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Background There is scarce evidence on the fourth dose of severe acute respiratory syndrome coronavirus 2 vaccines in chronic kidney disease (CKD) patients. We evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), haemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. Methods This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analysed factors associated with persistent negative humoral response and higher anti-Spike antibody titres as well as the efficacy of vaccination on coronavirus disease 2019 (COVID-19) severity. Results Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titres in HD (P = .001) and ND-CKD (P = .014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titres at 12 months were independently associated with repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titres and not being a KT recipient. Breakthrough COVID-19 was registered in 137 (6%) patients, 5% of whom required admission. Admitted patients had prior titres Conclusions A fourth vaccine dose increased anti-Spike antibody titres or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titres or KT recipients) derived the least benefit in terms of antibody titres. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titres.

Background Acute kidney injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in an MM patient population: standard dialysis procedure vs IHD with either polymethylmethacrylate (PMMA) or hemodiafiltration with endogenous reinfusion (HFR). Methods This was a multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary to MM requiring RRT were included. Patients that underwent IHD received six dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at 6 months follow-up. Results A total of 25 patients were included. Seventeen patients received IHD and eight standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, 14 (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared with those who remained in HD (92.9% vs 36.4%, P = .007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared with the standard dialysis group (P = .024). Conclusion Early reduction of FLC with IHD as an adjuvant treatment along with MM-targeted therapy may exert a positive impact on renal recovery.

SARS-CoV-2; Immune-mediated glomerulopathy; Vaccine SARS-CoV-2; Glomerulopatía inmunomediada; Vacuna SARS-CoV-2; Glomerulopatia immunomediada; Vacuna Background: Vaccination is a known trigger for the appearance of immune-mediated glomerulopathies (IMG). The appearance of IMG after SARS-CoV-2 vaccination with suspected causality has been described. Our aim is to analyze the incidence of IMG flares before and after SARS-CoV-2 vaccination in our center. Methods: All persons with native kidney biopsy (KB) from January 2019 to March 2022 in our center were included in the study. We compared the incidence of IMG before and after the start of vaccination. We also collected information about whether the patients had received a SARS-CoV-2 vaccine or have suffered from COVID in the six weeks before the IMG. We also evaluated the analytical characteristics of the outbreaks. Results: A total of 386 KB were studied. Of them, 86/218 (39.4%) were IMG performed pre- and 85/168 (50.6%) post-SV (029). The incidence of idiopathic nephrotic syndrome (INS), studied separately, was also significantly increased post-vaccination (n = 18 (10.7%)) compared to pre-vaccination (n = 11 (5%)) (p = 0.036). There were no differences in the incidence of vasculitis or IgA nephropathy. Up to 17 (20%) flares occurred 6 weeks before SARS-CoV-2 vaccination and only 2 (2.4%) within the first 6 weeks after SARS-CoV-2 infection. Within those 17 flares, the most common diagnosis was IgAN (n = 5 (29.4%)); a total of 14 (82.4%) received an mRNA vaccine and 9 (52.9%) took place after the 1st vaccine dose. There were 13 cases of minimal change disease (MCD) with debut/recurrence pre-SV and 20 MCD with debut/recurrence post-SV (p = 0.002). Conclusions: The incidence of IMG, INS and MCD flares in our center increased significantly after SARS-CoV-2 vaccination. Importantly, 20% of IMG flares took place within the first 6 weeks after receiving a vaccine dose, with the first dose being the riskiest one and IgAN the most frequent diagnosis. This research was funded by ISCIIII-FEDER and ISCIII-RETICS REDinREN, grant numbers PI17/00257, PI21/01292, RICORS RD21/0005/0016, Marató TV3 2020 421/C/2020, Marató TV3 2021 215/C/2021, and ERA-PerMed-JTC 2022 (ONAKI-ICI AC22/00029).

Budesonide; Transplant; Nephropathy Budesonida; Trasplante; Nefropatía Budesonida; Trasplantament; Nefropatia

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have proven to delay diabetic kidney disease (DKD) progression on top of the standard of care with the renin–angiotensin system (RAS) blockade. The molecular mechanisms underlying the synergistic effect of SGLT2i and RAS blockers is poorly understood. We gave a SGLT2i (empagliflozin), an angiotensin-converting enzyme inhibitor (ramipril), or a combination of both drugs for 8 weeks to diabetic (db/db) mice. Vehicle-treated db/db and db/m mice were used as controls. At the end of the experiment, mice were killed, and the kidneys were saved to perform a differential high-throughput proteomic analysis by mass spectrometry using isobaric tandem mass tags (TMT labeling) that allow relative quantification of the identified proteins. The differential proteomic analysis revealed 203 proteins differentially expressed in one or more experimental groups (false discovery rate < 0.05 and Log2 fold change ≥ ±1). Fourteen were differentially expressed in the kidneys from the db/db mice treated with empagliflozin with ramipril. Among them, MAP17 was up-regulated. These findings were subsequently validated by Western blot. The combined therapy of empagliflozin and ramipril up-regulated MAP17 in the kidney of a diabetic mice model. MAP17 is a major scaffolding protein of the proximal tubular cells that places transporters together, namely SGLT2 and NHE3. Our results suggest that SGLT2i on top of RAS blockade may protect the kidney by boosting the inactivation of NHE3 via the up-regulation of key scaffolder proteins such as MAP17.

