De novo glomerulitis associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: A single-center experience

Abstract

BackgroundNephrotic syndrome (NS) and proteinuria are uncommon, often unrecognized manifestations of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Only a few isolated case reports and case series involving smaller number of patients who developed NS after HSCT have been published.MethodsWe reviewed the renal histopathological examination findings and clinical records of 15 patients who developed proteinuria after HSCT at Seoul and Yeouido St. Mary′s Hospital (Seoul, Korea). We also measured the anti-PLA2R antibodies (M-type phospholipase A2 receptor) in the serum samples from the seven patients at the time of renal biopsy.ResultsAll patients had GVHD. The most common indication for biopsy was proteinuria (>1 g/day), with nine patients having nephrotic range proteinuria. The most common histopathological finding was membranous nephropathy (MN; n = 12). Other findings were membranoproliferative glomerulonephritis, C1q nephropathy, and diabetic nephropathy. Eleven patients were treated with immunosuppressive agents, and three patients were treated only with angiotensin II receptor blocker. The overall response rate, including complete remission (urinary protein level <0.3 g/day) and partial remission (urinary protein level = 0.31–3.4 g/day), was 73%. The mean follow-up period was 26 months, and none of the patients developed end-stage renal disease. All of the seven patients with MN had negative findings for anti-PLA2R antibodies, measured using an enzyme-linked immunosorbent assay kit.ConclusionIn this study the findings of 15 renal biopsies were analyzed and to our knowledge this is the largest clinicopathological study of GVHD-related biopsy-proven nephropathy. Approximately 80% of the patients were MN and 73% responded either partially or completely to immunosuppressive treatment. Currently, there is an increase in the incidence of GVHD-mediated renal disease, and therefore, renal biopsy is essential for diagnosing the nephropathy and preventing the progression of renal disease.

Minimal change disease after hematopoietic stem cell transplant: Manifestation of chronic graft-versus-host disease

“…Anti-PLA2r antibodies have not been identified in MN suggesting that other antigens are likely to serve as antibody targets. [5][6][7] In MCD, T cell activation may be the cause of cytokine and antibody-mediated injury and can occur without other signs of GVHD, as evidenced in our patient. 8,9 The largest series of NS after GVHD was published by Reddy et al 10 who followed 889 patients and evaluated who developed non-cardiac edema with only 9 patients (0.9%) having evidence of NS.…”

“…Minimal change disease was found in 15% of reports. 6 Similarly, Cho et al 7 reported in his cohort MN was the common glomerulopathy post HSCT. Anti-PLA2r antibodies have not been identified in MN suggesting that other antigens are likely to serve as antibody targets.…”

Nephrotic syndrome as a complication of chronic graft‐versus‐host disease after allogeneic haemopoietic stem cell transplantation

“…In idiopathic MN, PLA2R and thrombospondin type‐1 domain‐containing 7A (THSD7A), both expressed on podocytes, have been identified as autoantibody targets . In our cohort, as well as other series, anti‐PLA2R antibodies were not identified, suggesting that other antigens are likely to serve as antibody targets in MN post‐allo‐HSCT …”

“…Descriptions in the literature are limited to case reports and small case series. A literature search using the PubMed database with search terms ‘NS’, ‘renal failure’ and ‘haemopoietic transplant’ for publications in the English language since the year 2000 identified 10 case series (Table ) and 15 case reports, with a combined total of 67 cases. A pooled analysis was performed to identify key characteristics of this syndrome.…”

Emergence of Dipstick Proteinuria Predicts Overt Nephropathy in Patients Following Stem Cell Transplantation

“…The most frequent renal histological finding was MN, followed by minimal change disease. Focal glomerulosclerosis, proliferative glomerulonephritis, and IgA nephropathy were also reported, although the numbers of cases were very small [1,27]. Our study suggests that proteinuria may be insidiously emerging and increasing within 1 year after SCT in nephrotic syndrome patients, and that hematologists or transplant physicians tend to understate its incidence.…”