Nephropathy associated with the E3/E4 allelic variant of the APOE gene. Case 2

Brief information about the disease pathogenesis presented in the introduction to the previous case. Patient E., 27-year-old. Family history is remarkable for myocardial infarctions - patient’s father had recurrent myocardial infarctions and died at the age of 52 years. Our patient developed obesity and arterial hypertension with BP up to 170/110 mm Hg at the age of 13 years. In 2020 he had proteinuria, and his serum creatinine was 600 μmol/L; same year kidney biopsy was performed. At the time of biopsy he had morbid obesity (body weight 160 kg), and newly diagnosed diabetes mellitus, his BP was 140/90 mm Hg, total cholesterol 12.0 mmol/L, fasting glucose 6.3 mmol/L, serum creatinine 635 µmol/L, and proteinuria 17.0 g/24h without edema or biochemical criteria of nephrotic syndrome. Pathology examination revealed metabolic nephropathy with extensive secondary sub-globular glomerulosclerosis, with massive conglomerates of foamy cells ( Fig. 1), with lipid microthrombi in the glomerular capillaries ( Fig. 2), marked chronicity with extensive complete glomerulosclerosis, severe tubulointerstitial fibrosis and severe arteriolosclerosis. Based on the pathology findings, genetic testing for the APOE gene was strongly recommended, and the APOE-E3/E4 gene polymorphism was confirmed. June 2021 his serum creatinine was 640 µmol/L and eGFR 9 ml/min; and he was diagnosed with chronic kidney disease Stage 5. August 2021 he was started on kidney replacement therapy with peritoneal dialysis December 2021 kidney transplantation from relative donor (patient’s mother) was performed. The APOE gene has not been investigated in the mother or other family members. Thus, we report another case from a rare group of genetically determined lipid metabolism disorders, associated with a breakage in the APOE gene. The peculiarity of the case is the infrequent possibility to visualize lipid microthrombi in the glomerular capillaries. The disease progressed to the chronic kidney disease Stage 5, demanding kidney replacement therapy. In both cases, graft function prognosis is most important. For the described patient’s category, the issues of the recurrence of the metabolic nephropathy in the graft remains almost unstudied due to the rarity of the condition, which does not allow drawing valid conclusions so far. However, a very important general conclusion for all categories of kidney transplant recipients has been drawn by two independent groups of investigators: along with other well-established prognostic risk factors, such as donor’s age and the number of acute rejection episodes, the recipient’s APOE gene E3/E4 polymorphism is an independent negative prognostic factor and predictor of chronic transplant nephropathy [1, 2]. Informed patient consent for publication of clinical information and images was obtained.

аполипопротеин E, липидные микротромбы, протеинурия, apolipoprotein E, lipid microthrombi, proteinuria

1. Hernandez D., Salido E., Linares J. et al. Role of apolipoprotein E epsilon 4 allele on chronic allograft nephropathy after renal transplantation. Transplant Proc. 2004. 36(10):2982-4. doi: 10.1016/j.transproceed.2004.10.038

2. Cofan F., Cofan M., Rosich E. et al. Effect of apolipoprotein E polymorphism on renal transplantation. Transplant Proc. 2007. 39(7):2217-8. doi: 10.1016/j.transproceed.2007.06.011