Chronic kidney disease; Dialysis; Immunotherapy Enfermedad renal cronica; Diálisis; Inmunoterapia Malaltia renal crònica; Diàlisi; Immunoteràpia The new targeted cancer therapies including immune checkpoint inhibitors (ICIs) have been demonstrated to improve the survival of oncological patients, even in cases of metastatic cancer. In the past 5 years, several studies have revealed that ICI can produce several immune-mediated toxicities involving different organs, such as the skin, the gastrointestinal tract, the liver, and, of course, the kidney. The most frequent lesion of immunotoxicity in the kidney is acute interstitial nephritis (AIN), although other nephropathies have also been described as a consequence of the use of ICI, such as glomerulonephritis and acute thrombotic microangiopathy, among others. In addition, kidney rejection has also been reported in kidney transplant patients treated with ICI. Normally randomized clinical trials with ICI exclude patients with end-stage kidney disease, namely, patients undergoing dialysis and kidney transplant patients. Several important questions need to be addressed in relation to immunotherapy and patients with kidney disease: (a) when to start corticosteroid therapy in a patient with suspected acute kidney injury (AKI) related to ICI, (b) the moment of nephrologist referral and kidney biopsy indication, (c) management of ICI in patients undergoing dialysis, and (d) the effect of ICI in kidney transplantation, immunosuppressive personalized treatment, and risk of allograft rejection in kidney transplant patients. The objective of this review was to summarize the recently published literature on a wide spectrum of kidney disease patients with cancer and ICI. This review will address three main important groups of individuals with kidney disease and cancer immunotherapy, AKI associated with ICI, patients undergoing dialysis, and kidney transplant recipients. We believe that the information provided in this review will enlighten the personalized ICI treatment in individuals with a broader spectrum of kidney diseases. This research was funded by ISCIIII-FEDER and ISCIII-RETICS REDinREN, Grant Numbers PI17/00257, PI21/01292, RD16/0009/0030, and RICORS RD21/0005/0016. Enfermedad Glomerular Compleja del Sistema Nacional de Salud (CSUR), enfermedades glomerulares complejas.

BACKGROUND AND AIMS Chimeric Antigen Receptor (CAR)-T cell therapy has been a revolutionary treatment for hematological malignancies. Additionally, its potential use in solid tumors such as ovarian, prostate and lung neoplasms is currently being investigated with promising results (1). The most frequent complications after CAR T-cell therapy include cytokine release syndrome (CRS), neurotoxicity, infections, cytopenia and hypogammaglobulinaemia (2, 3, 4, 5). Acute kidney injury (AKI) occurs between 20–30%, mostly associated with cytokine release syndrome (CRS), hydroelectrolyte disorders and tumor lysis syndrome (TLS). The purpose of this study was to determine the demographics, laboratory results and clinical evolution of patients who have received CAR-T cell therapy to identify risk factors associated with AKI and long-term outcomes in these patients. METHOD We performed a retrospective review of the medical records of 115 patients with haematological neoplasms who received CD19-targeted CAR T-cell therapy at Vall d'Hebron Hospital between July 2018 and May 2021. Clinical and laboratory results of the first 60 days post-infusion were systematically examined and data was collected at the following days: +1, +7, +14, +21, +28 and +60. AKI was defined as the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, 1.5 to RESULTS A total of 24 (20.9%) of the 115 patients presented AKI after CAR-T cell therapy infusion. AKI was diagnosed by day +1 post-infusion in 3 (2.6%) patients, by day +7 in 13 (11.3%) patients, by day +14 in 1 (0.9%) patient, by day +21 in 2 (1.7%) patients, by day +28 in 2 patients (1.7%), by day +60 in 1 (0.9%) patient and 2 (1.7%) patients during the fludarabine and cyclophosphamide conditioning chemotherapy. Nineteen (79.2%) patients recovered kidney function within the first month after CAR-T infusion. Mean age was 61 ±14.8 years and 66.1% were male. Demographic and clinical characteristics are shown in Table 1 (AKI patients and non-AKI patients). Briefly, hypertension was present in 37.4% of patients, diabetes in 7.8%, chronic kidney disease in 13.9% and cardiovascular disease in 5.2%. Haematological neoplasms include diffuse large B-cell lymphoma (90.5%), B-cell acute lymphoblastic leukemia (5.2%), mantle lymphoma (3.5%) and primary mediastinal large B-cell lymphoma (0.68%). Among the types of CAR-T cell therapy, patients received tisagenlecleucel (49.6%), investigational products (27.8%), axicabtagen ciloleucelin (20%) and brexucabtagene autoleucel (2.6%). The most frequent complications were CRS (72.2%), febrile neutropenia (67%) and neurotoxicity (16.5%). Thirty-one (27%) patients required tocilizumab for CRS grade ≥ 2. A total of 5.2% of patients were admitted to the intensive care unit and 31.3% died. In the bivariate analysis, male sex, types of CAR-T cell therapy infused, and neurotoxicity were associated with AKI. Only male sex (1.26–21.9; P 0.23) and neurotoxicity (2.15–70.6; P 0.005) were identified as risk factors for AKI in multivariable analysis. In the actuarial survival analysis, levels of hemoglobin, creatinine, sodium and reactive C protein in day + 1 and in day +28 showed no statistically significant differences for mortality (Table 2). CONCLUSION CAR-T cell therapy has shown beneficial results in haematologic malignancies. In our study, 20.9% of patients developed AKI, especially in the first week of the CAR-T infusion. The majority of patients, a total of 79.2% of patients recovered kidney function within the first 28 days post-treatment, suggesting that AKI is a frequent but mild disease with a fast recovery in patients treated with CAR-T cells.

