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Sixteen renal transplant (RT) patients (10 men, 6 women, aged 49 +/- 10 years) with chronic hepatitis C received alpha interferon (IFN alpha) therapy (Intron A, Schering Plough) at a dose of 3 x 10(6) units s.c. 3 times a week, scheduled for 24 consecutive weeks. At the beginning of the study all had a stable renal function since at least 12 months (mean serum creatinine -SCr- 121 +/- 38 mmol/l). Fourteen patients were receiving cyclosporin A (CsA) either alone (1) or in combination with steroids and/or azathioprine -AZA- (double therapy: 8; triple therapy: 5); two patients were on conventional therapy. The mean daily doses of CsA were 2.6 mg/kd i.e. a mean whole blood trough level of 104 ng/ml. Six patients experienced renal failure either acute (5) or subacute (1) within 7 to 24 weeks after the start of IFN alpha therapy. Their mean SCr increased from 105 +/- 31 mmol/l to 207 +/- 63 mmol/l (p = 0.02) with de-novo proteinuria in one case (1 g/d) and an increase in pre-existing proteinuria in 2; 3 remained without proteinuria. The histological study showed in all cases a diffuse interstitial edema associated with dilatation of peritubular capillaries; mild inflammatory infiltrates were present in only 3 cases; mild glomerular lesions were not always found (glomerular ischemia, mesangial hypertrophy). There was no vascular lesions IFN alpha was withdrawn in these 6 patients, associated with methylprednisolone pulses in 5 cases. Renal function improved in two cases, stabilized in one and progressed to end stage renal failure in 3 within 4 to 12 months. Four patients had iterative renal biopsies showing in all cases diffuse interstitial fibrosis. This subgroup of patients did not statistically differ at the start of the study from those who did not develop renal failure according to baseline immunosuppression, HLA matching, total peripheral blood lymphocyte (PBL) count. PBL subtypes. INF alpha therapy was associated with acute or subacute renal failure in 37% of patients. The most prominent histological finding was a diffuse interstitial edema of rapid onset, without signs of cellular or vascular rejection. Thus we do not recommend to use IFN alpha therapy in RT patients with chronic hepatitis C, until the mechanisms of the subsequent renal failure be more understood.
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PMID:[Acute renal insufficiency in renal transplants treated with interferon-alpha for chronic hepatitis C]. 876 57

The importance of HLA matching for cadaver-donor transplants is often ignored due to the small (10%) difference in graft survival rates between the best and worst matched pairs. A new "fit and match" hypothesis is proposed to improve the predictive value of matching. Graft and functional survival rates of kidney transplants were calculated for living and cadaver-donors by the standard Kaplan and Meier methods. Mean discharge serum creatinine (SCr) values were computed after excluding patients who died or lost their grafts before discharge. Donor size, recipient size, age of donor kidney, damage caused by cold ischemia time, and mode of donor death all had substantial effects on the average SCr levels at discharge. These SCr levels correlated with one- and five-year graft survival rates. Transplants that had extremely different graft survival rates, such as those from living donors and cadaver donors, were found to have similar rates when reclassified by SCr levels at discharge. By examining the combined effects of the fit and match factors, transplants with the best fit and match exhibited a 95% one-year graft survival rate, whereas those with the worst fit and match had a 75% survival rate. This 20% difference increased to 36% after five years (84% vs. 48%). We conclude that the fit and match hypothesis provides a theoretical basis for devising a more critical method of predicting cadaver kidney transplant survival rates. Furthermore, it suggests a vital need to develop methods for estimating functional donor renal mass.
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PMID:Fit and match hypothesis for kidney transplantation. 878 7

