Distribution pattern of mesangial C4d deposits as predictor of kidney failure in IgA nephropathy

Mesangial C4d deposits have been associated with worse outcomes in Western patients with IgA nephropathy (IgAN), but there is limited data in Asians. Previously, a high proportion of stained glomeruli was often required for the classification of C4d positive (C4d+ve). Positive staining in lower proportion of staining would be classified as C4d-ve. This retrospective study evaluated the prognostic value of C4d+ve using a less stringent definition (one C4d+ve glomerulus) in Thai patients with IgAN (n = 120). Baseline findings and outcomes were compared between those with more extensive C4d staining patterns and those with more restricted staining. Clinico-pathologic parameters and risk for kidney outcomes (kidney failure or decline GFR50%) were compared between C4d+ve versus C4d-ve, and between different patterns: Focal (< 50%) versus Diffuse (≥ 50% of glomeruli); or Global (≥ 50) versus Segmental (< 50% of mesangial area). The hazard ratios were estimated using Cox proportional hazard models for Model 1 (Oxford score+ C4d) and Model 2 (Model 1+ clinical factors). C4d+ve (n = 81) had lower eGFR, more global sclerosis, and interstitial fibrosis than C4d-ve at baseline. The 5-year kidney survival for C4d+ve was lower (53.7%) than C4d-ve (89.7%); P = 0.0255. By univariate analysis, T1, T2, C4d+ve, eGFR<60, proteinuria were predictors of kidney outcome. By multivariate analysis, proteinuria, T1, T2 and C4d+ve were independent predictors (Model 2 HR (95% CI) C4d+ve: 3.24 (1.09–9.58), p = 0.034). Segmental had lower eGFR, higher tubulointerstitial fibrosis, and segmental sclerosis compared to Global pattern. Clinicopathological parameters were not different between Focal and Diffuse patterns. Outcomes were similar between staining patterns. In conclusion, C4d staining may be a valuable marker of poor prognosis in Asian patients with IgAN. Less stringent criteria for C4d+ve should be considered as no differences in outcomes were observed between more extensive staining with less extensive patterns. More studies are needed to identify the optimum criteria for C4d+ve.

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Established the first clinical prediction model regarding the risk of hyperuricemia in IgA nephropathy

10.21203/rs.3.rs-888732/v1 ◽

2021 ◽

Author(s):

Yin-Hong Geng ◽

Zhe Zhang ◽

Jun-Jun Zhang ◽

Bo Huang ◽

Zui-Shuang Guo ◽

...

Keyword(s):

Risk Factors ◽

Iga Nephropathy ◽

Interstitial Fibrosis ◽

Characteristic Curve ◽

Univariate Analysis ◽

Curve Analysis ◽

University Hospital ◽

Prediction Ability ◽

Decision Curve Analysis ◽

Incidence Risk

Abstract Objective. To construct a novel nomogram model that predicts the risk of hyperuricemia incidence in IgA nephropathy (IgAN) . Methods. Demographic and clinicopathological characteristics of 1184 IgAN patients in the First Affiliated Hospital of Zhengzhou University Hospital were collected. Univariate analysis and multivariate logistic regression were used to screen out hyperuricemia risk factors. The risk factors were used to establish a predictive nomogram model. The performance of the nomogram model was evaluated using an area under the receiver operating characteristic curve (AUC), calibration plots, and a decision curve analysis. Results. Independent predictors for hyperuricemia incidence risk included sex, hypoalbuminemia, hypertriglyceridemia, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), 24-hour urinaryprotein (24h TP), Gross and tubular atrophy/interstitial fibrosis (T). The nomogram model exhibited moderate prediction ability with an AUC of 0.834 ((95% CI 0.804–0.864)). The AUC from validation reached 0.787 (95% CI 0.736-0.839). The decision curve analysis displayed that the hyperuricemia risk nomogram was clinically applicable.Conclusion. Our novel and simple nomogram containing 8 factors may be useful in predicting hyperuricemia incidence risk in IgAN.

