Sodium-Glucose Cotransport Protein 2 Inhibitors in Patients With Type 2 Diabetes and Acute Kidney Disease.

Importance: Sodium-glucose cotransport protein 2 inhibitors (SGLT-2is) have demonstrated associations with positive kidney-related and cardiovascular outcomes in patients with type 2 diabetes. However, the association of SGLT-2is with outcomes among patients with type 2 diabetes and acute kidney disease (AKD) remains unclear. Objective: To examine the long-term associations of SGLT-2is with mortality, major adverse kidney events (MAKEs), and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes and AKD. Design, Setting, and Participants: This cohort study used global health care data (the TriNetX database) spanning from September 30, 2002, to September 30, 2022. Propensity score matching was used to select a cohort of patients, and follow-up was conducted with a maximum duration of 5 years (completed on September 30, 2022) or until the occurrence of an outcome or death. Intervention: The use of SGLT-2is. Main Outcomes and Measures: The primary outcomes measured were mortality, MAKEs, and MACEs. Adjusted hazard ratios (AHR) with 95% CIs were calculated to compare the risks between SGLT-2i users and nonusers, representing the mean treatment effect among the treated patients. Results: A total of 230 366 patients with AKD (mean [SD] age, 67.1 [16.4] years; 51.8% men and 48.2% women) were enrolled in the study, which had a median follow-up duration of 2.3 (IQR, 1.2-3.5) years. Among these, 5319 individuals (2.3%) were identified as SGLT-2i users. Among nonusers, the incidence of mortality was 18.7%, the incidence of MAKEs was 21.0%, and the incidence of MACEs was 25.8%. After propensity score matching, the absolute differences between SGLT-2i users and nonusers for incidence of mortality, MAKEs, and MACEs were 9.7%, 11.5%, and 12.3%, respectively. Based on the treated population, SGLT-2i use was associated with a significantly lower risk of mortality (AHR, 0.69 [95% CI, 0.62-0.77]), MAKEs (AHR, 0.62 [95% CI, 0.56-0.69]), and MACEs (AHR, 0.75 [95% CI, 0.65-0.88]) compared with nonuse. External validation using a multicenter cohort data set of 1233 patients with AKD patients who were SGLT-2i users confirmed the observed beneficial outcomes. Notably, the risk reduction associated with SGLT-2is remained significant even among patients without hypertension, those with advanced chronic kidney disease, and those not receiving other hypoglycemic agents. Conclusions and Relevance: In this cohort study of patients with type 2 diabetes and AKD, administration of SGLT-2is was associated with a significant reduction in all-cause mortality, MAKEs, and MACEs when compared with nonuse, underscoring the importance of SGLT-2is in care after acute kidney injury. These findings emphasize the potential benefits of SGLT-2is in managing AKD and mitigating the risks of major cardiovascular and kidney diseases.

Distinct Subtyping of Successful Weaning from Acute Kidney Injury Requiring Renal Replacement Therapy by Consensus Clustering in Critically Ill Patients.

Background: Clinical decisions regarding the appropriate timing of weaning off renal replacement therapy (RRT) in critically ill patients are complex and multifactorial. The aim of the current study was to identify which critical patients with acute kidney injury (AKI) may be more likely to be successfully weaned off RRT using consensus cluster analysis. Methods: In this study, critically ill patients who received RRT at three multicenter referral hospitals at several timepoints from August 2016 to July 2018 were enrolled. An unsupervised consensus clustering algorithm was used to identify distinct phenotypes. The outcomes of interest were the ability to wean off RTT and 90-day mortality. Results: A total of 124 patients with AKI requiring RRT (AKI-RRT) were enrolled. The 90-day mortality rate was 30.7% (38/124), and 49.2% (61/124) of the patients were successfully weaned off RRT for over 90 days. The consensus clustering algorithm identified three clusters from a total of 45 features. The three clusters had distinct features and could be separated according to the combination of urinary neutrophil gelatinase-associated lipocalin to creatinine ratio (uNGAL/Cr), Sequential Organ Failure Assessment (SOFA) score, and estimated glomerular filtration rate at the time of weaning off RRT. uNGAL/Cr (hazard ratio [HR] 2.43, 95% confidence interval [CI]: 1.36-4.33) and clustering phenotype (cluster 1 vs. 3, HR 2.7, 95% CI: 1.11-6.57; cluster 2 vs. 3, HR 44.5, 95% CI: 11.92-166.39) could predict 90-day mortality or re-dialysis. Conclusions: Almost half of the critical patients with AKI-RRT could wean off dialysis for over 90 days. Urinary NGAL/Cr and distinct clustering phenotypes could predict 90-day mortality or re-dialysis.

