Major Kidney Events Research Articles

Dipeptidyl peptidase 4 inhibitors reduce the risk of adverse outcomes after acute kidney injury in diabetic patients

Abstract Background Dipeptidyl peptidase 4 inhibitors (DPP4i) are considered safe for use in patients with diabetes mellitus (DM) and kidney dysfunction. To explore whether usage of DPP4i who recovered from dialysis requiring acute kidney injury (AKI) could reduce risk of future cardiac and kidney events. Methods We utilized the TriNetX platform to investigate whether the utilization of DPP4i in DM patients within 90 days with acute kidney disease (AKD) could reduce the risk of all-cause mortality, major kidney events (MAKE), and major adverse cardiovascular events (MACE) and re-dialysis. The patients were followed for five years or until the occurrence of significant outcomes, with cohort data collected from January 1, 2016, to September 30, 2022. Results The cohort utilizing DPP4i comprised 7 348 patients with AKD, while the control group encompassed 229 417 individuals. After applying propensity score matching, 7343 patients (age, 66.2 ± 13.4 years; male, 49.9%) who utilized DPP4i showed a significant reduction in the risk of all-cause mortality (aHR 0.89; E-value 1.50), major adverse kidney events (MAKE) (aHR 0.86; E-value 1.59), major adverse cardiovascular events (MACE) (aHR 0.91; E-value 1.44), and re-dialysis (aHR 0.73; E-value 2.10) after a median follow-up of 2.4 years. Conclusions We demonstrated that DM patients concurrently experiencing AKD, DPP4i usage could decrease the risk of mortality, MACE, MACE, and re-dialysis. These findings emphasize the pivotal role of tailored treatment strategies involving DPP4i for AKD patients.

Kidney outcomes associated with SGLT2 inhibitors compared to other glucose-lowering drugs: a real-world study from China.

This study aimed to investigate the association between the utilization of Sodium-dependent glucose cotransporters inhibitors (SGLT2i) in real-world settings and kidney outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) in mainland China. In a retrospective analysis of electronic medical records from West China Hospital of Sichuan University, patients with T2D and CKD were included. Patients were divided into two groups, those initiating treatment with SGLT2i and those receiving other glucose-lowering drugs (oGLDs). The primary focus lies in examining the impact of SGLT2i on the decline slope of eGFR and major kidney events in these patients. We enrolled 944 patients diagnosed with both T2D and CKD. Out of these, 605 patients were prescribed SGLT2i, while the remaining 339 patients received oGLDs. The median follow-up duration were 16.8 months and 20.6 months, respectively. Throughout the follow-up period, we observed a significant decrease in the rate of eGFR decline in patients using SGLT2i (4.94mL/min/1.73m2 per year reduction compared to oGLDs, 95% CI: 4.73-5.15). A total of 101 kidney composite endpoint events occurred, with 31 events in the SGLT2i group and 70 events in the oGLDs group. The use of SGLT2i was associated with a 65% decrease in the risk of kidney composite endpoint events (hazard ratio 0.35, 95% CI 0.19-0.63). In clinical practice, SGLT2i have shown favorable effects on kidney prognosis in patients with T2D and CKD in mainland China. These effects remain consistent across patients with varying risks of CKD progression. ChiCTR2300068497.

Development and validation of a prediction model for people with mild chronic kidney disease in Japanese individuals

BackgroundChronic kidney disease (CKD) poses significant health risks due to its asymptomatic nature in early stages and its association with increased cardiovascular and kidney events. Early detection and management are critical for improving outcomes.ObjectiveThis study aimed to develop and validate a prediction model for hospitalization for ischemic heart disease (IHD) or cerebrovascular disease (CVD) and major kidney events in Japanese individuals with mild CKD using readily available health check and prescription data.MethodsA retrospective cohort study was conducted using data from approximately 850,000 individuals in the PREVENT Inc. database, collected between April 2013 and April 2023. Cox proportional hazard regression models were utilized to derive and validate risk scores for hospitalization for IHD/CVD and major kidney events, incorporating traditional risk factors and CKD-specific variables. Model performance was assessed using the concordance index (c-index) and 5-fold cross-validation.ResultsA total of 40,351 individuals were included. Key predictors included age, sex, diabetes, hypertension, and lipid levels for hospitalization for IHD/CVD and major kidney events. Age significantly increased the risk score for both hospitalization for IHD/CVD and major kidney events. The baseline 5-year survival rates are 0.99 for hospitalization for IHD/CVD and major kidney events are 0.99. The developed risk models demonstrated predictive ability, with mean c-indexes of 0.75 for hospitalization for IHD/CVD and 0.69 for major kidney events.ConclusionsThis prediction model offers a practical tool for early identification of Japanese individuals with mild CKD at risk for hospitalization for IHD/CVD and major kidney events, facilitating timely interventions to improve patient outcomes and reduce healthcare costs. The models stratified patients into risk categories, enabling identification of those at higher risk for adverse events. Further clinical validation is required.

