scholarly journals Crescents and Global Glomerulosclerosis in Chinese IgA Nephropathy Patients: A Five-Year Follow-Up

2019 ◽  
Vol 44 (1) ◽  
pp. 103-112 ◽  
Author(s):  
Wei Peng ◽  
Yi Tang ◽  
Li Tan ◽  
Wei Qin
Keyword(s):  
Serum Creatinine ◽  
Iga Nephropathy ◽  
Treatment Modalities ◽  
Renal Outcome ◽  
Urine Protein ◽  
Lower Egfr ◽  
Global Glomerulosclerosis ◽  
Stage Renal Disease ◽  
End Stage

Background/Aims: This study aims to evaluate the clinical significance of crescent and global glomerulosclerosis formation on renal outcome in patients with IgA nephropathy (IgAN). Methods: Biopsy-proven primary IgAN patients from West China Hospital of Sichuan University were studied retrospectively between 2008 and 2015. Clinicopathological features and treatment modalities were recorded. The patients were divided into several groups on the basis of cellular and/or fibrocellular crescents scores and global glomerulosclerosis scores. Crescent (C) was scored according to the updated Oxford classification (C0/C1/C2). Global glomerulosclerosis (G) was scored according to the frequency of global glomerulosclerosis: G0 (≤25% of glomeruli), G1 (26–50% of glomeruli), and G2 (> 50% of glomeruli). The primary endpoint was defined as a 50% reduction in renal function or end stage renal disease. Patients were followed up for at least 12 months, or shorter if they reached study endpoints. 1328 patients with IgAN were recruited. Mean follow-up time was 46.1±23.6 months. The percentage of patients with C1 and C2 was 19.3% and 5.9% respectively. Higher crescent scores was associated with lower estimated glomerular filtration rates (eGFR), decreased serum albumin levels, increased amounts of urine protein, higher serum creatinine, as well as greater proportions of M1 and E1. The percentage of patients with G0, G1 and G2 was 70.5%, 20.7% and 8.8%, respectively. Elevated glomerulosclerosis scores were associated with lower eGFR levels, increased amounts of urine protein, higher levels of serum creatinine, higher incidences of arterial hypertension, as well as greater proportions of M1. There was a significantly higher proportion of T1/2 in patients with G2. In a multivariate model, crescent and global glomerulosclerosis were identified as independent predictors of decreased renal survival. Conclusion: Global glomerulosclerosis and crescents, as detected in renal biopsies, are strong predictors of long-term renal outcome of IgAN.

scholarly journals Absence of renal remission portends poor long-term kidney outcome in lupus nephritis

2021 ◽  
Vol 8 (1) ◽  
pp. e000533
Author(s):  
Valérie Pirson ◽  
Antoine Enfrein ◽  
Frédéric A Houssiau ◽  
Farah Tamirou
Keyword(s):  
Lupus Nephritis ◽  
Negative Impact ◽  
Renal Outcome ◽  
Class Iii ◽  
Treatment Change ◽  
Lower Egfr ◽  
Stage Renal Disease ◽  
End Stage

BackgroundThe very long-term consequences of absence of remission in lupus nephritis (LN) remain understudied.MethodsIn this retrospective analysis, we studied a selected cohort of 128 patients with biopsy-proven class III, IV or V incident LN followed for a median period of 134 months (minimum 25). Remission was defined as a urine protein to creatinine (uP:C) ratio <0.5 g/g and a serum creatinine value <120% of baseline. Renal relapse was defined as the reappearance of a uP:C >1 g/g, leading to a repeat kidney biopsy and treatment change. Poor long-term renal outcome was defined as the presence of chronic kidney disease (CKD).ResultsTwenty per cent of patients never achieved renal remission. Their baseline characteristics did not differ from those who did. Absence of renal remission was associated with a threefold higher risk of CKD (48% vs 16%) and a 10-fold higher risk of end-stage renal disease (20% vs 2%). Patients achieving early remission had significantly higher estimated glomerular filtration rate (eGFR) at last follow-up compared with late remitters. Accordingly, patients with CKD at last follow-up had statistically longer time to remission. Among patients who achieved remission, 32% relapsed, with a negative impact on renal outcome, that is, lower eGFR values and higher proportion of CKD (33% vs 8%).ConclusionEarly remission should be achieved to better preserve long-term renal function.