Overall one-, 5-, and projected 10-year graft survival rates were 81%, 58% and 39%, respectively for 51,442 cadaveric kidney transplants performed at 251 U.S. transplant centers from October 1987-December 1994. The comparable results for recipients of living donor kidneys were significantly higher, 91%, 75%, and 60% (p<0.001). One-year first cadaver graft survival rates improved from 77% for transplants performed in 1987-1988 to 84% for transplants performed in 1991-1992 (p<0.001). Recipients of second cadaveric transplants in 1987-1988 had a 69% one-year graft survival rate compared with 81% for those transplanted after 1990 (p<0.001). Graft survival rates have been stable since 1991. The percentage of broadly sensitized first transplant recipients decreased from 13% before 1991 to 7% after, and the one-year graft survival rates increased by 4-6% for both sensitized and nonsensitized recipients between the 2 periods (p<0.001). Among retransplanted patients, the percent of broadly sensitized recipients fell from 40-33% over the same periods (p<0.01). One-year graft survival rates increased by 7-8% for sensitized and nonsensitized patients (p<0.001). One-year graft survival rates improved from 74-83% for Blacks (p<0.001) and from 78-85% for non-Blacks (p<0.001) transplanted for the first time when comparing transplants performed in 1987-88 with those performed in 1993-94. The cause of donor death had a significant effect on graft survival. The 5-year graft survival rate was 61% for 28,923 recipients of trauma donor kidneys compared with 54% for 16,956 transplants from CVA donors (p<0.001). Kidneys from CVA donors increased from 28% of all cadaveric kidneys in 1988 to 38% in 1994. The donor's age was a more important determinant of long-term survival, however, and correlated strongly with the cause of donor death. Only 16% of CVA donors were reportedly age 30 or less, compared with 75% of trauma donors. First cadaver graft survival decreased by approximately 2% for each 12 hours of cold ischemia time. Although there was a significant increase in the incidence of delayed graft function from 19% when the CIT was less than 12 hours to 35% when the CIT was more than 36 hours, there was no significant long-term effect of cold ischemia time. The recent change in UNOS policy to share zero-HLA mismatched kidneys resulted in a 2-fold increase (from 8%-16%) in the number of HLA-matched transplants performed during the first 6 months following the change. The percentage of Blacks who have received matched kidneys following this change has increased from less than 2% to more than 5%, a 3-fold increase. The 163 Blacks who received an HLA-matched kidney prior to 1995 had a 65% 4-year graft survival rate compared with 53% for mismatched Blacks (p<0.001). The incidence of early rejections was also reduced by 25% among matched recipients and the graft half-life was 8 years compared with 5 years for mismatched Blacks. About 25% of HLA-matched kidneys were transplanted to ABO compatible but not identical recipients. Although the effect of the policy allowing compatible transplants did not result in a large number of type O kidneys transplanted to non-O recipients when only 8% of kidneys were shared, the recent change in allocation policy may be detrimental to type O waiting patients.
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PMID:The UNOS scientific renal transplant registry. United Network for Organ Sharing. 879 51

Graphs and tables published 10 years ago in our Clinical Kidney Transplants 1985 book are compared to current analyses. Impressive progress is apparent over the past decade. During this period, the effects of factors such as transfusion and the duration of first grafts on second grafts have disappeared, while the effects of factors such as cold ischemia time, regrafts and original disease have diminished in magnitude. Other factors, including HLA matching, donor age and race, continue to exhibit significant influence. It should be emphasized that most of these comparisons apply to one-year graft survival. Thus, our attention must now turn to factors which influence 10-year graft survival. Though 10 years is considered long-term survival to transplant physicians, for patients, it is but a brief period of life.
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PMID:Advances in kidney transplantation: 1985-1995. 879 86

Sixteen kidney transplant (KT) patients (10 men, 6 women, aged 49 +/- 10 years) with chronic hepatitis C alpha-interferon (IFN-alpha) therapy (Intron A, Schering Plough) at a dose of 3 x 10(6) units subcutaneously 3 times a week. The treatment was scheduled for 24 consecutive weeks. Each patient had had stable renal function for at least 12 months prior to IFN-alpha therapy (mean serum creatinine, SCr, 121 +/- 38 mmol/l). Fourteen patients were receiving cyclosporin-A (CsA)-based immunosuppression and 2 patients were on conventional therapy. The patients' SCr was checked every 2 weeks while on IFN-alpha, or weekly if it increased more than 15% from baseline. IFN-alpha was withdrawn if SCr increased more than 25% from baseline, in which case a kidney biopsy was performed. Six patients experienced either acute (n = 5) or subacute (n = 1) renal failure within 7-24 weeks after the onset of IFN-alpha therapy. Their mean SCr increased from 105 +/- 31 to 207 +/- 63 mmol/l (p = 0.02) with de novo proteinuria in 1 case (1 g/day) and an increase in preexisting proteinuria in 2. The other 3 patients did not develop proteinuria. In each case, histological study showed diffuse interstitial edema associated with dilation of the peritubular capillaries, whereas mild inflammatory infiltrates were present in only 3 cases and mild glomerular lesions were not always found (glomerular ischemia, mesangial hypertrophy). There were no vascular lesions. IFN-alpha was withdrawn in these 6 patients, in association with methylprednisolone pulses in 5 cases. Renal function improved in 2 cases, stabilized in 1 and progressed to end-stage renal failure in 3 within 4-12 months. Four of these patients had iterative renal biopsies which showed diffuse interstitial fibrosis in each case. The patients who developed renal failure did not statistically differ at the start of the study from those who did not, with respect to the following: baseline immunosuppression, HLA matching, total peripheral blood lymphocyte count or peripheral blood lymphocyte subtypes. IFN-alpha therapy was associated with acute or subacute renal failure in 37% of the patients. The most prominent histological finding was diffuse interstitial edema of rapid onset, without signs of cellular or vascular rejection. In conclusion, we do not recommend IFN-alpha therapy for KT patients with chronic hepatitis C, until the mechanisms of the subsequent renal failure are better understood.
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PMID:Acute renal failure in kidney transplant patients treated with interferon alpha 2b for chronic hepatitis C. 893 73