BACKGROUND AND AIMS Around 50%–60% lesions of non-diabetic nephropathy (NDN) have been identified in patients with diabetes and renal biopsy. NDN patients have a better renal prognosis and survival. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the work is to study the renal prognosis and survival of patients with DN with or without DR. METHOD Retrospective, observational, multicenter study of the pathological results of diabetic patients with renal biopsy was undertaken. A total of 18 Spanish centers have participated. RESULTS Cohort of 832 patients: 621 men (74.6%), median age 61.7 ± 12.8 years, median creatinine 2.8 ± 2.2 mg/dL and proteinuria 2.7 (1.2–5.4) g/24 h. Of them, 26.6% (n = 221) presented DR, 18.8% (n = 156) peripheral vasculopathy and 17.7% (n = 147) ischemic heart disease. On biopsy, 39.5% (n = 329) of patients had DN, 413 (49.6%) NDN and 90 (10.8%) mixed forms. We evidenced more DR in the DN group compared with the other two groups (44.1% versus 11.1% in NDN and 33.3% in mixed forms). Regarding renal prognosis, 58.9% (n = 109) of patients with DR and DN and mixed forms required RRT versus 40.7% (n = 88) of patients without DR. A total of 39.1% (n = 18) of patients with DR and NDN required renal replacement therapy (RRT) versus 23.9% (n = 79) of patients without DR. Regarding mortality, 28.6% (n = 50) of patients with DR and DN or mixed forms died during the follow-up versus 22.7% (n = 49) of patients without DR. A total of 15.2% (n = 7) of patients with DR and NDN died and 15.4% (n = 51) of patients without DR. In survival analysis (Kaplan—Meier curves), patients with DR had worse renal prognosis (P CONCLUSION The presence of DR and/or DN confers a worse renal prognosis. The diagnosis of diabetic microangiopathy in terms of retinopathy and/or diabetic nephropathy is crucial since it confers a worse renal prognosis indicating patients at risk of progression to end-stage renal disease.

BACKGROUND AND AIMS Between 50% and 60% of diabetics with renal involvement have nondiabetic nephropathy (NDN). Renal biopsy is crucial for renal diagnosis that includes diabetic nephropathy (DN), NDN or mixed form. The objective of the current study is to provide a tool in the daily clinical practice through a predictive model of NDN that is clue for the indication of renal biopsy. METHOD Observational, retrospective and multicenter study was undertaken of the pathological results of kidney biopsies in patients with diabetes from 2002 to 2014. A logistic regression analysis and the probability of presenting NDN was calculated using a punctuation score. RESULTS The cohort of 832 patients includes 621 men (74.6%), median age 61.7 ± 12.8 years, creatinine 2.8 ± 2.2 mg/dL and proteinuria 2.7 (1.2–5.4)g/24 h. Time of evolution of diabetes was 10.8 ± 8.6 years. 26.6% (n = 221) of patients presented diabetic retinopathy, 18.8% (n = 156) peripheral vasculopathy and 17.7% (n = 147) ischemic heart disease. A total of 288 patients (34.6%) presented microhematuria. A total of 39.5% (n = 329) presented DN, 49.6% (n = 413) NDN and 10.8% (n = 90) mixed forms. In the multivariate analysis, age (OR: 1.03; 1.01–1.04; P CONCLUSION In our study, ∼66% of biopsied patients with diabetes presented NDN. Microhematuria, absence of diabetic retinopathy, absence of peripheral vascular disease and older age were identified as independent risk factors for NDN. We obtained a score that increased as increased the probability of NDN. This could be in a next future a useful tool for renal biopsy indication in patients with diabetes and kidney disease.