Volume of Crescents Affects Prognosis of IgA Nephropathy in Patients without Obvious Chronic Renal Pathology

2021 ◽  
pp. 1-12
Author(s):  
Zaoqiang Lin ◽  
Lichang Liu ◽  
Rongling Zhang ◽  
Xuefei Lin ◽  
Fuhua Lu ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Kidney Tissue ◽  
Treatment Modalities ◽  
Renal Outcome ◽  
Renal Lesions ◽  
Increased Risk ◽  
Lower Egfr ◽  
The Oxford Classification ◽  
Renal Prognosis

<b><i>Introduction:</i></b> A working group on the Oxford classification of IgA nephropathy (IgAN) recently reported that crescents detected in the kidney tissue predicted a worse renal outcome. However, the effect of C1 lesion (crescents in &#x3c;1/4th of all glomeruli) and their volume on the prognosis of IgAN is still unclear. We explored the association of C1 lesion with the renal prognosis in IgAN patients without obvious chronic renal lesions (glomerulosclerosis &#x3c;25%, T score &#x3c;2). <b><i>Methods:</i></b> We investigated 305 biopsy-proven IgAN patients without obvious chronic renal lesions. Clinicopathologic features and treatment modalities were recorded. The patients were divided into several groups according to the presence or absence of a global crescent: no crescent (NC) group, only segmental crescent (SC) group, and global crescent (GC) group. The outcome was the survival from a combined event defined by a ≥15% decline in the estimated glomerular filtration rate (eGFR) after 1 year or ≥30% decline in the eGFR after 2 years. <b><i>Results:</i></b> Among all patients, 75.7% were in the NC group, 14.8% were in the SC group, and 9.5% were in the GC group. Compared with the NC group, patients in the SC group and the GC group had more urine protein, lower eGFR, and presented with more severe pathological change. During a median follow-up of 34.8 (26.16–57.95) months, the combined event occurred in 34 individuals (11.1%). In a multivariate model, the GC group (HR = 2.756, 95% CI = 1.068–7.109) was associated with an increased risk of the combined event. <b><i>Conclusions:</i></b> In IgAN patients without obvious chronic renal lesions, the GC group had more severe clinical and pathological manifestations than in the NC group. GC is an independent risk factor for the progression of IgAN renal function.

