderate certainty evidence) compared to placebo or standard care. Non-selective aldosterone antagonists plus ACEi or ARB had uncertain effects on protein excretion (2 studies, 139 participants: SMD -1.59, 95% CI -3.80 to 0.62, I² = 93%; very low certainty evidence) but may increase serum potassium (2 studies, 121 participants: MD 0.31 mEq/L, 95% CI 0.17 to 0.45, I² = 0%; low certainty evidence) compared to diuretics plus ACEi or ARB. Selective aldosterone antagonists may increase the risk of hyperkalaemia (2 studies, 500 participants: RR 1.62, 95% CI 0.66 to 3.95, I² = 0%; low certainty evidence) compared ACEi or ARB (or both). There were insufficient studies to perform meta-analyses for the comparison between non-selective aldosterone antagonists and calcium channel blockers, selective aldosterone antagonists plus ACEi or ARB (or both) and nitrate plus ACEi or ARB (or both), and non-steroidal mineralocorticoid antagonists and selective aldosterone antagonists. AUTHORS' CONCLUSIONS The effects of aldosterone antagonists when added to ACEi or ARB (or both) on the risks of death, major cardiovascular events, and kidney failure in people with proteinuric CKD are uncertain. Aldosterone antagonists may reduce proteinuria, eGFR, and systolic blood pressure in adults who have mild to moderate CKD but may increase the risk of hyperkalaemia, acute kidney injury and gynaecomastia when added to ACEi and/or ARB.
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Pre-eclampsia is associated with later kidney chronic disease and end-stage renal disease: Systematic review and meta-analysis of observational studies.
Ferreira, RC, Fragoso, MBT, Dos Santos Tenório, MC, Silva, JVF, Bueno, NB, Goulart, MOF, de Oliveira, ACM
Pregnancy hypertension. 2020;:71-85
Abstract
OBJECTIVES To assess whether there is a risk of kidney disease during the postpartum period of women who had preeclampsia (PE). STUDY DESIGN Observational trials were searched in the PubMed, Science Direct, Clinical trials, Cochrane, LILACS and Web of Science databases. The data extracted from the studies were systematized, and the risk of bias was evaluated for each of them. Meta-analyses were performed with studies that evaluated chronic kidney disease (CKD) and end-stage renal disease (ESRD), pooling the natural logarithms of the adjusted risk measures and the confidence intervals of each study in a random effects model. RESULTS Of the 4149 studies evaluated, 35 articles were included in the review, of which 3 of the CKD and 6 of the ESRD presented the necessary outcomes to compose the meta-analysis. A formal registration protocol was included in the PROSPERO database (number: CRD42019111821). There was a statistically significant difference between the development of CKD (hazard ratio (HR): 1.82, confidence interval to 95% (95% CI): 1.27-2.62, P < 0.01) and ESRD (HR: 3.01, confidence interval to 95% (95% CI): 1.92-4.70, P < 0.01) in postpartum women affected by PE. CONCLUSIONS PE was considered a risk factor for the onset of CKD and ESRD in the postpartum period. Thus, more research is needed to clarify the underlying mechanisms of this association, and to assist in determining the most appropriate and effective clinical conduct to prevent and/or treat such complications.
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Comparative efficacy and acceptability of treatments for restless legs syndrome in end-stage renal disease: a systematic review and network meta-analysis.
Huang, CW, Lee, MJ, Wang, LJ, Lee, PT, Tu, YK, Hsu, CW, Lin, PY
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(9):1609-1618
Abstract
BACKGROUND Restless legs syndrome (RLS) is common in end-stage renal disease (ESRD) patients and impairs health and quality of life significantly. However, the optimal treatment of RLS in ESRD patients is uncertain and less studied compared with idiopathic RLS patients. METHODS We conducted a systematic review and network meta-analysis to compare the efficacy and acceptability of treatments for RLS in ESRD patients. Randomized controlled trials (RCTs) by February 2019 in the PubMed, Cochrane Library, Embase and ClinicalTrials.gov were reviewed. RLS severity reduction was treated as treatment efficacy, and adverse events were treated as acceptable. Both outcomes were appraised using a random effects model expressed as standardized mean differences and odds ratios with 95% confidence intervals (CIs), respectively, and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities to obtain a hierarchy of interventions. RESULTS A total of 12 RCTs were included, comprising 9 interventions and 498 participants. All the interventions significantly improved RLS severity without critical side effects compared with placebo. Gabapentin achieved the greatest decrease of RLS severity [standardized mean difference (SMD) = 1.95, 95% CI 0.81-3.09 (SUCRA 79.3%)], despite its frequent adverse events [SMD = 0.18, 95% CI 0.02-1.50 (19.9%)]. The combination therapy of exercise plus dopamine agonist had better efficacy [SMD = 1.60, 95% CI 0.08-3.12 (59.8%)] and acceptability [SMD = 1.41, 95% CI 0.01-142.53 (63.9%)] compared with that of vitamin C plus vitamin E [SMD = 1.50, 95% CI 0.47-2.54 (56.6%); SMD = 0.32, 95% CI 0.04-2.86 (32.5%)]. CONCLUSIONS This network meta-analysis supports that gabapentin is the most effective treatment for RLS in ESRD patients. Exercise plus dopamine agonist is a favorable combination therapy concerning side effects. Future large RCTs with long-term treatment outcomes are necessary.