#1743 Kidney outcomes associated with SGLT2 inhibitors compared to other glucose-lowering drugs: a real-world study from China

Abstract Background and Aims Currently, there is insufficient real-world study on the kidney outcomes of SGLT2i in mainland Chinese patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). This study aimed to investigate the association between the utilization of Sodium-dependent glucose cotransporters inhibitors (SGLT2i) in real-world settings and kidney outcomes in patients with T2D and CKD in mainland China. Method In a retrospective analysis of electronic medical records from West China Hospital of Sichuan University, patients with T2D and CKD were included. Patients were divided into two groups, those initiating treatment with SGLT2i and those receiving other glucose-lowering drugs (oGLDs). The primary focus lies in examining the impact of SGLT2i on the decline slope of eGFR and major kidney events in these patients. Results We enrolled 944 patients diagnosed with both T2D and CKD. Out of these, 605 patients were prescribed SGLT2i, while the remaining 339 patients received oGLDs. The median follow-up duration were 16.8 months and 20.6 months, respectively. Throughout the follow-up period, we observed a significant decrease in the rate of eGFR decline in patients using SGLT2i (4.94 ml/min/1.73 m2 per year reduction compared to oGLDs, 95% CI: 4.73–5.15). A total of 101 kidney composite endpoint events occurred, with 31 events in the SGLT2i group and 70 events in the oGLDs group. The use of SGLT2i was associated with a 65% decrease in the risk of kidney composite endpoint events (hazard ratio 0.35, 95% CI 0.19–0.63). Conclusion In clinical practice, SGLT2i have shown favorable effects on kidney prognosis in patients with T2D and CKD in mainland China. These effects remain consistent across patients with varying risks of CKD progression.

The Efficacy and Safety of Reduced-Dose Oral Methylprednisolone in High-Risk Immunoglobulin A Nephropathy

IntroductionThe Therapeutic Effects of Steroids in IgA Nephropathy Global (TESTING) study reported that methylprednisolone reduces the risk of major kidney events in individuals with IgA nephropathy at high risk of disease progression compared to supportive care alone but is associated with increased serious adverse events (SAEs) primarily with full-dose therapy. The risk-benefit balance of the reduced-dose methylprednisolone regimen is examined in this pre-specified analysis of the reduced-dose cohort of the TESTING trial. MethodsBetween 2017-2019, patients with IgA nephropathy, proteinuria ≥1g/day despite 3 months of renin-angiotensin-system blockade and estimated glomerular filtration rate (eGFR) 30-120mL/min/1.73m2 were randomised to reduced-dose methylprednisolone 0.4mg/kg/day or placebo. The primary outcome was a composite of a 40% eGFR decline, kidney failure or death due to kidney disease. Results241 participants were randomised and followed-up for a median of 2.5 years (mean age 37 years, baseline eGFR 65mL/min/1.73m2, proteinuria 2.48g/day). Methylprednisolone was associated with fewer primary outcome events compared to placebo (7/121 vs 22/120, HR 0.24; 95% CI, 0.10-0.58, P = 0.002), lowered proteinuria and reduced eGFR rate of decline from baseline. The mean difference between methylprednisolone and placebo in proteinuria and eGFR from baseline was -1.15g/day and 7.9mL/min/1.73m2 (P <0.001) at 12 months respectively, but these benefits were lost over time. There were 7 vs 3 SAEs in the methylprednisolone vs placebo group (HR 1.97; 95% CI, 0.49-7.90) including 5 vs 2 infections. ConclusionReduced-dose methylprednisolone is effective in improving kidney outcomes in high-risk IgA nephropathy, however, is associated with a modestly higher number of SAEs compared to placebo.

Analysis of eGFR index category and annual eGFR slope association with adverse clinical outcomes using real-world Japanese data: a retrospective database study

ObjectivesReal-world clinical outcome data of patients with an above-normal estimated glomerular filtration rate (eGFR) and increasing eGFR over time (eGFR slope) are scarce. Although eGFR is commonly recorded, eGFR slopes...

ACE I/D Polymorphism, Plasma ACE Levels, and Long-term Kidney Outcomes or All-Cause Death in Patients With Type 1 Diabetes.

