This study from RARDR was undertaken to determine the prevalence, natural history and impact on graft survival of post-transplant FSGS in renal allograft recipients. From 1986 to 1995, 4,094 transplants were performed at MCW, UW, UC and UCSF, and were followed for a minimum of one year. FSGS was identified in 62 patients by renal histology, and 29 (47%) had biopsy proven FSGS as the cause of ESRD. There were 40 males, 37 Caucasians, 18 Blacks, 7 others; with a mean age of 38.2 years. Kidneys were from cadaver donors in 48 (72%) and living donors in 14 (28%). Clinical indication for biopsy were: proteinuria greater than 1 gm/24 hours (97%) and elevated serum creatinine (60%). The diagnosis of FSGS was made after a mean period of 87 days, 65% within 6 months and 86% within 2 years post transplantation. Average urine protein at the time of biopsy was 8.31.1 gms (range 0.4 - 26) and serum creatinine was 2.40.2 (range 0.8 - 5.7) mg/dL.
During the follow-up, 40 (65%) FSGS patients had lost their graft. The actuarial kidney survival (%) estimated by Kaplan-Meier method for patients with post-transplant FSGS and others with no biopsy proven glomerular disease are shown below:
| Post Txn | 6mo | 1yr | 1.5yrs | 2yrs | 3yrs | 4yrs | 5yrs |
| Tx FSGS (N=62) | 92% | 86% | 84% | 73% | 58% | 48% | 42% |
| Others | 92% | 89% | 88% | 86% | 82% | 80% | 76% |
Log-rank test, p=0.002.
The median survival for patients with and without post-transplant FSGS were 1,330 and 2,954 days, respectively. In conclusion, FSGS occurs very early post-transplantation. Native kidney diagnosis of FSGS was documented in about half the cases. Development of post-transplant FSGS is associated with high rate of graft failure.
"This research was funded by Hoffman-LaRoche, Inc., Nutley, New Jersey."
S. Hariharan, V. George, M.A. Adams, C. L. Davis, M. R. First, C.P. Johnson, A.M.Roza, F. Vincenti, V. J. Savin, Medical College of Wisconsin (MCW), Milwaukee, WI ; University of Washington (UW) Seattle, WA; University of Cincinnati (UC), OH and University of California (UCSF), San Francisco, CA.
A registry has been developed to evaluate the incidence of recurrent disease after transplant and its effect on transplant outcome. From 1986 to 1995, a total of 4,094 transplants were performed at MCW, UW, UC and UCSF. All patients were followed for a minimum of one year post-transplantation. During the follow-up, a total of 159 (3.9%) cases of recurrent disease were diagnosed by renal biopsy. There were more Blacks in the recurrent disease group than the overall group (24% vs 16%, p=0.02). Other characteristics such as gender, age, transplant #, and organ source were not significantly different in patients with and without recurrent disease. Primary glomerulonephritis was present in 123 patients, which included FSGS, 62; IgA Nephritis, 23; Membrano-Proliferative GN, 22; and Membranous Nephropathy (MN), 16. Other diagnosis included, Diabetic Nephropathy (DN), 18; immune complex GN, 10; HUS, 4; SLE, 3; and Oxalosis, 1.
The diagnosis of recurrent disease was made after a mean period of 422 days post-transplantation. The median kidney survival for patients with and without recurrent disease was 2,355 and 2,954 days, respectively. The actuarial kidney survival at 1, 3, and 5 years post-transplantation for patients without recurrence was 89%, 82%, and 76%. The corresponding values for patients with recurrence was 93%, 75%, and 59%, respectively (Log-rank, p=0.002). The following table shows actuarial kidney survival for individual diseases.
| Tx GN (N) |
FSGS (62) | MPGN (23) | MN (16) | IgN (23) | DN (18) |
| Original Disease by Bx (%) | 47 | 53 | 13 | 60 | - |
| Diagnosis post Tx (days) | 87 | 397 | 647 | 707 | 1819 |
| Proteinuria (gms/day) | 8.3 | 5.2 | 11.1 | 2.9 | 1.7 |
| Serum Creatinine (mg/dL) | 2.4 | 3.3 | 1.9 | 2.2 | 2.3 |
| Survival (%) 12 months | 86 | 81 | 100 | 100 | 100 |
| 24 | 73 | 50 | 100 | 100 | 100 |
| 36 | 58 | 44 | 76 | 94 | 76 |
| 48 | 48 | 31 | 68 | 81 | 68 |
| 60 | 42 | 25 | 68 | 81 | 59 |
In conclusion, recurrent disease is associated with lower graft survival. FSGS presents early and DN presents late after transplantation. MPGN has the worst graft survival, followed by FSGS, and graft loss due to IgAN occurs late. Future studies from our registry will identify risk factors and management strategies that will improve outcome.
"This research was funded by Hoffman-LaRoche, Inc., Nutley, New Jersey."
S. Hariharan, V. George, M. A. Adams, C. L. Davis, C.P. Johnson, M. R. First, V. R. Peddi, A.M.Roza, F. Vincenti, Medical College of Wisconsin (MCW), Milwaukee, WI; University of Washington (UW), Seattle, WA; University of Cincinnati (UC), OH and University of California (UCSF), San Francisco, CA.
