Role of C4d and CD68 in kidney biopsy as novel prognostic markers for IgA nephropathy; a single-center study from India

Introduction: IgA nephropathy (IgAN) is a common primary glomerulonephritis worldwide. C4d and CD68 could be useful prognostic markers in this disease. Objectives: This study was conducted to assess the clinical and prognostic implications of C4d and CD68 staining in patients with IgAN. Materials and Methods: This is a retrospective single-center observational study. Baseline characteristics and laboratory details were recorded. Renal biopsy was reported according to the MEST-C classification along with further staining for C4d and CD68 by immunohistochemistry. Primary and secondary outcomes were progression to end-stage renal disease (ESRD) and all-cause mortality during follow-up, respectively. The effect of C4d and CD68 along with other risk factors on outcomes was studied. Results: Sixty patients with primary IgAN were analyzed with a median follow-up of 17 months. Forty were males, with a mean age of 39±16 years, and median estimated glomerular filtration rate (eGFR) of 36.5 mL/min/1.73 m2 with a median urine protein/creatinine ratio of 1.9 g/g, at the time of kidney biopsy. In our patients, macroscopic hematuria (n=2: 3.3%) was rare, while 15 (25%) of patients had nephrotic-range proteinuria. Most biopsies showed sclerosis 43 (71.7%) followed by interstitial fibrosis and tubular atrophy (IFTA) 32(53.3%). Meanwhile, crescents were seen in 20 (33.3%). About 39 (65%) of patients had glomerular C4d positivity and 10 (16.7%) had tubulointerstitial CD68 positivity while, none having glomerular CD68 positivity. Glomerular C4d and tubulointerstitial CD68 positivity had lower eGFR, higher proteinuria at presentation (P<0.05) and faster progression to ESRD (glomerular C4d-odds ratio [OR]: 5.7 [95% CI: 1.4-22.5]); tubulointerstitial CD68 OR: 5.4 [ 95% CI: 1.2-23.95]. Other risk factors predicting progression were eGFR at presentation (OR: 0.9 [95% CI: 0.89-0.99], presence of sclerosis OR: 6.5 [95% CI: 1.32-32.06] and IFTA OR: 21.4 [ 95% CI: 4.3-108]). Conclusion: In our study, IgAN patients presented in the later stages of chronic kidney disease, with the majority being diagnosed at stage 3 of this disease. Macroscopic hematuria was rare and nephrotic syndrome and crescents were common. Glomerular C4d and tubulointerstitial CD68 were associated with lower eGFR and more rapid progression.