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Immunoglobulin A-nephropathy in Russian population: clinical and morphological presentation and long-term prognosis

Nephrology (Saint-Petersburg) ◽

10.36485/1561-6274-2019-236-45-60 ◽

2019 ◽

Vol 23 (6) ◽

pp. 45-60

Author(s):

V. A. Dobronravov ◽

T. O. Muzhetskaya ◽

D. I. Lin ◽

Z. Sh. Kochoyan

Keyword(s):

Iga Nephropathy ◽

Cox Regression ◽

Interstitial Fibrosis ◽

Immunoglobulin A ◽

Renin Angiotensin System ◽

Composite Endpoint ◽

Russian Population ◽

Progression Rate ◽

Tubular Atrophy ◽

Lower Egfr

AIM. The analysis of incidence, clinical and morphological manifestations, and the prognosis of IgA nephropathy in the Russian population.PATIENTS AND METHODS. Six hundred cases with primary IgA nephropathy (IgAN) from 1999 to 2019 were enrolled in the single-center retrospective study. Demographic and clinical parameters, morphrology data, and the treatment were analyzed. Three hundred forty seven patients were included in follow-up study. The following outcomes were evaluated: the occurrence of complete (PR) or partial remission (CR), death from all causes, the need for renal replacement therapy (RRT). The composite endpoint (RRT or eGFR decrease ≥ 50 % from the time of biopsy) was used to evaluate the risk of IgAN progression and associated factors.RESULTS. The period-average incidence of IgAN cases was 20.5 % of all indication biopsies and 31.7 % of primary immune glomerulopathies (with gradual increase to 41,5 % in last 5 years). At the time of the kidney biopsy, the proteinuria was 2.20 (1.10; 4.40) g/24h, eGFR – 69 ± 32 ml / min / 1.73 m2. Proportions of cases with arterial hypertension and with eGFR <60 ml / min / 1.73 m2 were 75 % and 36 %, respectively. The prevalence of histological changes in accordance with the MEST-C classification was as follows: M1 – 40.5 %, E1 -22.9 %, S1-70.2 %, T1-22 %, T2 – 9 %, C1-16.7 %, C2 – 4.4 %. Combined deposits of IgA and IgM (71.1 % of cases) were more frequent compared to IgA and IgG (9,6 %). In the followup period (27 (11; 61) month), 6 deaths from all causes were registered (1.7 %). The 10-year cumulative renal survival was 75 % (by dialysis) and 55 % (by composite endpoint). PR registered in 26 % of cases, CR – 24 %. PR / CR was more frequent in patients who received immunosuppression compared with patients on renin-angiotensin system blockers only (60 % vs. 40 %, p = 0.001). In multivariable Cox regression the independent factors associated with the risk of IgAN progression were: male gender, a younger age, higher blood pressure and hematuria, lower eGFR, interstitial fibrosis/ tubular atrophy (≥50 %), peritubular capillaritis and the presence of any crescents. Compared to the cohorts of other ethnic or geographical affiliation, analyzed IgAN cases were found to have more severe clinical and morphological presentations and faster progression rate.CONCLUSION. While being the most common glomerulopathy, IgAN in the Russian population has more pronounced clinical and morphological presentations and an unfavorable prognosis.

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Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy302 ◽

2018 ◽

Vol 35 (6) ◽

pp. 1002-1009 ◽

Cited By ~ 14

Author(s):

Rosanna Coppo ◽

Graziella D'Arrigo ◽

Giovanni Tripepi ◽

Maria Luisa Russo ◽

Ian S D Roberts ◽

...

Keyword(s):

Iga Nephropathy ◽

Validation Study ◽

Kidney Failure ◽

Interstitial Fibrosis ◽

Immunoglobulin A ◽

Immunoglobulin A Nephropathy ◽

Oxford Classification ◽

The Oxford Classification

Abstract Background It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. Methods In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1–10.8)]. Results In this extended analysis, M1, S1 and T1–T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%). Conclusion Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

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P0440EPIDEMIOLOGICAL AND CLINICAL CHARACTERSTICS OF IGA NEPHROPATHY PATIENTS IN TURKEY: TSN-GOLD WORKING GROUP

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0440 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Necmi Eren ◽

Meltem Gursu ◽

Egemen Cebeci ◽

Aydin Turkmen ◽

Hasan Haci Yeter ◽

...

