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Introduction: The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes., Methods: We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities., Results: Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9 g/g, and median serum creatinine was 3.2 mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen., Conclusion: The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV., Competing Interests: A.M. is investigator of CELGENE, ROCHE, CHUGAI funded trials with APHP, and Hôpital 15-20 promotion; A.M. received several fees for congress travels and expert use from LFB, SANOFI, SHIRE, and CELGENE., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Copeptin and intact fibroblast growth factor 23 (iFGF23) increase early during chronic kidney disease (CKD) and may be predictive of unfavourable outcomes. The aim of this study was to evaluate their respective associations with renal and vital outcomes in CKD patients., Methods: We included CKD patients from the NephroTest cohort with concomitant measurements of plasma copeptin and iFGF23 concentrations and isotopic glomerular filtration rate measurement (mGFR). The primary endpoint was a composite outcome including kidney failure (KF) (dialysis initiation, pre-emptive transplantation or a 57% decrease of mGFR, corresponding to doubling of serum creatinine) or death before KF. Hazard ratios (HRs) of the primary endpoint associated with log-transformed copeptin and iFGF23 concentrations were estimated by Cox models. The slope of mGFR over time was analysed using a linear mixed model., Results: A total of 329 CKD patients (243 men, mean age 60.3 ± 14.6 years) were included. Among them, 301 with an mGFR >15 ml/min/1.73 m 2 were included in survival and mGFR slope analyses. During a median follow-up of 4.61 years (quartile 1-quartile 3: 3.72-6.07), 61 KFs and 32 deaths occurred. Baseline iFGF23 concentrations were associated with the composite outcome after multiple adjustments {HR 2.72 [95% confidence interval (CI) 1.85-3.99]}, whereas copeptin concentrations were not [HR 1.01 (95% CI 0.74-1.39)]. Neither copeptin nor iFGF23 were associated with mGFR slope over time., Conclusion: Our study shows for the first time in population of CKD patients an independent association between iFGF23 and unfavourable renal and vital outcomes and shows no such association regarding copeptin, encouraging the integration of iFGF23 measurement into the follow-up of CKD., Competing Interests: M.C. received consulting fees from Withings, Home Biosciences, Usense, Alnylam Pharmaceuticals, Advicenne and Viatris and a grant from BioHealth Laboratory over the 3 years prior to submission. The other authors have no conflicts of interest. The results presented in this article have not been published previously in whole or part., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: We determine the benefit of pulsed methylprednisolone for improving kidney function in patients with sarcoidosis tubulointerstitial nephritis., Methods: We conducted a multicenter, prospective, randomized, open-label, controlled trial in patients with biopsy-proven acute tubulointerstitial nephritis caused by sarcoidosis at 21 sites in France. Patients were randomly assigned to receive a methylprednisolone pulse 15 mg/kg/day for 3 days, then oral prednisone (MP group) or oral prednisone 1 mg/kg/day alone (PRD group). The primary end point was a positive response at 3 months, defined as a doubling of estimated glomerular filtration rate (eGFR) compared with the eGFR before randomization., Results: We randomized 40 participants. Baseline eGFR before PRD was 22 mL/min/1.73m2 {interquartile range [IQR], 16-44} and before MP was 25 mL/min/1.73m2 (IQR, 22-36) (P = .3). The two groups did not differ in underlying pathological lesions, including mean percentage of interstitial fibrosis and intensity of interstitial infiltrate. In the intent-to-treat population, the median eGFR at 3 months did not significantly differ between the PRD and MP groups: 45 (IQR, 34-74) and 46 (IQR, 39-65) mL/min/1.73m2. The primary end point at 3 months was achieved in 16 of 20 (80%) PRD patients and 10 of 20 (50%) MP patients (P = .0467). The eGFR was similar between the two groups after 1, 3, 6, and 12 months of treatment. For both groups, eGFR at 1 month was strongly correlated with eGFR at 12 months (P < .0001). The two groups did not differ in severe adverse events., Conclusion: Compared with a standard oral steroid regimen, intravenous MP may have no supplemental benefit for renal function in patients with tubulointerstitial nephritis caused by sarcoidosis.Trial Registration: ClinicalTrials.gov: NCT01652417; EudraCT: 2012-000149-11., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Little is known about clinical characteristics and kidney outcomes in patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in a context of inflammatory bowel disease (IBD)., Methods: We conducted a retrospective multicentre