MO960RENAL TRANSPLANTATION FROM A LIVING DONOR WITH RENAL ARTERY FIBROMUSCULAR DYSPLASIA

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Eva Paraskevi Andronikidi ◽  
Glykeria Tsouka ◽  
Myrto Giannopoulou ◽  
Konstantinos Botsakis ◽  
Xanthi Benia ◽  
...  
Keyword(s):  
Renal Disease ◽  
Serum Creatinine ◽  
Renal Artery ◽  
Left Renal Artery ◽  
Close Monitoring ◽  
History Of ◽  
The Right ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims Renal transplantation is considered the most effective and less costly modality of renal replacement therapy in patients with end stage renal disease. The disparity between kidney allografts and recipients has led to a global effort to increase the pool of kidney donors. Accordingly, fibromuscular dysplasia (FMD) is no longer considered an absolute contraindication for kidney donation. The incidence of FMD is about 2.3%-5.8% in potential kidney donors. There are few cases in the literature where renal artery stenosis in allografts with known pre-transplantation FMD became worse after transplantation, indicating the importance of a proper follow up in the recipients. This is a case of a living kidney donor with no history of hypertension, proteinuria or elevated serum creatinine, whose intra-arterial digital subtraction angiography revealed FMD lesions in the left renal artery. Method Case report Results A 54-year-old Caucasian female with medical history of hypothyroidism took the decision to offer her kidney to her 37-year-old son who was diagnosed with end-stage renal disease five years ago secondary to diabetes mellitus type I. She had no history for diabetes, hypertension and renal disease. Her vital signs on admission were heart rate of 78 beats/min and blood pressure of 130/70 mmHg. Urinalysis, biochemical profile and serological evaluations were all within normal ranges. Blood urea was 36 mg/dL and serum creatinine was 0.6 mg/dL (eGFR 97ml/min/1.73m2). The abdominal ultrasound and renogram with Tc-99m DTPA showed no remarkable findings. On intra-arterial digital subtraction angiography an abnormal succession of dilatations and multifocal stenoses of the left renal artery, characteristic of medial FMD, was found. The right renal artery was normal. Apart from a dysfunctional permanent left femoral catheter, the patient had no other vascular access for hemodialysis because of Superior Vena Cava syndrome, so he needed urgent transplantation. Taking all of these into consideration, the patient was offered renal transplantation as the best option. A left open donor nephrectomy was performed; the renal artery was divided distal to the stenotic dysplastic area. The allograft was placed at the right iliac fossa of the recipient with arterial and venous anastomosis to the extrarenal iliac vessels. Post-operatively, the recipient had a delayed graft function lasted 13 days. On renal artery Doppler in the allograft we found increased resistance index (RI) that gradually normalized without any intervention. An immunosuppressive regiment of tacrolimus, mycophenolate and prednisone was administered according to our center protocol. At discharge serum creatinine was 1.7 mg/dL (eGFR: 50ml/min/1.73m2). At the year follow-up, the donor was normotensive and had near normal renal function (Cr:1.3mg/dL, eGFR: 70ml/min/1.73m2). The recipient has a well-controlled blood pressure receiving two antihypertensive drugs and maintains a satisfactory renal function. Conclusion Few cases with FMD in renal allografts from living and deceased donors have been described. In a review of 4 studies the authors concluded that the outcome of transplantation with allografts from living donors with medial FMD was satisfactory and these allografts could be used to increase the donor pool. Furthermore, it is strongly recommended to have a thorough pre-transplantation check of the donor as well as a close monitoring of both the donor and recipient after transplantation. This case shows that allografts harvested from carefully selected donors with renal arterial FMD can be successfully used, particularly in urgent conditions. Detailed pre-tranplantation imaging of donor’s renal arteries, selection of the appropriate screening method, as well as close monitoring of both donor and recipient for early interventions after transplantation is of paramount importance.

scholarly journals Proteinuria and serum creatinine after 12 months of treatment for lupus nephritis as predictors of long-term renal outcome: a case–control study

2022 ◽  
Vol 62 (1) ◽  
Author(s):  
Fernanda Nogueira Holanda Ferreira Braga ◽  
Marta Maria das Chagas Medeiros ◽  
Antonio Brazil Viana Junior ◽  
Matheus Eugênio de Sousa Lima ◽  
Levi Coelho Maia Barros ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Disease ◽  
Serum Creatinine ◽  
Roc Curve ◽  
End Stage Renal Disease ◽  
Renal Outcome ◽  
Renal Outcomes ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Lupus nephritis (LN) is a major source of morbidity and mortality in patients with systemic lupus erythematosus (SLE), with 10–25% of patients progressing to end-stage renal disease (ESRD). Objective This study aims to elucidate the predictive capabilities of 24-h proteinuria (24PTU) and serum creatinine (sCr) after 12 months of treatment with respect to long-term renal outcomes in LN in a single-center cohort of LN patients. Methods A retrospective analysis was performed on 214 patients diagnosed with LN followed in our center. Values of 24PTU and sCr were assessed at baseline and after 3, 6 and 12 months, and after 5 years and/or the last evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 for 3 months or longer. End-stage renal disease (ESRD) was defined as the need for permanent dialysis. Receiver operating characteristics curves (ROC) were used to test the best cut-off value of 24PTU and sCr at 12 months who predict bad long-term renal outcomes.  Results The mean follow-up period was 11.2 ± 7.2 years. The best cut-off values for 24PTU and sCr as predictor of CKD were, respectively, 0.9 g/24 h and 0.9 mg/dL. ROC curve for 24PTU had a slightly lower performance than ROC curve for sCr as predictor for CKD (PTU AUC = 0.68; sCr AUC = 0.70), but sensitivity and specificity were better for 24PTU (24PTU: sensitivity = 63.5%, specificity = 71.2%; sCr: sensitivity = 54.8%, specificity = 75.3%). When the outcome was ESRD the best cut-off points were 0.9 g/24hs and 1.3 mg/dL for 24PTU and sCr, respectively, and the curve performance was better for 24PTU (PTU AUC = 0.72; sCr AUC = 0.61). Conclusions In this ethnically diverse population with LN followed for a long time (> 10 years), levels of 24PTU > 0.9/day at 12 months was a good predictor of bad long-term renal outcome. The serum creatinine > 0.9 mg/dL and > 1.3 mg/dL at 12 months were also good predictors of CKD and ESRD, respectively. Patients with 24PTU < 0.9 g/day and sCr < 1.3 mg/dL at 12 months are not likely to develop ESRD because of the high negative predictive values (NPV) (93.2% and 82%). 24PTU and sCr are relevant as components for a treat-to-target strategy for LN treatment, since their high NPV corroborates their importance as good predictors of long-term renal outcome.