Keyword(s):

Iga Nephropathy ◽

Clinical Data ◽

Working Group ◽

Interstitial Fibrosis ◽

Renal Outcome ◽

Pathological Features ◽

Oxford Classification ◽

Tubular Atrophy ◽

Glomerular Diseases ◽

Lower Egfr

Abstract Background and Aims According to the data of the Turkish Society of Nephrology-Glomerular Diseases Working Group (TSN-GOLD Working Group), IgA nephropathy is the most common primary glomerular disease in Turkey. The purpose of this study was to investigate the epidemiological and clinical data of IgA nephropathy patients in Turkey. Method 4399 patients with primary glomerular diseases from 47 centers who were followed up between May 2009 and May 2019 were included in the study conducted by TSN-GOLD Working Group. 524 patients were excluded due to lack of pathological data. Among the remaining patients, demographic, clinical and laboratory data of 994 patients with IgA nephropathy were analyzed. Results The median age of the patients was 37 (28-47) years, and 37.3% of them were female. The laboratory and clinical data at the time of diagnosis is presented in Figure-1, and biopsy indications are described in Figure-2. The median number of glomeruli was 16 (IQR: 3.5-4.3), sclerotic glomeruli was 2 (IQR: 1-5), and segmental sclerotic glomeruli was 1 (IQR: 1-2). Exudative changes, subendothelial and subepithelial deposition were present in 566 patients (56.9%), 46 patients (4.6%) and in 38 patients (3.8%), respectively. 662 (66.1%) and 611 of the patients (61.4%) had tubular atrophy and interstitial fibrosis in varying degrees, respectively. 672 (%67.6) and 416 patients (%41.9) had interstitial inflammation and vascular changes, respectively. In immunofluorescence staining, 18%, 30.1%, 4.4%, 68% of the patients had IgG, IgM, C1q and C3 positivity, respectively. Crescentic glomeruli were detected in 227 patients (3.3 ± 3.1 glomeruli). Patients with crescentic glomeruli had significantly higher proteinuria and lower eGFR than the patients without [2203 mg/day (15-26078) vs 1807 mg/day (15-29112); p=0.001; 55.3 ml/min/1.73 m2 (3.72-141.9) vs 72 ml/min/1.73 m2 (3.84-150.81); p<0.001, respectively]. Oxford classification was applied to 544 patients. Endocapillary hypercellularity (E1), mesengial hypercellularity (M1), tubular atrophy and interstitial fibrosis (T1 and T2), segmental sclerosis (S1) were present in 126 (13%), 425 (42.8%), 306 (30.8%) and 325 patients (%32.7), respectively. Proteinuria levels were higher in patients with endocapillary hypertrophy, mesengial hypercellularity, tubular atrophy-interstitial fibrosis and segmental sclerosis. eGFR levels were lower in patients with endocapillary hypertrophy, tubular atrophy-interstitial fibrosis and segmental sclerosis (Figure-3). Conclusion In this study we found that, the most common presentation of IgA nephropathy patients in our country was asymptomatic urinary abnormalities followed by nephritic and nephrotic syndrome. Higher proteinuria and lower eGFR values in patients with crescentic glomeruli, support the adoption of crescentic lesions in the new Oxford classification (MEST-C) to predict more precise outcome of IgA nephropathy patients. The high number of patients to whom the Oxford classification was applied provided us with the opportunity to examine the clinical reflections of pathological features. Evaluation of the follow-up data of the patients will give us the possibility to reveal the effect of initial clinical and pathological features on clinical findings and renal outcome.

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Long term outcome of immunoglobulin A (IgA) nephropathy: A single center experience

PLoS ONE ◽

10.1371/journal.pone.0249592 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0249592

Author(s):

Rozita Mohd ◽

Nur Ezzaty Mohammad Kazmin ◽

Rizna Abdul Cader ◽

Nordashima Abd Shukor ◽

Yin Ping Wong ◽

...

Keyword(s):