BACKGROUND AND AIMS sodium-glucose 2 cotransporter inhibitors (SGLT2i) prevent cardiovascular events in diabetic patients. Moreover, their diuretic effect could attenuate the adverse events of endothelin receptor antagonists (ERA), which have also shown kidney protective effects in diabetes. The present study aimed to evaluate the beneficial cardiorenal impact of the combination of SGLT2i, ERA and ramipril versus treatment with ramipril alone in experimental diabetes. METHOD Twelve-week-old db/db mice were treated for 8 weeks with different combinations of an SGLT2i (empagliflozin, 10 mg/Kg/day), an ERA (atrasentan, 7 mg/Kg/day) and an RAS blocker (ramipril, 8 mg/Kg/day). Vehicle-treated diabetic and nondiabetic mice were included as controls. During the experiment, blood pressure (BP), glomerular filtration rate (GFR) and echocardiographic parameters were measured. Kidney and heart were collected at the end for histological studies. RESULTS The triple therapy with empagliflozin, atrasentan and ramipril was superior to ramipril alone in reducing BP (mean BP 61.0 mmHg versus 67.10 mmHg in the ramipril group), preventing diabetic hyperfiltration (214.3 μL/100 g/min GFR decrease versus 34.7 μL/100 g/min decrease in the ramipril group) (Figure 1), and improving echocardiographic parameters of diastolic dysfunction, including left atrium diameter and isovolumetric relaxation time. Moreover, the combined therapy offered protection against diabetic injury in kidney and heart by a reduction of mesangial matrix expansion (46.0% of glomerular mesangial matrix versus 46.9% in the ramipril group), as well as left ventricle cardiomyocyte hypertrophy (mean cardiomyocyte area 125 μm2 versus 131 μm2 in the ramipril group) and heart collagen deposition (Figure 1). CONCLUSION In experimental diabetes, combined therapy of ramipril, empagliflozin and atrasentan promotes both heart and kidney protective effects that outweigh the beneficial effects of ramipril alone.

BackgroundDiabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes.MethodsRetrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014.ResultsIn total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2–5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02–1.05, P ConclusionsThe most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.

Biobank; Chronic kidney disease; Kidney biopsy Biobanco; Enfermedad renal cronica; Biopsia renal Biobanc; Malaltia renal crònica; Biòpsia de ronyó Background and objectives: Kidney biopsy (KB) is the “gold standard” for the diagnosis of nephropathies and it is a diagnostic tool that presents a low rate of complications. Nowadays, biobank collections of renal tissue of patients with proven renal pathology are essential for research in nephrology. To provide enough tissue for the biobank collection, it is usually needed to obtain an extra kidney core at the time of kidney biopsy. The objective of our study is to evaluate the complications after KB and to analyze whether obtaining an extra core increases the risk of complications. Material and methods: Prospective observational study of KBs performed at Vall d’Hebron Hospital between 2019 and 2020. All patients who accepted to participate to our research biobank of native kidney biopsies were included to the study. Clinical and laboratory data were reviewed and we studied risk factors associated with complications. Results: A total of 221 patients were included, mean age 56.6 (±16.8) years, 130 (58.8%) were men, creatinine was 2.24 (±1.94) mg/dL, proteinuria 1.56 (0.506–3.590) g/24 h, hemoglobin 12.03 (±2.3) g/dL, INR 0.99 (±0.1), and prothrombin time (PT) 11.86 (±1.2) s. A total of 38 patients (17.2%) presented complications associated with the procedure: 13.1% were minor complications, 11.3% (n = 25) required blood transfusion, 1.4% (n = 3) had severe hematomas, 2.3% (n = 5) required embolization, and 0.5% (n = 1) presented arterio-venous fistula. An increased risk for complication was independently associated with obtaining a single kidney core (vs. 2 and 3 cores) (p = 0.021). Conclusions: KB is an invasive and safe procedure with a low percentage of complications. Obtaining an extra kidney core for research does not increase the risk of complications during the intervention, which remains low in concordance with previously published reports. The authors are current recipients of research grant from Red de Investigación Renal (REDINREN, RD16/0009/0030). (RICORS, RD21/0005/0016).