MO287REAL WORLD COMPARISON OF THE PREDICTIVE UTILITY OF INTERNATIONAL IGA RISK PREDICTION SCORE AND KIDNEY FAILURE RISK EQUATION IN IGA NEPHROPATHY PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sophia Mohammed ◽  
Rajkumar Chinnadurai ◽  
Arvind Ponnusamy
Keyword(s):  
Iga Nephropathy ◽  
Risk Prediction ◽  
Kidney Failure ◽  
Renal Outcome ◽  
Predictive Utility ◽  
Statistical Validation ◽  
Risk Equation ◽  
Failure Risk ◽  
Stage Renal Disease

Abstract Background and Aims IgA nephropathy is the most prevalent cause of glomerular disease worldwide. The international IgA risk prediction (IgAN) score is a well validated tool to predict the risk of 50% decline in eGFR or end stage renal disease (ESRD) at five years after biopsy in patients with IgA nephropathy. Also, the four variable kidney failure risk equation (KFRE) is another validated tool used to predict the two- and five-year risk of progression to ESRD of all cause chronic kidney disease (CKD 3-5). Our aim is to compare the predictive utility of IgAN score and the KFRE in a real-world cohort of Caucasian patients with long-term follow-up data. Method All available patients with biopsy-proven IgA nephropathy in our centre between January 2001 and December 2013 were included in this observational study. Baseline (biopsy date) data relevant to the scores including demographics, laboratory and the histopathological features were collated at the time of biopsy. Follow up data on renal functions and renal outcome (50% decline in eGFR or reaching ESRD) were collected until an arbitrary end date 31/12/2018. Results We had a total of 115 patients recorded over this 13-year period. The median age of our cohort at time of biopsy was 41 years. Men represented 71% of the cohort. At baseline 84% were hypertensive and 11% diabetic. 77% were on a renin-angiotensin blocker, with 53% being on a statin. Out of the 115 patients, 74 were eligible to undergo analysis. The percentage risk of reaching the endpoint (50% decline in eGFR or reaching ESRD) was calculated at 2 years and 5 years for all patients. These results can be seen in table 1 and 2. At 2 years, 7 patients had reached the endpoint: 2 patients had a &gt;50% decline in eGFR, 3 patients received RRT and 2 patients underwent transplantation. At 5 years, 14 patients had reached the endpoint: 3 patients had a &gt;50% decline in eGFR, 6 patients received RRT and 5 underwent transplantation. Conclusion Our data suggests that the KRFE tool underpredicts the risk of reaching endpoint, compared to the IgAN. Our study has helped to compare the two tools, but further statistical validation is required using a larger cohort.

scholarly journals Addition of eGFR and Age Improves the Prognostic Absolute Renal Risk-Model in 1,134 Norwegian Patients with IgA Nephropathy

2015 ◽  
Vol 41 (3) ◽  
pp. 210-219 ◽  
Author(s):  
Thomas Knoop ◽  
Ann Merethe Vågane ◽  
Bjørn Egil Vikse ◽  
Einar Svarstad ◽  
Bergrún Tinna Magnúsdóttir ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Prognostic Model ◽  
Risk Model ◽  
Area Under The Curve ◽  
Predicting Outcome ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage ◽  
French Cohort