Iga Nephropathy ◽

Primary Outcome ◽

Interstitial Fibrosis ◽

Univariate Analysis ◽

Tubular Atrophy ◽

Term Survival ◽

Long Term Outcome ◽

Time Average

Introduction IgA nephropathy (IgAN) has a heterogeneous presentation and the progression to end stage renal disease (ESRD) is often influenced by demographics, ethnicity, as well as choice of treatment regimen. In this study, we investigated the long term survival of IgAN patients in our center and the factors affecting it. Methods This study included all biopsy-proven IgAN patients with ≥ 1year follow-up. Patients with diabetes mellitus at diagnosis and secondary IgAN were excluded. Medical records were reviewed for demographics, clinical presentation, blood pressure, 24-hour urine protein, serum creatinine, renal biopsy and treatment received. The primary outcome was defined as combined event of 50% estimated glomerular filtration rate (eGFR) reduction or ESRD. Results We included 130 (74 females; 56 males) patients of mean age 38.0 ± 14.0 years and median eGFR of 75.2 (interquartile range (IQR) 49.3–101.4) ml/min/1.73m2. Eighty-four (64.6%) were hypertensive at presentation, 35 (26.9%) had nephrotic syndrome and 57 (43.8%) had nephrotic range proteinuria (NRP). Median follow-up duration was 7.5 (IQR 4.0–13.0) years. It was noted that 18 (13.8%) developed ESRD and 34 (26.2%) reached the primary outcome. Annual eGFR decline was -2.1 (IQR -5.3 to -0.1) ml/min/1.73m2/year, with median survival of 20 years. Survival rates from the combined event (50% decrease in eGFR or ESRD) at 10, 20 and 30 years were 80%, 53% and 25%, while survival from ESRD were 87%, 73% and 65%, respectively. In the univariate analysis, time-average proteinuria (hazard ratio (HR) = 2.41, 95% CI 1.77–3.30), eGFR <45ml/min/1.73m2 at biopsy (HR = 2.35, 95% CI 1.03–5.32), hypertension (HR = 2.81, 95% CI 1.16–6.80), mean arterial pressure (HR = 1.02, 95% CI 1.01–1.04), tubular atrophy/interstitial fibrosis score (HR = 3.77, 95% CI 1.84–7.73), and cellular/fibrocellular crescent score (HR = 2.44, 95% CI 1.19–5.00) were found to be significant. Whereas only time-average proteinuria (TA-proteinuria) remained as a significant predictor in the multivariate analysis (HR = 2.23, 95% CI 1.57–3.16). Conclusion In our cohort, TA-proteinuria was the most important predictor in the progression of IgAN, irrespective of degree of proteinuria at presentation.

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A Positive Dermcidin Expression Is an Unfavorable Prognostic Marker for Extramammary Paget’s Disease

Diagnostics ◽

10.3390/diagnostics11061086 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1086

Author(s):

Shun Ohmori ◽

Yu Sawada ◽

Natsuko Saito-Sasaki ◽

Sayaka Sato ◽

Yoko Minokawa ◽

...

Keyword(s):

Overall Survival ◽

Therapeutic Option ◽

Univariate Analysis ◽

Paget’S Disease ◽

Paget's Disease ◽

Positive Staining ◽

Extramammary Paget’S Disease ◽

Potential Biomarker ◽

The Impact ◽

Extramammary Paget's Disease

Extramammary Paget’s disease is recognized as an apocrine-origin cutaneous tumor and is localized in the intraepithelial skin lesion. However, its advanced form is intractable, and there is currently no therapeutic option with a satisfactory level of clinical outcome. Therefore, it is of great importance to identify a potential biomarker to estimate tumor advancement in extramammary Paget’s disease. Dermcidin is an antimicrobial peptide derived from the eccrine gland and is identified as a biomarker in various malignancies. To investigate the potential of dermcidin in extramammary Paget’s disease, we investigated dermcidin expression in tumors using the immunostaining technique. Although previous studies have reported that extramammary Paget’s disease has no positive staining against dermcidin, 14 out of 60 patients showed positive staining of dermcidin in our study. To clarify the characteristics of positive dermcidin in extramammary Paget’s disease, we investigated the clinical characteristics of positive dermcidin extramammary Paget’s disease patients. Positive dermcidin patients showed a significantly high frequency of lymph node metastasis. We next investigated the impact of positive dermcidin on overall survival. Univariate analysis identified that positive dermcidin showed a significantly increased hazard ratio in overall survival, suggesting that dermcidin might be a prognostic factor for extramammary Paget’s disease.

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Hyperuricemia and hypertriglyceridemia indicate tubular atrophy/interstitial fibrosis in patients with IgA nephropathy and membranous nephropathy

International Urology and Nephrology ◽

10.1007/s11255-021-02844-4 ◽

2021 ◽

Author(s):

Bingman Liu ◽

Liangyu Zhao ◽

Qingqing Yang ◽

Dongqing Zha ◽

Xiaoyun Si

Keyword(s):

Iga Nephropathy ◽

Membranous Nephropathy ◽

Interstitial Fibrosis ◽

Tubular Atrophy

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MO282EARLY RENAL RECOVERY AFTER A FIRST FLARE OF PAUCI IMMUNE GLOMERULONEPHRITIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0040 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Jeremy Zaworski ◽

Cyrille Vandenbussche ◽

Pierre Bataille ◽

Eric Hachulla ◽

Francois Glowacki ◽

...

