Search

BACKGROUND: Chronic kidney disease and heart failure are insulin resistant states associated with a high incidence of diabetes. We assessed the effect of dapagliflozin on new-onset type 2 diabetes in a pooled analysis of patient-level data from the DAPA-CKD and DAPA-HF trials.METHODS: This study is a pooled analysis of individual participant data from two phase 3, randomised, double-blind, placebo-controlled, multicentre, clinical trials. Participants with no history of diabetes and HbA1c less than 6·5% (48 mmol/mol) at baseline were included in this pooled analysis. New-onset type 2 diabetes was a prespecified exploratory endpoint in both DAPA-CKD and DAPA-HF trials and is the focus of this analysis. New-onset type 2 diabetes was identified by serial trial measurements of HbA1c (two consecutive values ≥6·5% [≥48 mmol/mol]) or following a clinical diagnosis of diabetes between trial visits. Time to new-onset type 2 diabetes was analysed in a Cox proportional Hazards model from random assignment to end of treatment.FINDINGS: 4003 participants (1398 [34·9%] from the DADA-CKD trial and 2605 [65·1%] from the DAPA-HF trial) were included in our analysis: 1995 (49·8%) had received dapagliflozin and 2008 (50·2%) had received placebo. Over a median follow-up of 21·2 months (IQR 16·0 to 25·4), 126 (6·3%) of 2008 patients in the placebo group (event rate 3·9 per 100 patient-years) and 85 (4·3%) of 1995 patients in the dapagliflozin group (event rate 2·6 per 100 patient-years) developed type 2 diabetes (hazard ratio 0·67 [95% CI 0·51 to 0·88]; p=0·0040). There was no heterogeneity between studies (p interaction 0·77) and there was no clear evidence that the effect of dapagliflozin varied in prespecified subgroups including sex, age, glycaemic status, BMI, glomerular filtration rate, systolic blood pressure, and baseline cardiovascular medication use. More than 90% of the participants who developed type 2 diabetes had prediabetes at baseline (HbA1c 5·7% to 6·4% [39 to 46 mmol/mol]). Mean HbA1c remained unchanged (placebo-adjusted change in the dapagliflozin group of -0·01% [95% CI -0·03 to 0·01], -0·1 mmol/mol [95% CI -0·3 to 0·1] at 12 months).INTERPRETATION: Treatment with dapagliflozin reduced the incidence of new-onset type 2 diabetes in participants with chronic kidney disease and HF without a reduction in HbA1c.FUNDING: AstraZeneca.

Background Despite renin–angiotensin–aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy. Methods In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2 and urinary albumin:creatinine ratio (UACR) 200–5000 mg/g (22.6–565 mg/mol) were randomized to dapagliflozin 10 mg once daily or placebo as an adjunct to standard care and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment). Results Of 104 participants with biopsy-confirmed FSGS, 45 were randomized to dapagliflozin and 59 to placebo. Mean (standard deviation) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73 m2 and median (interquartile range) UACR 1248 (749–2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomized to dapagliflozin and placebo, respectively [hazard ratio 0.62, 95% confidence interval (95% CI) 0.17, 2.17]. Dapagliflozin led to a larger acute reduction (standard error) in eGFR compared with placebo (−4.5, 95% CI −5.9 to −3.1 versus −0.9, −2.1 to 0.4 mL/min/1.73 m2/2 weeks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were −1.9 (−3.0, −0.9) and −4.0 (−4.9, −3.0) mL/min/1.73 m2/year, respectively (difference 2.0, 95% CI 0.6 to 3.5, mL/min/1.73 m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin. Conclusions Among DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared with placebo, although this difference was not statistically significant.

BACKGROUND: Dapagliflozin reduced the risk of kidney failure in patients with chronic kidney disease with and without type 2 diabetes in the DAPA-CKD trial. In this pre-specified analysis, we assessed the effect of dapagliflozin on the rate of change in estimated glomerular filtration rate (eGFR)-ie, the eGFR slope.METHODS: DAPA-CKD was a randomised controlled trial that enrolled participants aged 18 years or older, with or without type 2 diabetes, with a urinary albumin-to-creatinine ratio (UACR) of 200-5000 mg/g, and an eGFR of 25-75 mL/min per 1·73m2. Participants were randomly assigned (1:1) to oral dapagliflozin 10 mg once daily or placebo, added to standard care. In this pre-specified analysis, we analysed eGFR slope using mixed-effect models with different slopes from baseline to week 2 (acute eGFR decline), week 2 to end of treatment (chronic eGFR slope), and baseline to end of treatment (total eGFR slope). DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150, and is now complete.FINDINGS: Between Feb 2, 2017, and April 3, 2020, 4304 participants were recruited, of whom 2152 (50%) were assigned to dapagliflozin and 2152 (50%) were assigned to placebo. At baseline, the mean age was 62 years (SD 12), 1425 (33·1%) participants were women, 2906 (67·5%) participants had type 2 diabetes. The median on-treatment follow-up was 2·3 years (IQR 1·8-2·6). From baseline to the end of treatment, dapagliflozin compared with placebo slowed eGFR decline by 0·95 mL/min per 1·73 m2 per year (95% CI 0·63 to 1·27) in the overall cohort. Between baseline and week 2, dapagliflozin compared with placebo resulted in an acute eGFR decline of 2·61 mL/min per 1·73 m2 (2·16 to 3·06) in patients with type 2 diabetes and 2·01 mL/min per 1·73 m2 (1·36 to 2·66) in those without type 2 diabetes. Between week 2 and end of treatment, dapagliflozin compared with placebo reduced the mean rate of eGFR decline by a greater amount in patients with type 2 diabetes (mean difference in chronic eGFR slope 2·26 mL/min per 1·73 m2 per year [1·88 to 2·64]) than in those without type 2 diabetes (1·29 mL/min per 1·73 m2 per year [0·73 to 1·85]; pinteraction=0·0049). Between baseline and end of treatment, the effect of dapagliflozin compared with placebo on the decline of total eGFR slope in patients with type 2 diabetes was 1·18 mL/min per 1·73 m2 per year (0·79 to 1·56) and without type 2 diabetes was 0·46 mL/min per 1·73 m2 per year (-0·10 to 1·03; pinteraction=0·040). The total eGFR slope was steeper in patients with higher baseline HbA1c and UACR; the effect of dapagliflozin on eGFR slope was also more pronounced in patients with higher baseline HbA1c and UACR.INTERPRETATION: Dapagliflozin significantly slowed long-term eGFR decline in patients with chronic kidney disease compared with placebo. The mean difference in eGFR slope between patients treated with dapagliflozin versus placebo was greater in patients with type 2 diabetes, higher HbA1c, and higher UACR.FUNDING: AstraZeneca.

OBJECTIVES: The purpose of this paper was to investigate the effects of dapagliflozin in chronic kidney disease (CKD) patients, with and without heart failure (HF).BACKGROUND: Patients with CKD, with and without type 2 diabetes, were enrolled in the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial. Some patients had HF at baseline.METHODS: A total of 4,304 participants were randomized to dapagliflozin 10 mg daily or placebo. The primary composite endpoint was ≥50% decline in estimated glomerular filtration rate, end-stage kidney disease, or kidney/cardiovascular death. Secondary endpoints were a kidney composite (primary endpoint minus cardiovascular death), the composite of cardiovascular death/HF hospitalization, and all-cause death. Analysis of outcomes according to HF history was prespecified.RESULTS: HF patients (n = 468; 11%) were older and had more coronary disease, atrial fibrillation, and type 2 diabetes. Mean estimated glomerular filtration rate was similar in patients with and without HF. Rates of HF hospitalization/cardiovascular death and death from any cause were higher in HF patients, but the secondary kidney failure outcome occurred at the same rate in people with and without HF. Dapagliflozin reduced the risk of the primary outcome equally in patients with HF (HR: 0.58 [95% CI: 0.37-0.91]) and without HF (HR: 0.62 [95% CI: 0.51-0.75]) (P interaction = 0.59). The proportional risk-reductions were similar in patients with and without HF for the cardiovascular death/HF hospitalization composite (HR: 0.68 [95% CI: 0.44-1.05] vs HR: 0.70 [95% CI: 0.51-0.97], respectively; P interaction = 0.90), and all-cause death (HR: 0.56 [95% CI: 0.34-0.93] vs HR: 0.73 [95% CI: 0.54-0.97], respectively; P interaction = 0.39), although absolute risk reductions were larger in HF patients. Adverse event rates were low and did not differ among patients with or without HF.CONCLUSIONS: Dapagliflozin reduced the risk of kidney failure and cardiovascular death/HF hospitalization and prolonged survival in CKD patients with or without type 2 diabetes, independently of history of HF. (A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease [DAPA-CKD]; NCT03036150).

