Kidney Pathology after Hematologic Cell Transplantation—A Single-Center Observation Study of Indication Biopsies and Autopsies

Abstract

Hematopoietic cell transplantation (HCT) is an increasingly used treatment for hematologic malignancies as well as for nonmalignant diseases. Kidney impairment remains an important early and late post-transplantation complication. Although numerous histopathological changes have been reported, the pathophysiology remains incompletely understood. Furthermore, correlations between clinical findings and morphological changes have not been well studied. Between 2000 and 2016, 17 recipients of allogeneic (n = 12) or autologous (n = 5) HCT underwent kidney biopsy for either proteinuria or deterioration of kidney function at our center. The most common biopsy findings were therapy-related changes with thrombotic microangiopathy (n = 5), calcineurin inhibitor toxicity (n = 4), and membranous glomerulonephritis (n = 3), representing the majority of cases in this category. In addition, kidney findings from 137 autopsies performed between 1995 and March 2017 were analyzed. The most common changes were acute kidney injury (n = 55), most likely due to the patients' premortal deteriorated state, and thrombotic microangiopathy (n = 14). Several cases demonstrated involvement by either infectious agents (n = 6) or tumors (n = 9). Distinct kidney diseases, such as glomerulonephritis, were rare (3% of cases). Uncommon and yet rarely described diagnoses for this patient cohort were IgG4-related tubulointerstitial nephritis and fibrillary nephritis. This study provides a comprehensive overview of the histomorphological findings in kidney biopsy specimens from HCT recipients. Along with treatment-related complications, one putative correlate of chronic GVHD of the kidney could be documented: membranous glomerulonephritis. In contrast, no morphological correlate of acute GVHD of the kidney was identified. Findings at the time of autopsy varied greatly, spanning a wider range than those of indication biopsies.

Renal post-mortem findings in myeloproliferative and myelodysplastic/myeloproliferative neoplasms

“…In concordance with our previous study on the post-mortem findings of HCT patients [ 13 ], we confirm a higher rate of acute tubular damage in MPN-patients treated with HCT. These patients had prominent features of fulminant graft versus host disease (GvHD) or tumor relapse which may be a possible explanation for the acute kidney injury seen.…”

“…Thus, a causal relationship between diffuse mesangial sclerosis and MPNS/CMML is possible, although it may not become clinically evident due to renal impairment or In concordance with our previous study on the postmortem findings of HCT patients [13], we confirm a higher rate of acute tubular damage in MPN-patients treated with HCT. These patients had prominent features of fulminant graft versus host disease (GvHD) or tumor relapse which may be a possible explanation for the acute kidney injury seen.…”

Membranous Glomerulopathy After Autologous Hematopoietic Stem Cell Transplant in a Patient With Multiple Myeloma

“…Membranous glomerulopathy is one the of most common diagnosis in renal biopsies from patients with HSCT and has been acknowledged as a manifestation of GVHD. 4 A clear-cut distinction between a primary and a secondary membranous glomerulonephritis is difficult to establish in this case because the results of anti-PLA2R serology performed after initiating treatment were negative. Nevertheless, considering that the patient was postautologous bone marrow transplant, including the presence of tubuloreticular inclusions in endothelial cells and C1q in immunofluorescence, a secondary etiology can be favored.…”

“…In theory, patients who undergo autologous HSCT should not be at risk of GVHD; nonetheless, it has been reported that up to 10% of these patients can have GVHD involving the skin, gastrointestinal tract, and liver. 4 It has been hypothesized that autologous GVHD is due to an autoimmune mechanism in which autoreactive T cells recognize self-major histocompatibility complex class II antigens and B cells produce autoantibodies. 5 In addition, there is evidence that interferon gamma may be a critical mediator for the development of autologous GVHD.…”

“…2 There were 2 different studies that aimed to characterize renal biopsy findings in patients who underwent HSCT, either autologous or allogenic, for various indications, including MM, which have described membranous glomerulopathy (MGN), thrombotic microangiopathy, focal and segmental glomerulosclerosis, minimal change disease, acute tubular injury, tubulointerstitial nephritis, and another less common diagnosis. 3,4 We present a case of MGN after autologous HSCT in a patient with MM. Unique histologic features are highlighted, and the issue of whether a MGN can be a manifestation of autologous GVHD is discussed.…”