Background: Predicting outcome in individual patients with IgA nephropathy (IgAN) is difficult but important. For this purpose, the absolute renal risk (ARR) model has been developed in a French cohort to calculate the risk of end-stage renal disease (ESRD) and death. ARR (0-3) is scored in individual IgAN patients based on the presence of proteinuria ≥1 g/24 h, hypertension, and severe histopathological lesions (1 point per risk factor). We have validated the ARR model in a Norwegian cohort of IgAN patients and tested whether adding data on initial estimated glomerular filtration rate (eGFR) and age improved prediction. Methods: IgAN patients diagnosed between 1988 and 2012 were identified in the Norwegian Kidney Biopsy Registry, and endpoints were identified by record linkage with the Norwegian Renal Registry (ESRD) and the Population Registry (deaths). Results: We identified 1,134 IgAN patients. The mean duration of follow-up was 10.2 years (range 0.0 to 25.7 years). Two hundred and fifty one patients developed ESRD and there were 69 pre-ESRD deaths. The ARR model significantly stratified the IgAN cohort according to risk of ESRD/death. The inclusion of eGFR and age significantly improved the ARR prognostic model; in the receiver operator characteristics (ROC) analysis, area under the curve (AUC) at 10-years of follow-up increased from 0.79 to 0.89, p < 0.001. Conclusions: ARR is a suitable prognostic model for stratifying IgAN patients according to the risk of ESRD or death. Including initial eGFR and age in the model substantially improved its accuracy in our nationwide cohort.

scholarly journals Proteinuria and Psoriasis Risk: A Nationwide Population-Based Study

2021 ◽  
Vol 10 (11) ◽  
pp. 2356
Author(s):  
Eun Hui Bae ◽  
Bongseong Kim ◽  
Su Hyun Song ◽  
Tae Ryom Oh ◽  
Sang Heon Suh ◽  
...  
Keyword(s):  
International Classification Of Diseases ◽  
Population Based ◽  
Renal Outcome ◽  
Persistent Proteinuria ◽  
Inflammatory Dermatosis ◽  
Classification Of Diseases ◽  
Icd 10 ◽  
Stage Renal Disease ◽  
End Stage

Psoriasis, a chronic inflammatory dermatosis, has been associated with chronic kidney disease or end-stage renal disease. However, the association of the changes or amount of proteinuria with psoriasis development has not been evaluated. Using the Korean National Health Screening database, we assessed psoriasis development until 2018 in 6,576,851 Koreans who underwent health examinations in 2009 and 2011. Psoriasis was defined using the International Classification of Diseases, 10th revision (ICD-10) code L40. The risk of psoriasis was evaluated according to change in proteinuria (never [Neg (no proteinuria)/Neg], new [Neg/Pos (proteinuria present)], past [Pos/Neg] and persistent [Pos/Pos] proteinuria) and the proteinuria amount. During a median 7.23-year follow-up, 162,468 (2.47%) individuals developed psoriasis. After adjustments, the hazard ratio (HR) for psoriasis was higher in the persistent proteinuria group (1.32 [1.24–1.40]) than in the never proteinuria group. The past proteinuria group showed better renal outcome (1.03 [1.00–1.07]) than the new (1.05 [1.01–1.07]) and never proteinuria (reference, 1.00) groups did. The amount of random urine proteinuria was associated with increased HR for psoriasis. Subgroup analyses for age, sex, estimated glomerular filtration rate (eGFR), hypertension and diabetes showed that the persistent proteinuria group had a higher risk of psoriasis than the never proteinuria group, especially at eGFR < 60 mL/min/1.73 m2. Persistent proteinuria is associated with psoriasis risk, and the proteinuria amount significantly affects psoriasis development.

Nierenbeteiligung bei Spondylarthritiden: Spezifisch oder unabhängig?