BACKGROUND: In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized, placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in patients with CKD with or without type 2 diabetes. METHODS: Adults with eGFR of 25–75 ml/min per 1.73 m(2) and urinary albumin-to-creatinine ratio of 200–5000 mg/g had been randomized to receive dapagliflozin 10 mg/d or placebo. Here, we conducted a prespecified analysis of dapagliflozin’s effects in patients with stage 4 CKD (eGFR,30 ml/min per 1.73 m(2)) at baseline. The primary end point was a composite of time to ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Secondary end points were a kidney composite (same as the primary end point but without cardiovascular death), a composite of cardiovascular death or heart failure hospitalization, and all-cause death. RESULTS: A total of 293 participants with stage 4 CKD received dapagliflozin and 331 received placebo. Patients with stage 4 CKD randomized to dapagliflozin experienced a 27% (95% confidence interval [95% CI]: −2 to 47%) reduction in the primary composite endpoint, and 29% (−2 to 51%), 17% (−53 to 55%), and 32% (−21 to 61%) reductions in the kidney, cardiovascular and mortality endpoints, respectively, relative to placebo. Interaction P-values were 0.22, 0.13, 0.63, and 0.95, respectively, comparing CKD stages 4 versus 2/3. The eGFR slope declined by 2.15 and 3.38 ml/min per 1.73 m(2) per year in the dapagliflozin and placebo groups, respectively (P=0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest. CONCLUSIONS: Among patients with stage 4 CKD and albuminuria, the effects of dapagliflozin were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.

Background: The SARS-CoV-2 pandemic has strained healthcare systems worldwide. Increasing age and comorbidities, as CKD are associated with worse outcomes. Information is needed to assist the decision-making process for ICU admission. The aim of this study was to evaluate mortality rates of COVID-19 CKD patients, percentage of patients admitted to ICU and the role of CKD as a risk factor (RF) for mortality. Methods: Prospective cohort study from a referral center for COVID-19 in Mexico City. All patients hospitalized between March 2020 and March 2021 with complete follow up were included. Subjects were segregated into 4 groups: 1) CKD stages 3-4 (CKD3-4, n=109), 2) renal replacement therapy (RRT, n=103), 3) kidney transplant (KT, n=31), and 4) patients without CKD (no CKD, n=2520). We registered if ICU admission was requested and if patients were admitted or rejected. RF associated with mortality were evaluated by Cox-regression analysis. Results: Mean age of the population was 56 years (IQR 46-67), 1697 (61%) were male, 837 (30%) had diabetes, and 1105 (40%) were obese. The group of CKD3-4 patients was older (median 62 years, IQR 38-86), diabetic (58%), and had higher incidence of acute kidney injury (76%). ICU admission was requested for 52 (48%), 32 (31%), 10 (32%), and 1043 (41%) patients in the CKD3-4, RRT, KT, and no CKD groups, respectively (p

Background: Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and renal events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease. Methods: In the DAPA-CKD trial (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomly assigned to dapagliflozin 10 mg once daily or placebo. The primary end point was a composite of sustained decline in estimated glomerular filtration rate ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The secondary end points were a kidney composite outcome (primary end point, minus cardiovascular death), the composite of hospitalization for heart failure or cardiovascular death, and all-cause death. In a prespecified subgroup analysis, we divided patients into primary and secondary prevention subgroups according to history of cardiovascular disease. Results: Secondary prevention patients (n=1610; 37.4%) were older, were more often male, had a higher blood pressure and body mass index, and were more likely to have diabetes. Mean estimated glomerular filtration rate and median urinary albumin-to-creatinine ratio were similar in the primary and secondary prevention groups. The rates of adverse cardiovascular outcomes were higher in the secondary prevention group, but kidney failure occurred at the same rate in the primary and secondary prevention groups. Dapagliflozin reduced the risk of the primary composite outcome to a similar extent in both the primary (hazard ratio, 0.61 [95% CI, 0.48–0.78]) and secondary (0.61 [0.47–0.79]) prevention groups ( P -interaction=0.90). This was also true for the composite of heart failure hospitalization or cardiovascular death (0.67 [0.40–1.13] versus 0.70 [0.52–0.94], respectively; P -interaction=0.88), and all-cause mortality (0.63 [0.41–0.98] versus 0.70 [0.51–0.95], respectively; P -interaction=0.71). Rates of adverse events were low overall and did not differ between patients with and without cardiovascular disease. Conclusions: Dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalization for heart failure, and prolonged survival in people with chronic kidney disease, with or without type 2 diabetes, independently of the presence of concomitant cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036150.

Aim: \ud To evaluate whether atrasentan plasma exposure explains between-patient variability in urinary albumin-to-creatinine ratio (UACR) response, a surrogate for kidney protection, and B-type natriuretic peptide (BNP) response, a surrogate for fluid expansion.\ud \ud Methods: \ud Type 2 diabetic patients with chronic kidney disease (n = 4775) received 0.75 mg atrasentan for 6 weeks in the active run-in period. Individual area under the concentration-time-curve (AUC) was estimated using a population pharmacokinetic model. The association between atrasentan AUC, other clinical characteristics, and UACR and BNP response, was estimated using linear regression.\ud \ud Results: \ud The median atrasentan AUC was 43.8 ng.h/mL with a large variation among patients (2.5th-97.5th percentiles [P]: 12.6 to 197.5 ng.h/mL). Median UACR change at the end of enrichment was −36.0% and median BNP change was 8.7%, which also varied among patients (UACR, 2.5th-97.5th P: −76.2% to 44.5%; BNP, 2.5th-97.5th P: −71.5% to 300.0%). In the multivariable analysis, higher atrasentan AUC was associated with greater UACR reduction (4.88% per doubling in ng.h/mL [95% confidence interval {CI}: 6.21% to 3.52%], P

Introduction: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). It is unknown if hospital-acquired AKI (HA-AKI) and community-acquired AKI (CA-AKI) convey a distinct prognosis. Methods: The study aim was to evaluate the incidence and risk factors associated with both CA-AKI and HA-AKI. Consecutive patients hospitalized at a reference center for COVID-19 were included in this prospective cohort study. Results: We registered 349 (30%) AKI episodes in 1,170 hospitalized patients, 224 (19%) corresponded to CA-AKI, and 125 (11%) to HA-AKI. Compared to patients with HA-AKI, subjects with CA-AKI were older (61 years [IQR 49–70] vs. 50 years [IQR 43–61]), had more comorbidities (hypertension [44 vs. 26%], CKD [10 vs. 3%]), higher Charlson Comorbidity Index (2 points [IQR 1–4] vs. 1 point [IQR 0–2]), and presented to the emergency department with more severe disease. Mortality rates were not different between CA-AKI and HA-AKI (119 [53%] vs. 63 [50%], p = 0.66). In multivariate analysis, CA-AKI was strongly associated to a history of CKD (OR 4.17, 95% CI 1.53–11.3), hypertension (OR 1.55, 95% CI 1.01–2.36), Charlson Comorbidity Index (OR 1.16, 95% CI 1.02–1.32), and SOFA score (OR 2.19, 95% CI 1.87–2.57). HA-AKI was associated with the requirement for mechanical ventilation (OR 68.2, 95% CI 37.1–126), elevated troponin I (OR 1.95, 95% CI 1.01–3.83), and glucose levels at admission (OR 1.05, 95% CI 1.02–1.08). Discussion/Conclusions: CA-AKI and HA-AKI portend an adverse prognosis in CO­VID-19. Nevertheless, CA-AKI was associated with a higher comorbidity burden (including CKD and hypertension), while HA-AKI occurred in younger patients by the time severe multiorgan disease developed.