The deletion (D) allele of the ACE insertion/deletion (I/D) polymorphism is a risk factor for diabetic kidney disease. We assessed its contribution to long-term kidney outcomes and all-cause death in patients with long-standing type 1 diabetes. A total of 1,155 participants from three French and Belgian cohorts were monitored for a median duration of 14 (interquartile range 13) years. The primary outcome was the occurrence of end-stage kidney disease (ESKD) or a 40% drop in the estimated glomerular filtration rate (eGFR). Secondary outcomes were the individual components of the primary outcome, rapid decline in eGFR (steeper than -3 mL/min/1.73 m2 per year), incident albuminuria, all-cause death, and a composite ESKD or all-cause death. Hazard ratios (HRs) for XD versus II genotype and for baseline plasma ACE levels were computed by Cox analysis. Genotype performance in stratifying the primary outcome was tested. Genotype distribution was 954 XD and 201 II. The primary outcome occurred in 20% of XD and 13% of II carriers: adjusted HR 2.07 (95% CI 1.32-3.40; P = 0.001). Significant associations were also observed for rapid decline in eGFR, incident albuminuria, ESKD, all-cause death, and ESKD or all-cause death. Baseline plasma ACE levels were higher in XD carriers and significantly associated with an increased risk of the primary outcome. The ACE genotype enhanced net reclassification improvement (0.154, 95% CI 0.007-0.279; P = 0.04) and integrated discrimination improvement (0.012, 95%CI 0.001-0.021; P = 0.02) for primary outcome stratification. The D-allele of the ACE I/D polymorphism was associated with an increased risk of major kidney events and all-cause death in patients with long-standing type 1 diabetes.

Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study

Cardiovascular and kidney outcome trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors slow progression of chronic kidney disease in patients with type 2 diabetes with or without chronic kidney disease. The aim of this study was to assess whether these benefits extend to patients with type 2 diabetes treated in routine clinical practice. CVD-REAL 3 was a multinational observational cohort study in which new users of SGLT2 inhibitors and other glucose-lowering drugs with measurements of estimated glomerular filtration rate (eGFR) before and after (within 180 days) initiation were identified via claims, medical records, and national registries in Israel, Italy, Japan, Taiwan, and the UK. Propensity scores for SGLT2 inhibitor initiation were developed in each country, with 1:1 matching with initiators of other glucose-lowering drugs. Propensity score included (in addition to other clinical and demographic variables) baseline eGFR and eGFR slope before SGLT2 inhibitor or other glucose-lowering drug initiation. The main outcome measure was rate of eGFR decline (slope) calculated with a linear mixed regression model. Differences in eGFR slope between SGLT2 inhibitors and other glucose-lowering drugs were calculated and pooled. We also assessed a composite outcome of 50% eGFR decline or end-stage kidney disease. After propensity matching, there were 35 561 episodes of treatment initiation in each group, from 65 231 individual patients. Dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, tofogliflozin, and luseogliflozin accounted for 57·9%, 34·1%, 5·7%, 1·4%, 0·5%, and 0·4% of SGLT2 inhibitor initiation episodes, respectively. At baseline, 29 363 (41·3%) of 71 122 initiations were in women, mean age was 61·3 years, mean HbA1c was 72 mmol/mol (8·71%), and mean eGFR was 90·7 mL/min per 1·73 m2. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other glucose-lowering drugs 1·53 mL/min per 1·73 m2 per year, 95% CI 1·34-1·72, p<0·0001). During a mean follow-up of 14·9 months, 351 composite kidney outcomes occurred: 114 (3·0 events per 10 000 patient-years) among initiators of SGLT2 inhibitors and 237 (6·3 events per 10 000 patient-years) among initiators of other glucose-lowering drugs (hazard ratio 0·49, 95% CI 0·35-0·67; p<0·0001). These findings were consistent across countries (pheterogeneity 0·10) and prespecified subgroups. In this large, international, real-world study of patients with type 2 diabetes, initiation of SGLT2 inhibitor therapy was associated with a slower rate of kidney function decline and lower risk of major kidney events compared with initiation of other glucose-lowering drugs. These data suggest that the benefits of SGLT2 inhibitors on kidney function identified in clinical trials seem to be largely generalisable to clinical practice. AstraZeneca.

Combination of Changes in Estimated GFR and Albuminuria and the Risk of Major Clinical Outcomes.

