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.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.In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.
Abstract Background and Aims The detailed mechanism of interstitial fibrosis in CKD has not been clarified. In this study, we focused on semaphorin class 3C (SEMA3C), a secreted protein expressed in the renal tubules, that is involved in embryonic kidney development [1], and investigated the relationship between SEMA3C and renal tubular damage and interstitial fibrosis. Methods < Clinical research> We investigated the correlation between serum SEMA3C concentration and the renal tubular damage marker urinary β2 microglobulin (β2MG) concentration in the 191 patients who underwent kidney biopsy from 2017 to 2021 at Yamagata University. < In vivo study> We generated proximal tubule-specific SEMA3C knockout mice (PT-SEMA3C KO) from male mice (C57BL/6) using the Cre/loxP system. The PT-SEMA3C KO group and control group were fed a 0.2% adenine diet for 5 weeks to induce CKD. The area of interstitial fibrosis/tubular atrophy (IFTA) region was assessed by Masson-Trichrome staining. Results < Clinical research> The median age of the patients was 54 (IQR 38-68) years, 94 men and 97 women. Median serum SEMA3C concentration was 0.14 (IQR 0.07-0.35) ng/ml. Median urinary β2MG levels was 0.22 (IQR 0-1.79) mg/gCr. Spearman's correlation analysis showed a significant negative correlation between serum SEMA3C and urinary β2MG levels (r=-0.208, P=0.005), but no correlation between eGFR and Urinary protein/ creatinine. < In vivo study> IFTA region was 5.6% in the control group, compared to 11.2% in the PT-SEMA3C KO group (p=0.031). Interstitial fibrosis was significantly suppressed in the PT-SEMA3C KO mice (Fig. 1). Conclusion Our clinical and in vivo results indicate that serum SEMA3C is associated with renal tubular damage and interstitial fibrosis.
high eUNa and eUNa/K, were associated with faster renal function decline in term of standardized coefficients: b¼-0.07 (<0.001) and b¼-0.05(<0.001), respectively.eUK taken alone was neither associated with signifiant improvement nor decline of renal function, when adjusting for baseline eGFR: b¼0.02 (p¼0.30).CONCLUSIONS: These results suggest that dietary sodium and potassium intakes may play a role in kidney function decline.
Tumor lysis syndrome has historically been associated with hyperuricemia and uric acid crystal deposition. We present three cases of tumor lysis syndrome resulting in renal failure in the context of normouricema, highlighting the spectrum of clinical presentations and mechanisms of renal damage. Two cases occurred following the treatment of hematological malignancies and were associated with hyperphosphatemia; the third resulted from ischemic necrosis following transarterial chemoembolization of a hepatic tumor. We also discuss the role of renal biopsy in the investigation of tumor lysis syndrome.
INTRODUCTION AND AIMS: Impaired cytomegalovirus (CMV)-specific cellmediated immunity (CMV-CMI) is a major cause of CMV reactivation and associated complications in solid-organ transplantation.Reliably assessing CMV-CMI is desirable to individually adjust antiviral and immunosuppressive therapy.The aim of this study was to evaluate the suitability of T-TrackV R CMV, a novel immune-monitoring IFN-c ELISpot assay, to survey CMV-CMI in renal transplant recipients.METHODS: A prospective, longitudinal, multicenter study was conducted in a cohort of 96 intermediate risk (D-/R+, D+R+) renal transplant recipients under preemptive antiviral strategy, over 6 months post-transplantation. T-TrackV R CMV was used to quantify CMV-reactive effector cells in response to T-activated V R pp65 and IE-1 proteins.CMV viral load (quantitative PCR or pp65 antigenemia) and related complications, opportunistic infections and graft function were also monitored. RESULTS: 95% and 88-92% T-TrackV R CMV assays were positive pre-and posttransplantation, respectively.CMV-specific response was reduced following immunosuppressive treatment and increased in patients with graft rejection, indicating the ability of the ELISpot assay to monitor patients' immunosuppressive state.Interestingly, median pp65-induced SFC level was 9-fold higher in patients with self-clearing viral load compared to antivirally-treated patients (534 vs. 60 SFC/200,000 cells; n=10; p<0.001) prior to first detection of viral load, suggesting that the response to pp65 represents a potential immunocompetence marker. CONCLUSIONS: Altogether, T-TrackV R CMV is a highly sensitive IFN-c ELISpot assay, suitable for the immune monitoring of renal transplant recipients, and with a potential use for the risk assessment of CMV-related clinical complications.
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