Postmortem examination of the kidney in allogeneic hematopoietic stem cell transplantation recipients: possible involvement of graft-versus-host disease

Abstract

To investigate the association between graft-versus-host disease (GVHD) and renal injury after allogeneic stem cell transplantation (allo-SCT), we compared autopsy findings of 26 consecutive allo-SCT recipients with two control groups: patients with hematologic malignancies who received cytotoxic chemotherapy alone (Control 1, n = 21) and those with non-hematologic diseases (Control 2, n = 12). We evaluated the following renal pathology; renal tubulitis, allograft glomerulitis, intimal arteritis, allograft nephropathy, and peritubular capillaritis. These changes were found in 11 allo-SCT recipients and 10 patients in Control 1, but none in Control 2. While overall frequency of renal impairments was similar between allo-SCT recipients and Control 1 (3/26 vs. 1/21), allo-SCT recipients were more likely to have renal tubulitis and peritubular capillaritis compared to Control 1 (5/26 vs. 1/21), but less likely to present with glomerulitis (1/26 vs. 6/21). Grade III-IV acute or extensive-type chronic GVHD were seen in all of the three patients with renal tubulitis and four of the five patients with peritubular capillaritis. Allo-SCT recipients with severe GVHD tended to have tubulitis and peritubular capillaritis. These findings have implications of some renal impairment attributable to GVHD.

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

“…23,38,40 In their study of 26 autopsy cases, El-Seisi et al 38 noted substantial interstitial fibrosis, as we found in our group, but they also found tubulitis of unspecified degree in 67% of autopsied hematopoietic cell transplant patients, although they did not find an association of tubulitis with clinical GVHD. In a study of seven hematopoietic cell transplant patients with thrombotic microangiopathy, Mii et al 23 noted mild or moderate interstitial inflammation in all patients (two biopsy, five autopsy).…”

“…8,14,16,19,38,39 A few single-center studies of autopsy kidney specimen in the hematopoietic cell transplant population have been reported, including one large study focused primarily on thrombotic microangiopathy. 20,21,38,40 We retrospectively reviewed our single-center experience with renal pathology in specimens from three groups of hematopoietic cell transplant recipients. These included patients with core kidney biopsies for clinical renal dysfunction, in which we characterized three glomerulonephridities not previously reported in the hematopoietic cell transplant population.…”

Acute kidney injury following HCT: incidence, risk factors and outcome

“…First, the absence of GVHD in autologous HCT, which can contribute to renal lesion directly through cytokine-and immune-related injury, including glomerular deposits causing nephrotic syndrome, and tubulitis; or indirectly through nephrotoxicity induced by CYA used in prophylaxis against GVHD. [23][24][25] In addition, severe GVHD with diarrhoea and dehydration, and CMV reactivation because of treatment of GVHD with high-dose prednisolone can also contribute to GVHDassociated nephrotoxicity. 26,27 Second, because there are no foreign cells in myeloablative autologous HCT, more rapid engraftment occurs (resulting in less cytopenia, sepsis and nephrotoxicity induced by antimicrobials).…”

“…[23][24][25] In addition, severe GVHD with diarrhoea and dehydration, and CMV reactivation because of treatment of GVHD with high-dose prednisolone can also contribute to GVHD-associated nephrotoxicity. 26,27 CMV reactivation itself increased the risk for the occurrence of AKI in nonmyeloablative HCT.…”

Acute kidney injury in HCT: an update

“…First, the absence of GVHD in autologous HCT, which can contribute to renal lesions directly through cytokine-and immune-related injury, including glomerular deposits causing nephrotic syndrome and tubulitis; or indirectly through nephrotoxicity induced by calcineurin inhibitors used in prophylaxis against GVHD. 23,24 Furthermore, severe GVHD with diarrhea and consequent dehydration, as well as CMV reactivation due to treatment of GVHD with high-dose prednisolone can likewise contribute to GVHD-associated nephrotoxicity. 12,25 Second, since there are no foreign cells in myeloablative autologous HCT, engraftment occurs more rapidly (resulting in less cytopenia, sepsis and antimicrobe-induced nephrotoxicity).…”