Introduction: Renal injury is an adverse effect of vascular endothelial growth factor (VEGF) inhibitor therapy. We investigated factors associated with renal injury and renal outcomes by VEGF inhibitor type in lung cancer. Methods: This retrospective cohort included 441 lung cancer patients treated with VEGF inhibitors. The primary cohort comprised 376 patients with an estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m2, negative dipstick proteinuria, and no hematuria at baseline; 65 patients underwent exploratory analysis. The primary composite renal outcome was incident proteinuria and/or eGFR decline >20% from baseline within 1 year. Cox models adjusted for clinical, tumor, and treatment covariates. Landmark and overlap-weighted sensitivity analyses were performed. Proteinuria and eGFR decline were analyzed separately. Results: The primary composite renal outcome occurred in 250 patients (66.5%); among patients with an event, the median time to first event was 92.0 days. Diabetes mellitus (adjusted hazard ratio [aHR], 1.89; 95% confidence interval [CI], 1.17-3.05), higher body mass index (BMI) (aHR per 1-kg/m2 increase, 1.05; 95% CI, 1.00-1.09), and lower hemoglobin (aHR per 10-g/L increase, 0.86; 95% CI, 0.79-0.94) were independently associated with the primary outcome. VEGF inhibitor type was not associated with the primary outcome (overall p = 0.690), with similar overlap-weighted results. Incident proteinuria occurred in 120 patients (31.9%) and was associated with diabetes and lower hemoglobin; eGFR decline >20% occurred in 188 patients (50.0%) and was associated with lower hemoglobin. Platinum-containing chemotherapy showed a time-varying association with incident proteinuria. Conclusion: The primary composite renal outcome was common during the first year of VEGF inhibitor therapy. In the primary cohort, diabetes mellitus, higher BMI, and lower baseline hemoglobin were associated with this outcome, whereas no statistically significant association was observed for VEGF inhibitor type. These findings warrant validation in independent cohorts.
Abstract Introduction: Four-level graded organ response criteria provide a more refined alternative to traditional binary classification in systemic light chain (AL) amyloidosis. However, the prognostic value of graded renal responses for kidney outcomes requires further validation. Methods: We retrospectively analyzed 475 patients with renal AL amyloidosis who achieved at least a hematologic partial response. Renal responses were categorized as renal complete response (RenCR), renal very good partial response (RenVGPR), renal partial response (RenPR), and renal no response (RenNR) based on reductions in 24-hour proteinuria, in the absence of a ≥25% worsening of serum creatinine. The composite kidney outcome served as the primary renal endpoint. Results: Among the 475 enrolled patients, RenCR, RenVGPR, RenPR, and RenNR accounted for 17.7%, 46.1%, 15.1%, and 21.1%, respectively. Deeper renal responses were associated with better overall survival (OS) and a lower risk of the composite kidney outcome. The 5-year OS rates were 98.8% (RenCR), 93.5% (RenVGPR), 68.5% (RenPR), and 46.8% (RenNR) (P < 0.001). The median time to composite kidney outcome was not reached, 158 months, 63 months, and 36 months, respectively (P < 0.001). Landmark analyses, time-varying covariate Cox regression, competing risk regression, and subgroup analyses further supported the independent prognostic value of graded renal responses. Time-dependent receiver operating characteristic (ROC) curve analyses demonstrated that graded renal response criteria performed better than two-level classifications for predicting the composite kidney outcome. Conclusions: Graded renal response criteria provided superior discrimination in predicting the composite kidney outcome, with deeper responses associated with better survival.
