Thrombotic microangiopathy triggered by podocytopathy

Abstract

Thrombotic microangiopathy (TMA) is a rare group of diseases characterized by microangiopathic hemolytic anemia, thrombocytopenia, and target organ damage. It can be divided into primary and secondary TMA. Herein we report a case of TMA associated to a primary glomerular disease. We report the case of a 31-year-old Black male from Cape Verde admitted in March 2018 with nephrotic syndrome and upper gastrointestinal bleeding, the latter due to severe erythematous gastritis. He was discharged after clinical stabilization. The patient came to Portugal 8 months later. On admission, he presented with rapid deterioration of kidney function and hyperkalemia. The etiologic study revealed microangiopathic hemolytic anemia, nephrotic syndrome and microscopic hematuria. Immunologic study and viral serology were negative. ADAMTS13 activity and inhibitor testing were within normal range, genetic complement evaluation showed CFH-H3 in homozygosity, functional complement studies revealed decreased function of alternative pathway. Kidney biopsy was consistent with the diagnosis of TMA, and electron microscopy was compatible with minimal change disease. Patient underwent plasmapheresis with resolution of hemolysis, fluid overload and recovery of renal function. Two months later, he presented with nephrotic syndrome and started prednisolone with remission. Six months later, the nephrotic syndrome relapsed, and it became steroid-, MMF-, and rituximab-resistant. Tacrolimus was initiated, achieving partial remission. Atypical hemolytic uremic syndrome is an uncommon disease and is rarely reported as secondary to glomerular diseases. This case showcases the challenges regarding treatment options in a resistant glomerulopathy and the implications of therapeutic choices and kidney outcomes with the coexisting TMA.

Keywords: minimal change disease; nephrotic syndrome; thrombotic microangiopathy.

Figure 1. A: (H & E × 20) Membranoproliferative glomerulonephritis (MPGN)-like pattern with hyperlobulated glomerular tufts, light proliferation of mesangial and endothelial cells, and double contouring of basement membranes (arrow). B: (H & E × 20) MPGN-like pattern, presence of an endoluminal thrombus in the vascular pole. C: (PAS × 20) MPGN-like pattern, presence of double contour of basement membrane (arrow).

Figure 2. Electron microscopy × 5,000: Extensive podocyte foot process effacement in a preserved basement membrane area, compatible with podocytopathy.

Figure 3. Proposed mechanism of glomerulopathies-associated atypical hemolytic uremic syndrome. Reprinted from “Atypical haemolytic uraemic syndrome with underlying glomerulopathies. A case series and a review of the literature.” by Manenti L et al., Nephrol Dial Transplant. 2013; 28: 2246-2259. Copyright © 2013, Oxford University Press. Reprinted with permission.