International IgA Nephropathy Research Articles

Using prediction models to improve care and communicate risk: updated modeling for children with IgA nephropathy

Clinical risk prediction models are being generated at an increasing rate. One important component is the identification of groups for whom such models might require recalibration to retain their desired performance. To this end, an update of the postbiopsy International IgA Nephropathy Prediction Tool for children has been published in this issue of Kidney International. We review the methods used and generalizability in practice, along with broader concepts in model development and application.

Conventional machine learning-based prediction models did not outperform the International IgA Nephropathy Prediction Tool.

Immunoglobulin A nephropathy (IgAN) is a major cause of end-stage kidney disease (ESKD). The International IgA Nephropathy Prediction Tool (IIgAN-PT) predicts IgAN prognosis, but improvement in the prediction performance using machine learning (ML)-based methods is needed. We analyzed 4,425 biopsy-confirmed patients with IgAN and ≥6 months of follow-up from nine tertiary university hospitals in Korea. The study population was divided into development and validation cohorts. Using the collected 87 clinicodemographic and pathological variables, ML-based prediction models for ESKD or estimated glomerular filtration rate were constructed: 1) the conventional CatBoost model, 2) the optimized CatBoost model with Cox proportional hazards, 3) the deep Cox proportional hazards model, and 4) the deep Cox mixture model. The area under the curve (AUC) and calibration plots were used to investigate the discriminative and calibration performance of the models, which were then compared with those of the IIgAN-PT full model. The full model showed excellent performance (AUC [95% confidence interval] for 5-year outcome, 0.896 [0.8530.940]), with acceptable calibration results. The ML-based models showed good performance in predicting adverse kidney outcomes and revealed acceptable discrimination performance in the external validation (AUC [95% confidence interval] for the 5-year outcome: 1) 0.829 [0.791-0.866]; 2) 0.847 [0.804-0.890]; 3) 0.823 [0.784-0.862]; and 4) 0.832 [0.794-0.870]), although they underestimated the external validation cohort risks. With the validation data, the overall performance of the IIgAN-PT was non-inferior to that of the ML-based model. Conclusions: Our ML-based models showed good performance in predicting adverse kidney outcomes in patients with IgAN but they did not outperform the IIgAN-PT.

Post-conference review of oral session 6 and short talk in the 17th international IgA nephropathy conference, Tokyo 2023.

Oral session 6 titled 'Clinical Trial 1' and the short talk on 'Landscape of Clinical Trials in IgAN-What's beyond the Horizon?' took place on 30 September 2023 in the symposium venue. The short talk highlighted the increase in IgAN trials in the last decade and the challenges of global clinical trials from the site investigator perspective. The talk also underlined the importance of relooking and repurposing already available and approved therapeutics. There were six oral sessions that focussed mainly on the interim results of ongoing clinical trials as well as early phase results with new investigational agents.

Application of the updated International IgA Nephropathy Prediction Tool in children one or two years post-biopsy

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one-year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R2D (51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two-years after biopsy. Trajectories of eGFR after a baseline one-year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to revaluate risk one- or two-years after biopsy.

#177 Assessment and comparison of physician gaps related to clinical knowledge of IgA nephropathy

Abstract Background and Aims Understanding physician gaps related to IgA nephropathy (IgAN) can inform development of tools to improve physician knowledge and competence related to both diagnosis and treatment. Additionally, comparisons among specialists (nephrologists) and generalists (primary care physicians, PCPs) can segment educational needs for combined or customized education to close identified gaps. Method A survey instrument of 25 multiple choice, knowledge- and case-based questions allowed participants to assess their clinical knowledge related to IgAN. The survey was available online to physicians without monetary compensation or charge. Respondent confidentiality was maintained and responses were de-identified and aggregated prior to analyses. Initial data collection occurred from March 16, 2023 to May 19, 2023. Results In total, 98 nephrologists and 57 PCPs completed the full assessment within the data collection period. Conclusion This assessment of physicians’ clinical knowledge yielded important insights into gaps related to IgAN. Both nephrologists and PCPs need education on pathophysiology of IgAN and emerging treatment pathways, role of proteinuria and risk correlations to ESRD with IgAN, clinical use of the International IgAN Prediction Tool, and KDIGO recommendations for managing IgAN. PCPs need additional education on basic IgAN prevalence as well as clinical strategies for diagnosis. Further studies are planned to assess the effect of medical education on decreasing these clinical practice gaps.

