The role of renal biopsy in the prognosis of patients with İGA nephropathy

Aim: In this study, we aimed to determine whether the staining of biopsy materials of patients diagnosed with IgA nephropathy with C4d, IL-10, PDGF and TGF-beta immunohistochemical stains, which are known to be associated with pathogenesis, would contribute to the determination of progression to end-stage renal failure and early treatment modality when evaluated together with demographic, histopathological and clinical data. Materials and Method: Our study included 59 patients aged 18 years and older who were diagnosed with primary IgA nephropathy after kidney biopsy at Necmettin Erbakan University Meram Medical Faculty Nephrology Clinic between January 2015 and January 2022. Demographic data of the patients such as age, gender, blood group examined during biopsy, and urea (mg/dL), creatinine (mg/dL), eGFR (50 mL/min/1.73 m²), 24-hour urine proteinuria (mg/dL) values, 1 year after biopsy, and the latest laboratory values found in the system were compared. C4d, IL-10, PDGF and TGF-β immunohistochemical staining was positive and negative, and its relationship with IgA prediction tool rates including GFR levels at the time of diagnosis, MEST-C score, annual GFR and proteinuria changes, treatment responses, and 1 and 5-year periods were evaluated. Results: The study included 59 patients diagnosed with primary IgA nephropathy. 24 of the patients were female and 35 were male. The mean age of all patients was 39.4814.81 years and the mean age at diagnosis was 37.6112.82 years. Hypertension was present in 70% (n=41) patients and there were no other comorbidities. The mean follow-up period was 42.9823.5 months. The mean GFR at the time of diagnosis was 66.6129.7 ml/min, creatinine 1.430.8 mg/dL, proteinuria 26702110 mg/dL and CRP 7.5111.5 mg/dL. All 59 patients were on RAS blockers and 69% (n=40) were added immunosuppressive therapy. All pathology blocks of 59 patients were stained with TGF-beta. 56% (n=33) of the blocks were stained with C4d, 96.6% (n=57) with PDGF and 62.7% (n=37) with IL-10. Those stained with TGF-beta, PDGF and IL-10 were numbered according to the intensity of the staining. TGF-beta stained according to severity was mild in 30.5% (n=18), moderate in 45.8% (n=27), and severe in 23.7% (n=14). . Of those stained with PDGF, 50.8% (n=30) were mild, 37.3% (n=22) were moderate, and 8.5% (n=5) were severe. Of those stained with IL-10, 39% (n=23) were mild, 20.3% (n=12) were moderate, and 3.4% (n=2) were severe. Staining with C4d antibody was evaluated according to the localization of the dye and the percentage of staining of the stained localization. Localizations were grouped into three sections as mesengial/perimesengial (m/pm) staining in glomeruli, peripheral staining and non-specific staining in sclerotic glomeruli. The stained localization was considered focal if it showed less than 50% staining, and diffuse if it showed more than 50% staining. Those with M/pm staining and staining more than 50% of the glomeruli were 10 blocks, while those with m/pm staining less than 50% of the glomeruli were 7 blocks. The number of blocks with more than 50% peripheral staining of the glomeruli was 7, and the number of blocks with less than 50% peripheral staining of the glomeruli was 2. There were 7 blocks with less than 50% non-specific staining in the sclerotic glomerular segment. When patients with GFR values below and above 60 were compared, it was found that the intensity of staining with TGF-beta and PDGF was higher in patients with GFR < 60 (p=0.004, p=0.008, respectively). Severely stained TGF-beta and PDGF stains had a higher rate of progression to end-stage renal disease after 1 year (p=0.002, p=0.001, respectively). The rate of staining with C4d and IL-10 in patients with a GFR below 60 was higher than the group with a GFR above 60 at the time of biopsy (p=0.002, p=0.033, respectively). The rate of progression to ESRD, calculated with the 1-year and 5-year IgA Prediction Tool formula, was higher in the C4d-stained group than in the non-C4d-stained group (p=0.001, p=0.001, respectively). The rate of progression to ESRD, calculated with the 1-year and 5-year IgA Prediction Tool formula, was higher in the IL-10 stained group than in the IL-10 stained group (p=0.001, p=0.001, respectively). Traditional criteria such as gender, age at diagnosis, GFR and proteinuria at diagnosis, and immunohistochemical stains were included in the binary regression analysis. IL-10 was identified as an independent predictor of clinical progression. It was determined that the IL-10 stained group was 4.9 times more unresponsive to treatment than the unstained group (p= 0.008). Conclusions: In our study, immunohistochemical staining of renal biopsy preparation with IL-10 was found to be associated with unfavourable renal survival. It is promising that IL-10 provides a guide to predict the prognosis of IgA nephropathy in the early period. However, since the number of patients in our study was limited, studies involving a larger patient population are needed.