BACKGROUND AND OBJECTIVES: Atrasentan reduces the risk of kidney failure but increases the risk of edema and, possibly, heart failure. Patients with severe CKD may obtain greater absolute kidney benefits from atrasentan but may also be at higher risk of heart failure. We assessed relative and absolute effects of atrasentan on kidney and heart failure events according to baseline eGFR and urinary albumin-creatinine ratio (UACR) in a post hoc analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The effect of atrasentan versus placebo in 3668 patients with type 2 diabetes and CKD with elevated albuminuria was examined in the SONAR trial. We used Cox proportional hazards regression analysis to study effects on the primary kidney outcome (composite of doubling of serum creatinine, kidney failure, or kidney death) and heart failure hospitalization across subgroups of eGFR (RESULTS: Atrasentan reduced the relative risk of the primary kidney outcome (hazard ratio, 0.71; 95% confidence interval, 0.58 to 0.88) consistently across all subgroups of baseline eGFR and UACR (all P interaction >0.21). Patients in the highest UACR and lowest eGFR subgroups, in whom rates of the primary kidney outcome were highest, showed the largest absolute benefit (all P interaction 0.09).CONCLUSIONS: Atrasentan reduced the relative risk of the primary kidney outcome consistently across baseline UACR and eGFR subgroups. The absolute risk reduction was greater among patients in the lowest eGFR and highest albuminuria category who were at highest baseline risk. Conversely, the relative and absolute risks of heart failure hospitalization were similar across baseline UACR and eGFR subgroups.Clinical Trial registry name and registration number: Study of Diabetic Nephropathy with Atrasentan (SONAR), NCT01858532.

BACKGROUND: Whether early reduction in albuminuria with atrasentan treatment predicts its long-term kidney-protective effect is unknown.METHODS: To assess the long-term effects on kidney outcomes of atrasentan versus placebo in the SONAR trial, we enrolled patients who had type 2 diabetes and CKD (stage 2-4) and a urinary albumin creatinine ratio (UACR) of 300-5000 mg/g; participants were receiving maximum tolerated renin-angiotensin system inhibition. After 6 weeks exposure to 0.75 mg/day atrasentan (enrichment period), participants were randomized (stratified by UACR response during enrichment, ranging from ≤60% to >0%) to continue atrasentan or transition to placebo. Primary kidney outcome was a composite of sustained serum creatinine doubling or ESKD.RESULTS: UACR response to atrasentan during enrichment persisted throughout the double-blind treatment phase and predicted the primary kidney outcome, whereas UACR levels with placebo remained below pre-enrichment values in the two highest UACR response strata, and exceeded pre-enrichment values in the two lowest strata. As a result, early UACR response to atrasentan during enrichment was also associated with the primary kidney outcome during placebo. Accordingly, the predictive effect of early albuminuria changes during atrasentan was eliminated after placebo correction, leading to a consistent relative risk reduction for the primary kidney outcome with atrasentan compared with placebo, irrespective of the initial UACR response. The difference between atrasentan and placebo in UACR during double-blind treatment was also consistent across UACR response strata.CONCLUSIONS: Our findings do not support UACR response as a causal predictor of atrasentan's treatment effect. However, the variable trajectory in UACR with placebo, aspects of the trial design, day-to-day variability in albuminuria, and potential long-lasting effects of atrasentan may have contributed.

BACKGROUND: Reductions in albuminuria are associated with a subsequent lower risk of kidney failure in patients with chronic kidney disease. The SGLT2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes and normal or near-normal kidney function. Whether this effect persists in patients with chronic kidney disease with and without type 2 diabetes is unknown. We assessed the effects of dapagliflozin on albuminuria in patients with chronic kidney disease with and without type 2 diabetes in the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial.METHODS: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 sites in 21 countries. Patients were eligible for the trial if they had chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) between 25 mL/min per 1·73 m2 and 75 mL/min per 1·73 m2 and a urinary albumin-to-creatinine ratio (UACR) between 200 mg/g and 5000 mg/g (22·6 to 565·6 mg/mmol). Participants were randomly assigned to dapagliflozin 10 mg (AstraZeneca; Gothenburg, Sweden) once daily or matching placebo, in accordance with the sequestered, fixed randomisation schedule, using balanced blocks to ensure an approximate 1:1 ratio. Change in albuminuria was a pre-specified exploratory outcome of DAPA-CKD. Regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to microalbuminuria or normoalbuminuria (FINDINGS: Between Feb 2, 2017, and April 3, 2020, 4304 patients were recruited and randomly assigned to either dapagliflozin (n=2152) or placebo (n=2152). Median UACR was 949 mg/g (IQR 477 to 1885). Overall, compared with placebo, dapagliflozin reduced geometric mean UACR by 29·3% (95% CI -33·1 to -25·2; pINTERPRETATION: In patients with chronic kidney disease with and without type 2 diabetes, dapagliflozin significantly reduced albuminuria, with a larger relative reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR, suggest that part of the protective effect of dapagliflozin in patients with chronic kidney disease might be mediated through pathways unrelated to reduction in albuminuria.FUNDING: AstraZeneca.

Background Heart failure (HF) is highly prevalent in patients with chronic kidney disease (CKD) and the severity of kidney impairment increases risk of HF, highlighting the deleterious interplay between the conditions. The DAPA-CKD trial showed that dapagliflozin reduced the risk of kidney failure and HF hospitalization in patients with CKD. Purpose This prespecified analysis of DAPA-CKD aimed to determine the effects of dapagliflozin on kidney, cardiovascular and mortality outcomes according to presence or absence of HF. Methods DAPA-CKD (NCT03036150) was a randomized, double blind, controlled trial, which enrolled 4,304 participants with CKD. Participants were randomized to dapagliflozin 10 mg/day or placebo, as adjunct to standard care, and were followed for a median 2.4 years. The primary endpoint was a composite of sustained decline in eGFR ≥50%, end-stage kidney disease, or renal or cardiovascular death. Key secondary endpoints included a composite of cardiovascular death or HF hospitalization and all-cause mortality. Results Overall, 468 (11%) participants had a HF diagnosis at baseline. Participants with HF were older (65.3 vs 61.4 years) and more frequently diagnosed with type 2 diabetes (77% vs 66%) compared with those without HF; mean eGFR was similar (43.2 vs 43.1 mL/min/1.73m2) in the two groups. The primary outcome occurred more frequently in those with versus without HF (8.8 vs 5.7 events per 100 patient-years, respectively). The effect of dapagliflozin on the primary outcome was consistent among those with (hazard ratio [HR] 0.58; 95% CI 0.37, 0.91) or without HF (HR 0.62; 95% CI 0.51, 0.75; p-interaction 0.59). The composite of cardiovascular death or HF hospitalization (HR 0.68; 95% CI 0.44, 1.05 vs 0.70; 95% CI 0.51, 0.97; p-interaction 0.90), and the relative risk reduction for mortality (HR 0.56; 95% CI 0.34, 0.93; vs 0.73; 95% CI 0.54, 0.97; p-interaction 0.39) were also consistent in those with or without HF. Conclusion Patients with co-existing CKD and HF are at high risk of kidney and cardiovascular events and premature mortality. Dapagliflozin consistently reduced the proportional risk of these events, regardless of the presence or absence of HF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AstraZeneca