Background and Hypothesis In France, ≥70-year-old patients represent 50% of all individuals starting kidney replacement therapy. In the absence of contraindications, kidney transplantation should be proposed up to the age of 85 years. The aim of this study was to evaluate the influence of age and comorbidities on the 1-year mortality rate after transplantation, length of hospital stay after transplantation, and readmission rates in older adults. Methods Cross-referencing clinical data from the Renal Epidemiology and Information Network (REIN) registry and healthcare utilization data from the French National Health Data (SNDS) database allowed identifying all ≥65-year-old patients who started kidney replacement therapy in France between January 1, 2017 and December 31, 2018, and who underwent a first kidney transplantation before December 31, 2020 (n = 749). Follow-up was to December 31, 2021. Cox proportional hazards models were used to analyze survival, and multilevel logistic regression models to evaluate hospitalization outcomes. Results In the ≥65-year-old patients identified (n = 749), the age group did not have an independent effect on 1-year survival rate. Conversely, age was correlated with longer initial hospitalization (OR = 2.15, 95% CI [1.3-3.5]) and longer cumulative hospital stay during the first year post-transplant (OR = 2.04, 95% CI [1.2-3.3]). Peripheral artery disease was associated with a nearly 2-fold increased risk of death during the first year following kidney transplantation (HR=1.97, 95% CI [1.02-3.82]). Conclusion While peripheral artery disease was associated with reduced 1-year survival after kidney transplantation, no significant association was found between age group and mortality. However, a trend toward lower survival was observed in recipients aged >75 years. In addition, older age was associated with prolonged initial hospitalization and rehospitalization in the first post-transplant year, potentially impacting quality of life.
Introduction: Complement dysregulation, particularly through the alternative pathway, is a key pathogenic driver of IgA nephropathy (IgAN). While genetic studies implicate the CFH-CFHRs genomic locus in disease susceptibility, the precise roles of factor H (FH) and FH-related protein 3 (FHR-3) in IgAN pathogenesis remain incompletely understood. This study investigated circulating FHR-3 and FH levels in IgAN patients to evaluate their involvement in complement dysregulation and their potential as disease biomarkers or therapeutic targets. Methods: Circulating FHR-3 and FH levels were measured in 201 IgAN patients and 55 healthy controls. Associations with clinical parameters and histopathological features were evaluated in IgAN patients. Results: Both proteins were significantly elevated in IgAN patients compared to controls (FHR-3: 2.66 +/- 1.51 vs. 1.74 +/- 1.31 & micro;g/mL, p < 0.001; FH: 507.10 +/- 206.39 vs. 351.68 +/- 120.66 & micro;g/mL, p < 0.001), although their levels showed no correlation. Notably, these proteins exhibited opposing clinical associations: elevated FHR-3 levels correlated with enhanced glomerular C3 deposition (p = 0.011) and reduced plasma C3 (p = 0.016), whereas elevated FH levels were associated with diminished C3 deposition (p = 0.017) and increased plasma C3 (p < 0.001). Furthermore, FHR-3 levels increased while FH levels decreased with advancing glomerular C3 deposition intensity. The combination of circulating FHR-3 and FH levels demonstrated superior performance in predicting glomerular C3 deposition intensity compared to either biomarker alone. Conclusion: These findings demonstrate that FHR-3 and FH function as antagonistic complement regulators in IgAN, with FHR-3 primarily functioning in promoting local complement activation and FH maintaining both systemic and local complement homeostasis. Our results highlight the potential of these proteins as disease biomarkers and therapeutic targets.
Introduction: Acute kidney injury (AKI) is a prevalent and detrimental complication following cardiac surgery, with significant effects on both in-hospital and long-term morbidity and mortality. This study aims to evaluate the association between postoperative hyperglycemia and the risk of AKI following coronary artery bypass grafting (CABG). Methods: This retrospective cohort study included patients undergoing CABG from January 2013 to December 2021. Postoperative hyperglycemia was defined as blood glucose levels ≥ 150 mg/dL for ≥ 3 hours in the first 72 hours after surgery. The primary outcome was AKI within the 7 days after surgery. Propensity scores matching and generalized linear mixed models were performed to assess the association between hyperglycemia and outcomes. Results: Among the included 32,742 patients, 8,600 (26.3%) patients were classified as postoperative normoglycemia. Postoperative normoglycemia was associated with a significantly decreased risk of AKI (47.2% vs 52.2%; aRR, 0.91 [95% CI, 0.88 to 0.93]; P < 0.001). Furthermore, the occurrence of in-hospital major adverse cardiovascular and kidney events (MACKEs) was statistically lower in patients without postoperative hyperglycemia (3.7% vs 5.1%; aRR, 0.74 [95% CI, 0.64 to 0.86]; P < 0.001). Importantly, the association was more pronounced in patients without preexisting diabetes. Conclusions: Among patients undergoing CABG, postoperative hyperglycemia is associated with a higher risk of AKI and in-hospital MACKEs. This effect of is more pronounced in patients without preexisting diabetes. These findings support further investigation of targeted glycemic control, with a specific focus on distinct patient populations.