study with a centralized histological review to analyse the presentation, therapeutic management and outcome of 24 patients suffering from IBD-associated IgAN relative to a cohort of 134 patients with primary IgAN without IBD., Results: Crohn's disease and ulcerative colitis accounted for 75 and 25% of IBD-associated IgAN cases, respectively. IBD was diagnosed before IgAN in 23 cases (a mean of 9 years previously) and was considered active at IgAN onset in 23.6% of patients. Hypertension was present in 41.7% of patients. The urinary protein:creatinine ratio exceeded 100 mg/mmol in 70.8% of patients (mean 254 mg/mmol). Estimated glomerular filtration rate (eGFR) was >60 mL/min/1.73 m2 in 13/24 patients and only 1 patient required dialysis. In the Oxford mesangial hypercellularity, endocapillary cellularity, segmental sclerosis and interstitial fibrosis/tubular atrophy with crescents classification of renal biopsies, 57% were M1, 48% E1, 76% S1, 57% T1-2 and 38% C1-2. Steroids were administered in 50% of cases. After a mean follow-up of 7.2 years, 4 patients (16.7%) had a poor kidney outcome: end-stage renal disease (n = 3) or a >50% decrease in eGFR from initial values (n = 1). A similar evolution was observed in patients with primitive IgAN., Conclusions: This first case series suggests that IBD-associated IgAN has frequent inflammatory lesions at onset and variable long-term outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: The spectrum of interferon-β (IFN-β)-associated nephropathy remains poorly described and the potential features of this uncommon association remain to be determined., Methods: In this study we retrospectively analysed the clinical, laboratory, histological and therapeutic data of patients with biopsy-proven renal disease in a context of IFN-β treatment administered for at least 6 months., Results: Eighteen patients (13 women, median age 48 years) with biopsy-proven renal disease occurring during IFN-β therapy were included. The median exposure to IFN-β (14 patients were treated with IFN-β1a and 4 patients with IFN-β1b) was 67 months (range 23-165 months). The clinical presentation consists in hypertension (HT; 83%), malignant HT (44%), proteinuria (protU) >1 g/g (94%), reduced renal function (78%), biological hallmark suggesting thrombotic microangiopathy (TMA; 61%), oedematous syndrome (17%) or nephritic syndrome (11%). The pathological findings included typical features of isolated TMAs in 11 cases, isolated focal segmental glomerulosclerosis (FSGS) lesions in 2 cases and 5 cases with concomitant TMA and FSGS lesions. An exploration of the alternative complement pathway performed in 10 cases (63%) did not identify mutations in genes that regulate the complement system. The statistical analysis highlighted that the occurrence of IFN-β-associated TMA was significantly associated with Rebif, with a weekly dose >50 µg and with multiple weekly injections. In all cases, IFN-β therapy was discontinued. Patients with TMA lesions received other therapies, including corticosteroids (44%), eculizumab (13%) and plasma exchanges (25%). At the end of a 36-month median follow-up, persistent HT and persistent protU were observed in 61% and 22% of patients, respectively. Estimated glomerular filtration rate <60 mL/min/1.73 m 2 was present in 61% of patients., Conclusions: IFN-β-associated nephropathy must be sought in the case of HT and/or protU onset during treatment. When TMA and/or FSGS are observed on renal biopsy, early discontinuation of IFN-β is essential., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Objective: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small-vessel vasculitis characterized by asthma, hypereosinophilia and ANCA positivity in 40% of patients. Renal involvement is rare and poorly described, leading to this renal biopsy-proven based study in a large EGPA cohort., Methods: We conducted a retrospective multicentre study including patients fulfilling the 1990 ACR criteria and/or the 2012 revised Chapel Hill Consensus Conference criteria for EGPA and/or the modified criteria of the MIRRA trial, with biopsy-proven nephropathy., Results: Sixty-three patients [27 women, median age 60 years (18-83)] were included. Renal disease was present at vasculitis diagnosis in 54 patients (86%). ANCA were positive in 53 cases (84%) with anti-MPO specificity in 44 (83%). All patients had late-onset asthma. Peripheral neuropathy was present in 29 cases (46%), alveolar haemorrhage in 10 (16%). The most common renal presentation was acute renal failure (75%). Renal biopsy revealed pauci-immune necrotizing GN in 49 cases (78%). Membranous nephropathy (10%) and membranoproliferative GN (3%) were mostly observed in ANCA-negative patients. Pure acute interstitial nephritis was found in six cases (10%); important interstitial inflammation was observed in 28 (44%). All patients received steroids with adjunctive immunosuppression in 54 cases (86%). After a median follow-up of 51 months (1-296), 58 patients (92%) were alive, nine (14%) were on chronic dialysis and two (3%) had undergone kidney transplantation., Conclusion: Necrotizing pauci-immune GN is the most common renal presentation in ANCA-positive EGPA. ANCA-negative patients had frequent atypical renal presentation with other glomerulopathies such as membranous nephropathy. An important eosinophilic interstitial infiltration was observed in almost 50% of cases., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Chronic kidney disease is associated with a high cardiovascular risk. Compared with glomerular filtration rate-matched CKD patients (CKDps), we previously reported a 2.7-fold greater risk of global mortality among kidney transplant recipients (KTRs). We then examined aortic stiffness [evaluated by carotid-femoral pulse wave velocity (CF-PWV)] and cardiovascular risk in KTRs compared with CKDps with comparable measured glomerular filtration rate (mGFR)., Methods: We analysed CF-PWV in two cohorts: TransplanTest (KTRs) and NephroTest (CKDps). Propensity scores were calculated including six variables: mGFR, age, sex, mean blood pressure (MBP), body mass index (BMI) and heart rate. After propensity score matching, we included 137 KTRs and 226 CKDps. Descriptive data were completed by logistic regression for CF-PWV values higher than the median (>10.6 m/s)., Results: At 12 months post-transplant, KTRs had significantly lower CF-PWV than CKDps (10.1 versus 11.0 m/s, P = 0.008) despite no difference at 3 months post-transplant (10.5 versus 11.0 m/s, P = 0.242). A lower occurrence of high arterial stiffness was noted among KTRs compared with CKDps (38.0% versus 57.1%, P < 0.001). It was especially associated with lower mGFR, older age, higher BMI, higher MBP, diabetes and higher serum parathyroid hormone levels. After adjustment, the odds ratio for the risk of high arterial stiffness in KTRs was 0.40 (95% confidence interval 0.23-0.68, P < 0.001)., Conclusions: Aortic stiffness was significantly less marked in KTRs 1 year post-transplant than in CKDps matched for GFR and other variables. This observation is compatible with the view that the pathogenesis of post-transplant cardiovascular disease differs, at least in part, from that of CKD per se ., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Muscle wasting predicts mortality in patients with end-stage renal disease (ESRD), but its role in the progression of chronic kidney disease (CKD) is uncertain. We studied CKD outcomes associated with low muscle mass, assessed by urinary creatinine excretion (UCr)., Methods: The NephroTest cohort included 1429 patients with CKD stages 1-4 and both measured glomerular filtration rate (mGFR) (by (51)Cr-EDTA) and estimated glomerular filtration rate (eGFR) (by CKD-Epidemiology Collaboration equation). We used cause-specific Cox models to estimate hazard ratios (HRs) for the competing risks of ESRD and death associated with gender-specific UCr quartiles., Results: UCr was 13.6 ± 3.2 mmol/24 h (0.17 ± 0.05 mmol/kg/24 h) in men and 9.2 ± 2.1 (0.14 ± 0.05) in women. It was positively associated with mGFR, but not with eGFR. Over a median follow-up of 3.6 (2.1-5.8) years, 229 patients developed ESRD and 113 patients died before ESRD. Compared with patients in the highest UCr quartile, those in the lowest quartile had a higher crude HR (95% confidence interval) for pre-ESRD death: 4.3 (2.4-7.7), which was weakened, but remained statistically significant, independent of demographics, mGFR and several other factors: 2.1 (1.04-4.3). Their crude ESRD risk was not higher: HR: 0.95 (0.65-1.4), and even tended to be lower after adjusting for mGFR and log-proteinuria: HR: 0.70 (0.45-1.1). Adjustment for eGFR instead of mGFR reversed this relationship: HR: 1.7 (1.1-2.7)., Conclusions: In early stage CKD, low UCr is associated with higher risk for mortality, but not for ESRD. Using creatinine-based equation to adjust for GFR may bias the relationship of UCr with ESRD risk., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Fanconi-Bickel syndrome is a rare autosomal-recessive disorder caused by mutations in the SLC2A2 gene coding for the glucose transporter protein 2 (GLUT2). Major manifestations include hepatomegaly, glucose intolerance, post-prandial hypoglycaemia and renal disease that usually presents as proximal tubular acidosis associated with proximal tubule dysfunction (renal Fanconi syndrome). We report a patient harbouring a homozygous mutation of SLC2A2 who presented a dramatic exacerbation of metabolic acidosis in the context of a viral infection, owing to both ketosis and major urinary bicarbonate loss. The kidney biopsy revealed nuclear and cytoplasmic accumulation of glycogen in proximal tubule cells, a lack of expression of GLUT2, and major defects of key proteins of the proximal tubule such as megalin, cubilin and the B2 subunit of H(+)-ATPase. These profound alterations of the transport systems most likely contributed to proximal tubule alterations and profound bicarbonate