Chronic kidney disease (CKD) is increasing in incidence and prevalence worldwide.¹ Rates of progression to kidney failure vary among individuals with CKD and depend on the severity of kidney disease, comorbid conditions, and risk of dying before kidney failure onset.^2,3 Interventions to slow CKD progression, planning for initiation of dialysis and transplant, and early creation of arteriovenous fistula have been advocated, but these strategies may be expensive and are associated with risks. Treatment would ideally be recommended only for patients at high risk of progression and for whom the benefit exceeds the harm.^4,5

Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0·83 (95% CI 0·74-0·94), decreasing to 0·78 (0·66-0·92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction<0·0001). In individuals with baseline ACR of 300 mg/g or higher, a 30% decrease in ACR over 2 years was estimated to confer a more than 1% absolute reduction in 10-year risk of end-stage kidney disease, even at early stages of chronic kidney disease. Results were generally similar when we used change in PCR and when study populations from clinical trials were assessed. Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change in albuminuria as a surrogate endpoint for end-stage kidney disease in clinical trials of progression of chronic kidney disease in the setting of increased albuminuria. US National Kidney Foundation and US National Institute of Diabetes and Digestive and Kidney Diseases.

Objective: To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality.Design: Individual participant data meta-analysis.Setting: Cohorts from 40 countries with data collected between 1970 and 2017.Participants: Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607).Main outcome measures: GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m²) and all cause mortality.Results: Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index.Conclusions: Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

Background Concerns for hyperkalaemia limit the use of mineralocorticoid receptor antagonists (MRAs). The frequency of MRA‐associated hyperkalaemia in real‐world settings and the extent of subsequent MRA discontinuation are poorly quantified. Methods and results Observational study including all Stockholm citizens initiating MRA therapy during 2007–2010. Hyperkalaemias were identified from all potassium (K⁺) measurements in healthcare. MRA treatment lengths and dosages were obtained from complete collection of pharmacy dispensations. We assessed the 1‐year incidence and clinical hyperkalaemia predictors, and quantified drug prescription changes after an episode of hyperkalaemia. Overall, 13 726 new users of MRA were included, with median age of 73 years, 53% women and median plasma K⁺ of 3.9 mmol/L. Within a year, 18.5% experienced at least one detected hyperkalaemia (K⁺ > 5.0 mmol/L), the majority within the first 3 months of therapy. As a comparison, hyperkalaemia was detected in 6.4% of propensity‐matched new beta‐blocker users. Chronic kidney disease (CKD), older age, male sex, heart failure, peripheral vascular disease, diabetes and concomitant use of angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, beta‐blockers and diuretics were associated with increased hyperkalaemia risk. After hyperkalaemia, 47% discontinued MRA and only 10% reduced the prescribed dose. Discontinuation rates were higher after moderate/severe (K⁺ > 5.5 mmol/L) and early in therapy (<3 months from initiation) hyperkalaemias. CKD participants carried the highest risk of MRA discontinuation in adjusted analyses. When MRA was discontinued, most patients (76%) were not reintroduced to therapy during the subsequent year. Conclusion Among real‐world adults initiating MRA therapy, hyperkalaemia was very common and frequently followed by therapy interruption, especially among participants with CKD.

Background: Concerns about hyperkalemia limit the use of angiotensin‐converting enzyme inhibitors ( ACE ‐I) and angiotensin receptor blockers ( ARB s), but guidelines conflict regarding potassium‐monitoring protocols. We quantified hyperkalemia monitoring and risks after ACE ‐I/ ARB initiation and developed and validated a hyperkalemia susceptibility score. Methods and Results: We evaluated 69 426 new users of ACE ‐I/ ARB therapy in the Stockholm Creatinine Measurements ( SCREAM ) project with medication initiation from January 1, 2007 to December 31, 2010, and follow‐up for 1 year thereafter. Three fourths (76%) of SCREAM patients had potassium checked within the first year. Potassium >5 and >5.5 mmol/L occurred in 5.6% and 1.7%, respectively. As a comparison, we propensity‐matched new ACE ‐I/ ARB users to 20 186 new β‐blocker users in SCREAM : 64% had potassium checked. The occurrence of elevated potassium levels was similar between new β‐blocker and ACE ‐I/ ARB users without kidney disease; only at estimated glomerular filtration rate <60 mL/min per 1.73 m ² were risks higher among ACE ‐I/ ARB users. We developed a hyperkalemia susceptibility score that incorporated estimated glomerular filtration rate, baseline potassium level, sex, diabetes mellitus, heart failure, and the concomitant use of potassium‐sparing diuretics in new ACE ‐I/ ARB users; this score accurately predicted 1‐year hyperkalemia risk in the SCREAM cohort (area under the curve, 0.845, 95% CI : 0.840–0.869) and in a validation cohort from the US ‐based Geisinger Health System (N=19 524; area under the curve, 0.818, 95% CI : 0.794–0.841), with good calibration. Conclusions: Hyperkalemia within the first year of ACE ‐I/ ARB therapy was relatively uncommon among people with estimated glomerular filtration rate >60 mL/min per 1.73 m ² , but rates were much higher with lower estimated glomerular filtration rate. Use of the hyperkalemia susceptibility score may help guide laboratory monitoring and prescribing strategies.

Background—: Acute kidney injury (AKI) is a common complication after coronary artery bypass grafting (CABG) and is associated with adverse outcomes. However, the relationship between AKI after CABG and the long-term risk of end-stage renal disease (ESRD) is unknown. Methods and Results—: This study included 29 330 patients who underwent primary isolated CABG in Sweden between 2000 and 2008. AKI was classified according to the Acute Kidney Injury Network (AKIN) classification: stage 1, >0.3 mg/dL (>26 μmol/L) or 50% to 100% increase; stage 2, 100% to 200% increase; and stage 3, >200% increase from the preoperative to postoperative serum creatinine level. Cox proportional hazards regression analysis was used to calculate hazard ratios with 95% confidence intervals for ESRD in AKIN stage 1 and stage 2 to 3. Postoperative AKI occurred in 13% of patients. During a mean follow-up of 4.3±2.4 years, 123 patients (0.4%) developed ESRD, including 50 (1.6%) in AKIN stage 1, 29 (5.2%) in AKIN stage 2 to 3, and 44 (0.2%) without AKI after CABG. After multivariable adjustment, the hazard ratio for ESRD was 2.92 (95% confidence interval, 1.87–4.55) for AKIN stage 1 and 3.81 (95% confidence interval, 2.14–6.79) for AKIN stage 2 to 3. Conclusions—: This nationwide study of patients who underwent CABG found that a small increase in the postoperative serum creatinine level was associated with an almost 3-fold increase in the long-term risk of ESRD after adjustment for a number of confounders, including preoperative renal function.