Background: SGLT2 inhibitors and MRAs reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and mineralocorticoid receptor antagonists (MRA) eplerenone alone and in combination in patients with CKD. Methods: We conducted a randomized open-label cross-over trial in patients with urinary albumin excretion ≥100 mg/24-hour, eGFR 30-90 mL/min/1.73m2, 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 wash-out 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/1.73m2, median UACR 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks treatment with dapagliflozin, eplerenone, and dapagliflozineplerenone was -19.6% (95%CI -34.3, -1.5), -33.7% (95%CI -46.1, -18.5), and -53.0% (95%CI -61.7, -42.4; p<0.001 vs dapagliflozin; p=0.0127 vs eplerenone). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozineplerenone (r=-0.13; p=0.473; r=-0.08; p=0.658 respectively). Hyperkalemia was more frequently reported with eplerenone (N=8, [17.4%]) compared to dapagliflozin (N=0, [0%]) or dapagliflozin-eplerenone (N=2, [4.3%]; Pbetween-groups=0.0033). Conclusion: 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.

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10–20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications.

The high incidence of cardiovascular events in chronic kidney disease (CKD) warrants an accurate evaluation of risk aimed at reducing the burden of disease and its consequences. The use of biomarkers to identify patients at high risk has been in use in the general population for several decades and has received mixed reactions in the medical community. Some practitioners have become staunch supporters and users while others doubt the utility of biomarkers and rarely measure them. In CKD patients numerous markers similar to those used in the general population and others more specific to the uremic population have emerged; however their utility for routine clinical application remains to be fully elucidated. The reproducibility and standardization of the serum assays are serious limitations to the broad implementation of these tests. The lack of focused research and validation in randomized trials rather than ad hoc measurement of multiple serum markers in observational studies is also cause for concern related to the clinical applicability of these markers. We review the current literature on biomarkers that may have a relevant role in field of nephrology.

In this subanalysis of a randomized trial, EAT was an independent predictor of mortality in incident hemodialysis patients after ~4 years of follow-up. These hypothesis-generating findings will need confirmatory evidence.