Background . There is controversy regarding the association between hypovitaminosis D and COVID-19 outcomes. Aim of the study . We assessed the association between 25-hydroxyvitamin D levels and COVID-19 outcomes in hospitalized subjects with severe SARS-CoV-2 infection. Methods . Retrospective cohort study. Serum 25-hydroxyvitamin D levels of subjects with severe COVID-19 pneumonia were measured at hospital admission, between March 17th, 2020, and March 1st, 2021. Results . Out of 2,908 patients, 571 (19.6%) had vitamin D deficiency (defined as a serum 25-hydroxyvitamin D level

Aims People with type 2 diabetes mellitus (T2DM) have a greater risk of cardiovascular disease and major adverse cardiovascular events (MACE), which become more common as kidney function declines. Canagliflozin reduced the risk of MACE (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) in patients with T2DM and high cardiovascular risk or nephropathy in the CANVAS Program and CREDENCE trial. Risk of MACE by kidney status had not been examined in Hispanic participants. Materials and methods This post hoc analysis included integrated, pooled data from the CANVAS Program and CREDENCE. The effects of canagliflozin versus placebo on MACE were assessed in subgroups by baseline eGFR ( 60mL/min/1.73 m2 ) overall and in the Hispanic cohort. Hazard ratios (HRs) and 95% CIs were estimated using Cox regression models, with subgroup by treatment interaction terms added to test for heterogeneity. Results A total of 14,543 participants were included; 3029 (20.8%) self-identified as Hispanic. In the overall population, canagliflozin reduced the risk of MACE compared with placebo (HR, 0.83; 95%CI, 0.75, 0.92), with no heterogeneity observed across eGFR subgroups (interaction P=0.22). In the Hispanic cohort, canagliflozin also reduced the risk of MACE (HR, 0.71; 95%CI, 0.55, 0.92) with no heterogeneity by baseline eGFR (interaction P=0.25), including among the highest-risk Hispanic participants with baseline eGFR Conclusion Canagliflozin reduced the risk of MACE overall and among Hispanic participants with T2DM and high cardiovascular risk or nephropathy in the CANVAS Program and CREDENCE, without heterogeneity by baseline eGFR. This article is protected by copyright. All rights reserved.

Immunoglobulin A (IgA) nephropathy is a common form of glomerulonephritis, which despite use of renin-angiotensin-aldosterone-system blockers and immunosuppressants, often progresses to kidney failure. In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial, dapagliflozin reduced the risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes, including those with IgA nephropathy. Participants with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10mg or placebo, as adjunct to standard care. The primary composite endpoint was a sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from a kidney disease-related or cardiovascular cause. Of 270 participants with IgA nephropathy (254 [94%] confirmed by previous biopsy), 137 were randomized to dapagliflozin and 133 to placebo, and followed for median 2.1 years. Overall, mean age was 51.2 years; mean eGFR, 43.8 mL/min/1.73m2; and median urinary albumin-to-creatinine ratio, 900 mg/g. The primary outcome occurred in six (4%) participants on dapagliflozin and 20 (15%) on placebo (hazard ratio, 0.29; 95% confidence interval, 0.12, 0.73). Mean rates of eGFR decline with dapagliflozin and placebo were −3.5 and −4.7 mL/min/1.73m2/year, respectively. Dapagliflozin reduced the urinary albumin-to-creatinine ratio by 26% relative to placebo. Adverse events leading to study drug discontinuation were similar with dapagliflozin and placebo. There were fewer serious adverse events with dapagliflozin, and no new safety findings in this population. Thus, in participants with IgA nephropathy, dapagliflozin reduced the risk of chronic kidney disease progression with a favorable safety profile.

OBJECTIVE The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status. RESEARCH DESIGN AND METHODS We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200–5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. RESULTS Of 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio [HR] 0.62 [95% CI 0.39, 1.01]), prediabetes (HR 0.37 [0.21, 0.66]), and type 2 diabetes (HR 0.64 [0.52, 0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes. CONCLUSIONS Dapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status.

Introduction: CANA reduced the risk of MACE (cardiovascular [CV] death, nonfatal myocardial infarction, and nonfatal stroke) in the CANVAS Program and CREDENCE trials of patients with type 2 diabetes with high CV risk or nephropathy, respectively, regardless of baseline eGFR. The risk of MACE by renal status had not been examined in Hispanic participants, who have a higher MACE burden. Methods: This analysis used integrated data from the CANVAS Program (N = 10,142) and CREDENCE (N = 4401). The effects of CANA versus placebo on MACE were assessed in subgroups defined by baseline eGFR ( 60 mL/min/1.73 m2) overall and in the Hispanic subgroup. Results: Of the 14,540 participants with baseline eGFR values, 3028 (21%) self-identified as Hispanic. In the overall population, CANA reduced the risk of MACE (HR, 0.83; 95% CI, 0.75, 0.92), with consistent effects across eGFR subgroups (interaction P value = 0.22; Figure). In the Hispanic subgroup, CANA also reduced the risk of MACE (HR, 0.71; 95% CI, 0.55, 0.92) regardless of eGFR (interaction P value = 0.25). Even the highest risk Hispanic participants with baseline eGFR Conclusion: CANA reduced the risk of MACE overall and among Hispanic participants from the CANVAS Program and CREDENCE, regardless of baseline eGFR. Disclosure M. R. Weir: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Vifor Pharma Management Ltd. J. Gogate: Employee; Self; Janssen Research & Development, LLC. C. Damaraju: Employee; Self; Janssen Research & Development, LLC. R. Correa-rotter: Consultant; Self; GlaxoSmithKline plc., Other Relationship; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Inc., Speaker’s Bureau; Self; AbbVie Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceutical Co. K. W. Mahaffey: Consultant; Self; Abbott, Amgen Inc., Anthos, AstraZeneca, Baim Institute for Clinical Research, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals, Inc., CSL Behring, Elsevier, Inova, Intermountain Health, Johnson & Johnson, Medscape, Mount Sinai, Mundipharma International, MyoKardia, National Institutes of Health, Novartis Pharmaceuticals Corporation, Novo Nordisk, Otsuka America Pharmaceutical, Inc., Portola Pharmaceuticals, Inc., Regeneron Pharmaceuticals Inc., SmartMedics, Theravance Biopharma, Research Support; Self; Afferent, AHA, Amgen Inc., Apple, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Cardiva Medical, Inc, Eidos, Ferring Pharmaceuticals Inc., Gilead Sciences, Inc., Google, Johnson & Johnson, Luitpold Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., National Institutes of Health, Novartis Pharmaceuticals Corporation, Sanifit, Sanofi, St. Jude Medical. Funding Janssen Scientific Affairs, LLC