#1063 Presentation, treatment, and outcome of IgA nephropathy in children: comprehensive characterization of a Croatian single centre cohort

Abstract Background and Aims IgA nephropathy (IgAN) is a complex disease diagnosed only upon evaluation of a kidney biopsy. Since the threshold to perform this invasive procedure is higher and symptoms usually more indolent in children, the true prevalence might be underestimated, with fewer studies examining the presentation, treatment, and outcome of IgAN in paediatric population. Moreover, there is a substantial heterogeneity of clinical presentation and pathological features between geographical locations, with fewer data available for region of central and southern Europe. We therefore aim to provide a conscientious description of a paediatric IgAN cohort followed for an extended period of time in a centre caring for most of the Croatian paediatric patients. Method Single centre retrospective study of children newly diagnosed as IgAN since 2011 and followed for >2 years in a tertiary referral centre for paediatric nephrology of the Republic of Croatia. Results Total of 15 paediatric (<18 years) patients were included, of which 11 (73%) were male, 14 Caucasians and 1 of Roma origin. All the patients had proteinuria (>150 mg/day) and hematuria (>5 RBC/mm3 in uncentrifuged urine) at the time of the biopsy, with the mean age of 12.2 ± 3.6 years. The median eGFR was 87 (69 – 111) mL/min/1.73m2 and the median value of proteinuria 260 (150 – 370) mg/day. More specifically, 2 patients had mild proteinuria (<20 mg/kg/day), 12 had moderate (20 – 50 mg/kg/day) and 1 had nephrotic range (>50 mg/kg/day). The results of biopsy in terms of MEST-C score showed M1 in 4, E1 in none, S1 in 3, T1 in 4, T2 in 0, C1 in 2 and C2 in none of the patients. The IF was positive for IgA and C3 in all patients, and in 1 for C1q. There was no significant correlation between C3 intensity values (0-4+) and 24 h proteinuria (r = 0.49, p = 0.06) or eGFR (r = −0.22, p = 0.43). Hypertension (≥95 percentile for age) was present in 2 (13%) patients. The median risk of a 30% decline in eGFR or progression to end-stage renal disease 5 years after renal biopsy calculated by International IgAN prediction tool for use in paediatric patents was 8.03% (4.58 – 11.27). Initial presenting episode was treated with ACEi in 7 (47%) and with glucocorticoids in 4 (27%) patients. There was no significant difference in proteinuria (p = 0.19) or risk of decline in eGFR or progression to ESRD (p = 0.16) among treated and untreated patients. In all of the treated patients proteinuria reached a target of <20 mg/kg during the median time of 11 (6 – 21) months. The median follow up was 6.5 (2.8 – 11.1) years. During the follow up 5 patients experienced first relapse of proteinuria, 3 had second and none had third relapse. None of the patients had adverse event related to medications. None were treated with renal replacement therapy or other immunomodulatory drugs. Tonsillectomy was performed in two patients with a substantial improvement of haematuria episodes reported by caregivers. Omega-3 polyunsaturated fatty acid was used in 1 patient. While none of the patients developed CKD during the follow up, none have reached complete renal remission defined as eGFR >90 ml/min/1.73m2, proteinuria <150 mg/day and RBC < 5/mm3 in urinalysis. Conclusion All the patients in our cohort had indolent disease with proteinuria, along with low risk of decline in eGFR or progression to ESRD after biopsy. Almost half of them were treated with ACEi, and a quarter with glucocorticoids, all with beneficial response. Nevertheless, none of the patients in the cohort achieved full renal remission due to the persistent hematuria. While there are few well performed studies on the treatment of IgAN in adult patients, to date, there are no high-quality randomised studies on immunosuppressing and other drugs, as well as nutritional and other interventions in children with IgAN, prompting a case-to-case decision regarding the use of various therapeutic modalities. Therefore, well characterized cohorts from around the globe might provide further reassurance for physicians taking care of children with this intricating disease, support when deciding to commence the intervention and inform while selecting the most appropriate form.

