María Jesús Puchades

Background Sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with CKD. We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and MRA eplerenone alone and in combination in patients with CKD. Methods We conducted a randomized open-label crossover trial in patients with urinary albumin excretion ≥100 mg/24 hr, eGFR 30–90 ml/min per 1.73 m 2 , who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-week treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in random order, separated by 4-week washout periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline. Results Of 57 patients screened, 46 were randomly assigned (mean eGFR, 58.1 ml/min per 1.73 m 2 ; median UACR, 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks of treatment with dapagliflozin, eplerenone, and dapagliflozin-eplerenone was –19.6% (95% confidence interval [CI], –34.3 to –1.5), –33.7% (95% CI, –46.1 to –18.5), and –53% (95% CI, –61.7 to –42.4; P <0.001 versus dapagliflozin; P =0.01 versus eplerenone). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozin-eplerenone ( r =–0.13; P =0.47; r =–0.08; P =0.66, respectively). Hyperkalemia was more frequently reported with eplerenone ( n =8; 17.4%) compared with dapagliflozin ( n =0; 0%) or dapagliflozin-eplerenone ( n =2; 4.3%; P between-groups =0.003). Conclusions Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenone resulted in a robust additive UACR-lowering effect. A larger trial in this population is required to confirm long-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment. Clinical Trial registry name and registration number: European Union Clinical Trials Register, EU 2017–004641–25.

Type 2 diabetes mellitus (T2DM) represents the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESKD), and diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes. Despite advances in the nephroprotective treatment of T2DM, DKD remains the most common complication, driving the need for renal replacement therapies (RRT) worldwide, and its incidence is increasing. Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin-angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of anti-hyperglycemic drugs shown to improve cardiovascular and renal events in DKD. In this regard, GLP-1RA offer the potential for adequate glycemic control in multiple stages of DKD without an increased risk of hypoglycemia, preventing the onset of macroalbuminuria and slowing the decline of glomerular filtration rate (GFR) in diabetic patients, also bringing additional benefit in weight reduction, cardiovascular and other kidney outcomes. Results from ongoing trials are pending to assess the impact of GLP-1RA treatments on primary kidney endpoints in DKD.

Abstract Aims Continuous ambulatory peritoneal dialysis (CAPD) has been proposed as an additional therapeutic resource for patients with advanced congestive heart failure (CHF). The objective of this study was to determine the therapeutic role of CAPD, in terms of surrogate endpoints, in the management of patients with advanced CHF and renal dysfunction. Methods and results A total of 57 candidates with New York Heart Association (NYHA) class III/IV CHF, renal dysfunction (glomerular filtration rate < 60 mL/min/1.73 m2), persistent fluid congestion despite loop diuretic treatment, and at least two previous hospitalizations for acute heart failure (AHF) were invited to be included in the CAPD programme; however, 25 patients were finally included. The primary outcome was evaluated by the change at 6 and 24 weeks for the Minnesota Living With Heart Failure Questionnaire (MLWHFQ), the 6 min walk test (6MWT), NYHA class, serum natriuretic peptides [brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP)], serum carbohydrate antigen 125 (CA125), and hospitalization rates for AHF. CAPD was associated with a substantial improvement in the MLWHFQ (−21.3, P < 0.001; and −20.4, P < 0.001), the 6MWT (54.0, P < 0.001; and 45.6, P = 0.023), and NYHA class (−1.0, P < 0.001; and −1.4, P < 0.001) at 6 and 24 weeks, respectively. The Ln(CA125) decreased markedly (−0.8, P = 0.003; and −0.98, P = 0.003), with no effect on BNP and NT-proBNP. There was a marked reduction in the number of days hospitalized for AHF (6 month post-CAPD vs. 6 months pre-CAPD: −84%; P < 0.001). Conclusions In advanced CHF and renal dysfunction, CAPD was associated with short/mid-term improvement in severity parameters, with an acceptable rate of side effects.

The clinical spectrum of coronavirus disease 2019 (COVID-19) infection ranges from asymptomatic infection to severe pneumonia with respiratory failure and even death. More severe cases with higher mortality have been reported in older patients and in those with chronic illness such as hypertension, diabetes or cardiovascular diseases. In this regard, patients with chronic kidney disease (CKD) have a higher rate of all-type infections and cardiovascular disease than the general population. A markedly altered immune system and immunosuppressed state may predispose CKD patients to infectious complications. Likewise, they have a state of chronic systemic inflammation that may increase their morbidity and mortality. In this review we discuss the chronic immunologic changes observed in CKD patients, the risk of COVID-19 infections and the clinical implications for and specific COVID-19 therapy in CKD patients. Indeed, the risk for severe COVID-19 is 3-fold higher in CKD than in non-CKD patients; CKD is 12-fold more frequent in intensive care unit than in non-hospitalized COVID-19 patients, and this ratio is higher than for diabetes or cardiovascular disease; and acute COVID-19 mortality is 15-25% for haemodialysis patients even when not developing pneumonia.