Introduction:
Complement 3 glomerulonephritis (C3GN) is a rare and progressive complement-mediated kidney disease having a prevalence of 1-3 per million population. It is challenging to diagnose C3GN because of it’s clinical heterogeneity. Definitive diagnosis of C3GN requires a kidney biopsy and is diagnosed by dominant C3 staining in the glomeruli of immunofluorescence intensity ≥ 2 orders of magnitude higher than any other immune reactant. Most patients present with proteinuria, hematuria and occasionally hypertension. Unfortunately more than half of adults affected by this will progress to kidney failure, needing dialysis or transplant within 10 years. Many immunosuppressive therapies have been tried in C3GN including steroids ,MMF, CNIs , Complement inhibitors. Some patients with crescenteric GN may need aggressive therapy with immunosuppression and plasmapheresis. Still the prognosis is poor which indicates the diverse etiopathogenesis of the disease. In this context, we’ll be reporting a case of a young male HbH disease patient presenting with features of nephritic syndrome and biopsy showing C3 glomerulonephritis.
Methods:
A 32 year old non diabetic non hypertensive male who is a known case of HbH disease presented with swelling of the face and lower limbs since 5 days, associated with hematuria. There was no history of fever or sore throat in the past 3 months. Clinical evaluation revealed an average body built with anemia and was normotensive. Hemogram showed microcytic hypochromic anemia (Hb – 8 g/dl), RFT normal , LFT shows slightly raised bilirubin level (T. Bil 5 mg/dl) with normal lipid profile. Urine examination reveled protein 3+ , RBC 130 cells/HPF and 24 hr urinary protein is 1000mg. USG Abdomen showed chronic calculous cholecystitis, splenomegaly, and normal size kidneys and bladder. HPLC report was compatible with Alpha Thalassemia HbH disease . Non invasive workup for nephritic syndrome including ANA, dsDNA, viral markers, ASO titre, TSH were unremarkable.C3 and C4 levels were 52 mg/dl and 15mg/dl respectively. Kidney biopsy was done to establish the diagnosis of Glomerulonephritis
Results:
Kidney Biopsy showed Mesangial and endocapillary proliferative glomerulonephritis with cellular crescents over 1/19 of sampled glomerulus. Extensive deposition golden brown pigment granules in tubular epithelial cell cytoplasm which are positive for iron/ hemosiderin (Perl’s) stain. Interstitial fibrosis and tubular atrophy was observed in less than 10% nephrons. DIF studies reveal mesangial 3+ and capillary wall 2+ staining for C3 only. Biopsy confirmed the diagnosis of C3 Glomerulonephritis . As proteinuria and hematuria were persistent , the patient was managed with Prednisolone and Mycophenolate mofetil and is on follow up.
Conclusions:
While extensive studies have been done for association of sickle cell disease with glomerulonephritis, not many studies have been done in patients of HbH disease.C3 Glomerulonephritis is a very rare disease as such, and no case of C3GN associated with HbH disease has been reported in literature elsewhere and this will be the first case reporting C3 glomerulonephritis in a HbH disease patient. Further extensive studies should be done to find the association of C3GN with HbH disease.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.