2021 ◽  
pp. 1-3
Author(s):  
Sibylle von Vietinghoff
Keyword(s):  
Renin Angiotensin System ◽  
Renal Outcome ◽  
Frequent Use ◽  
Tnf Α ◽  
Ckd Stage ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage ◽  
Egfr Decline

<b>Introduction:</b> IgA nephropathy (IgAN) can be associated with spondyloarthritis (SpA). The course of SpA-associated IgAN remains largely unknown due to the absence of large cohorts. <b>Methods:</b> This retrospective study included patients with biopsy-proven IgAN and definite SpA. Kidney biopsies were centrally examined and scored according to the IgAN Oxford Classification. Thirty-two patients fulfilled the inclusion criteria, with a male:female ratio of 9:1 and median age of 27 and 37 years at SpA and IgAN diagnosis, respectively. HLA-B27 was positive in 90% of cases, and most patients (60%) presented with ankylosing spondylitis. The mean baseline estimated glomerular filtration rate (eGFR) was 84 ± 26 ml/min per 1.73 m<sup>2</sup>, and the urine protein-to-creatinine ratio was 0.19 g/mmol. <b>Results:</b> Renal biopsy revealed frequent presence of crescents (33%) and interstitial inflammation (18%). Despite almost constant use of renin-angiotensin system inhibitors, combined with steroids in 13 of 32 patients, renal outcome was particularly poor. After a median follow-up of 5.9 years, 4 patients (12.5%) reached end-stage renal disease and 41% of patients experienced a &#x3e;50% decrease of eGFR. The mean annual eGFR decline rate was –4.3 ± 6.7 ml/min per 1.73 m<sup>2</sup>. The risk of reaching class IV or V chronic kidney disease (CKD) stage during follow-up was associated with the presence of hypertension, level of proteinuria, and baseline S- and T-scores of the Oxford. <b>Conclusion:</b> SpA-associated IgAN is associated with a poor renal outcome, despite frequent use of steroids. Tumor necrosis factor (TNF)-α blockade did not appear to influence the rate of eGFR decline in this setting.

P0228THE NEFIGARD TRIAL: THE EFFECT OF NEFECON® (BUDESONIDE) IN PATIENTS WITH PRIMARY IGA NEPHROPATHY AT RISK OF DEVELOPING END-STAGE RENAL DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jonathan Barratt ◽  
Andrew Stone ◽  
Jens Kristensen
Keyword(s):  
Placebo Group ◽  
Renal Disease ◽  
Iga Nephropathy ◽  
End Stage Renal Disease ◽  
Primary Outcome ◽  
Stage Renal Disease ◽  
End Stage ◽  
Full Approval

Abstract Background and Aims Since the first description of IgA nephropathy (IgAN) over 50 years ago, it has been recognised that the mucosal immune system plays a crucial role in the pathogenesis of this common global cause of kidney failure. Recently, particular attention has focussed on the importance of the gut-associated lymphoid tissue (GALT) as the potential source of the poorly O-galactosylated IgA1 that triggers the formation of nephritogenic immune complexes in IgAN. Pathway analysis based on a large meta-analysis of genome wide association studies identified the intestinal immune network for IgA production as the most enriched KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway in IgAN. Furthermore, separate studies have shown that the IgA in glomerular IgA deposits is indistinguishable from mucosal IgA. The therapeutic potential of selectively targeting GALT was demonstrated in the NEFIGAN trial (NCT01738035), which assessed the safety and efficacy of a novel targeted-release formulation of budesonide (NEFECON®), designed to deliver budesonide to the GALT-rich distal ileum in patients with IgAN. After 9 months’ treatment, urine protein–creatinine ratio (UPCR) was reduced by 29.3% in the NEFECON® 16 mg group compared with the placebo group. Estimated glomerular filtration rate (eGFR) dropped 4.7 ml/min/1.73 m2 in the placebo group with no deterioration seen in the NEFECON® 16 mg group. Incidence of patients reporting adverse events was similar in all groups. These data led to the design of the NefIgArd study which aims to assess the efficacy, safety, and tolerability of NEFECON® 16 mg in patients with IgAN at risk of end-stage renal disease. Method The NefIgArd study is a randomised, double-blind, placebo-controlled Phase 3 trial, with two parts – PART A a 15–35-day screening period, 9-month treatment and 3-month follow-up period; and PART B a 12-month no-treatment follow-up period (Figure). The study is recruiting across 146 nephrology clinics in 19 countries. Patients must be at least 18 years old with biopsy-confirmed primary IgAN and persistent proteinuria &gt;1 g/24 h and eGFR between 35 and 90 ml/min per 1.73 m2 (CKD-EPI) despite optimised renin–angiotensin system blockade. Patients are randomised on a 1:1 ratio to NEFECON® 16 mg/day or placebo. Consistent with the Kidney Health Initiative White Paper “Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy” published in early 2019, the primary outcome of Part A is to assess the effect of NEFECON® 16 mg on 24 h UPCR at 9 months compared with placebo. The Part B primary outcome is based on data presented at the NKF/FDA/EMA workshop in March 2018 that supported eGFR slope as an endpoint for full approval and will assess the effect of NEFECON® 16 mg on a 2-year eGFR-based endpoint compared with placebo. In comparison with other studies that are recruiting, we believe that the relatively short period required to provide validation of the surrogacy of proteinuria reduction will significantly reduce the risks of non-protocol treatments and loss of patients from the study that could dilute the true treatment effect of NEFECON®. Results As of 1 January 2020, 207 patients have been randomised, and Part A is expected to complete in Q4 2020, with Part B completing in 2022. To ensure the NefIgArd study results are fully translatable to the global IgAN population, NefIgArd will also open in China in 2020. Conclusion The NefIgArd study builds on the experience of the NEFIGAN trial, the largest commercially sponsored study ever completed in IgAN. The design of the NefIgArd study has used state-of-the-art data to evaluate kidney outcomes, using proteinuria as a reasonably likely surrogate of the effect of NEFECON® on long-term kidney outcomes and confirming long-term renoprotection using an NKF/FDA/EMA-suggested eGFR-based endpoint as a basis for full approval.

