Immunotherapy and the Spectrum of Kidney Disease: Should We Individualize the Treatment?

Chronic kidney disease; Dialysis; ImmunotherapyEnfermedad renal cronica; Diálisis; InmunoterapiaMalaltia renal crònica; Diàlisi; ImmunoteràpiaThe 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

The Presence of ANCA in IgA Crescentic Nephropathy Does Not Lead to Worse Prognosis with Intensive Rescue Treatment

Nefropatía por IgA; Autoanticuerpos anticitoplasma de neutrófilosIgA nephropathy; Antineutrophil cytoplasmic autoantibodiesNefropatia per IgA; Anticossos anticitoplasma de neutròfilsBackground: 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

Epidemiology of Immune-Mediated Glomerulopathies before and after SARS-CoV-2 Vaccination: A Tertiary Referral Hospital Experience

SARS-CoV-2; Immune-mediated glomerulopathy; VaccineSARS-CoV-2; Glomerulopatía inmunomediada; VacunaSARS-CoV-2; Glomerulopatia immunomediada; VacunaBackground: 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)

Enteric Budesonide in Transplant and Native IgA Nephropathy: Real-World Clinical Practice

Budesonide; Transplant; NephropathyBudesonida; Trasplante; NefropatíaBudesonida; Trasplantament; Nefropati

Risk factors for non-diabetic renal disease in diabetic patients

Background. Diabetic 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. Methods. Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. Results. In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 6 12.8 years, creatinine was 2.8 6 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2–5.4) g/24 h. About 39.5% (n ¼ 329) of patients had DN, 49.6% (n ¼ 413) NDRD and 10.8% (n ¼ 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n ¼ 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) ¼ 1.03, 95% CI: 1.02–1.05, P < 0.001], microhaematuria (OR ¼ 1.51, 95% CI: 1.03–2.21, P ¼ 0.033) and absence of diabetic retinopathy (DR) (OR ¼ 0.28, 95% CI: 0.19–0.42, P < 0.001) were independently associated with NDRD. Kaplan–Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P ¼ 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P ¼ 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P ¼ 0.002), higher creatinine (P ¼ 0.01) and DN (P ¼ 0.015) were independent risk factors for mortality. Conclusions. The 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

Acute kidney injury in patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. We 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. ICPi-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. Patients 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

Acute kidney injury in patients treated with immune checkpoint inhibitors

Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi- AKI) has emerged as an important toxicity among patients with cancer.Methods We 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. Results ICPi- 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 ICPiAKI.Conclusions Patients 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