There is robust evidence that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of adverse cardiovascular and kidney outcomes. The DAPA-CKD trial (NCT03036150) demonstrated a significant risk reduction in participants with chronic kidney disease (CKD), with and without type 2 diabetes, treated with dapagliflozin 10 mg once daily compared with placebo, as an adjunct to standard care. In this prespecified analysis, we compared the efficacy and safety of dapagliflozin according to baseline glycemic status. The trial included individuals with CKD with an estimated glomerular filtration rate (eGFR) of 25 to 75 mL/min/1.73 m2 and a urinary albumin-to-creatinine ratio of 200 to 5000 mg/g. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes. We analyzed results by baseline glycemic status based on the American Diabetes Association criteria for HbA1c level In conclusion, dapagliflozin reduced the risk of kidney and cardiovascular events independent of baseline glycemic status. Disclosure F. Persson: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Mundipharma International, Novo Nordisk, Advisory Panel; Spouse/Partner; AstraZeneca, Bristol-Myers Squibb Company, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Mundipharma International, Novo Nordisk. R. D. Toto: Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Medscape Education, Otsuka America Pharmaceutical, Inc., Quest Diagnostics, Reata Pharmaceuticals, Inc., Relypsa Inc. A. Langkilde: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. D. C. Wheeler: Advisory Panel; Self; Merck Sharp & Dohme Corp., Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, GlaxoSmithKline plc., Janssen Global Services, LLC., Mundipharma International, Tricida, Inc., Speaker’s Bureau; Self; Amgen Astellas BioPharma, Astellas Pharma Inc., Napp Pharmaceuticals, Vifor Pharma Management Ltd. H. L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook, CSL Behring, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, LLC, Merck & Co., Inc., Mitsubishi Corporation Life Sciences Limited, Mundipharma International, Novo Nordisk, Retrophin, Inc., Research Support; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC. Dapa-ckd study group: n/a. P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. P. Vart: None. G. M. Chertow: Advisory Panel; Self; Ardelyx, Baxter, Cricket Health, DURECT Corporation, Gilead Sciences, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Self; Akebia Therapeutics, Inc., AstraZeneca, Vertex Pharmaceuticals Incorporated. F. Hou: Consultant; Self; AstraZeneca. J. J. Mcmurray: Other Relationship; Self; AbbVie Inc., Amgen Inc., AstraZeneca, Bayer AG, Cytokinetics Inc., DalCor Pharmaceuticals, Merck & Co., Inc., Novartis AG, Servier Laboratories, Theracos, Inc. R. Correa-rotter: Consultant; Self; GlaxoSmithKline plc., Other Relationship; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Inc., Speaker’s Bureau; Self; AbbVie Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceutical Co. H. S. Bajaj: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., Sanofi, Tricida, Inc. B. Stefansson: Employee; Self; AstraZeneca. Funding AstraZeneca

The DAPA-CKD trial demonstrated a significant reduction in the risk of adverse kidney and cardiovascular outcomes in participants with chronic kidney disease (CKD), with and without type 2 diabetes (T2D), treated with dapagliflozin 10 mg once daily compared to placebo (randomized 1:1). This pre-specified analysis explored the effect of dapagliflozin on incident T2D in the cohort without diabetes enrolled in DAPA-CKD. A subgroup of 1,398 participants with CKD, no prior history of diabetes, and HbA1c Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. A. Langkilde: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. D. C. Wheeler: Advisory Panel; Self; Merck Sharp & Dohme Corp., Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, GlaxoSmithKline plc., Janssen Global Services, LLC., Mundipharma International, Tricida, Inc., Speaker’s Bureau; Self; Amgen Astellas BioPharma, Astellas Pharma Inc., Napp Pharmaceuticals, Vifor Pharma Management Ltd. H. L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook, CSL Behring, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, LLC, Merck & Co., Inc., Mitsubishi Corporation Life Sciences Limited, Mundipharma International, Novo Nordisk, Retrophin, Inc., Research Support; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC. Dapa-ckd study group: n/a. P. Vart: None. G. M. Chertow: Advisory Panel; Self; Ardelyx, Baxter, Cricket Health, DURECT Corporation, Gilead Sciences, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Self; Akebia Therapeutics, Inc., AstraZeneca, Vertex Pharmaceuticals Incorporated. F. Hou: Consultant; Self; AstraZeneca. N. Jongs: None. J. J. Mcmurray: Other Relationship; Self; AbbVie Inc., Amgen Inc., AstraZeneca, Bayer AG, Cytokinetics Inc., DalCor Pharmaceuticals, Merck & Co., Inc., Novartis AG, Servier Laboratories, Theracos, Inc. R. Correa-rotter: Consultant; Self; GlaxoSmithKline plc., Other Relationship; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Inc., Speaker’s Bureau; Self; AbbVie Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceutical Co. B. Stefansson: Employee; Self; AstraZeneca. R. D. Toto: Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Medscape Education, Otsuka America Pharmaceutical, Inc., Quest Diagnostics, Reata Pharmaceuticals, Inc., Relypsa Inc. Funding AstraZeneca

Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28–0.85) for kidney events and 1.13 (95% CI: 1.03–2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population.

Vitamin D deficiency is common in peritoneal dialysis (PD) patients, so its supplementation has been advocated as potentially beneficial.Double-blind, placebo-controlled, randomized clinical trial. Subjects on PD treated with high calcium peritoneal dialysate (Ca 3.5 mEq/l) and serum levels of 25-hydroxi vitamin D (25D) 20 ng/ml were randomized to receive cholecalciferol (4800 IU/daily) or placebo for 16 weeks. The outcome measures were the effects on the osteogenic biomarkers osteoprotegerin (primary endpoint), intact fibroblast growth factor-23 (iFGF23), osteocalcin, osteopontin, iPTH, 1,25-dyhydroxivitamin D (1,25D), and interleukin-6.Fifty-eight subjects were randomly assigned. Baseline characteristics were similar in both groups. Cholecalciferol supplemented subjects had a significant increase in serum 25D (from 11.4 ± 5.0 to 28.3 ± 10.3 ng/ml), 1,25D and iFGF23 compared with placebo group. iFGF23 levels increased an average of 10,875 pg/ml per month (95% CI 11,778-88,414) in the cholecalciferol group and was unchanged in the placebo group (2829 pg/ml, 95% CI - 2181 to 14,972). Extremely high iFGF23 levels ( 30,000 pg/ml) were observed in 74% of subjects receiving cholecalciferol although iFGF23 returned to baseline values after 32 weeks of withdrawal. The observed changes in iFGF23 correlated with 1,25D levels and were not modified by other variables. No difference was observed between groups in osteoprotegerin or other osteogenic biomarkers levels.Cholecalciferol supplementation increases serum 25D levels in subjects on PD exposed to high calcium dialysate, yet it induces an exponential increase of iFGF23 in most patients, which disappear after withdrawal of supplementation and may be a major concern for this maneuver.

Background and Aims Reductions in albuminuria are consistently associated with a subsequent lower risk of kidney failure. The sodium glucose co-transporter 2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes. Whether this effect persist in patients with chronic kidney disease (CKD) with and without diabetes is unknown. We therefore assessed and compared the effects of dapagliflozin on albuminuria in patients with CKD with and without type 2 diabetes from the DAPA-CKD trial. Method We randomized 4304 patients with CKD and an eGFR of 25-75 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g to dapagliflozin (10 mg once daily) or placebo. Change in albuminuria was a pre-specified exploratory outcome. We used regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to micro- or normoalbuminuria ( Results Median (25th to 75th Percentile) UACR was 949 (477-1885) mg/g. In patients with and without type 2 diabetes baseline median UACR was 1017 mg/g and 861 mg/g, respectively. Dapagliflozin, compared to placebo, reduced UACR by 29.3% (95% confidence interval [CI] 25.2, 33.1; p Conclusion In patients with CKD with and without type 2 diabetes dapagliflozin significantly reduced albuminuria, with a larger reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR suggest that part of dapagliflozin’s protective effect in patients without diabetes is mediated through pathways unrelated to UACR reduction.

This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function. HJLH and DC are co-primary authors. The DAPA-CKD Trial Committees and Investigators are listed in the Appendix.