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Interstitial Fibrosis ◽

Univariate Analysis ◽

Renal Recovery ◽

Neurological Involvement ◽

Factors Associated ◽

Stage Renal Disease ◽

End Stage

Abstract Background and Aims Renal involvement is a severe manifestation of ANCA-associated vasculitis. Patients often progress to end-stage renal disease. The potential for renal recovery after a first flare has seldom been studied. Our objectives were to describe the evolution of the estimated glomerular filtration rate (eGFR) and identify factors associated with the change in eGFR between diagnosis and follow-up at 3 months (ΔeGFRM0–M3) in a cohort of patients with a first flare of pauci-immune glomerulonephritis. Methods This was a retrospective study over the period 2003–2018 of incident patients in the Nord-Pas-de-Calais (France). Patients were recruited if they had a first histologically-proven flare of pauci immune glomerulonephritis with at least 1 year of follow up. Kidney function was estimated with MDRD-equation and analysed at diagnosis, 3rd, 6th and 12th months. The primary outcome was ΔeGFRM0–M3. Factors evaluated were histological (Berden classification, interstitial fibrosis, percentage of crescents), clinical (extra-renal manifestations, sex, age) or biological (severity of acute kidney injury, dialysis, ANCA subtype). Results One hundred and seventy-seven patients were included. The eGFR at 3 months was significantly higher than at diagnosis (mean ± standard deviation, 40 ± 24 vs 28 ± 26 ml/min/1.73 m2, p < 0.001), with a ΔeGFRM0–M3 of 12 ± 19 ml/min/1.73 m2. The eGFR at 12 months was higher than at 3 months (44 ± 13 vs 40 ± 24 ml/min/1.73m2, p = 0.003). The factors significantly associated with ΔeGFRM0–M3 in univariate analysis were: sclerotic class according to Berden classification, percentage of interstitial fibrosis, percentage of cellular crescents, acute tubular necrosis, neurological involvement. The factors associated with ΔeGFRM0–M3 in multivariate analysis were the percentage of cellular crescents and neurological involvement. The mean increase in eGFR was 2.90 ± 0.06 ml/min/1.73m2 for every 10-point gain in the percentage of cellular crescents. ΔeGFRM0–M3 was not associated with the risks of end-stage renal disease or death in long-term follow-up. Conclusions Early renal recovery after a first flare of pauci-immune glomerulonephritis occurred mainly in the first three months of treatment. The percentage of cellular crescents was the main independent predictor of early renal recovery.

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Is mycophenolate mofetil combined with low-dose prednisone a treatment option for advanced IgA nephropathy? A 10-year follow-up case and brief literature review

European Journal of Inflammation ◽

10.1177/2058739218802680 ◽

2018 ◽

Vol 16 ◽

pp. 205873921880268

Author(s):

Qijun Wan ◽

Yongcheng He ◽

Hongtao Chen ◽

Hongping Liu ◽

Saodong Luan ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Iga Nephropathy ◽

Treatment Option ◽

Low Dose ◽

Interstitial Fibrosis ◽

Immunosuppressive Treatment ◽

Channel Blockers ◽

Tubular Atrophy ◽

Dose Prednisone

IgA nephropathy (IgAN) is now widely recognized as the most common primary glomerulonephritis worldwide, especially in China. The immunosuppressive treatment option for IgAN is still controversial. Previously, we proved that mycophenolate mofetil (MMF; Shanghai Roche, China) combined with low-dose prednisone was an effective and safe option for biopsy-proven mild to moderate IgAN patients in a short term of follow-up. This article we first reported the safety and efficacy of this regimen in a 42-year-old male biopsy-proven advanced 10-year follow-up IgAN case (Lee’s Class V; the patient was biopsied 10 years ago, so the Oxford Mesangial hypercellularity Endocapillary hypercellularity Segmental glomerulosclerosis Tubular atrophy/interstitial fibrosis (MEST) classification was not used). The mycophenolate and prednisone were only given for a limited time. The other main medications included calcium channel blockers and antiplatelet agents. Clinical and laboratory indexes were aperiodic assessed during the 10-year follow-up. The serum creatinine decreased from 356 to around 210 μmol/L and urine excretion protein reduced from 3.4 g/d to about 0.5 g/d after 6 months of the initiation of this regimen, respectively. These perfect treatment effects could maintain well during the whole follow-up period. No obvious complications were observed.

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