External Validation of the International IgA Nephropathy Prediction Tool in Older Adult Patients.

The International IgA Nephropathy Prediction Tool (IIgAN-PT) can predict the risk of End-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥ 50% for adult IgAN patients. Considering the differential progression between older adult and adult patients, this study aims to externally validate its performance in the older adult cohort. We analyzed 165 IgAN patients aged 60 and above from six medical centers, categorizing them by their predicted risk. The primary outcome was a ≥50% reduction in estimated glomerular filtration rate (eGFR) or kidney failure. Evaluation of both models involved concordance statistics (C-statistics), time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier survival curves, and calibration plots. Comparative reclassification was conducted using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). The study included 165 Chinese patients (median age 64, 60% male), with a median follow-up of 5.1 years. Of these, 21% reached the primary outcome. Both models with or without race demonstrated good discrimination (C-statistics 0.788 and 0.790, respectively). Survival curves for risk groups were well-separated. The full model without race more accurately predicted 5-year risks, whereas the full model with race tended to overestimate risks after 3 years. No significant reclassification improvement was noted in the full model without race (NRI 0.09, 95% CI: -0.27 to 0.34; IDI 0.003, 95% CI: -0.009 to 0.019). : Both models exhibited excellent discrimination among older adult IgAN patients. The full model without race demonstrated superior calibration in predicting the 5-year risk.

External Validation of the International Prognosis Prediction Model of IgA Nephropathy

Background The International IgA Nephropathy (IgAN) Network developed and validated two prognostic prediction models for IgAN, one incorporating a race parameter. These models could anticipate the risk of a 50% reduction in estimated glomerular filtration rate (eGFR) or progression to end-stage renal disease (ESRD) subsequent to an IgAN diagnosis via renal biopsy. This investigation aimed to validate the International IgA Nephropathy Prediction Tool (IIgANPT) within a contemporary Chinese cohort. Methods Within this study,185 patients diagnosed with IgAN via renal biopsy at the Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, between January 2012 and December 2021, were encompassed. Each patient’s risk of progression was assessed utilizing the IIgANPT formula. The primary outcome, a 50% decline in eGFR or progression to ESRD, was examined. Two predictive models, one inclusive and the other exclusive of a race parameter, underwent evaluation via receiver-operating characteristic (ROC) curves, subgroup survival analyses, calibration plots, and decision curve analyses. Results The median follow-up duration within our cohort spanned 5.1 years, during which 18 patients encountered the primary outcome. The subgroup survival curves exhibited distinct separations, and the comparison of clinical and histological characteristics among the risk subgroups revealed significant differences. Both models demonstrated outstanding discrimination, evidenced by the areas under the ROC curve at five years: 0.882 and 0.878. Whether incorporating the race parameter or not, both prediction models exhibited acceptable calibration. Decision curve analysis affirmed the favorable clinical utility of both models. Conclusions Both prognostic risk evaluation models for IgAN exhibited remarkable discrimination, sound calibration, and acceptable clinical utility.

Impact of Kidney Biopsy Findings Including Oxford MEST-C Scores on Kidney Outcomes in IgA Vasculitis Nephritis (IgAVN): A Study of the International IgA Nephropathy Network

Impact of Kidney Biopsy Findings Including Oxford MEST-C Scores on Kidney Outcomes in IgA Vasculitis Nephritis (IgAVN): A Study of the International IgA Nephropathy Network

External validation of the pediatric International IgA Nephropathy Prediction Tool in a central China cohort.