Urinary Biomarkers Can Predict Weaning From Acute Dialysis Therapy in Critically Ill Patients.

CONTEXT.­: Critically ill patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT) have a poor prognosis. Several urinary AKI biomarkers have been proposed to predict renal recovery, but with limited discriminatory ability. OBJECTIVE.­: To validate the predictive performances of novel biomarkers to identify which critical patients with AKI may successfully wean from RRT. DESIGN.­: We prospectively recorded and analyzed clinical variables at several time points: (1) before starting RRT, (2) at the time of weaning off RRT, and (3) 24 hours after stopping RRT. A total of 140 critically ill patients who received RRT at a multicenter referral hospital from August 2016 to January 2019 were enrolled. The outcomes of interest were the ability to wean from RRT and 90-day mortality. RESULTS.­: The 90-day mortality rate was 13.6% (19 of 140), and 47.9% (67 of 140) of the patients were successfully weaned from RRT. Cluster analysis showed that the following biomarkers were correlated with estimated glomerular filtration rate at the time of weaning off RRT: urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, hemojuvelin, C-C motif chemokine ligand 14, interleukin 18, and liver-type fatty acid-binding protein (L-FABP). Among these, urinary L-FABP/creatinine (uL-FABP/Cr) at the time of weaning off RRT showed the best predictive performance for mortality (area under the receiver operating characteristic curve = 0.79). Taking mortality as a competing risk, Cox proportional hazards analysis indicated that a low uL-FABP/Cr (log) level was an independent prognostic factor for weaning from RRT (subdistribution hazard ratio, 0.35; P = .01). CONCLUSIONS.­: uL-FABP/Cr at the time of weaning off RRT could predict weaning from RRT and 90-day mortality.

Spectrum of cancer patients receiving renal biopsy.

BACKGROUND: The frontier of onco-nephrology, particularly renal complications of cancer and treatment, remains unexplored. We revisit the fundamental tool of diagnosing kidney disease, renal biopsy, in cancer patients with renal manifestation. METHODS: Patients who received renal biopsy from July 2015 to July 2019 were analyzed. Primary outcomes included end-stage renal disease (ESRD), mortality, and catastrophic outcome defined as either ESRD or mortality. A Cox proportional hazards model and Kaplan-Meier technique were used to assess the association with outcome measurements and survival analyses. Immunosuppression after renal biopsy and response to the treatment were evaluated. RESULTS: Among the 77 patients, the median age was 66 years (interquartile range [IQR] 59-73 years) and 46 (59.7%) were male. At the time of renal biopsy, 57 patients (74%) had various degrees of renal insufficiency. Tubulointerstitial damage score, quantified by renal pathology, were associated with higher hazards of ESRD (hazard ratio [HR], 1.77; 95% confidence interval [95% CI], 1.20 to 2.61; P = 0.004) and catastrophic outcome (HR, 1.30; 95% CI, 0.99 to 1.70; P = 0.058). The response rate to immunosuppression was lower in those diagnosed with tubulointerstitial nephritis (1 of 4 patients, 25%) than those with glomerulopathy (10 of 20 patients, 50%). CONCLUSION: Renal biopsy may improve diagnostic accuracy and assist in treatment guidance of cancer patients with renal manifestation. Renal biopsy should be encouraged with clinical indication. Collaboration between oncologists and nephrologists is of paramount importance to provide more comprehensive care for caner patients.

Successful Treatment of a Critically Ill COVID-19 Patient Using Continuous Renal Replacement Therapy With Enhanced Cytokine Removal and Tocilizumab: A Case Report.

The COVID-19 pandemic has caused multiple deaths worldwide. Since no specific therapies are currently available, treatment for critically ill patients with COVID-19 is supportive. The most severe patients need sustained life support for recovery. We herein describe the course of a critically ill COVID-19 patient with multi-organ failure, including acute respiratory failure, acute kidney injury, and fulminant cytokine release syndrome (CRS), who required mechanical ventilation and extracorporeal membrane oxygenation support. This patient with a predicted high mortality risk was successfully managed with a careful strategy of oxygenation, uremic toxin removal, hemodynamic support, and most importantly, cytokine-targeted intervention for CRS, including cytokine/endotoxin removal, anti-cytokine therapy, and immune modulation. Comprehensive cytokine data, CRS parameters, and biochemical data of extracorporeal removal were provided to strengthen the rationale of this strategy. In this report, we demonstrate that timely combined hemoperfusion with cytokine adsorptive capacity and anti-cytokine therapy can successfully treat COVID-19 patients with fulminant CRS. It also highlights the importance of implementing cytokine-targeted therapy for severe COVID-19 guided by the precise measurement of disease activity.