Whether combining changes in eGFR and urine albumin-to-creatinine ratio (UACR) is more strongly associated with outcomes compared with either change alone is unknown. We analyzed 8766 patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation Observational (ADVANCE-ON) study. Changes in eGFR and UACR (baseline to 2 years) were defined as ≥40% decrease, minor change, and ≥40% increase. The primary outcome was the composite of major macrovascular (nonfatal or fatal myocardial infarction, nonfatal or fatal stroke, or cardiovascular death), major kidney events (requirement for kidney replacement therapy or kidney death), and all-cause mortality. Over a median of 7.7 years of follow-up, 2191 primary outcomes were recorded. Strong linear associations between eGFR and UACR changes and subsequent risk of the outcome were observed. For eGFR, the hazard ratios were 1.58 (95% confidence interval [95% CI], 1.27 to 1.95) for a decrease ≥40% and 0.82 for an increase ≥40% (95% CI, 0.64 to 1.04) compared with minor change. For UACR, the hazard ratios were 0.96 (95% CI, 0.85 to 1.07) for a decrease ≥40% and 1.32 (95% CI, 1.19 to 1.46) for ≥40% increase compared with minor change. Compared with dual minor changes, both an eGFR decrease ≥40% and a UACR increase ≥40% had 2.31 (95% CI, 1.67 to 3.18) times the risk of the outcome, with evidence of interaction between the two markers. Clinically meaningful decreases in eGFR and increases in UACR over 2 years, independently and in combination, were significantly associated with higher risk of major clinical outcomes.

Biomarker-guided Intervention to Prevent Acute Kidney Injury After Major Surgery: The Prospective Randomized BigpAK Study.

To determine the impact of renal biomarker-guided implementation of the Kidney Disease Improving Global Outcomes (KDIGO) care bundle on the incidence of acute kidney injury (AKI) after major noncardiac surgery in a single-center unblinded randomized clinical trial. Early optimization of volume status and discontinuation of nephrotoxic medication before the occurrence of AKI may be the crucial step to reduce preventable AKI. The urinary biomarker-triggered KDIGO care bundle (early optimization of fluid status, maintenance of perfusion pressure, discontinuation of nephrotoxic agents) was compared to standard intensive care unit (ICU) care in 121 patients with an increased AKI risk after major abdominal surgery that was determined by urinary biomarker (inhibitor of metalloproteinase-2 × insulin-like growth factor-binding protein 7) >0.3. Incidence of overall AKI, severity of AKI, length of stay, major kidney events at discharge, and cost effectiveness were evaluated. The overall stages of AKI were not statistically different between the 2 groups, but in patients with inhibitor of metalloproteinase-2 × insulin-like growth factor-binding protein 7 values of 0.3 to 2.0 a subgroup analysis demonstrated a significantly reduced incidence of AKI 13/48 (27.1%) in the intervention group compared to control 24/50 (48.0%, P = 0.03). Incidence of moderate and severe AKI (P = 0.04), incidence of creatinine increase >25% of baseline value (P = 0.01), length of ICU, and hospital stay (P = 0.04) were significantly lower in the intervention group. Intervention was associated with cost reduction. There were no significant differences regarding renal replacement therapy, in-hospital mortality, or major kidney events at hospital discharge. Early biomarker-based prediction of imminent AKI followed by implementation of KDIGO care bundle reduced AKI severity, postoperative creatinine increase, length of ICU, and hospital stay in patients after major noncardiac surgery.

Risks of all-cause mortality and major kidney events in patients with new-onset primary open-angle glaucoma: a nationwide long-term cohort study in Taiwan

ObjectiveCardiovascular risk factors are associated with primary open-angle glaucoma (POAG) in the general population. However, long-term mortality and major kidney events in patients with new-onset POAG remain unclear.MethodsUsing the Taiwan...

Long-term consequences of acute kidney injury in the perioperative setting.

Recent studies indicate that acute kidney injury (AKI) and chronic kidney disease (CKD) are interconnected syndromes. Although the majority of patients who suffer an episode of AKI will recover laboratory indices suggesting complete or near complete recovery of renal function, a significant portion of post-AKI survivors will develop major kidney events, including development of late-stage CKD, need for renal replacement therapies, and death. Our review highlights epidemiology of adverse post-AKI events, association of AKI with late development of nonrenal adverse outcomes, use of bedside equations that facilitate prognostication of adverse renal outcomes of AKI, and how variability in serum creatinine values in individual patients, even among those with normal baseline renal function may indicate risk for the development of CKD. Use of common laboratory parameters such as serum creatinine and albumin, along with certain clinical and demographic markers, individualize patients at high risk of complications and in need of close postdischarge follow-up. Evidence that 'organ crosstalk' following a major AKI episode may increase the risk of heart failure, stroke, and hypertension, places its survivors in a special patient category deserving active efforts to minimize risk for cardiovascular events. AKI is a major cause for acute in-hospital mortality and development of both late-stage CKD and cardiovascular events. Perioperative care to prevent AKI must challenge the notion that a single normal point of contact serum creatinine value substantially reduces the likelihood of its occurrence.