Glomerular Endothelial Injury in Patients with Non-Renal Transplants: Are We Missing Subclinical Thrombotic Microangiopathy?
Yael B Kushner, Fahim A Malik, A Bernard Collins, Robert K Holmes, R Neal Smith, Robert B Colvin. Massachusetts General Hospital, Boston
Background: Approximately 20% of recipients of heart, liver, lung or bone marrow transplants develop chronic renal failure. This study aimed to elucidate the value of the renal biopsy, the contribution of thrombotic microangiopathy (TMA) and a novel means to assess glomerular endothelial damage.
Design: An institutional database containing 9,729 renal biopsies identified 32 patients with non-renal transplants (heart, lung, liver, and bone marrow). Clinicopathologic parameters were extracted and biopsies were reviewed by a pathologist. Ultrastructural signs of glomerular endothelial damage were assessed using a novel scoring system. The degree of endothelial fenestration was measured in 5-10 glomerular capillary loops; 10 patients with minimal change disease (MCD) were scored for comparison.
Results: The median patient age was 49 (range 20-74). Median time from transplant to renal biopsy was 42 months (range 1-168). The renal diagnoses were: 19 focal segmental glomerulosclerosis (FSGS), including 5 with features of collapsing FSGS; 9 TMA; 4 immune complex glomerulonephritis, including 2 with HCV-related disease and one with IgA nephropathy; 25 with arteriolar hyalinosis; and 20 with more than 25% interstitial fibrosis (many had more than one diagnosis). The mean serum creatinine at the time of biopsy was 3.7 (+/-1.9). Median platelet count was 169,000/mm2 (+/-70,000). Glomeruli had fewer endothelial fenestrations compared with controls with MCD (45 +/-31% vs 89 +/-7%, respectively; p<0.001). Loss of endothelial fenestrations was present in 77% of the biopsies, including 75% of the patients with collapsing FSGS. The percent of endothelial area with fenestrations was correlated with the platelet count (p<0.05), even though most of the patients did not have diagnostic signs of TMA. 18 patients progressed to end-stage renal disease (ESRD) and/or required renal transplantation.
Conclusions: Patients with non-renal transplants frequently develop renal failure, which in this series was biopsied late in the course. TMA, likely related to calcineurin inhibitors, has been associated with poor renal survival in these patients. Glomerular endothelial injury is known to be a feature of TMA, and, as assessed by our novel scoring system using ultrastructural findings, may allow detection of subclinical TMA in the absence of typical clinical or light microscopic features. Patients with subclinical TMA may benefit from modified treatment modalities to reduce their risk of progression to ESRD.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 249, Wednesday Afternoon