loss., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Context: Vitamin D deficiency is common in patients with chronic kidney disease (CKD). Current guidelines recommend treatment strategies in these patients similar to those for the general population, but the vitamin D nutritional status sufficient to prevent PTH levels from increasing in CKD is unknown. OBJECTIVE, MAIN OUTCOME MEASURE: Our aim was to study the relation between circulating PTH and 25(OH)D levels and to search for a 25(OH)D threshold associated with a significant PTH increase., Design, Setting, and Patients: In the hospital-referred NephroTest cohort study, we measured 25(OH)D, PTH, and glomerular filtration rate (mGFR) by ⁵¹Cr-EDTA renal clearance in 929 adult patients with nondialysis CKD stages 1 to 5 and no vitamin D supplementation. Patients' mean age was 60.1 ± 14.7 years; 71% were men, and 9% were black. Their median mGFR was 37.8 mL/min/1.73 m²., Results: We found a 25(OH)D threshold of 8 ng/mL with an upper limit of 20 ng/mL (95% confidence interval) by linear piecewise regression modeling of log-PTH for 25(OH)D adjusted for mGFR, age, race, and ionized calcium level. The smoothed curve confirmed that PTH concentration rose steeply when circulating 25(OH)D levels fell to less than 20 ng/mL., Conclusions: Spontaneous 25(OH)D levels greater than 20 ng/mL seem sufficient to control serum PTH in CKD patients. This result reinforces guidelines to supplement vitamin D only if less than 30 ng/mL.

Background: Castleman disease (CD), or angiofollicular lymph-node hyperplasia, is an atypical lymphoproliferative disorder with heterogeneous clinical manifestations. Renal involvement in CD has been described in only single-case reports, which have included various types of renal diseases., Methods: Nineteen patients with histologically documented CD and renal biopsies available were included. Clinical features and renal histological findings were reviewed, and the available samples were immunolabelled with anti-vascular endothelial growth factor (VEGF) antibody., Results: Nineteen CD cases were identified: 89% were multicentric, and 84% were of the plasma-cell or mixed type. Four cases (21%) were associated with human immunodeficiency virus (HIV) infection. Among HIV-negative patients, two main patterns of renal involvement were found: (i) a small-vessel lesions group (SVL) (60%) with endotheliosis and glomerular double contours in all patients and with superimposed glomerular/arteriolar thrombi or mesangiolysis in most; and (ii) AA amyloidosis (20%). Renal histology was more heterogeneous among HIV-positive patients. Decreases in glomerular VEGF were observed only in some patients with SVL, whereas VEGF staining was normal in all other histological groups. Interestingly, glomerular VEGF loss associated with SVL was correlated with plasma C-reactive protein levels, a marker of CD activity., Conclusions: Small-vessel lesions are the most frequent renal involvement in CD, whereas loss of glomerular VEGF is correlated with CD activity and could have a role in SVL pathophysiology.

Background: Renal fibrosis, a common complication of hypertension and diabetes is considered as a non-curable disease and is characterized by the abnormal accumulation of collagen I within the kidney. Chronic inhibition of nitric oxide (NO) synthesis is a model of hypertension associated with the development of nephroangiosclerosis. The present study investigated whether halt of NO inhibition leads to the regression of renal sclerotic lesions., Methods: The NO deficiency (N(G)-nitro-L-arginine methylester; L-NAME) model of hypertension was applied in transgenic mice harbouring the luciferase reporter gene under the control of the collagen I-alpha2 chain promoter., Results: Systolic pressure gradually increased following the administration of L-NAME, and reached 160 mmHg after 8-10 weeks. Activation of collagen I gene within the renal vasculature preceded the blood pressure increase and was accompanied by the appearance of sclerotic glomeruli and tubulointerstitial infiltration. After renal lesions had been established (20 weeks), animals were divided in three subgroups for an additional experimental period of 10 weeks: first group continued to receive L-NAME, in the second, L-NAME administration was stopped to allow endogenous NO synthesis and in the third the removal of L-NAME was combined with endothelin receptor antagonism. Removal of L-NAME decreased, without normalizing, systolic pressure and collagen I gene activity; renal morphology was substantially improved, and tubulointerstitial infiltration disappeared. Combination of L-NAME removal with endothelin antagonism normalized collagen I gene expression and further improved renal morphology without further decreasing blood pressure., Conclusion: Manipulating the balance between NO/vasoconstrictors in favour of NO could provide a curative approach against renal inflammatory and fibrotic complications associated to hypertension.