Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

Validation of a Histologic Scoring Index for C3 Glomerulopathy.

RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.

Hypogonadism associated with muscle atrophy, physical inactivity and ESA hyporesponsiveness in men undergoing haemodialysis.

BACKGROUND: Testosterone deficiency (hypogonadism) is common among men undergoing haemodialysis, but its clinical implications are not well characterized. Testosterone is an anabolic hormone that induces erythrocytosis and muscle synthesis. We hypothesized that testosterone deficiency would be associated with low muscle mass, physical inactivity and higher dosages of erythropoietin-stimulating agents (ESA). METHODS: Single-center cross-sectional study of 57 male haemodialysis patients. None of the patients was undergoing testosterone replacement therapy. Total testosterone was measured in serum. Body composition (by bioelectrical impedance analysis) and physical activity (by the use of pedometers) were assessed. Patients with testosterone levels below the normal range were considered hypogonadal. RESULTS: Mean testosterone level was 321±146ng/dL; 20 patients (35%) were hypogonadal. Hypogonadal patients were older and had lower mean arterial blood pressure, higher interleukin-6 levels, lower lean body mass and higher fat body mass. A negative association between testosterone and normalized ESA dose was found in uni- and multivariate regression analyses. Testosterone levels directly correlated with lean body mass regardless of confounders. Hypogonadal patients had lower physical activity than their counterparts [2753±1784 vs. 4291±3225steps/day (p=0.04)]. The relationship between testosterone and physical activity was independent of age, comorbidities and inflammatory markers, but dependent on the proportion of muscle mass. CONCLUSION: Hypogonadism is common in our male haemodialysis population and is associated with higher ESA doses, reduced muscle mass and lower physical activity. The link between low testosterone levels and physical inactivity may conceivably relate to reduced muscle mass due to inadequate muscle protein synthesis.

Cystatin C as a predictor of mortality and cardiovascular events in a population with chronic kidney disease.

Background. We examine whether cystatin C, a surrogate marker of renal function, could identify patients with chronic kidney disease (CKD) with an increased risk of renal disease progression, death, or cardiovascular events. Methods. Data were obtained for 180 patients, with a diagnosis of chronic renal failure based on serum creatinine estimated glomerular filtration rate (eGFRcreat) <90 mL/min/1.73 m(2). This population was grouped in tertiles according to cystatin C and creatinine values at baseline. Cardiovascular events and overall mortality were estimated for each tertile. Predictors of overall mortality and for the development of renal disease progression were analyzed. Results. The median age was 75 years (interquartile range 69-82) and the median eGFRcreat 38 mL/min m(2) (interquartile range 33-49). Overall mortality was lower on the first and on the second tertiles of cystatin C than on the third one (HR = 0.060; 95% CI: 0.008-0.447 and HR = 0.094; 95% CI: 0.022-0.406, resp.). Deaths related to the creatinine tertiles followed the same pattern, but differences were not as large. Cardiovascular mortality was lower on the second than on the third cystatin C tertile (HR = 0.198; 95% CI: 0.040-0.987), but it did not show differences on the first and the second creatinine tertiles compared with the third one (HR = 0.126; 95% CI: 0.013-1.265 and HR = 0.403; 95% CI: 0.093-1.740). The only independent predictors of mortality during followup were baseline cystatin C (OR = 0.100; 95% CI: 0.021-0.463) and baseline uric acid (OR = 1.377; 95% CI: 1.070-1.773). Conclusion. Cystatin C may be an alternative to creatinine for detecting a high risk of death and cardiovascular events in a population with CKD.

Body composition in patients on haemodialysis: relationship between the type of haemodialysis and inflammatory and nutritional parameters.

INTRODUCTION: Overweight and obesity are associated to a higher cardiovascular risk and mortality in the general population and conflicting findings exist in the dialysis population. Adipokines (Leptin, adiponectin) produced in adipocytes may play a role in that process, and inflammatory parameters (CRP, IL-6) may be markers for it. Nevertheless, obtaining dry weight is today one of the main aims of adequacy in dialysis because overhydration is a clear mortality predictor. OBJECTIVES: The aim of this study was to analyse body composition using an impedance spectroscopy technique in patients on haemodialysis (HD): and evaluate overweight and overhydration prevalence and its possible relation with adipokines, inflammatory and nutritional parameters, HD technique (Conventional [CHD], on-line haemodiafiltration [OL-HFD]) and erythropoietin needs. METHODS: In a cross-sectional observational study, a pre-HD multifrequency bioimpedance spectroscopy (BIS) was performed in the middle of the week on 77 HD outpatients: 56 CHD and 21 OL-HFD. Patients were considered overweight when Body Mass Index (BMI) was ≥25kg/m² and overhydrated when overhydration normalised for extracellular water was higher than 0.15l. Clinical and biochemical parameters were analysed and IL-6, leptin and adiponectin levels were determined. This information was analysed in overweight and non-overweight, regular and overhydrated patients and both HD techniques. RESULTS: 50% of patients fulfilled overweight criteria and 21% were pre-HD overhydrated. Overweight patients had a superior fat and extracellular water content (P<.001). Leptin (P=.001) and CRP (P=.036) levels were higher and adiponectin levels were lower (P=.003). An inverse correlation did exist between BMI and lean mass (P=.01). Nutritional markers (prealbumin, albumin, total proteins, creatinine and transferrin) were related to lean mass (P=.05). Comparing both HD techniques, a lower fat content was observed in OL-HFD (P=.049) without overhydration differences. In the univariate analysis, age, fat, extracellular/intracellular water ratio, leptin, hipoadiponectinaemia, lower lean mass and CHD technique were predictors of overweight. In the multivariate analysis, hipoadiponectinaemia (OR: 0.86; IC: 0.76-0.98), lean mass (OR: 0.89; IC: 0.84-0.94) and OL-HFD technique (OR: 0.200; IC: 0.04-0.99) predicted the absence of overweight. CONCLUSION: This observational study emphasises the high prevalence of overweight in the outpatient haemodialysis population, as long as overweight is related with fat and extracellular water. Furthermore, it is accompanied by higher inflammation and leptin levels and lower levels of adiponectin. The use of the OL-HFD technique is associated to less overweight and fat content. Bioimpedance may prove to be a valuable ally for decisions regarding weight changes in dialysis patients.

Obstructive ARF caused by an inflammatory abdominal aortic aneurysm.

Inflammatory abdominal aortic aneurysms are rare entities characterized by dense fibrosis typically enveloping the aortic wall and adjacent structures with distinctive clinical features that differentiate them from typical atherosclerotic aneurysms. The inflammatory process can involve the renal excretory pathways, causing ureteral obstruction in 20% of cases. The authors report 2 cases of complete obstructive anuria secondary to inflammatory aneurysms and discuss the most appropriate management for these situations of hydronephrosis. Surgical repair of the aneurysm usually leads to regression of the inflammatory reaction.