Histopathology of Chronic Kidney Disease after Allogeneic Hematopoietic Cell Transplantation: A Multi-Center Observational Study of Kidney Biopsies

Background Renal dysfunction is a common complication of allogeneic hematopoietic cell transplantation (Allo-HCT) with proven negative impact on early and long-term mortality. The cumulative incidence of chronic kidney disease(CKD) after Allo- HCT varies from 13~60% in adult studies to as high as 62% in children. So far, most knowledge on chronic renal impairment in the context of Allo-HCT is based on clinical and laboratory findings. Causes of CKD are diverse, usually overlapping, and poorly understood. Kidney biopsies are performed in less than 5% patients with CKD, the pathophysiology of idiopathic CKD remains obscure. We conducted a multi-center clinicopathologic study of Allo-HCT patients with CKD to described the histopathologic spectrum of renal manifestations.

Methods and Results Between 2005 and 2018, 24 recipients(17 males and 7 females) of Allo-HCT underwent kidney biopsy for either proteinuria or deterioration of kidney function at four centers. The median age was 43.8 (7.2~54.3) years, and the median time from Allo-HCT to kidney biopsy was 17.2(2.0~74.6)months. Evidence for GVHD was found in 20 (83.3%) patients. Among the 24 patients, 10 patients had a large amount of proteinuria (24-hour urine protein > 3.5 g/L), and 12 patients had elevated serum creatinine (Scr >110μmol/l). The most common pathological findings of kidney biopsy were GVHD (n=8), membranous nephropathy (MN, n=5), thrombotic microangiopathy (TMA, n=4), BK virus nephropathy (n=2), and we also found ischemic nephropathy, chronic interstitial nephritis, minimal change disease (MCD), GVHD with TMA, MN with focal segmental glomerular sclerosis (FSGS), MCD with acute tubular injury, BK virus nephropathy combined with calcineurin inhibitor nephrotoxicity in one case. The follow-up data showed 3 died of recurrent malignancy, 6 loss to follow-up , the median follow-up time was 18.3(12.3~120.2)months. Of the 18 patients, 8 (44.4%) had an estimated glomerular filtration rate (eGFR) of less than 60 ml/(min1.73m2), 5 (27.8%) still had moderate proteinuria.

Conclusions A wide spectrum of renal pathologic findings can be observed in Allo-HCT patients. Either severe proteinuria or elevated serum creatinine were common presentations in this unique setting, which can be due to GVHD , MN, TMA, BK virus nephropathy , MCD, FSGS, and overlapping lesions. Kidney biopsies are necessary to establish the underlying cause of CKD in Allo-HCT patients.