The objective of the study was to determine if it is justified to use the scarce resources of cadaveric kidneys on HLA-sensitized patients, by reviewing the initial and long-term outcome of cadaveric renal transplantation at Uppsala University Hospital, Sweden. Between January 1988 and December 1994, 402 renal transplantations were performed. The patients were divided into one group of sensitized recipients (peak panel antibody reactivity > or = 25%; n = 84) and a second of non-sensitized recipients (panel reactive antibodies < 25%; n = 318). The groups were comparable in terms of recipient and donor age, gender, HLA-A, -B and -DR mismatches and numbers of diabetics. None of the sensitized patients received a six-antigen-matched kidney. For the non-sensitized group, life table analysis showed a 1-year actuarial graft survival (GS) of 91.8% and a 4-year GS of 84.4%. The corresponding GSs for the sensitized group were 79.9% and 68.7%, respectively (P < 0.01). The statistical significance vanished if patients with primary non-function were excluded. When excluding donors above 55 years of age, kidneys with cold ischemia time above 20 h, and two-antigen (HLA-DR) mismatches, there was no detectable difference between the non-sensitized and sensitized groups at 1-year or 4-year GS. Although there is a statistical significance in GS between non-sensitized and sensitized recipients of a kidney transplant, this does not differ from other risk groups such as diabetics, rheumatoid disease sufferers or elderly recipients. We therefore conclude that the sensitized patient should be accepted on the waiting list for a kidney transplant and that it is worthwhile to do the utmost to transplant this category of patients. Our data indicate that kidney GS in sensitized recipients is more affected by negative risk factors such as older donors, long cold ischemia time and two-antigen HLA-DR mismatch, than the non-sensitized recipient. To improve the outcome, those negative factors should be avoided or reduced.
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PMID:Is kidney transplantation in sensitized recipients justified? 895 90

The purpose of this retrospective study was to evaluate results of non-heart-beating donor (NHBD) kidney transplantation. Between Jan 1986 and Dec 1994, 80 out of 582 cadaveric kidneys were harvested from NHBD (31.9 min +/- 24 after cardiac arrest). The results in the NHBD group (76 recipients) were compared with those obtained after transplantation of kidneys harvested from heart-beating donors (HBD) with respect to early graft function, and the graft and recipient's survival. Both groups were matched for sex, age, PRA level, number of HLA mismatches, and cold ischemia time. Triple immunosuppression therapy was used in both groups. Acute tubular necrosis (ATN) was observed significantly more frequently in the NHBD group (50 of 76 recipients vs 33 of 100 in the HBD group). The striking finding of this study was that the occurrence of primary non-function was the same in both groups and that the main cause of it was acute rejection. The 1-year patient and graft survival rates were 98.7% and 81.6% for the NHBD group and 99% and 90% for the HBD group, respectively. There was also no statistical difference in the serum creatinine concentration in both groups. We concluded that despite an increased incidence of ATN in the NHBD kidney recipients, the long-term results are good and comparable with those in the HBD group.
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PMID:Transplantation of kidneys harvested from non-heart-beating donors: early and long-term results. 895 97

