Histopathological Features of Sickle Cell Nephropathy in the Arab-Indian Haplotype.

INTRODUCTION

Sickle cell disease (SCD), an autosomal recessive disorder caused by hemoglobin S, leads to red blood cell sickling and multiorgan damage, including sickle cell nephropathy (SCN). While SCN histopathological changes are well described, data from the Middle East region, where the Arab-Indian (AI) haplotype is common, are limited. We hypothesized that SCN in patients in Saudi Arabia shows histopathological features similar to those in other regions, reflecting a shared renal injury mechanism.

METHODS

This single-center retrospective study analyzed kidney biopsies from adults with SCD in the Eastern Province of Saudi Arabia from 2012 to 2023. Histological specimens were examined using hematoxylin and eosin, periodic acid-Schiff stain, Masson trichrome stain, Jones silver stain, and immunofluorescence. Haplotype genotyping was performed using a nuclease allelic discrimination assay with target-specific primers and TaqMan probes labeled with VIC and FAM. Clinical and biochemical data were collected at the time of biopsy and at the last follow-up.

RESULTS

Twelve biopsies were included in the study (median age 44 years, 50% female). Median serum creatinine was 91.5 µmol/L (interquartile range [IQR] 59-130), and 24-h urinary protein was 3,300 mg (IQR 1,181-5,725). Of 9 patients tested, seven had homozygous AI haplotype, one had heterozygous AI, and one had BEN/CAR/CAM. Histopathology showed tubular hemosiderosis (92%), global sclerosis (75%), glomerular hypertrophy (75%), sickled red blood cells (58%), focal segmental glomerulosclerosis (42%), and glomerular basement membrane duplication (33%). These findings mirror SCN patterns in other haplotypes.

CONCLUSIONS

In Saudi patients with SCD with predominant AI haplotype, SCN histopathological features align with those reported globally, suggesting a consistent renal pathogenesis across haplotypes. This study improves our understanding of SCN in the AI haplotype, supporting standardized treatment methods and further research into preventing progression.