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

COVID-19; Nefritis tubulointersticial aguda; Biòpsia de ronyó COVID-19; Nefritis tubulointersticial aguda; Biopsia de riñón COVID-19; Acute tubulointerstitial nephritis; Kidney biopsy Novel coronavirus disease infection (coronavirus disease 2019, COVID-19) was declared a global pandemic in March 2020 and since then has become a major public health problem. The prevalence of COVID-19 infection and acute kidney injury (AKI) is variable depending on several factors such as race/ethnicity and severity of illness. The pathophysiology of renal involvement in COVID-19 infection is not entirely clear, but it could be in part explained by the viral tropism in the kidney parenchyma. AKI in COVID-19 infection can be either by direct invasion of the virus or as a consequence of immunologic response. Diverse studies have focused on the effect of COVID-19 on glomerulonephritis (GN) patients or the ‘novo’ GN; however, the effect of COVID-19 in acute tubulointerstitial nephritis (ATIN) has been scarcely studied. In this article, we present five cases with different spectrums of COVID-19 infection and ATIN that may suggest that recent diagnosis of ATIN is accompanied by a worse clinical prognosis in comparison with long-term diagnosed ATIN. This research was funded by ISCIIII-FEDER and ISCIII-RETICS REDinREN, grant number PI17/00257, PI21/01292, RD16/0009/0030, and RICORS RD21/0005/0016. Enfermedad Glomerular Compleja del Sistema Nacional de Salud (CSUR), enfermedades glomerulares complejas.

Nefropatía por IgA; Autoanticuerpos anticitoplasma de neutrófilos IgA nephropathy; Antineutrophil cytoplasmic autoantibodies Nefropatia per IgA; Anticossos anticitoplasma de neutròfils Background: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The concomitant presence of both crescentic proliferation and anti-neutrophil cytoplasmic autoantibodies (ANCA) in this pathology represents a rare coincidence. However, it is not clear to what extent the presence of ANCA (IgA or IgG) in these patients could have any clinical significance. The aim of the current work is to describe the presence of ANCA (IgA or IgG) in patients with IgAN and crescentic proliferation and its possible clinical implications. Methods: We retrospectively recruited all patients in our center with a histological diagnosis of IgAN with crescentic proliferation between January 2013 and December 2020. The main demographic and clinicopathologic data, fundamental histological characteristics, as well as the treatments implemented and main kidney outcomes, were collected and analyzed at a 6 and 12-month follow-up. Results: Between January 2013 and December 2020, a total of 17 adults were diagnosed with concomitant crescentic proliferation through a kidney biopsy of IgAN. Five (29.4%) patients showed ANCA, three (60%) showed IgA-ANCA and two (40%) showed IgG-ANCA. All ANCA-positive patients had some degree of crescentic proliferation. At diagnosis, the mean age of patients was 48 years old (range: 27–75). Nine of them were women (52%) and the most common clinical presentation was hypertension (71%). At the time of biopsy, the mean serum creatinine and proteinuria were 2.2 mg/dL (DS 1.42) and 3.5 g/mgCr (DS 1.22), respectively, with no statistical differences between ANCA-positive and -negative patients. Histological analyses showed that 11 out of the 12 (91%) ANCA-negative IgAN patients displayed less than 25% cellular crescents, whereas 100% of ANCA-positive IgAN patients displayed more than 25% cellular crescents (p = 0.04). Notably, five (30%) patients displayed fibrinoid necrosis, with four of them (80%) being IgAN-ANCA-positive (p = 0.01). Only one ANCA-negative patient needed renal replacement therapy (RRT) upon admission (5%). The mean serum creatinine and proteinuria were 1.94 mg/dL (DS 1.71) and 1.45 g/gCr (DS 1.78), respectively, within 6 months of immunosuppressive therapy. At 12-month follow-up, the mean creatinine was 1.57 mg/dL (DS 1). Four (23.5%) patients needed RRT at the end of the follow-up and four (23.5%) patients died. Conclusions: Probably due to the limited number of IgAN-ANCA-positive and IgAN-ANCA-negative patients, no significant differences were found between the clinical and laboratory characteristics. IgAN-ANCA-negative patients seemed to display less extracapillary proliferation than IgAN-ANCA-positive patients, who tended to show significantly higher fibrinoid necrosis. There were no differences regarding renal prognosis and patient survival after aggressive immunosuppressive therapy within 6 and 12 months when comparing the two samples.

