Abstract
Immunoglobulin A nephropathy (IgAN) is the most prevalent form of primary chronic glomerulonephritis. Around 20–40% patients progress variably to end-stage renal disease (ESRD) within 20 years of onset. Histological classification is essential, however, there are limitations in predicting the prognosis based on this information alone. Currently there is no validated tool to predict disease progression. Therefore, we combined both clinical and histological parameters to risk stratify patients of IgAN. Patients with biopsy proven IgAN from 2014 January to June 2019 were included. Independent pathological variables like mesangial hypercellularity(m), endocapillary proliferation(e), segmental and global sclerosis(s&g), interstitial fibrosis, tubular atrophy(t), crescents(c) and vascular lesions(v) – intimal hyalinosis, luminal narrowing and endothelial prominence were taken into account and divided into four histological grades (HG). 24-hour urinary protein excretion (UPE) values and estimated glomerular filtration rate(eGFR) were applied to a prognostic-predictive equation - [threshold score (− 1.86) = 0.722 + 0.364 × UPE − 0.046 × eGFR] for clinical grading (CG). In addition to above, serum uric acid, hypertension at the time of biopsy and haematuria was also compared for their effect on progression to ESRD. Association between clinical and histological variables at the time of renal biopsy with the incidence of subsequent ESRD were analysed using univariate logistic regression analysis along with Chi square and Fischer exact test. We also analysed association of variables with ESRD by calculating odds ratio and 95% confidence interval. 69 IgAN patients were included in the study with a mean age of 33.83 +11.05 years and eGFR of 54.85ml/min per 1.73 m2 with majority being males (60.9%). Mean proteinuria was 4.26 + 2.86 g/d of which 37 (53.6%) were in nephrotic range, of which 19(51.4%) progressed to ESRD. Only 21.7%(n=15) received steroids and 62.3%(n=43) received renin-angiotensin system (RAAS) inhibitors, of which 6.7%(n=1) and 2.3%(n=1) progressed to ESRD respectively. Among pathological variables global glomerulosclerosis (p=0.003, OR=4.4) and vascular lesions (p=0.002, OR=3.25) had significant association with ESRD progression. Vascular lesions were seen in 33.3% patients who had 3.25 times risk of progressing to ESRD. Most of our patients belonged to CG3(42%) or 4(38%). 30.4% patients who developed ESRD were in CG4 at presentation. Renal biopsy findings classified patients into HG1(15.9%), HG2(13%) and HG3 & 4(71%). 16 patients in HG3 & 4 progressed to ESRD as compared to 4(19%) in HG2 and 1(4.8%) HG1. Our study concluded that chronic lesions like global glomerular sclerosis and vascular lesions showed significant association to progression to ESRD in IgAN patients rather than any of the classically described MEST-C scoring from oxford classification. Considering the fact that UPE and eGFR significantly predict progression to ESRD, our population needs different predictive prognostic equation derived from multicentre study for clinical grading and need to consider wider spectrum of histopathological lesions to predict risk groups and prognosis to ESRD in IgAN patients.
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