This study aimed to externally validate the pediatric International IgA Nephropathy (IgAN) Prediction Tool updated from the adult IgAN Prediction Tool. 439 children with biopsy-confirmed idiopathic IgAN were enrolled in this external validation study. The primary outcome was a 30% decline in eGFR or end-stage kidney disease. We evaluated the discrimination using Harrell's C-index, the receiver operating characteristic (ROC) curve, and Kaplan-Meier curves for four risk groups (< 16th [low risk], ∼16 to < 50th [intermediate risk], ∼50 to < 84th [high risk], and ≥ 84th percentiles [highest risk] of linear predictor). Calibration was assessed using calibration plots. The median follow-up time of the 439 patients was 4.5 (2.7-6.8) years, and 27 patients reached the primary outcome. Compared with the reported cohorts, our cohort was more contemporary, with milder proteinuria at biopsy, and had lower proportions of S1 and T1 lesions. Harrell's C-index and area under the ROC curve at 5years were < 0.7 for both the models with and without race. The Kaplan-Meier curves of the risk groups were not well separated for the two models, only separated completely between the highest-risk group and the others for the model without race. The two models generally overestimated the risk of the primary outcome, CONCLUSION: The model without race could accurately distinguish the highest-risk patients from patients with low, intermediate, and high risk for kidney progression. Discrimination and calibration for the full model with or without race were unsatisfactory in this contemporary cohort in central China.

Validation of the children international IgA nephropathy prediction tool based on data in Southwest China.

Immunoglobulin A nephropathy (IgAN) is one of the most common kidney diseases leading to renal injury. Of pediatric cases, 25%-30% progress into end-stage kidney disease (ESKD) in 20-25 years. Therefore, predicting and intervening in IgAN at an early stage is crucial. The purpose of this study was to validate the availability of an international predictive tool for childhood IgAN in a cohort of children with IgAN treated at a regional medical centre. An external validation cohort of children with IgAN from medical centers in Southwest China was formed to validate the predictive performance of the two full models with and without race differences by comparing four measures: area under the curve (AUC), the regression coefficient of linear prediction (PI), survival analysis curves for different risk groups, and R2D. A total of 210 Chinese children, including 129 males, with an overall mean age of 9.43 ± 2.71 years, were incorporated from this regional medical center. In total, 11.43% (24/210) of patients achieved an outcome with a GFR decrease of more than 30% or reached ESKD. The AUC of the full model with race was 0.685 (95% CI: 0.570-0.800) and the AUC of the full model without race was 0.640 (95% CI: 0.517-0.764). The PI of the full model with race and without race was 0.816 (SE = 0.006, P < 0.001) and 0.751 (SE = 0.005, P < 0.001), respectively. The results of the survival curve analysis suggested the two models could not well distinguish between the low-risk and high-risk groups (P = 0.359 and P = 0.452), respectively, no matter the race difference. The evaluation of model fit for the full model with race was 66.5% and without race was 56.2%. The international IgAN prediction tool has risk factors chosen based on adult data, and the validation cohort did not fully align with the derivation cohort in terms of demographic characteristics, clinical baseline levels, and pathological presentation, so the tool may not be highly applicable to children. We need to build IgAN prediction models that are more applicable to Chinese children based on their particular data.

Validation of the international IgA nephropathy prediction tool in a French cohort beyond 10 years after diagnosis.