Dapagliflozin is a highly selective sodium-glucose cotransporter 2 inhibitor associated with stabilization of estimated glomerular filtration rate (eGFR); reductions in glycated hemoglobin (HbA1c), systolic blood pressure, body weight, and albuminuria; and a small and consistent increase in hematocrit [1–4]. This data set is based on the associated article [5] analyzing data from 5325 patients with type 2 diabetes from 14 placebo-controlled, phase 3 (one phase 2/3), double-blind dapagliflozin treatment studies of 24–104 weeks’ duration. Data on dapagliflozin's effects (vs. placebo) on hemoglobin (Hb), hematocrit, serum albumin, serum total protein concentrations, urine albumin/creatinine ratio, eGFR, heart rate, blood pressure, body weight, and safety in patients with type 2 diabetes with and without anemia were pooled and analyzed. Patients were divided into two groups according to baseline Hb levels: anemia (Hb 16.5 g/dL in men and >16.0 g/dL in women). Because anemia commonly occurs in patients with diabetes and chronic kidney disease [6], the data can be of value to further analyze trends in relevant physiological and pathophysiological parameters. CC BY 4.0Corresponding author: E-mail address: correarotter@gmail.com (R. Correa-Rotter).

AIM Severe hypocalcaemia following parathyroidectomy for secondary or tertiary hyperparathyroidism (SHPT/THPT) is scarcely studied. We aimed to describe and identify risk factors for early and persistent hypocalcaemia after parathyroidectomy. METHODS Retrospective pair-matched cohort study. We assessed 87 dialysis patients with SHPT (n = 73) or THPT (n = 14) paired with 146 subjects with primary hyperparathyroidism (PHPT) who underwent parathyroidectomy and were followed for 12 months. Early severe hypocalcaemia was defined as a free Ca ≤0.8 mmol/L [3.2 mg/dl] or corrected Ca ≤1.87 mmol/L [7.5 mg/dl] within 48 h. After parathyroidectomy and persistent hypocalcaemia, as an elemental Ca intake >3.0 g/day to achieve corrected Ca >2 mmol/L [8.0 mg/dl]. RESULTS Early severe hypocalcaemia occurred in 77% (67/87) versus 6.8% (10/146) of subjects with SHPT/THPT and PHPT, respectively (p

Background: Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause. Methods: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200–5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25–75 mL/min per 1·73m2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150. Findings: The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0–2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52–0·79) and those without diabetes (0·50, 0·35–0·72; pinteraction=0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45–0·73] vs 0·51 [0·34–0·75]; Pinteraction=0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53–0·92] vs 0·79 [0·40–1·55]; Pinteraction=0·78), and all-cause mortality (0·74 [0·56–0·98] vs 0·52 [0·29–0·93]; Pinteraction=0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51–0·78), glomerulonephritides (n=695; 0·43, 0·26–0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44–1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29–1·19; Pinteraction=0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes. Interpretation: Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease. Funding: AstraZeneca.

Aims Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death. Methods and results DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200–5000 mg/g and an estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo. Conclusion In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.

Background The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium–glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. Methods In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). Results Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). Conclusions Participants with a wide range of underlying kidney diseases receiving renin–angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2–4 and increased albuminuria, with and without T2D.

This study aimed to compare the effect of the use of a renal-specific oral nutritional supplement (RS-ONS) during hemodialysis sessions and the use of RS-ONS at home on the incidence of intradialytic hypotension.A single-center, 12-week, open-label, randomized controlled clinical trial was conducted. The intervention was a RN-ONS divided into two portions: 100 and 137 mL. The first portion was given after 1 hour of hemodialysis (HD) treatment, while the second portion was given 45 minutes before the end of HD. The research staff registered the baseline and final nutritional parameters and systolic arterial pressure (SAP) from the screen of the HD device during 36 HD sessions. Hypotension symptoms were also recorded every hour during each HD session. The nutritional and functional status was also assessed.We registered a total of 16 hypotensive events during 1082 HD sessions: 9 were in patients supplemented at home (551 HD sessions) and 7 occurred in patients supplemented during HD P = .668. Incidence of intradialytic hypotension (IH) during 1082 HD sessions was 1.4%. The total malnutrition inflammation score (MIS) decreased in both groups (P .01), and the percentage of cachexia improved in the supplemented-during-HD group (P .05).In this randomized controlled trial, intradialytic hypotension events did not increase with the RS-ONS during HD treatment. This strategy appears to be a safe anabolic nutritional strategy for the prevention of PEW, selecting stable patients and administering a fractioned volume of the supplement after the first hour of HD treatment. More studies with larger samples size are required to confirm these findings.

Background and Aims The FGF23-lowering effect of different phosphate-sources (vegetable versus animal) in low-phosphorus diets are scarcely known. In this trial, we assess the effect on intact FGF23 (iFGF23) of two low-phosphorus diets, animal versus mixed (vegetable + animal), in dialysis patients. Method A randomized, two-center, open-label, clinical trial was performed. Subjects on stable dialysis for >6 months with P>4.5 mg/dL were randomized into a mixed-based (3 ounces equivalent of animal protein + 3 ounces equivalent of legumes) vs. animal-based (6 ounce equivalent of animal protein) low phosphorus diet with equivalent nutrients (phosphorus Results 556 subjects were screened, only 57 subjects (37 hemodialysis[HD] and 18 peritoneal dialysis[PD]) were randomized. Age, sex, phosphate-binders use, and other baseline characteristics were similar between groups. Baseline iFGF23 levels were 7394 (IQR 2379-16629) and 6859 (1543-17521) ng/mL in mixed-based and animal-based groups respectively (p=0.62). Both groups had a significant decrease in iFGF23 after 12 weeks of intervention (iFGF23 change: -285 [IQR -3002 to 227] ng/mL, p Conclusion Dietary phosphorus restriction for 12 weeks with animal-based or mixed-based phosphorus sources similarly decreases iFGF23 concentration in HD or PD patients.

Introduction: Patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 frequently develop severe acute kidney injury (AKI). Although continuous renal replacement therapy is the standard of care for critically ill patients, prolonged intermittent renal replacement therapy (PIRRT) may be a feasible option. We aimed to describe the tolerability and security of PIRRT treatments in COVID-19 patients with ARDS who required mechanical ventilation and developed severe AKI. Methods: We prospectively analyzed patients who underwent PIRRT treatments at a COVID-19 reference hospital in Mexico City. Intradialytic hypotension was defined as a systolic blood pressure decrease of ≥20 mm Hg or an increase of 100% in vasopressor dose. Results: We identified 136 AKI cases (60.7%) in 224 patients admitted to the intensive care unit. Among them, 21 (15%) underwent PIRRT (130 sessions) due to stage 3 AKI. The median age of the cohort was 49 (range 36–73) years, 17 (81%) were male, 7 (33%) had diabetes, and the median time between symptoms onset and PIRRT initiation was 12 (interquartile range [IQR] 7–14) days. The median of PIRRT procedures for each patient was 5 (IQR 4–9) sessions. In 108 (83%) PIRRT sessions, the total ultrafiltration goal was achieved. In 84 (65%) PIRRT procedures, there was a median increase in norepinephrine dose of +0.031 mcg/kg/min during PIRRT (IQR 0.00 to +0.07). Intradialytic hypotensive events occurred in 56 (43%) procedures. Fifteen (12%) PIRRT treatments were discontinued due to severe hypotension. Vasopressor treatment at PIRRT session onset (OR 6.2, 95% CI 1.4–28.0, p: 0.02) and a pre-PIRRT lactate ≥3.0 mmol/L (OR 4.63, 95% CI 1.3–12.8, p: 0.003) were independently and significantly associated with the risk of hypotension during PIRRT. During follow-up, 11 patients (52%) recovered from AKI and respiratory failure and 9 (43%) died. Several adaptations to our PIRRT protocol during the COVID-19 outbreak are presented. Conclusions: PIRRT was feasible in the majority of COVID-19 patients with ARDS and severe AKI, despite frequent transitory intradialytic hypotensive episodes. PIRRT may represent an acceptable alternative of renal replacement therapy during the COVID-19 outbreak.

We read with great interest and appreciation the careful consideration and analysis by Ambagtsheer et al. of the most critical ethical objections to Global Kidney Exchange (GKE). Ambagtsheer et al. conclude that implementation of GKE is a means to increase access to transplantation ethically and effectively.1,2 These conclusions by their European Society of Transplantation (ESOT) committee on Ethical, Legal and Psychological Aspects of Transplantation (ELPAT) represent a step forward toward a greater understanding and an open, honest debate about GKE.

