Graft versus host disease-dependent renal dysfunction after hematopoietic stem cell transplantation

Abstract

Nephropathy is an important complication in hematopoietic stem cell transplantation (HSCT) wherein multifactorial causes, i.e., radiation, drug toxicity, graft versus host disease (GVHD), are thought to contribute renal dysfunction. Here, we report a 10-year-old boy with high-risk acute myelocytic leukemia and severe but partially reversible renal dysfunction. The patient initially received umbilical cord blood transplantation (UCBT) with CY 120 mg/kg and kidney unshielded 12 Gy of total body irradiation. After the leukemic relapse, he received allogenic bone marrow transplantation (BMT) 270 days after the first transplantation. Two months later, his renal function started to deteriorate and urinary protein increased gradually to 1 g/day. Four months after BMT, by the symptoms of severe GVHD, the dose of tacrolimus, utilized to avoid GVHD, was increased although his serum Cre level elevated to 2.97 mg/dL. Serum Cre level improved to 2.0 mg/dL paralleled with GVHD improvement. Renal histological findings showed severe interstitial edema, features of thrombotic microangiopathy (TMA), and C4d deposition along the glomerular capillaries and peritubular capillaries. We suggested that control of GVHD had benefitted to ameliorate renal function of the patient. Treatment for GVHD improved renal dysfunction and TMA of our patients. Moreover, renal biopsy was powerful to elucidate the exact origin of renal dysfunction after HSCT.

Keywords: Bone marrow transplant nephropathy; Calcineurin inhibitor nephrotoxicity; Interstitial edema; Mesangiolysis; Thrombotic microangiopathy; Total body irradiation.

Fig. 1

Clinical course after bone marrow transplantation. Serum creatinine level of our patient ascended gradually after infectious events. Because of renal dysfunction, tacrolimus dose was reduced gradually from 1 mg per day to 0.1 mg per day. After GVHD became obvious, tacrolimus dose was increased to 0.5 mg per day which was effective for renal function recovery

Fig. 2

Renal histological findings of the patient 8 months after second HSCT. a Diffuse fibrosis, edema and infiltration of lymphocytes are observed in interstitial area in Masson’s Trichrome staining. Diffuse interstitial fibrosis is accompanied by lymphoid cells infiltration. Note glomeruli are diffusely collapsed with widening of urinary space. b Slightly thickened wall of arteriole is observed in Periodic acid-Schiff staining. c Segmental mesangiolysis is notable and double contour in glomerular basement membrane. Periodic acid methenamine silver staining d. C4d deposition was detected along the glomerular capillaries and peritubular capillaries