The International IgA Nephropathy Network developed a tool (IINN-PT) for predicting the risk of end-stage renal disease (ESRD) or a 50% decline in the estimated glomerular filtration rate (eGFR). We aimed to validate this tool in a French cohort with longer follow-up than previously published validation studies. The predicted survival of patients with biopsy-proven immunoglobulin A nephropathy (IgAN) from the Saint Etienne University Hospital cohort was computed with IINN-PT models with or without ethnicity. The primary outcome was the occurrence of either ESRD or a 50% decline in eGFR. The models' performances were evaluated through c-statistics, discrimination and calibration analysis. There were 473 patients with biopsy-proven IgAN, with a median follow-up of 12.4 years. Models with and without ethnicity showed areas under the curve (95% confidence interval) of 0.817 (0.765; 0.869) and 0.833 (0.791; 0.875) and R2D of 0.28 and 0.29, respectively, and an excellent discrimination of groups of increasing predicted risk (P<.001). The calibration analysis was good for both models up to 15 years after diagnosis. The model without ethnicity exhibited a mathematical issue of survival function after 15 years. The IINN-PT provided good performances even after 10 years post-biopsy as showed by our study based on a cohort with a longer follow-up than previous cohorts (12.4 versus <6 years). The model without ethnicity exhibited better performances up to 15 years but became aberrant beyond this point due to a mathematical issue affecting the survival function. Our study sheds light on the usefulness of integrating ethnicity as a covariable for prediction of IgAN course.

External Validation of the International IGA Nephropathy Prediction Tool Among a Filipino Cohort of Patients

External Validation of the International IGA Nephropathy Prediction Tool Among a Filipino Cohort of Patients

Automated Prediction of Kidney Failure in IgA Nephropathy with Deep Learning from Biopsy Images.

Digital pathology and artificial intelligence offer new opportunities for automatic histologic scoring. We applied a deep learning approach to IgA nephropathy biopsy images to develop an automatic histologic prognostic score, assessed against ground truth (kidney failure) among patients with IgA nephropathy who were treated over 39 years. We assessed noninferiority in comparison with the histologic component of currently validated predictive tools. We correlated additional histologic features with our deep learning predictive score to identify potential additional predictive features. Training for deep learning was performed with randomly selected, digitalized, cortical Periodic acid-Schiff-stained sections images (363 kidney biopsy specimens) to develop our deep learning predictive score. We estimated noninferiority using the area under the receiver operating characteristic curve (AUC) in a randomly selected group (95 biopsy specimens) against the gold standard Oxford classification (MEST-C) scores used by the International IgA Nephropathy Prediction Tool and the clinical decision supporting system for estimating the risk of kidney failure in IgA nephropathy. We assessed additional potential predictive histologic features against a subset (20 kidney biopsy specimens) with the strongest and weakest deep learning predictive scores. We enrolled 442 patients; the 10-year kidney survival was 78%, and the study median follow-up was 6.7 years. Manual MEST-C showed no prognostic relationship for the endocapillary parameter only. The deep learning predictive score was not inferior to MEST-C applied using the International IgA Nephropathy Prediction Tool and the clinical decision supporting system (AUC of 0.84 versus 0.77 and 0.74, respectively) and confirmed a good correlation with the tubolointerstitial score (r=0.41, P<0.01). We observed no correlations between the deep learning prognostic score and the mesangial, endocapillary, segmental sclerosis, and crescent parameters. Additional potential predictive histopathologic features incorporated by the deep learning predictive score included (1) inflammation within areas of interstitial fibrosis and tubular atrophy and (2) hyaline casts. The deep learning approach was noninferior to manual histopathologic reporting and considered prognostic features not currently included in MEST-C assessment. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_26_CJN01760222.mp3.

Long-Term Outcomes of Patients with IgA Nephropathy Categorized by the International IgAN Risk Prediction Tool and by the Degree of Hematuria at Diagnosis

