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Background and objectivesC3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen.Design, setting, participants, & measurements We conducted a retrospective, multicenter, observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy (n=81) or dense deposit disease (n=16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure).ResultsThe study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse.ConclusionsThe beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.

Antibiotic resistance has turned into a global public health issue. Enterococci are intrinsically resistant to many antimicrobials groups. These bacteria colonize dairy and meat products and integrate the autochthonous microbiota of mammal’s gastrointestinal tract. Over the last decades, detection of vanA genotype in Enterococcus faecium from animals and from food of animal origin has been reported. Vancomycin-resistant E. faecium has become a prevalent nosocomial pathogen. Hospitalized patients are frequently treated with broad-spectrum antimicrobials and this leads to an increase in the presence of VanA or VanB vancomycin-resistant enterococci in patients’ gastrointestinal tract and the risk of invasive infections. In humans, E. faecium is the main reservoir of VanA and VanB phenotypes. Acquisition of high-level aminoglycoside resistance is a significant therapeutic problem for patients with severe infections because it negates the synergistic effect between aminoglycosides and a cell-wall-active agent. The aac(6′)-Ie-aph (2″)-Ia gene is widely spread in E. faecalis and has been detected in strains of human origin and in the food of animal origin. Enzyme AAC(6′)-Ie-APH(2″)-Ia confers resistance to available aminoglycosides, except to streptomycin. Due to the fast dissemination of this genetic determinant, the impact of its horizontal transferability among enterococcal species from different origin has been considered. The extensive use of antibiotics in food-producing animals contributes to an increase in drug-resistant animal bacteria that can be transmitted to humans. Innovation is needed for the development of new antibacterial drugs and for the design of combination therapies with conventional antibiotics. Nowadays, semi-purified bacteriocins and probiotics are becoming an attractive alternative to the antibiotic in animal production. Therefore, a better understanding of a complex and relevant issue for Public Health such as high-level vancomycin and gentamicin resistance in enterococci and their impact is needed. Hence, it is necessary to consider the spread of vanA E. faecium and high-level gentamicin resistant E. faecalis strains of different origin in the environment, and also highlight the potential horizontal transferability of these resistance determinants to other bacteria.

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OBJECTIVEOur aim was to analyze the performance of two scores developed for predicting diabetes in nontransplant populations for identifying kidney transplant recipients with a higher new-onset diabetes mellitus after transplantation (NODAT) risk beyond the first year after transplantation.RESEARCH DESIGN AND METHODSWe analyzed 191 kidney transplants, which had at least 1-year follow-up posttransplant. First-year posttransplant variables were collected to estimate the San Antonio Diabetes Prediction Model (SADPM) and Framingham Offspring Study–Diabetes Mellitus (FOS-DM) algorithm.RESULTSAreas under the receiver operating characteristic curve of FOS-DM and SADPM scores to predict NODAT were 0.756 and 0.807 (P < 0.001), respectively. FOS-DM and SADPM scores over 75 percentile (hazard ratio 5.074 and 8.179, respectively, P < 0.001) were associated with NODAT.CONCLUSIONSBoth scores can be used to identify kidney recipients at higher risk for NODAT beyond the first year. SADPM score detects some 25% of kidney transplant patients with an eightfold risk for NODAT.

Introduction The association between a change in proteinuria over time and its impact in kidney prognosis has not been analyzed in C3 glomerulopathy. This study aims to investigate the association between the longitudinal change in proteinuria and the risk of kidney failure. Methods Retrospective, multicenter observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. A joint modeling of linear mixed-effects models was applied to assess the underlying trajectory of a repeatedly measured proteinuria, and a Cox model to evaluate the association of this trajectory with the risk of kidney failure. Results The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15 dense deposit disease, with a median age of 26 years (range 13–41). During a median follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in proteinuria showed a strong association with the risk of this outcome, with a doubling of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed that a ≥ 50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (HR: 0.79; 95% CI : 0.56–0.97; p &lt; 0.001). This association was also found when the ≥50% proteinuria reduction was observed within the first 6 and 12 months of follow-up. Conclusion The longitudinal change in proteinuria is strongly associated with the risk of kidney failure. The change in proteinuria over time can provide clinicians a dynamic prediction of kidney outcomes.

Hypertension is a prevalent complication that occurs in 80-85% of all kidney transplant recipients. The pathogenesis of post-transplant hypertension is multifactorial and includes pre-transplant hypertension, donor hypertension, renin secretion from the native kidney, graft dysfunction, recurrent disease and immunosuppressive treatment. Hypertension negatively affects transplant and patient survival outcomes; cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic renal disease and after successful renal transplantation. Hypertension is a well-known risk factor for CVD and it is frequently associated with other CVD risk factors. Despite increased awareness of the adverse effects of hypertension in both graft and patient survival, long-term studies have shown that arterial hypertension in the transplant population has not been adequately controlled. Resistant hypertension (RH) is defined as office blood pressure (oBP) that remains above goal (oBP ≥ 140/90 or 130/80 mmHg) in patients with diabetes or chronic kidney disease despite the concurrent use of three antihypertensive agents, at full doses, one of them being a diuretic. Despite studies in the general population and the high prevalence of hypertension in renal transplant patients, data about RH are very scarce and the prevalence of RH in renal transplant patients is unknown and could be associated with a worse prognosis.

Background C3 glomerulopathy is a rare and heterogeneous complement-driven disease. It is often challenging to accurately predict in clinical practice the individual kidney prognosis at baseline. We herein sought to develop and validate a prognostic nomogram to predict the long-term kidney survival. Methods Retrospective, multicenter observational cohort study in 35 nephrology departments belonging to the GLOSEN group. The dataset was randomly divided into training group (n = 87) and validation group (n = 28). The least absolute shrinkage and selection operator (LASSO) regression was used to screen the main predictors of kidney outcome, and used to build the nomogram. Accuracy of the nomogram was assessed by discrimination and risk calibration, in the training and validation sets. Results The study group comprised 115 patients, of whom 46 patients (40%) reached kidney failure in a median follow-up of 49 months (range 24–112). No significant differences were observed in baseline estimated glomerular filtration rate (eGFR), proteinuria or total chronicity score of kidney biopsy, between patients in the training versus those in the validation set. The selected variables by LASSO were eGFR, proteinuria and total chronicity score. Based on Cox model a nomogram was developed for the prediction of kidney survival at 1-, 2-, 5- and 10-years from diagnosis. The C-index of the nomogram was 0.860 (95% confidence interval 0.834–0.887), and calibration plots showed optimal agreement between predicted and observed outcomes. Conclusions We constructed and validated a practical nomogram with good discrimination and calibration, to predict the risk of kidney failure in C3G patients at 1-, 2-, 5- and 10-years.