Chronic kidney disease; Diabetic nephropathy; Endothelin receptor antagonists Enfermedad renal crónica; Nefropatía diabética; Antagonistas de los receptores de endotelina Malaltia renal crònica; Nefropatia diabètica; Antagonistes dels receptors d'endotelina Treatments with sodium–glucose 2 cotransporter inhibitors (SGLT2i) or endothelin receptor antagonists (ERA) have shown cardiorenal protective effects. The present study aimed to evaluate the cardiorenal beneficial effects of the combination of SGLT2i and ERA on top of renin–angiotensin system (RAS) blockade. Type 2 diabetic mice (db/db) were treated with different combinations of an SGLT2i (empagliflozin), an ERA (atrasentan), and an angiotensin-converting enzyme inhibitor (ramipril) for 8 weeks. Vehicle-treated diabetic mice and non-diabetic mice were included as controls. Weight, blood glucose, blood pressure, and kidney and heart function were monitored during the study. Kidneys and heart were collected for histological examination and to study the intrarenal RAS. Treatment with empagliflozin alone or combined significantly decreased blood glucose compared to vehicle-treated db/db. The dual and triple therapies achieved significantly greater reductions in diastolic blood pressure than ramipril alone. Compared to vehicle-treated db/db, empagliflozin combined with ramipril or in triple therapy significantly prevented GFR increase, but only the triple combination exerted greater protection against podocyte loss. In the heart, empagliflozin alone or combined reduced cardiac isovolumetric relaxation time (IVRT) and left atrium (LA) diameter as compared to vehicle-treated db/db. However, only the triple therapy was able to reduce cardiomyocyte area. Importantly, the add-on triple therapy further enhanced the intrarenal ACE2/Ang(1-7)/Mas protective arm of the RAS. These data suggest that triple therapy with empagliflozin, atrasentan and ramipril show synergistic cardiorenal protective effects in a type 2 diabetic mouse model. The following study was funded with Spanish government grants (FONDO DE INVESTIGACIÓN SANITARIA-FEDER, ISCIII (PI17/00257 and RICORS RD21/0005/0016)) and with financial support from Boehringer Ingelheim Pharma GmbH. The funders had no role in study design, analyses, interpretation of the data, drafting of the manuscript, or decision to submit the manuscript for publication. The funders were allowed to comment on the manuscript prior to publication; however, the final wording was at the full discretion of the investigators.

Acute kidney injury; Immune checkpoint inhibitors; Immune-related hepatitis Lesión renal aguda; Inhibidores del punto de control inmunitario; Hepatitis relacionada con el sistema inmunitario Lesió renal aguda; Inhibidors del punt de control immunitari; Hepatitis associada a la immunitat There are differences in recommendations for the management of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs). To assess the real-world management of irAEs, three surveys regarding ICI-induced hepatitis (IIH), renal irAEs, and myositis were developed and sent to experts in each area. Fifty-six surveys were completed (17 IIH, 20 renal irAEs, and 19 myositis). All experts agreed on performing imaging in every suspected case of severe IIH. Sixty-five percent agreed on performing a liver biopsy in patients not responding to corticosteroids. The most common indication for corticosteroid use (59%) was for severe IIH not improving after discontinuation of ICIs. Additionally, 60% of the experts agreed on performing a biopsy for stage 2/3 acute kidney injury (AKI), and 70% recommended imaging for any stage of AKI. Thirty-five percent favored corticosteroids in AKI patients with creatinine levels 2–3-fold above baseline. For myositis, 58% would recommend a muscle biopsy in a patient with weakness and creatine kinase levels of 5000 U/L; 47% would also opt for an endomyocardial biopsy when the troponin levels are increased. Fifty-eight percent recommended oral corticosteroids for myositis, and 37% recommended additional therapy, mainly immunoglobulins. These results show substantial differences in expert practice patterns for the management of severe liver, kidney, and muscular irAEs. This research was funded by ISCIIII-FEDER and ISCIII-RETICS REDinREN (grant numbers PI17/00257, PI21/01292, RD16/0009/0030, and RICORS RD21/0005/0016) and Enfermedad Glomerular Compleja del Sistema Nacional de Salud (CSUR) enfermedades glomerulares complejas. Supported in part by the University of Texas MD Anderson’s Cancer Center Support Grant from the National Cancer Institute (NCI P30 CA016672).

Background and Aims IgA nephropathy (IgAN) is the most common glomerulonephritis. The presence of ANCAs in this pathology represents a rare coincidence. However, it is not clear if the presence of IgA or IgG ANCAs in these patients could have clinical significance. We aim to describe the presence of IgA and IgG ANCAs in patients diagnosed with IgAN with crescents, and its possible clinical implications. Method Retrospective study from 2013 to 2020, it included all patients diagnosed by kidney biopsy of IgAN with extracapillary proliferation. Outpatient follow-up time was up to 24 months. Demographics and clinicopathologic data, ANCAs subtype, characteristics of the biopsy and treatment at the time of diagnosis/follow up was recollected. Results From 2013 to 2020, 17 adults were diagnosed with IgAN and extracapillary proliferation. 5 patients presented ANCAs, 3 (17%) were IgA ANCAs and 2 (11%) were IgG ANCAs. At diagnosis, the median age was 48 years old (27-75 years, sd. 15), with 9 women (52%). At the time of diagnosis, the most common clinical presentation was hypertension (71%). The laboratory analysis showed that median hemoglobin was 11.7 mg/dl (8.4-14.9 mg/dL, sd. 1.5), median creatinine was 2.2 mg/dL (0.55-5.7 mg/dL, sd. 1.4) and median proteinuria was 3.5 g/mgCr (0.1-12 g/mgCr, sd. 3.5). 7 patients (41%) presented extracapillary proliferation less than 25%, 7 patients presented it between 25% and 50%, and 3 patients (17%) had it in more than 50%. 5 (30%) patients presented fibrinoid necrosis. 1 (6%) patient needed renal replacement therapy upon admission. In terms of treatment, all patients with ANCAs IgAN received endovenous steroids and cyclophosphamide. The mean follow-up time was 6 months. Oral steroids (59%) and mycophenolate (41%) were the most frequent treatments. At six months, the median creatinine was 1.9 mg/dL (0.4-7, sd. 1.78) and the median proteinuria was 1.45 g/gCr (0.12-5.9, sd. 1.84 g/gCr). 3 patients developed end-stage chronic kidney disease and requiring substitute renal therapy; 4 patients died. Statistical analysis did not show differences in clinical characteristics, demographics, kidney function, proteinuria, need for renal therapy replacement or mortality according to the presence or subtype of ANCA. ANCA negative patients presented less than 25% of extracapillary proliferation in renal biopsy (p = 0.04). ANCA positive patients presented more fibrinoid necrosis than ANCA negative patients (p=0.01). Conclusion Given the limited size of our sample, our results do not allow us to be conclusive, showing no significant differences between the ANCA subtypes. However, from the point of renal biopsy, it is observed that patients with negative ANCAs present less extracapillary proliferation; and that patients ANCA positive presented more fibrinoid necrosis.