Introduction: Within 30 years, 20–50% of IgA nephropathy (IgAN) patients progress to end-stage kidney disease (ESKD). Identifying these patients can be difficult since renal function may deteriorate after being stable for years. The International IgAN Risk Prediction tool (IgAN-RPT) combines histologic lesions and clinical risk factors to predict renal outcome up to 5 or 7 years of follow-up. The clinical value beyond 7 years is unknown and microhematuria data has not been assessed. Methods: We studied the long-term renal outcome of 95 Swedish IgAN patients from the derivation cohort for the IgAN-RPT. The median follow-up was 11.2 years. Microhematuria at baseline was defined as high-degree by microscopy measurement of >10 red blood cell/high-power field of view or urine dipstick grading of 2–3. Primary outcome was defined as a 50% decrease in estimated glomerular filtration rate or ESKD. Results: The mean predicted 5-year risk for increasing quartiles was 0.95%, 2.57%, 5.88%, and 23.31% and the observed 5-year-outcome was 0%, 0%, 0%, and 33.33%. During continued follow-up, 0%, 4.2%, 21.7%, and 75.0% of patients reached the primary outcome. ROC curve analysis identified the 5-year risk thresholds of under 4% and over 11% for very low and very high-risk patients, respectively. High-degree microhematuria was not significantly associated with renal outcome (p = 0.14). Conclusions: The IgAN-RPT identifies long-term high- and low-risk patients, which can guide decisions on the frequency of clinical control visits and the selection of patients for clinical trials. Patients with intermediate risk remain a clinical challenge with an urgent need for novel biomarkers and treatments. Microhematuria could be a valuable marker of inflammatory activity, but measurement needs to be standardized for implementation in risk prediction tools.

External validation of the international prediction tool in Korean patients with immunoglobulin A nephropathy.

BackgroundThe International IgA Nephropathy Prediction Tool (International IgA Nephropathy Prediction Tool) has been recently developed to estimate the progression risk of immunoglobulin A nephropathy (IgAN). This study aimed to evaluate the clinical performance of this prediction tool in a large IgAN cohort in Korea.MethodsThe study cohort was comprised of 2,064 patients with biopsy-proven IgAN from four medical centers between March 2012 and September 2021. We calculated the predicted risk for each patient. The primary outcome was occurrence of a 50% decline in estimated glomerular filtration rate (eGFR) from the time of biopsy or end-stage kidney disease. The model performance was evaluated for discrimination, calibration, and reclassification. We also constructed and tested an additional model with a new coefficient for the Korean race.ResultsDuring a median follow-up period of 3.8 years (interquartile range, 1.8–6.6 years), 363 patients developed the primary outcome. The two prediction models exhibited good discrimination power, with a C-statistic of 0.81. The two models generally underestimated the risk of the primary outcome, with lesser underestimation for the model with race. The model with race showed better performance in reclassification compared to the model without race (net reclassification index, 0.13). The updated model with the Korean coefficient showed good agreement between predicted risk and observed outcome.ConclusionIn Korean IgAN patients, International IgA Nephropathy Prediction Tool had good discrimination power but underestimated the risk of progression. The updated model with the Korean coefficient showed acceptable calibration and warrants external validation.

Application of the International IgA Nephropathy Prediction Tool one or two years post-biopsy

The International IgA Nephropathy (IgAN) Prediction Tool is the preferred method in the 2021 KDIGO guidelines to predict, at the time of kidney biopsy, the risk of a 50% drop in estimated glomerular filtration rate or kidney failure. However, it is not known if the Prediction Tool can be accurately applied after a period of observation post-biopsy. Using an international multi-ethnic derivation cohort of 2,507 adults with IgAN, we updated the Prediction Tool for use one year after biopsy, and externally validated this in a cohort of 722 adults. The original Prediction Tool applied at one-year without modification had a coefficient of variation (R2) of 55% and 54% and four-year concordance (C statistic) of 0.82 but poor calibration with under-prediction of risk (integrated calibration index (ICI) 1.54 and 2.11, with and without race, respectively). Our updated Prediction Tool had a better model fit with higher R2 (61% and 60%), significant increase in four-year C-statistic (0.87 and 0.86) and better four-year calibration with lower ICI (0.75 and 0.35). On external validation, the updated Prediction Tool had similar R2 (60% and 58%) and four-year C-statistics (both 0.85) compared to the derivation analysis, with excellent four-year calibration (ICI 0.62 and 0.56). This updated Prediction Tool had similar prediction performance when used two years after biopsy. Thus, the original Prediction Tool should be used only at the time of biopsy whereas our updated Prediction Tool can be used for risk stratification one or two years post-biopsy.

