Patterns of Renal Dysfunction and Profile of Kidney Biopsies in Hematopoietic Stem Cell Transplant Recipients

Abstract

Introduction: Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes.

Material and methods: Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients.

Results: The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9-30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft "mesangiolysis" was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, p = 0.04). "Associated extra-renal GvHD" occurred in 11/19 (57.9%) allogenic recipients. Patients with "associated extra-renal GvHD" had significantly more deaths (6/11, 60% vs. 0, p = 0.02) but comparable renal outcomes.

Conclusion: Renal GvHD can present with or without "associated extra-renal GvHD" after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.

Keywords: Graft versus host disease; Hematopoietic stem cell transplant; Mesangiolysis; Nephrotic syndrome; Thrombotic microangiopathy.

Fig. 1.

Flowchart of GRACE-GVHD cohort selection. BMT, bone marrow transplant; HSCT, hematopoietic stem cell transplant; IRGN, infection-related glomerulonephritis; PBSCT, peripheral blood stem cell transplant; TMA, thrombotic microangiopathy.

Fig. 2.

Thrombotic microangiopathy pattern in allogenic transplant recipients. a Focal glomerular mesangiolysis, aneurysmal capillary dilatation with fragmented red blood cells (H&E stain, original magnifications ×200). b C4d-positive TMA with diffuse interstitial inflammation with tubulitis (H&E stain, original magnifications ×200). c C4d immunohistochemistry displaying glomerular mesangial staining and also non-diagnostic staining of plasma within the capillary aneurysm. Note the adjacent arteriole does not show any staining. d Transmission electron microscopic image displaying acute microangiopathic changes with increased subendothelial lucency of glomerular capillary loops, entrapped red blood cells, and few flocculent debris (magnification ×4,000).

Fig. 3.

Nephrotic syndrome pattern in allogenic transplant recipients. a Minimal change disease – glomerulus with no diagnostic abnormality (H&E stain, original magnification ×200). b Minimal change disease – electron microscopic image displaying glomerular capillary loops with severe >90% podocyte foot process effacement (magnification ×4,000). c Membranous nephropathy – glomerulus with global thickening of capillary walls suggestive of membranous pattern of injury (PAS stain, original magnification ×200). d Membranous nephropathy – immunofluorescence microscopy showing diffuse global fine granular capillary wall staining for IgG.