Aims: Anemia is common in type 2 diabetes (T2D), particularly in patients with kidney impairment, and often goes unrecognized. Dapagliflozin treatment increases hemoglobin and serum erythropoietin levels. We investigated the effect of dapagliflozin 10-mg/day on hemoglobin in T2D patients with and without anemia.Methods: Data from 5325 patients from 14 placebo-controlled, dapagliflozin-treatment studies of at least 24-weeks duration were pooled. Dapagliflozin's effects (vs. placebo) on hemoglobin, serum albumin, estimated glomerular filtration rate (eGFR), systolic blood pressure, body weight, and safety in patients with and without anemia were evaluated.Results: At baseline, 13% of all T2D patients and 28% of those with chronic kidney disease (eGFRConclusions: Treatment with dapagliflozin can correct and prevent anemia in T2D patients. A gradual increase in hemoglobin beyond week 4 may indicate an erythropoiesis-stimulating effect of sodium-glucose cotransporter 2 inhibition.(c) 2020 Published by Elsevier Inc.

Introduction Despite a systematic increase in the coverage of patients with end-stage renal disease (ESRD) who have received dialytic therapies and transplantation over the past 2 decades, the Mexican health system currently still does not have a program to provide full coverage of ESRD. Our aim was to analyze mortality in patients with ESRD without health insurance. Methods This was a prospective cohort study of 850 patients with advanced chronic kidney disease (CKD). Risk factors associated with death were calculated using a Cox's proportional hazards model. We used the statistical package SPSS version 22.0 for data analysis. Results The mean age of patients was 44.8 ± 17.2 years old. At the time of hospital admission, 87.6% of the population did not have a social security program to cover the cost of renal replacement treatment, and 91.3% of families had an income below US$300 per month. During the 3 years of the study, 28.8% of the cohort patients were enrolled in 1 of Mexico's social security programs. The 3-year mortality rate was of 56.7% among patients without access to health insurance, in contrast to 38.2% of patients who had access to a social security program that provided access to renal replacement therapy (P < 0.001). Risk factor analysis revealed that not having health insurance increased mortality (risk ratio: 2.64, 95% confidence intervals: 1.84−3.79; P = 0.001). Conclusion Mexico needs a coordinated National Kidney Health and Treatment Program. A program of this nature should provide the basis for an appropriate educational and intervention strategy for early detection, prevention, and treatment of patients with advanced chronic kidney disease.

AIMS: Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin-to-creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit.MATERIALS AND METHODS: SONAR is a randomized, double-blind, placebo-controlled trial with approximately 3500 participants who have stage 2-4 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin-angiotensin system inhibitor.RESULTS: After 6 weeks of exposure to atrasentan 0.75 mg once daily (enrichment period), participants with ≥30% UACR decrease and no tolerability issues (responders) were randomly assigned to placebo or atrasentan 0.75 mg/day. The responder group will be used for primary efficacy and safety analyses. Approximately 1000 participants with CONCLUSION: SONAR aims to determine whether atrasentan added to guideline-recommended therapies safely reduces the risk of CKD progression and delays the onset of end-stage renal disease in patients with type 2 diabetes and nephropathy. SONAR also aims to establish whether the enrichment of patients based on their initial "surrogate" response to atrasentan will deliver a trial design in accord with personalized treatment of diabetic kidney disease.

Aim To derive a simple risk score to predict the individual risk of major complications for patients undergoing a percutaneous renal biopsy procedure of native kidneys. Methods The risk score was derived from a cohort of 1205 adult patients subjected to percutaneous renal biopsy and assigned to training and validation datasets. Factors associated with major complications were derived from univariate analysis and then modelled by stepwise multivariate logistic regression. Based on the odds ratio, independent predictors were assigned a weighted integer. The risk score is calculated from the sum of the integers. Results The overall incidence of major complications was 3.2%. Independent factors associated with MC were lower pre-biopsy haemoglobin, lower platelets, higher blood urea nitrogen, documented chronic kidney disease features in pre-biopsy ultrasound (US) and the presence of haematoma in the post-biopsy US. A score for pre-biopsy evaluation included the first four predictors and stratified patients in three categories with increasing risk at higher scores (low-risk 0.1%, moderate-risk 3.0% and high-risk 26.1%). The score demonstrated good discriminative power (AUC = 0.872). The addition of post-biopsy US findings increased the discriminative power (AUC = 0.938). A higher post-biopsy risk score was also associated with a higher incidence of MC (low-risk 0.2%, moderate-risk 2.7%, high-risk 16.9%). Conclusion The risk of major complications after a percutaneous renal biopsy can be assessed by a simple risk score calculated from readily available information.

The International Society of Nephrology has adopted a proactive approach to defining the current state of kidney care and unmet needs through a multifaceted Closing the Gaps initiative. As part of this initiative, the International Society of Nephrology convened a meeting of experts to develop an approach to tackle acute kidney injury and chronic kidney disease (CKD). This manuscript expands on the recently published International Society of Nephrology CKD Roadmap and reports on the discussions of the working group assigned to the task of reviewing the global impact of complication of CKD. The working group defined the following goals: Goal 1: Optimize the management of anemia and endocrine and metabolic abnormalities associated with CKD. The impact of these conditions at a global level is not well understood, particularly in regions where renal replacement therapy is not readily available. Some treatment regimens may be affordable in low- and middle-income countries and if implemented, could have an impact on the burden of suffering associated with CKD. Goal 2: Improve the prevention and management of cardiovascular complications linked to CKD. Most research on cardiovascular complications of CKD has focused on atherosclerotic diseases (myocardial infarction, ischemic stroke, and peripheral gangrene). There has been growing recognition that other forms of cardiovascular diseases, such as heart failure, valvular disease and arrhythmias, have a major impact on patient outcomes. Much less is known about the mechanisms and treatment of these non-atherosclerotic complications. Goal 3: Improve the diagnosis and management of symptoms associated with CKD. Symptom management is one of the greatest challenges in the management of CKD, with limited knowledge about the mechanisms associated with the development of these common problems and how best to characterize them into usable clinical phenotypes. Improved understanding of the complications of CKD may alleviate suffering and prolong life among millions of people worldwide both in developed countries and in regions where renal replacement therapy is not widely available.

We assessed the effect of atrasentan therapy on a pre-specified panel of 13 urinary metabolites known to reflect mitochondrial function in patients with diabetic kidney disease. This post-hoc analysis was performed using urine samples collected during the RADAR study which was a randomized, double-blind, placebo-controlled trial that tested the effects of atrasentan on albuminuria reduction in patients with type 2 diabetes and nephropathy. At baseline, four of the 13 metabolites, quantified by gas-chromatography mass spectrometry, were below detectable levels, and six were reduced in patients with eGFR

Patients with Fabry disease (FD) are at a high risk for developing chronic kidney disease and cardiovascular disease. The availability of specific but costly therapy has elevated the profile of this rare condition. This KDIGO conference addressed controversial areas in the diagnosis, screening, and management of FD, and included enzyme replacement therapy and nonspecific standard-of-care therapy for the various manifestations of FD. Despite marked advances in patient care and improved overall outlook, there is a need to better understand the pathogenesis of this glycosphingolipidosis and to determine the appropriate age to initiate therapy in all types of patients. The need to develop more effective specific therapies was also emphasized.