Validation of the International IgA Nephropathy Prediction Tool in the Greek Registry of IgA Nephropathy.

BackgroundImmunoglobulin A nephropathy (IgAN) is among the commonest glomerulonephritides in Greece and an important cause of end-stage kidney disease (ESKD) with an insidious chronic course. Thus, the recently published International IgAN prediction tool could potentially provide valuable risk stratification and guide the appropriate treatment module. This study aimed to externally validate this prediction tool using a patient cohort from the IgAN registry of the Greek Society of Nephrology.MethodsWe validated the predictive performance of the two full models (with or without race) derived from the International IgAN Prediction Tool study in the Greek Society of Nephrology registry of patients with IgAN using external validation of survival prediction models (Royston and Altman). The discrimination and calibration of the models were tested using the C-statistics and stratified analysis, coefficient of determination () for model fit, and the regression coefficient of the linear predictor (βPI), respectively.ResultsThe study included 264 patients with a median age of 39 (30–51) years where 65.2% are men. All patients were of Caucasian origin. The 5-year risk of the primary outcome (50% reduction in estimated glomerular filtration rate or ESKD) was 8%. The for the full models with and without race when applied to our cohort was 39 and 35%, respectively, and both were higher than the reported for the models applied to the original validation cohorts (26.3, 25.3, and 35.3%, respectively). Harrel's C statistic for the full model with race was 0.71, and for the model without race was 0.70. Renal survival curves in the subgroups (<16th, ~16 to <50th, ~50 to <84th, and >84th percentiles of linear predictor) showed adequate separation. However, the calibration proved not to be acceptable for both the models, and the risk probability was overestimated by the model.ConclusionsThe two full models with or without race were shown to accurately distinguish the highest and higher risk patients from patients with low and intermediate risk for disease progression in the Greek registry of IgAN.

International IgA Nephropathy Network (IIgANN) Risk Prediction and Longitudinal Outcomes in the First South-Asian Prospective IgA Nephropathy Cohort (GRACE-IgANI)

International IgA Nephropathy Network (IIgANN) Risk Prediction and Longitudinal Outcomes in the First South-Asian Prospective IgA Nephropathy Cohort (GRACE-IgANI)

A Pilot Study to Predict Risk of IgA Nephropathy Progression Based on miR-204 Expression

IntroductionImmunoglobulin (Ig)A nephropathy (IgAN) is the most frequently diagnosed primary glomerulonephritis worldwide. Despite the common diagnostic feature of mesangial IgA-containing immune complex deposition, the clinical course of the disease is extremely variable, with 30% of patients developing end-stage kidney disease within 20 years of diagnosis. Therefore, identifying which patients are likely to progress is paramount.ResultsIn this pilot study, we found that urinary exosomal miR-204 expression was significantly reduced in IgAN compared with healthy subjects. However, there was no difference in miR-204 expression between IgAN and non-IgAN chronic kidney disease controls. Analysis of miR-204 expression in kidney biopsy cores by next-generation sequencing followed by quantitative polymerase chain reaction validation in independent cohorts demonstrated that expression of miR-204 was significantly lower in IgAN compared with thin-membrane nephropathy but not compared with membranous nephropathy. Patients with IgAN at high risk of future progression had significantly lower expression of miR-204 than those at low risk of progression. Cortical localization indicated that miR-204 was preferentially expressed in the interstitium compared with glomeruli in IgAN nonprogressors and that this distribution was lost in IgAN progressors. Receiver operating characteristic curve analysis between the 2 IgAN cohorts revealed an area under the curve of 0.82. In addition, miR-204 expression correlated with known clinicopathological prognostic risk factors. Importantly, incorporating miR-204 into the International IgAN risk prediction tool improved the diagnostic power of the algorithm to predict risk of progression.ConclusionAdditional large-scale studies are now needed to validate the additive value of miR-204 in improving risk prediction in IgAN and more broadly in chronic kidney disease.