Introduction:
Amyloidosis is a disease characterized by extra cellular deposition of insoluble, misfolded beta sheet fibrils causing various organ injuries including Kidneys. The most prevalent forms of renal Amyloidosis include AL and AA Amyloidosis. Mutations in various apolipoprotein genes can also lead to non neuropathic, hereditary form of renal Amyloidosis. Of that, apolipoprotein A- II associated Amyloidosis is an exceedingly rare form caused by nucleotide replacement in the STOP codon of Apo A- II gene resulting in a variant of apoA- II with a 21-residue peptide extension on the Carboxyl terminus. Apolipoprotein A- II associated Amyloidosis clinically presents with nephrotic range proteinuria and progressive renal failure. Treatment options for renal Amyloidosis include only dialysis and renal transplant. Literature survey shows only three cases of apolipoprotein A-II associated Amyloidosis with successful renal transplantation across the globe. Here, we report the first case of renal amyloidosis associated with a novel apoA-II variant, 101Argext21 from Asia who underwent successful renal transplantation.
Methods:
Case Presentation:
A 35 year old male of Asian origin, presented to the Nephrology department at our hospital in South Tamil Nadu, three years ago with complaints of frothy urination. There was a history of unexplained renal failure requiring dialysis and eventually death in his father and paternal uncle. On evaluation, he was found to have Nephrotic range proteinuria (Urine PCR 3.864 mg/ mg), hypertension (BP 190/80 mm of hg) and renal failure (Creatinine 4.1mg/ dL). Serum Electrophoresis was negative for monoclonal gammopathy. Renal biopsy done on August 2021 showed Secondary Amyloidosis with negative Serum AA involving predominantly the glomeruli and vascular structures. A normal Echocardiography with negative Abdominal fat pad biopsy for IHC Serum AA ruled out systemic Amyloidosis. Genetic analyses revealed heterozygous mutation in ApoA-II on exon 4 with resultant variant 101Argext21. His renal failure worsened progressively and he became Dialysis dependent for two years. As multiple literature reviews showed excellent graft function post renal transplant ( 9-14 years ) with low risk for recurrence in patients with apolipoprotein A-II amyloidosis, our patient was also counselled regarding renal transplant. His mother was identified as a potential donor and he underwent live related, ABO compatible renal transplant. Post operative period was uneventful. He was maintained on triple immunosuppressive therapy and his renal parameters reached a nadir creatinine of 1.1 mg/ dL. Post transplant he had a sustained graft function with current creatinine of 1.2 mg/ dL, normal urine routine and normal blood pressures.
Results:
Conclusions:
This case from India, highlights a novel variant 101Argext21 causing apolipoprotein A-II associated renal amyloidosis and it’s clinical characteristics . Unexplained renal failure in his father and uncle suggests probable familial association. Genetic analyses is an useful tool to determine different gene mutations causing Amyloidosis. Renal transplantation seems to be a beneficial treatment option as the literature assures stable graft function post renal transplant with low risk of recurrence.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.