Background and Aims Kidney biopsy (KB) is the “gold standard” to diagnose nephropathies in our renal patients and it is a procedure with a low rate of complications. Obtaining material for kidney biopsy biobank requires the extraction of one more renal cylinder. The main objective of our study is to analyze the characteristics of a cohort of patients with KB, the safety of the establishment of a renal biopsy biobank with the objective to obtain at least one core of kidney biopsy for research purposes. Method Observational and prospective study of kidney biopsies performed in our center from January 2019 and 2020. We started a collection of kidney biopsy samples to obtain a biobank at January 2019. Therefore, in patients who accepted, instead of two cylinders, three cylinders were obtained during the procedure when possible. Clinical and laboratory data of the patients were reviewed and we looked for risk factors for complications, including the number of cylinders obtained in the procedure. Results We reviewed a cohort of 221 patients in whom we performed a kidney biopsy at our hospital. Eight patients (3.6%) underwent trans-jugular renal biopsy, which we have eliminated from the analysis. Of the remaining 213, 126 (59.2%) were men, the mean age was 56.8 (± 16.9) years, 122 (57.3%) patients had hypertension, 46 (23%) were diabetics, 14 (6.5%) were under anticoagulant treatment and 35 (16.4%) were under antiplatelet treatment. Regarding the analytical values, the mean creatinine was 2.22 (± 1.9) mg / dl, protein / creatinine urine ratio 1119.6 [448.3-2957.9] mg / gr, 44.6% (n = 95) had microhematuria, the median hemoglobin pre-KB was 12.1 (± 2.3) g / dL, 254380 (± 8873) platelets, INR 0.98 (± 0.09), prothrombin time of 11.8 (± 1.16) seconds, systolic blood pressure was 135 (± 24.3) mmHg, diastolic blood pressure was 76 (± 15.5) mmHg. The median kidney size was 11 (± 1.23) cm and cortical size was 1.7 (± 0.65) cm. In 113 (53.1%) patients the right kidney was biopsied. 69.5% (n = 148) of the patients 3 renal sample cylinders were obtained, 27.2% (n = 58) 2 cylinders and in 3.3% (n = 7) one cylinder. We did not found differences regarding of renal and cortical size in the patients according to the number of cylinders obtained. We observed that patients in whom 3 cylinders were had a higher percentage of renal biopsy in the left kidney (p = 0.028). We evidenced minor complications in 13.6% (n = 29) and 3.3% (n = 7) major complications. Patients with complications in KB were older (p = 0.039) and had a higher INR (p = 0.031). Patients with one renal cylinder Jin KB, presented a higher percentage of complications with 57.1% vs 17.2% two cylinders and 14.9% with three cylinder (p =0.014). We did not find differences in terms of complications according to the laterality of kidney biopsy (right vs left). Conclusion Kidney biopsy is a procedure with a low complication rate. Obtaining three renal biopsy cylinders for biobank has not shown an increase in the rate of complications, which remains similar than previously published reports. Our results suggest that the complications are observed mainly in the first and/or second cylinder, and in that case the third core is not performed.