Membranous nephropathy (MN) is an uncommon form of glomerulonephritis in renal allografts. This study illustrates the outcome of 16 cases of recurrent/de novo MN in renal allografts. A total of 4,967 renal transplants between six renal transplant centers (MCW, WU, UCSF, UW, UC, UL) were retrospectively analyzed for recurrent/de novo disease. A total of 16 cases (0.3%) of recurrent/de novo MN were identified in this population. Demographic patterns of the 16 were as follows: 14 males, 2 females, 10 white, 2 black, and 4 others. Their mean age was 41 yrs (range 25-56). Ten of 16 had cadaveric renal transplants. The native renal disease was known in 12 cases; 6 had MN; 3 had other forms of glomerulonephritis; and polycystic kidney disease, Alport's syndrome, and obstructive uropathy were seen in 1 each. MN was diagnosed by renal transplant biopsy after a mean period of 22 months (range 3-79 months). Renal biopsy was indicated through a combination of proteinuria and increased serum creatinine. There were 6 cases (37.5%) of recurrent MN and 10 (62.5%) de novo MN. In 68% of cases, the diagnosis was made within 2 years post-transplantation.
The diagnosis of recurrence (n=6) occurred after a mean period of 15 months, and in de novo (n=10), 29 months post-transplantation (p=0.116). All patients were followed for a mean period of 62 months (range 18-115). During follow-up, eight (50%) of the patients lost their allografts. Actuarial kidney survival established by Kaplan-Meier for 1, 2, 3, 4 and 5 yrs was 94%, 87%, 73%, 54%, and 45%. Corresponding values for the remainder of the renal transplants were 85%, 81%, 78%, 72%, and 67% (Log-rank test, p<0.0001). The timing of recurrence did not differ in patients who experienced graft loss and those with a functioning graft (21 vs 24 months, p=0.796). The duration of follow-up after transplantation was similar in patients with and without graft loss (p=0.427).
In conclusion, 1) 37.5% had recurrent MN, and 62.5% had de novo MN; 2) MN is associated with poor long-term graft survival (50% had lost their allografts); 3) in 2/3 of these cases, MN was diagnosed within 2 years post- transplantation; and 4) time to diagnosis was shorter in recurrence compared to de novo MN.
"This research was funded by Hoffman-LaRoche, Inc., Nutley, New Jersey."
A.W. Piering, D. Brennan, R. Ouseph, F. Vincenti, C. Davis, M.R. First, S. Hariharan. Medical College of Wisconsin, Washington University, University of Louisville, University of California, San Francisco, University of Washington, University of Cincinnati.
A retrospective study was initiated through RADR, to evaluate the impact of recurrent/de novo diseases after txn. From Oct., 1987 to Dec., 1996, a total of 4,913 renal tx were performed between MCW, UC, UCSF, UL, UW, and WU. These patients were followed for a minimum of 1 year. A total of 167 (3.4%) cases of recurrent/de novo diseases were diagnosed by renal biopsy. These patients were compared to 4,746 patients who did not have recurrent disease. Forms of GN seen were FSGS, 57; IgA Nephritis, 22; MPGN, 18; and Membranous Nephropathy, 16. Others include: Diabetic Nephropathy, 19; Immune Complex GN, 12; Crescentic, 6; HUS, 8; SLE, 4; Anti-GBM, 2; and other, 4.
During the follow-up period, there were significantly more graft failures in the recurrent disease group, 55 % vs 25%, p<0.001. The actuarial 1, 2, and 5 year kidney survival for those with recurrence was 86.5%, 78.5%, and 39.8%. The corresponding survival for those without recurrence was 85%, 81%, and 68%, respectively (Log-rank test, p<0.0001). Multivariate analysis using Cox Proportional Hazard Model for graft failure was performed to identify risk factors. Cadaveric tx, re-txs, elevated PRA, and recurrent disease were identified as risk factors for allograft failure. The relative risk (RR) for graft failure due to recurrent disease was 1.9 (1.57-2.40), p<0.0001. The RR for graft failure due to recurrent FSGS was 2.25 (1.6-3.1), p=0.0001, and for MPGN was 2.37 (1.3-4.2), p=0.003, and for HUS/TTP was 5.36 (2.2-12.9), p=0.0002. The RR was not significant for recurrent IgAN: 1.45, (0.75-2.8), P=0.26, and Diabetic Nephropathy 1.17 (0.63-2.2), p=0.60.
In conclusion, recurrent disease 1) is associated with poorer long-term survival; 2) RR of allograft loss is double 3) the RR for graft failure was highest with HUS/TTP, followed by MPGN and FSGS.
S. Hariharan, C. Pelz, V. George, M.B. Adams, D. Brennan, C.L. Davis, C.P. Johnson, M.R. First, V.R. Peddi, R. Ouseph, A.M. Roza, F. Vincenti. Medical College of Wisconsin (MCW), University of Washington, Seattle (UW), University of Cincinnati (UC), University of California, San Francisco (UCSF).
Please be aware that medical advice, diagnoses and physician references cannot be obtained from this site.