IgA Nephropathy Recurrence after Kidney Transplantation: Role of Recipient Age and Human Leukocyte Antigen-B Mismatch

2020 ◽  
Vol 51 (5) ◽  
pp. 357-365
Author(s):  
Lida M. Rodas ◽  
Estibaliz Ruiz-Ortiz ◽  
Adriana Garcia-Herrera ◽  
Arturo Pereira ◽  
Miquel Blasco ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Iga Nephropathy ◽  
Protective Factor ◽  
Human Leukocyte ◽  
Clinical Indication ◽  
Renal Outcome ◽  
Leukocyte Antigen ◽  
Risk Of Progression ◽  
Stage Renal Disease ◽  
End Stage

Background: Recurrence of immunoglobulin (Ig)A nephropathy (rIgAN) is a growing cause of kidney allograft dysfunction. This study was aimed at investigating factors associated with rIgAN and the subsequent progression to end-stage renal disease (ESRD). Methods: Retrospective study including consecutive patients with IgA nephropathy (IgAN) who received a kidney transplant in our center between 1992 and 2016 and had a renal biopsy by clinical indication. The date of detection of chronic kidney disease (CKD) 5 was used as renal outcome. Results: Eighty-six kidney transplants were performed in patients with IgAN, 38 (44%) were from living donors (related n = 26). rIgAN was diagnosed in 23 allografts (27%). Renal function and proteinuria at the end of the follow-up period were worst in the rIgAN patients compared to those without rIgAN (2.2 vs. 1.4 mg/dL, p = 0.014, and 1.16 vs. 0.49 g/day, p = 0.005, respectively). Risk of rIgAN and progression to CKD 5 decreased with patient’s age (hazard ratio [HR] 0.95, 95% CI 0.92–0.98, p = 0.002, and HR 0.97, 95% CI 0.83–0.97, p = 0.008 per year, respectively). Patients with rIgAN had a higher risk of progression to CKD 5 (HR 6.7, 95% CI 1.3–35.7, p = 0.025). Full donor-recipient mismatch in the human leukocyte antigen (HLA)-B loci decreased the risk of rIgAN (HR 0.22, 95% CI 0.06–0.76, p = 0.017). Conclusions: rIgAN was an independent risk factor for ESRD after renal allograft. Younger age increased the risk of rIgAN and CKD 5. Conversely, HLA-B mismatching was a potential protective factor for rIgAN of this glomerular disease.

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