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Effectiveness and Safety of Bariatric Surgery in Patients with End-Stage Chronic Kidney Disease or Kidney Transplant.
Guggino, J, Coumes, S, Wion, N, Reche, F, Arvieux, C, Borel, AL
Obesity (Silver Spring, Md.). 2020;(12):2290-2304
Abstract
OBJECTIVE This study aimed to evaluate (1) the effectiveness, complications, and postoperative access to transplantation in end-stage chronic kidney disease (ECKD) and (2) the effectiveness and complications of bariatric surgery in patients who had already undergone kidney transplant. METHODS A systematic review and meta-analysis of mortality and complications rates were performed. Thirty studies were reviewed. RESULTS After bariatric surgery, patients with ECKD had similar postoperative weight loss to patients from the general population. Meta-analysis showed post-bariatric surgery rates of 2% (95% CI: 0%-3%) for mortality and 7% (95% CI: 2%-14%) for complications. Approximately one-fifth of the patients had access to a transplant. This rate may be underestimated because of the short duration of follow-up. The lack of control groups did not allow for a conclusion on the role of bariatric surgery in facilitating access to kidney transplantation. In patients who had received a kidney transplant, bariatric surgery seemed to improve renal function but increased graft-rejection risk, possibly because of changes in the bioavailability of immunosuppressant drugs. CONCLUSIONS Bariatric surgery yields significant weight loss in patients with ECKD that improves patients' chances of accessing a transplant but does not guarantee it; however, the risk for complications and death is higher than in other patients. After transplantation, bariatric surgery-induced weight loss appeared to positively impact the function of the grafted kidney, but careful monitoring of immunosuppressant medications is required.
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Intradialytic training in patients with end-stage renal disease: a systematic review and meta-analysis of randomized clinical trials assessing the effects of five different training interventions.
Ferrari, F, Helal, L, Dipp, T, Soares, D, Soldatelli, Â, Mills, AL, Paz, C, Tenório, MCC, Motta, MT, Barcellos, FC, et al
Journal of nephrology. 2020;(2):251-266
Abstract
OBJECTIVE Patients with end-stage renal disease (ESRD) undergoing hemodialysis may have reduced dialysis adequacy (Kt/V), low cardiorespiratory fitness, and worse prognosis. Different types of intradialytic training (IDT) may serve as an adjunct therapy for the management of the ESRD. This systematic review and meta-analysis aimed to assess the impact of different types of IDT on clinical outcomes and functional parameters in ESRD. METHODS PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus, SPORTDiscus, and Google Scholar were searched for randomized clinical trials in adult patients with ESRD which compared IDT with usual care (UC), without language restrictions and published up to July 2019; a handsearch of references was also performed. Certainty of evidence was assessed using GRADE, and risk of bias in primary studies with the RoB 1.0 tool. RESULTS Fifty studies were included (n = 1757). Compared to UC, aerobic IDT improved Kt/V (WMD = 0.08), VO2peak (WMD = 2.07 mL/kg/min), 6-minute walk test (6MWT) distance (64.98 m), reduced systolic blood pressure (- 10.07 mmHg) and C-reactive protein (- 3.28 mg/L). Resistance training increased 6MWT distance (68.50 m). Combined training increased VO2peak (5.41 mL/kg/min) and reduced diastolic blood pressure (- 5.76 mmHg). Functional electrostimulation (FES) and inspiratory muscle training (IMT) improved 6MWT distance (54.14 m and 117.62 m, respectively). There was no impact on total cholesterol, interleukin-6, or hemoglobin levels. There was no difference in incidence of adverse events between the IDT and control groups. The certainty of evidence was variable according to the GRADE scale, with most outcomes rated very low certainty. The risk of bias assessment of primary studies showed unclear risk in most. CONCLUSIONS Aerobic, resistance, and combined training during hemodialysis, as well as FES and IMT, demonstrated to be effective for the treatment of the patient with ESRD. Our data should be interpreted in light of the unclear risk of bias of most evaluated articles and the low to very low certainty of evidence for evaluated outcomes. PROSPERO REGISTRATION ID CRD42017081338. DATA SHARING REPOSITORY https://osf.io/fpj54/.
