Nephrotic Syndrome after Hematopoietic Cell Transplantation

Abstract

Glomerular disease associated with nephrotic syndrome has rarely been recognized as a distinct complication of allogeneic hematopoietic cell transplantation. Case reports in the English and Japanese literature since 1988 have described variable glomerular histology, comprising mainly membranous glomerulonephritis (MGN) in almost two thirds and minimal change disease (MCD) in nearly one quarter of patients. Review of the literature reveals a close temporal relationship between the development of nephrotic syndrome shortly after cessation of immunosuppression and the diagnosis of chronic graft-versushost disease (GVHD). An association of glomerular disease with simultaneous GVHD was seen in 47% of patients overall. Nephrotic syndrome followed GVHD within 5 months in 60% of the combined MCD and MGN reports. A decrease in immunosuppressive medication use was linked to nephrotic syndrome occurrence within 9 months in 63% of patients with MCD and MGN. MCD occurred earlier after hematopoietic cell transplantation, was diagnosed sooner after medication change, and exhibited a better prognosis in comparison with MGN. Glomerular lesions after hematopoietic cell transplantation may therefore represent the renal manifestation of GVHD. Further studies are warranted to delineate the pathogenesis of this complication.

Renal pathology in hematopoietic cell transplant recipients: a contemporary biopsy, nephrectomy, and autopsy series

“…8,11,14,16,18,39,45 We encountered focal segmental glomerulosclerosis in 3 of 14 (21%, patient nos. 6-8) patients with renal biopsy.…”

“…[7][8][9] Numerous descriptive studies, derived from groups of kidney core biopsy specimens from hematopoietic cell transplant recipients with renal dysfunction, have characterized the most common types of glomerulonephritis in hematopoietic cell transplant patients. 8,[10][11][12][13][14][15][16][17][18] These include membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis. In addition, acute and chronic thrombotic microangiopathy, or 'transplant-associated thrombotic microangiopathy,' has been shown to occur commonly in hematopoietic cell transplant recipients, 8,14,[17][18][19][20][21][22][23][24][25] with smaller reported numbers of membranoproliferative glomerulonephritis, proliferative glomerulonephritis, ANCA-associated glomerulonephritis, and IgA nephropathy.…”

Renal pathology in hematopoietic cell transplantation recipients

“…[1][2][3] In the acute setting, renal failure may be due to renal toxicity of medications (chemotherapeutic, antibiotic, or immunosuppressive), tumor lysis syndrome, renal ischemia (including hypovolemia, veno-occlusive disease, etc), sepsis, infection (bacterial, fungal, or viral), or effects of radiation. [4][5][6] A hemolytic-uremia-like syndrome, often referred to as bone marrow transplant nephropathy, may manifest later (3-6 months or post-transplantation later), and classically shows histopathologic features of thrombotic microangiopathy with endothelial injury. [4][5][6][7] Although exposure of kidneys to radiation during hematopoietic cell transplantation has been hypothesized as a risk factor for bone marrow transplant nephropathy, studies have shown conflicting data regarding renal shielding and long-term renal insufficiency.…”

“…[4][5][6] A hemolytic-uremia-like syndrome, often referred to as bone marrow transplant nephropathy, may manifest later (3-6 months or post-transplantation later), and classically shows histopathologic features of thrombotic microangiopathy with endothelial injury. [4][5][6][7] Although exposure of kidneys to radiation during hematopoietic cell transplantation has been hypothesized as a risk factor for bone marrow transplant nephropathy, studies have shown conflicting data regarding renal shielding and long-term renal insufficiency. 5,[8][9][10][11][12] Other causes of thrombotic microangiopathy must be considered in hematopoietic cell transplant recipients, including exacerbation of endothelial injury by chemotherapy, immune-mediated injury, and perhaps most notably, cyclosporine inhibitor toxicity, given as prophylaxis or treatment for graft-versus-host disease.…”

“…Graft-versus-host disease may occur in the acute (1-3 months post-transplantation), or chronic setting (delayed until 4-12 months post hematopoietic cell transplantation), and most commonly involves skin, liver, and gut; chronic graft-versus-host disease may also manifest features of autoimmune collagenvascular disease. 2,3, 13 Brukamp et al 4 recently summarized evidence suggesting that membranous glomerulonephritis is a glomerular manifestation of chronic graft-versus-host disease.…”