Renal retransplantation can be hampered by the presence of anti-HLA alloantibodies. Previous studies have documented in vitro and in vivo suppression of these antibodies by intravenous immunoglobulins (IVIg). We conducted a randomized study in 41 patients, who have received a second cadaveric transplant between 1989 and 1994. They all were treated with a quadruple-immunosuppressive protocol. In addition, 21 patients received 0.4 g/kg/day of IVIg, on the first 5 days after transplantation. The two groups of patients were identical for age, sex, duration of the first graft, duration of cold ischemia, anti-HLA sensitization, HLA matching, the number of acute rejection episodes, and the incidence of cytomegalovirus infection. The 5-year survival rate was significantly higher in the group of patients treated with IVIg: 68% versus 50% in the control group. The only significant factor associated with IVIg infusion and better survival was a shorter delay of graft function (3.4 +/- 1.0 days versus 9.9 +/- 1.6 days). In conclusion, this randomized study demonstrates that IVIg treatment is associated with better long-term graft survival in retransplanted patients. This beneficial effect may be related to a long-lasting immunosuppressive effect of IVIg and/or to an early protective effect of the graft against ischemia.
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PMID:Long-term benefit of intravenous immunoglobulins in cadaveric kidney retransplantation. 897 Jun 26

Rupture of a renal allograft (RAR) is an uncommon but serious complication of renal transplantation. A recent RAR prompted a review of our experience, with the purpose of (1) identifying conditions that may predispose this complication and (2) defining strategies for prevention. A 5-yr, consecutive living-related (LRD) and cadaver donor (CD) cohort of 331 patients was studied retrospectively. Twelve patients (3.6%) had RAR. Donor characteristics, procurement and preservation conditions, and recipient characteristics were major study categories. Data analysis was computer-based and included multivariate analysis. The nine White and two Black cadaver donors were "ideal", mean age 29 yr, with mean high creatinine (CR) of 1.3 and terminal CR of 1.1 mg/dl and mean terminal urine output of 423 ml/min. Nine of 11 CD had low-dose dopamine use (terminal, mean 8, range 5-13 micrograms/kg/min). Eleven of 11 donors had procurement en-bloc, 9 of which were multiple organ procurement. All had 4+/4+ flush and cold storage with UW solution. Mean cold ischemia time (CIT) was 22 h, 28 min (range 15 h, 16 min to 40 h). For patients with RAR mean age was 39 yr; there were 12 Black patients and 7 males, 5 females. HLA match was 1 antigen (AG) for 3, 2 AG for 8, and 4 AG for 1 (mean 1.9). Nine patients had delayed or declining renal function requiring dialysis. The panel reactive antibody was at peak, mean 47% (range 0-100%) and current, mean 18% (range 0-84%). Six of 12 had OKT3 therapy at time of RAR and six had biopsies. Day of RAR was mean 10, median 9 (range 4-21). Pain and drop in hematocrit were observed in most. There was one fatality (8%), and all kidneys were removed. All kidneys showed at least minimal rejection but six had severe acute tubular necrosis (ATN) with edema and minimal rejection. Statistically significant associations with RAR were older recipient age (p = 0.01), donor-recipient race mismatch (White donor to Black recipient) (p = 0.007), and dialysis requirement (p < 0.001). Other variables were not statistically correlated: gender, race, CIT, transplant number, LRD vs. CD, peak or current PRA, and total HLA and BDR mismatch. The data suggest that ATN and rejection act synergistically to cause RAR and that early delayed function requires intensive and perhaps novel immunosuppression, especially in Black recipients.
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PMID:Renal allograft rupture: a clinical review. 899 57

Long-term prognosis in kidney transplant recipients depends on multiple factors. To investigate whether mild proteinuria within the first 6 months following transplantation is a determinant of the long-term function and survival of kidney transplants, 357 patients transplanted between 1980 and 1990 were retrospectively examined over a period of 5 years. 25.5% of the patients developed an early proteinuria between 0.25 and 1.0 g/day over 6 or more months. This group was well matched concerning gender, age of recipient, underlying disease, time on hemodialysis, donor age, cold ischemia time and HLA mismatches with the group without proteinuria (n = 266). Five-year transplant survival in the group with proteinuria was 58.9% in contrast to 85.6% in recipients without proteinuria. Intermittent proteinuria did not worsen long-term prognosis. Proteinuria of 12 months or longer further reduced 5-year transplant survival to 42.6%. Over the whole observation period, serum creatinine in recipients with proteinuria was about 0.5 mg/dl higher as compared with patients without proteinuria. No correlation between proteinuria and gender, age of recipient, duration of hemodialysis, age of donor, cold ischemia time and mismatches could be detected. In conclusion, early proteinuria apparently is not due to established donor or recipient factors. However, there is a strong correlation of proteinuria with worse transplant function and survival.
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PMID:Influence of proteinuria on long-term transplant survival in kidney transplant recipients. 904 35


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