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Efficacy and safety of cinacalcet compared with other treatments for secondary hyperparathyroidism in patients with chronic kidney disease or end-stage renal disease: a meta-analysis.
Sun, Y, Tian, B, Sheng, Z, Wan, P, Xu, T, Yao, L
BMC nephrology. 2020;(1):316
Abstract
BACKGROUND It is controversial for the effect and safety between cinacalcet and other treatments in treating secondary hyperparathyroidism for patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD). METHODS Embase, PubMed, and Cochrane Library were searched through Feb 2017. 21 randomized controlled trials were included. We calculated the pooled mean difference (MD), relative risk (RR) and corresponding 95% confidence interval (CI). RESULT Patients received calcimimetic agents had significantly decreased serum parathyroid hormone (MD = - 259.24 pg/mL, 95% CI: - 336.23 to - 182.25), calcium (MD = - 0.92 mg/dL, 95% CI: - 0.98 to - 0.85) and calcium phosphorus product (MD = - 5.97 mg2/dL2, 95% CI: - 9.77 to - 2.16) concentration compared with control treatment. However, the differences in cardiovascular mortality and all-cause mortality between calcimimetics agents and control group were not statistically significant. The incidence of nausea (RR = 2.13, 95% CI: 1.62 to 2.79), vomiting (RR = 1.99, 95% CI: 1.78 to 2.23) and hypocalcemia (RR = 10.10, 95% CI: 7.60 to 13.43) in CKD patients with calcimimetics agents was significantly higher than that with control treatment. CONCLUSION Cinacalcet improved the biochemical parameters in CKD patients, but did not improve all-cause mortality and cardiovascular mortality. Moreover, cinacalcet can cause some adverse events.
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Comparisons of Three Main Treatments on Renoprotective Effects in Diabetes Mellitus.
Huang, Q, Li, K, Li, M, Xu, G
Iranian journal of kidney diseases. 2019;(1):36-47
Abstract
INTRODUCTION Antihypertension, intensive glucose control (IGC), and lipid lowering were the main therapeutic strategies in diabetes mellitus. However, the comparative effects of them on renoprotection remain unclear. MATERIALS AND METHODS We searched the PubMed, EMBase, and Cochrane Library up to May 18, 2017, for studies with comparative interventions on regression, end-stage renal disease and all-cause death in diabetes mellitus. Statistical analysis was done using the Bayesian network meta-analysis (NMA). The surface under the cumulative ranking area and median rank were calculated to rank the interventions. RESULTS A total of 73 randomized controlled trials with 13 3703 participants were included for the comparisons of 14 interventions. Angiotensin-converting enzyme inhibitor plus angiotensin receptor blocker (ACEI-ARB) ranked first in regression (odds ratio, 62; 95% confidence interval, 5.2 to > 999); ACEI-ARB also ranked first in end-stage renal disease decline (odds ratio, 0.58, 95% confidence interval, 0.39 - 0.85), followed by IGC hemoglobin A1c less than 6.5% (odds ratio, 0.58, 95% confidence interval, 0.36 - 0.90). The ACEI plus calcium channel blocker reduced all-cause death leaving other interventions insignificant (odds ratio, < 0.001; 95% confidence interval, < 0.001 to 0.30). ). The surface under the cumulative ranking area analyses also matched the result ranks. CONCLUSIONS Compared with antihypertension interventions, IGC including IGC hemoglobin A1c less than 6.5% and lipid lowering, ACEI-ARB showed the best renoprotective effects.
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Association of vitamin D receptor TaqI and ApaI genetic polymorphisms with nephrolithiasis and end stage renal disease: a meta-analysis.
