Renal Pathology Associated With Hematopoietic Stem Cell Transplantation

Abstract

The kidney is subject to a large variety of injurious factors before, during, and after hematopoietic stem cell transplantation (HCT), leading to a high incidence of acute kidney injury in the peritransplant period. Chronic kidney disease is estimated to impact 15% to 20% of HCT recipients. Although renal biopsies may be deferred in the setting of thrombotic microangiopathy, acute self-limited impairment, or slowly progressive functional decline, in many patients renal biopsy yields important diagnostic insight to guide treatment. Light microscopic, immunofluorescence, and ultrastructural analysis often reveals a number of concurrent abnormalities in glomeruli, tubules, interstitium, and vessels. Meta-analysis of the literature reveals that membranous nephropathy is the most commonly reported glomerular lesion in the setting of HCT, followed by minimal change disease. Autopsy and biopsy studies show that clinical criteria lack sensitivity and specificity for renal acute and chronic thrombotic microangiopathy. Viral infection and other causes of interstitial nephritis and tubular injury are important findings in HCT renal biopsies, which in many instances may not be clinically suspected. Given the complexity and variability of HCT protocols, clinicopathologic correlation is needed.

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

“…[1][2][3][4] Although some of these current methods of hematopoietic cell transplant tend to be less toxic, many patients still experience significant renal injury because of exposure to a multitude of factors including cytotoxic conditioning agents, radiation, immunosuppression, infection, ischemia, and graft-versus-host disease (GVHD). [5][6][7][8] Acute kidney injury is associated with medications (chemotherapeutic, antibiotic, immunosuppressive), tumor lysis syndrome, renal ischemia, infections, or radiation, whereas chronic kidney injury, including glomerulonephridities, has been associated with chronic GHVD, medications, sequelae of acute injury, ischemia, other comorbidities, and recurrent/secondary malignancy. [7][8][9] Numerous descriptive studies, derived from groups of kidney core biopsy specimens from hematopoietic cell transplant recipients with renal dysfunction, have characterized the most common types of glomerulonephritis in hematopoietic cell transplant patients.…”

“…[5][6][7][8] Acute kidney injury is associated with medications (chemotherapeutic, antibiotic, immunosuppressive), tumor lysis syndrome, renal ischemia, infections, or radiation, whereas chronic kidney injury, including glomerulonephridities, has been associated with chronic GHVD, medications, sequelae of acute injury, ischemia, other comorbidities, and recurrent/secondary malignancy. [7][8][9] Numerous descriptive studies, derived from groups of kidney core biopsy specimens from hematopoietic cell transplant recipients with renal dysfunction, have characterized the most common types of glomerulonephritis in hematopoietic cell transplant patients. 8,[10][11][12][13][14][15][16][17][18] These include membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis.…”

“…[7][8][9] Numerous descriptive studies, derived from groups of kidney core biopsy specimens from hematopoietic cell transplant recipients with renal dysfunction, have characterized the most common types of glomerulonephritis in hematopoietic cell transplant patients. 8,[10][11][12][13][14][15][16][17][18] These include membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis. In addition, acute and chronic thrombotic microangiopathy, or 'transplant-associated thrombotic microangiopathy,' has been shown to occur commonly in hematopoietic cell transplant recipients, 8,14,[17][18][19][20][21][22][23][24][25] with smaller reported numbers of membranoproliferative glomerulonephritis, proliferative glomerulonephritis, ANCA-associated glomerulonephritis, and IgA nephropathy.…”

“…8,[10][11][12][13][14][15][16][17][18] These include membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis. In addition, acute and chronic thrombotic microangiopathy, or 'transplant-associated thrombotic microangiopathy,' has been shown to occur commonly in hematopoietic cell transplant recipients, 8,14,[17][18][19][20][21][22][23][24][25] with smaller reported numbers of membranoproliferative glomerulonephritis, proliferative glomerulonephritis, ANCA-associated glomerulonephritis, and IgA nephropathy. 8,18,[26][27][28][29][30][31][32][33][34][35][36][37] In studies also examining nonglomerular pathology, kidney specimens also show concomitant tubulointerstitial and vascular changes in hematopoietic cell transplant patients.…”

“…In addition, acute and chronic thrombotic microangiopathy, or 'transplant-associated thrombotic microangiopathy,' has been shown to occur commonly in hematopoietic cell transplant recipients, 8,14,[17][18][19][20][21][22][23][24][25] with smaller reported numbers of membranoproliferative glomerulonephritis, proliferative glomerulonephritis, ANCA-associated glomerulonephritis, and IgA nephropathy. 8,18,[26][27][28][29][30][31][32][33][34][35][36][37] In studies also examining nonglomerular pathology, kidney specimens also show concomitant tubulointerstitial and vascular changes in hematopoietic cell transplant patients. 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.…”