Search

Background The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial assessed dapagliflozin versus placebo, in addition to standard therapy, in patients with chronic kidney disease (CKD) and albuminuria, and was terminated prematurely due to overwhelming efficacy. The study objective was to model the long-term clinical outcomes of DAPA-CKD beyond the trial follow-up. Methods A Markov model extrapolated event incidence per 1000 patients and CKD progression rates for patients receiving dapagliflozin or placebo over a 10-year time horizon. We derived treatment-specific CKD stage transition matrices using DAPA-CKD trial data. We extrapolated relevant efficacy endpoints using parametric survival equations for all-cause mortality and generalized estimating equations for recurrent events. Results When extrapolated over a 10-year period, patients randomized to dapagliflozin spent more time in CKD stages 1–3 and less in stages 4–5 than placebo [0.65 (95% CrI 0.41, 0.90) and –0.23 (95% CrI -0.45, 0.00) years per patient, respectively]. Dapagliflozin prevented an estimated 83 deaths and 51 patients initiating kidney replacement therapy per 1000 patients over 10 years. Predicted rates of hospitalized heart failure and abrupt declines in kidney function were reduced (19 and 39 estimated events per 1000 patients, respectively). Conclusions Adding dapagliflozin to standard therapeutic management of CKD is expected to have long-term cardiorenal benefit beyond what has been demonstrated in the DAPA-CKD trial, with patients predicted to live longer with fewer complications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Patients undergoing haemodialysis (HD) are often discouraged from eating fruits and vegetables because of fears of hyperkalaemia and undernutrition, yet evidence to support these claims is scarce. We here explore the association between adherence to a healthy plant-based diet with serum potassium, surrogates of nutritional status and attainment of energy/protein intake targets in HD patients. Methods We performed an observational single-centre study of stable patients undergoing HD with repeated dietary assessment every 3 months. Patients were provided with personalized nutritional counselling according to current guidelines. The diet was evaluated by 3-day food records and characterized by a healthy plant-based diet score (HPDS), which scores positively the intake of plant foods and negatively animal foods and sugar. The malnutrition inflammation score (MIS) and serum potassium were also assessed at each visit. We used mixed-effects models to evaluate the association of the HPDS with markers of nutritional status, serum potassium levels and attainment of energy/protein intake targets. Results After applying inclusion and exclusion criteria, a total of 150 patients contributing to 470 trimestral observations were included. Their mean age was 42 years [standard deviation (SD) 18] and 59% were women. In multivariable models, a higher HPDS was not associated with serum potassium levels or odds of hyperkalaemia {potassium >5.5 mEq/L; odds ratio [OR] 1.00 [95% confidence interval (CI) 0.94–1.07] per HPDS unit higher}. Patients with a higher HPDS did not differ in terms of energy intake [OR for consuming <30 kcal/kg day 1.05 (95% CI 0.97–1.13)] but were at risk of low protein intake [OR for consuming <1.1 g of protein/kg/day 1.11 (95% CI 1.04–1.19)]. A higher HPDS was associated with a lower MIS, indicating better nutritional status. Conclusions In patients undergoing HD, adherence to a healthy plant-based diet was not associated with serum potassium, hyperkalaemia or differences in energy intake. Although these patients were less likely to reach daily protein intake targets, they appeared to associate with better nutritional status over time. [ABSTRACT FROM AUTHOR]

Background Recent cardiovascular outcome trials have shown that sodium–glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to CKD patients without type 2 diabetes or cardiovascular disease is unknown. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial (NCT03036150) will assess the effect of the SGLT2 inhibitor dapagliflozin on renal and cardiovascular events in a broad range of patients with CKD with and without diabetes. Methods DAPA-CKD is a randomized, double-blind, placebo-controlled, trial in which ∼4300 patients with CKD Stages 2–4 and elevated urinary albumin excretion will be enrolled. The vast majority will be receiving a maximum tolerated dose of a renin–angiotensin system inhibitor at enrolment. Results After a screening assessment, eligible patients with a urinary albumin:creatinine ratio ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 are randomly assigned to placebo or dapagliflozin 10 mg/day. Enrolment is monitored to ensure that at least 30% of patients do not have diabetes and that no more than 10% have an eGFR >60 mL/min/1.73 m2. The primary endpoint is a composite of a sustained decline in eGFR of ≥50%, end-stage renal disease, renal death or cardiovascular death. The trial will conclude when 681 primary renal events have occurred, providing 90% power to detect a 22% relative risk reduction (α level of 0.05). Conclusion DAPA-CKD will determine whether the SGLT2 inhibitor dapagliflozin, added to guideline-recommended therapies, safely reduces the rate of renal and cardiovascular events in patients across multiple CKD stages with and without diabetes. [ABSTRACT FROM AUTHOR]