Background COVID-19 infection manifests as pneumonia associated with multiple organ failure, and death. Acute kidney injury is a risk factor for mortality. There is limited scientific literature on COVID-19 infection and allergic tubulointerstitial nephritis, its clinical course and short- and long-term prognosis. Method We performed a retrospective study where medical records of 60 patients with histological diagnosis of allergic tubulointerstitial nephritis from January 2009 to November 2020. In these patients, we studied the incidence of COVID-19 infection, clinical characteristics and prognosis from March to the actual date. Results Of 60 patients with allergic tubulointerstitial nephritis, 6 (10%) patients were diagnosed with COVID-19. The first case, an 85-year-old woman with a history of metastatic melanoma treated with nivolumab and allergic tubulointerstitial nephritis by immunobiological agents in 2018, diagnosed with mild COVID-19 infection in April 2020 without deterioration of renal function in controls at 3 and 6 months of follow-up. The second case, a 51-year-old woman with a history of large B-cell lymphoma with plasmacytic differentiation and progression to multiple myeloma of lambda light chains and allergic tubulointerstitial nephritis due to chemotherapy since 2019, admitted for acute pyelonephritis and PRES syndrome secondary to first dose of bortezomib complicated with COVID-19 nosocomial pneumonia and acute pancreatitis treated with corticosteroids and broad spectrum antibiotic therapy; she died of abdominal refractory septic shock. The third patient, a 64-year-old man without prior renal impairment, was admitted for severe COVID-19 pneumonia and acute kidney injury secondary to acute tubulointerstitial nephritis of uncertain etiology that required orotracheal intubation and continuous veno-venous hemodiafiltration for a week who received methylprednisolone in bolus for 3 days and continued treatment with corticosteroid therapy with complete recovery of renal function and improvement in proteinuria at 3 months of follow-up. The fourth patient, an 82-year-old woman with acute kidney injury AKIN 3 secondary to acute allergic tubulointerstitial nephritis related to ciprofloxacin complicated with severe COVID-19 nosocomial pneumonia, who died despite ventilatory support and high-dose steroids therapy and tocilizumab. The fifth patient, a 75-year-old with a history of metastatic lung adenocarcinoma treated with immunobiological agents and allergic tubulointerstitial nephritis in 2018, admitted in march 2020 for mild COVID-19 pneumonia treated with steroids and hydroxychloroquine without deterioration of respiratory and kidney function. The sixth patient, an 86-years-old man with acute kidney injury AKIN 3 due to acute allergic tubulointerstitial nephritis secondary to proton-binding inhibitors and nosocomial COVID-19 infección with improvement of kidney function with steroids therapy only. Conclusion Our 6 patients with allergic tubulointerstitial nephritis and COVID-19 infection presented different spectrum of the disease. It seems that nosocomial COVID-19 infection in patients admitted with recent diagnosis of acute allergic tubulointerstitial nephritis presented a worse clinical prognosis compared with long-term diagnosed acute tubulointerstitial nephritis. Further studies with a larger sample size are needed.

Background and Aims Angiotensin converting enzyme 2 (ACE2) is one of the components of the renin-angiotensin system (RAS) that mainly degrades angiotensin II to angiotensin-(1-7). ACE2 is predominantly expressed in the kidney and the heart, but it has been evidenced in type 2 alveolar lung cells, where it acts as a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, a controversy arose as to whether the use of RAS blockers could increase ACE2 lung expression and the risk infection by COVID-19. This study aimed to investigate the effect of an ACE inhibitor (Ramipril) on ACE2 expression in experimental diabetes. Method 12 weeks old diabetic db/db mice (n=7) were given ramipril (8 mg/Kg/day) during 8 weeks or the respective vehicle. db/m (n=7) vehicle-treated non-diabetic mice were included as controls. ACE2 mRNA expression and enzymatic activity were studied in kidney, heart and lung samples of these animals to identify if the diabetic condition or treatment with ramipril modulated ACE2 expression. Results In vehicle-treated diabetic db/db animals, ACE2 mRNA expression was significantly increased in the kidney (p Conclusion ACE2 is increased in the kidney and the lung, and decreased in the heart of diabetic mice. Ramipril treatment restores ACE2 levels. The results suggest that ACE inhibitors do not increase ACE2 expression and the activity decrease exerted in the lung may be protective against COVID-19 infection.

BACKGROUND AND OBJECTIVES: Diabetic kidney disease is the leading cause of end-stage chronic kidney disease. The renin-angiotensin-aldosterone system (RAAS) blockade has been shown to slow the progression of diabetic kidney disease. Our objectives were: to study the percentage of patients with diabetic kidney disease treated with RAAS blockade, to determine its renal function, safety profile and assess whether its administration is associated with increased progression of CKD after 3 years of follow-up. MATERIALS AND METHODS: Retrospective study. 197 diabetic kidney disease patients were included and divided into three groups according to the treatment: patients who had never received RAAS blockade (non-RAAS blockade), patients who at some point had received RAAS blockade (inconstant-RAAS blockade) and patients who received RAAS blockade (constant-RAAS blockade). Clinical characteristics and analytical variables such as renal function, electrolytes, glycosylated haemoglobin and glomerular filtration rate according to chronic kidney disease -EPI and MDRD formulas were assessed. We also studied their clinical course (baseline, 1 and 3 years follow-up) in terms of treatment group, survival, risk factors and renal prognosis. RESULTS: Non-RAAS blockade patients had worse renal function and older age (p