espanolAntecedentes: Se ha demostrado que la nutricion oral intradialisis (ION) mejora muchos resultados clinicos, incluida la reduccion de la mortalidad, en pacientes con hemodialisis (HD). A pesar de los beneficios, ION esta infrautilizado en muchos paises. Objetivo: El objetivo de nuestro estudio fue determinar la percepcion de los profesionales de la salud (HCP) en nuestro entorno sobre el uso de ION en pacientes sometidos a HD. Metodos: Encuesta aplicada a HCP en Mexico que trabajo o habia trabajado en una unidad de HD en su localidad. Resultados: de 272 profesionales de la salud que respondieron la encuesta, el 74.3% creia que el uso de ION tiene al menos un efecto beneficioso; De estos, los mas frecuentemente mencionados fueron una mejora en la calidad de vida (QoL) (54.7%) seguida de una mejora en la albumina serica (37.9%) y el anabolismo muscular (31.6%). Sin embargo, el 49% considera que su uso implica algunos riesgos. De los encuestados, el 22% informo que sus unidades de HD permitian a los pacientes consumir alimentos o suplementos durante las sesiones de HD; La principal razon dada para prohibir la introduccion de alimentos o suplementos fue la politica de la clinica (41%). Conclusiones: el personal encuesto opiniones heterogeneas con respecto a ION, pero la mayoria cree que puede mejorar la calidad de vida o el estado nutricional de los pacientes. Sin embargo, el uso de ION es poco comun en nuestro pais, ya que va en contra de las regulaciones internas de la mayoria de las unidades HD. EnglishBackground: Intradialytic oral nutrition (ION) has been shown to improve many clinical outcomes, including lowering mortality, in hemodialysis (HD) patients. Despite the benefits, ION is underused in many countries. Objective: The objective of our study was to determine the perception of health-care professionals (HCP) in our environment of the use of ION in patients undergoing HD. Methods: Survey applied to HCP in Mexico who worked or had worked in an HD unit in their locality. Results: From 272 HCP who answered the survey, 74.3% believed that the use of ION has at least one beneficial effect; of these, the most frequently mentioned were an improvement in quality of life (QoL) (54.7%) followed by an improvement in serum albumin (37.9%) and muscle anabolism (31.6%). However, 49% consider that its use involves some risks. Of the respondents, 22% reported that their HD units allowed patients to consume food or supplements during HD sessions; the main reason given to forbid the introduction of food or supplements was the clinic’s policy (41%). Conclusions: The personnel surveyed heterogeneous opinions regarding ION, but most believe that it may improve the QoL or the nutritional status of the patients. Nevertheless, the use of ION is uncommon in our country as it is against the internal regulations of most HD units. (REV INVEST CLIN. 2019;71:255-64)

Background It is known that one of the leading causes of morbidity in chronic kidney disease (CKD) is the anemic syndrome. Although the pathogenic mechanisms of anemia are multiple, erythropoietin deficiency appears as the dominant factor. Patients in hemodialysis (HD) have a high prevalence of protein energy wasting (PEW) that may explains the poor response to Erythropoietin (EPO). Methods Retrospective cohort study of patients on HD from January to December 2014. The participants were classified according to a diagnostic of PEW using the “Malnutrition Inflammation Score” (MIS) and bioimpedance analysis (BIA) measurement of body composition at the start of erythropoietin therapy and after 3 months of follow up. We performed descriptive statistics and analyzed the differences between groups with and without PEW considering their responsiveness. In addition, we calculated the relative risk of EPO resistance, considering p value

The aim of this study was to evaluate the prevalence of thyroid dysfunction in a cohort of healthy individuals in Mexico City, as well as to investigate the potential associations of these results with their estimated iodine intake (EII) as reflected by their 24-hour urinary iodine excretion (24-h UIE). From the SALMEX cohort, 683 adults provided an appropriate 24-h urine sample. Thyroid function tests and thyroid antibody concentrations were determined in the participants’ sera. We analyzed discrepancies between the commonly used urinary parameters to determine the iodine intake status and the performance of thyroglobulin (Tg) as a biomarker of its status in the adult population. The prevalence of dysthyroidism was high, being similar to other studies. Subclinical hypothyroidism was detected in 5.0% of individuals, clinical hypothyroidism in 1.8% of individuals, and sub-clinical hyperthyroidism in 2.8% of individuals. The median EII was 285 μg/d (IQR 215.0–369.0); 94% of individuals had EII >150 µg/d recommended daily allowance (RDA) in adults. The urinary iodine concentration (UIC) and the UIE had relative biases in their averages of 34.4%. The Tg median was 7.21 ng/mL. The prevalence of increased Tg was 6.15%. There was no correlation between Tg and EII (r= 0.019, p= 0.606). Thyroid dysfunction was highly prevalent in this population. Our cohort revealed a slight discrepancy between dysthyroidism manifestations and iodine intake markers; the latter represent a population with adequate iodine intake. Further studies are necessary to clearly define the prevalence of thyroid dysfunction as well as the iodine nutritional status in Mexico.

Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

In developed countries, trends in adjusted end-stage renal disease incidence rate are displaying a rising trend, particularly in the older age group. These trends pose major challenges to healthcare systems, given the greater healthcare utilization by and more comorbid conditions among elderly adults. Older patients with kidney disease face both a shortened life expectancy and a high symptom burden. They will benefit from early supportive care interventions. The goal of supportive care is to relieve suffering and to support the best possible quality of life for patients and their families, regardless of their stage of disease or the need for other therapies, in accordance with their values and preferences. Developing a patient-centered approach, with a patient-centered care plan, which includes conservative, nondialytic care, is increasingly recognized as an important issue when caring for advanced chronic kidney disease patients, in particular those who are elder and with multiple comorbidities. When treating these patients, unavoidably, ethical issues arise. Current clinical practice guidelines consider some of them, but there is a lack of comprehensive information about the full range of relevant ethical issues in this condition. Palliative care is sometimes referred to as supportive care; its goal is always to achieve the best possible quality of life by controlling symptoms, relieving pain, and restoring functional capacity while respecting the patients personal, cultural, and spiritual beliefs and practices.

Background Patients with chronic kidney disease (CKD) are at high risk of adverse renal and cardiovascular (CV) outcomes, particularly heart failure. We investigated the effects of dapagliflozin inpatients with CKD, with and without type 2 diabetes (T2D). DAPA-CKD is the first trial to test the effects of a SGLT2 inhibitor on renal and CV outcomes in CKD patients without T2D and included patients with a lower eGFR than in prior trials. Methods We enrolled CKD patients with and withoutT2D with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and UACR200-5000 mg/g, randomized (1:1) to dapagliflozin (10 mg once daily) or placebo. Patients were maintained on a stable dose of ACE inhibitor or ARB for ≥4 weeks before screening, if not contraindicated. The primary composite endpoint was worsening of kidney function (≥50% decline in eGFR, occurrence of end-stage kidney disease [ESKD]), or renal or CV death. Secondary endpoints were (in hierarchical order): (1) renal composite (primary endpoint without CV death); (2) composite of CV death or hospitalization for heart failure (hHF); and (3) death from any cause. The trial was stopped early following routine review by the data monitoring committee, because of overwhelming evidence of efficacy. Results Overall, 4304 patients were randomized at386 centers in 21 countries; 2152 to dapagliflozin, 2152 to placebo. The mean age was 62 years and 67% were male. Mean eGFR was 43.1 mL/min/1.73m2 and mean UACR was 949 mg/g. At baseline, 2906 (67.5%) patients had T2D, 96% had a history of hypertension, 37% other CV disease, and 11% heart failure. 4174(97%) were receiving an ACEi/ARB or another renin-angiotensin system blocker. Baseline characteristics were balanced between treatment groups. The sponsor has announced that in DAPA-CKD the primary and each of the secondary endpoints was reduced significantly by dapagliflozin compared with placebo. Conclusions Dapagliflozin significantly reduced the risk of CKD progression, the incidence of CV death/hHF, and prolonged survival in patients with CKD, with and without T2D. This presentation will report the prespecified primary and secondary outcomes in detail, along with additional information on heart failure outcomes. (Funded by AstraZeneca; NCT03036150)