Hussain, T, Naushad, SM, Ahmed, A, Alamery, S, Mohammed, AA, Abdelkader, MO, Alkhrm, NAN
BMC medical genetics. 2019;(1):193
Abstract
BACKGROUND The deficiency of vitamin D receptor (VDR) or its ligand, vitamin D3, is linked to the development of renal diseases. The TaqI (rs731236) and ApaI (rs7975232) polymorphisms of VDR gene are widely studied for their association with renal disease risk. However, studies have largely been ambiguous. METHODS Meta-analysis was carried out to clarify the association of TaqI (2777 cases and 3522 controls) and ApaI (2440 cases and 3279 controls) polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN) and end stage renal disease (ESRD). RESULTS The VDR TaqI C-allele under allele contrast was significantly associated with ESRD in both fixed effect and random effect models, and ApaI C-allele with ESRD only under fixed effect model. Cochrane Q-test showed no evidence of heterogeneity for TaqI polymorphism and a significant heterogeneity for Apa I polymorphism. No publication bias was observed for both the polymorphisms. CONCLUSIONS The present meta-analysis identifies TaqI and ApaI polymorphisms of VDR gene as risk factors for renal diseases.
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SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis.
Neuen, BL, Young, T, Heerspink, HJL, Neal, B, Perkovic, V, Billot, L, Mahaffey, KW, Charytan, DM, Wheeler, DC, Arnott, C, et al
The lancet. Diabetes & endocrinology. 2019;(11):845-854
Abstract
BACKGROUND The effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors on kidney failure, particularly the need for dialysis or transplantation or death due to kidney disease, is uncertain. Additionally, previous studies have been underpowered to robustly assess heterogeneity of effects on kidney outcomes by different levels of estimated glomerular filtration rate (eGFR) and albuminuria. We aimed to do a systematic review and meta-analysis to assess the effects of SGLT2 inhibitors on major kidney outcomes in patients with type 2 diabetes and to determine the consistency of effect size across trials and different levels of eGFR and albuminuria. METHODS We did a systematic review and meta-analysis of randomised, controlled, cardiovascular or kidney outcome trials of SGLT2 inhibitors that reported effects on major kidney outcomes in people with type 2 diabetes. We searched MEDLINE and Embase from database inception to June 14, 2019, to identify eligible trials. The primary outcome was a composite of dialysis, transplantation, or death due to kidney disease. We used random-effects models to obtain summary relative risks (RRs) with 95% CIs and random-effects meta-regression to explore effect modification by subgroups of baseline eGFR, albuminuria, and use of renin-angiotensin system (RAS) blockade. This review is registered with PROSPERO (CRD42019131774). FINDINGS From 2085 records identified, four studies met our inclusion criteria, assessing three SGLT2 inhibitors: empagliflozin (EMPA-REG OUTCOME), canagliflozin (CANVAS Program and CREDENCE), and dapagliflozin (DECLARE-TIMI 58). From a total of 38 723 participants, 252 required dialysis or transplantation or died of kidney disease, 335 developed end-stage kidney disease, and 943 had acute kidney injury. SGLT2 inhibitors substantially reduced the risk of dialysis, transplantation, or death due to kidney disease (RR 0·67, 95% CI 0·52-0·86, p=0·0019), an effect consistent across studies (I2=0%, pheterogeneity=0·53). SGLT2 inhibitors also reduced end-stage kidney disease (0·65, 0·53-0·81, p<0·0001), and acute kidney injury (0·75, 0·66-0·85, p<0·0001), with consistent benefits across studies. Although we identified some evidence that the proportional effect of SGLT2 inhibitors might attenuate with declining kidney function (ptrend=0·073), there was clear, separate evidence of benefit for all eGFR subgroups, including for participants with a baseline eGFR 30-45 mL/min per 1·73 m2 (RR 0·70, 95% CI 0·54-0·91, p=0·0080). Renoprotection was also consistent across studies irrespective of baseline albuminuria (ptrend=0·66) and use of RAS blockade (pheterogeneity=0·31). INTERPRETATION SGLT2 inhibitors reduced the risk of dialysis, transplantation, or death due to kidney disease in individuals with type 2 diabetes and provided protection against acute kidney injury. These data provide substantive evidence supporting the use of SGLT2 inhibitors to prevent major kidney outcomes in people with type 2 diabetes. FUNDING None.