Predicting long-term graft survival in adult kidney transplant recipients

The ability to accurately predict a population's long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population's long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS) projections were calculated and compared with the population's actual graft survival. The projection curves were created using a two-part estimation model that (1) fits a Kaplan-Meier survival curve immediately after transplant (Part A) and (2) uses truncated observational data to model a survival function for long-term projection (Part B). Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted survival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%). Excellent predictability (41.3%) can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population's long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.     

Predictors of graft survival in pediatric living-related kidney transplant recipients

BACKGROUND: A successful kidney transplant from a living-related donor (LRD) remains the most effective renal replacement therapy for children with end-stage renal failure. The use of LRD kidneys results in decreased time on dialysis, increased graft survival, and better function compared with kidneys transplanted from cadaver donors. We retrospectively analyzed data from the United Network of Organ Sharing (UNOS) Scientific Renal Transplant Registry to determine risk factors for graft loss in children who received an LRD kidney. METHODS: Data was obtained from the UNOS Scientific Renal Transplant Registry on 2418 children ranging in age from 0 to 18 years who underwent an LRD kidney transplantation between January 1988 and December 1994. Multivariate analysis of graft survival was performed using Kaplan-Meier and Cox regression models. RESULTS: The effects of age, pretransplantation dialysis, early rejection, and race were found to significantly affect graft survival. Gender, peak panel-reactive antibody, and ABO blood type were not found to be significant risk factors. Infants <2 years of age initially had the worst graft survival; however, over time their results stabilized, and at 7 years estimated graft survival was good (71%). Adolescents ranging in age from 13-18 years had the best initial graft survival, but as time went on graft survival worsened (55%). Patients who underwent pretransplantation dialysis had a relative risk for graft loss of 1.77 (P<0.001), whereas those who had an early rejection had a relative risk for graft loss of 1.41 (P<0.002). African-Americans had a significantly higher relative risk for graft loss than either Caucasians (1.57, P<0.0005) or Hispanics (2.01, P<0.0003). CONCLUSIONS: Predictors of graft survival for children who receive LRD kidney transplants include age at transplantation, pretransplantation dialysis, early rejection, and race. Over time, adolescents and African-Americans seem to have the lowest graft survival.     

Influence of hyperglycemia and hyperuricemia on long-term transplant survival in kidney transplant recipients

Long-term prognosis in kidney transplant recipients depends on multiple factors. The purpose of this study was to quantify the influence of hyperuricemia and hyperglycemia (elements of the so-called 'syndrome X', i.e., a combination of metabolic disorders like hyperuricemia, diabetes mellitus, hyperlipidemia, and hypertension) on organ function in 350 kidney transplant recipients who had received 375 kidney transplants up to 1990 and in whom sex, age of recipient and donor, nephrologic disease, duration of dialysis, human leukocyte antigen (HLA) classification, and duration of transplant ischemia had been well matched. We found the influence of hyperuricemia on graft survival to be statistically significant (p < or = 0.05), while a statistically significant correlation between hyperglycemia and graft survival could not be detected in the present study. The transplant survival rates 2, 4, and 5 yr post-kidney-transplantation were 96.7, 80.7, and 78.7 in normogylcemic patients vs. 96.9, 85, and 82.7% in hyperglycemic ( > 100 mg,dL) kidney transplant recipients (p > 0.05). Transplant survival in hyperuricemic patients (male, > 8 mg dL; female, > 6.2 mg/dL) 2, 4, and 5 yr post-transplantation was significantly reduced (92.2, 70.6, and 68.8% vs. 98.1, 85.6, and 83.3%), as compared to normouricemic recipients. A combined presence of both hyperuricemia and hyperglycemia probably influencing the prognosis post-kidney-transplantation failed to reach the level of statistical significance. We found a significant correlation between age of recipients and plasma glucose (p < or = 0.01) and between serum uric acid concentrations and diuretic therapy (p < or = 0.05) and gender (p < or = 0.(5). In conclusion, hyperuricemia after kidney transplantation seems to reduce graft survival, whereas an influence of the carbohydrate metabolism has to be denied.     

Favorable graft survival in renal transplant recipients with polycystic kidney disease

Graft survival in the autosomal dominant polycystic kidney disease (ADPKD) transplant population at our center was compared to other end stage renal disease (ESRD) transplant recipients (excluding diabetics). There were 1512 adult cadaveric renal transplants carried out at our center between 1989 and 2002. After exclusions, 1372 renal grafts were included in the study. Using Kaplan-Meier methods, patient and graft survival were determined and compared between the two groups. Mean age at transplant was significantly older for the ADPKD group of patients. The age adjusted graft survival at 5 years was 79% for ADPKD patients compared to 68% in the controls. Patient survival for ADPKD patients improved from 89% at 5 years to 95% when age adjusted. Using the Cox proportional hazards models to compare ADPKD with other causes of ESRD (including recipient age and other variables) in a multifactorial model, ADPKD was significant at the 5% level (p=0.036). This study demonstrates a graft and patient survival advantage in ADPKD patients when age-matched compared to other ESRD patients.     

Poor graft outcome in recipients with de novo donor-specific anti-HLA antibodies after living related kidney transplantation

Antibody-mediated rejection (AMR) is now widely recognized as a major problem in organ transplantation. This study was conducted to investigate the relationship between newly developing anti-HLA antibodies post-transplantation (de novo Abs) and the outcome of living related kidney transplantation (LRKT). The subjects included 87 patients who had received living donor kidney allografts at our institution. Panel reactive Ab assay (Flow-PRA) and graft biopsies were performed in all the recipients before and 6 months after the LRKT. The incidence of AMR, the donor specificity and time of appearance of the de novo Abs were retrospectively studied. Among the 87 LRKT recipients, 47 (54%) showed negative/negative (N/N) results, 15 (17%) showed positive/positive (P/P) results, 12 (14%) showed positive/negative results (P/N), and 13 (15%) showed negative/positive (N/P) results (de novo Abs) in the pre-/post-transplant Flow-PRA analysis. Among the 13 cases with de novo Abs, 5 (38%) had donor-specific Abs (DSA) and the remaining 8 (62%) had nondonor-specific Abs, as determined by LAB single antigen analysis. Eighty percent of the recipients with DSA showed evidence of AMR in the graft biopsies. The 5-year graft survival rate of the recipients with de novo Abs (N/P) was 69%, as compared with 96% in the N/N, 88% in the P/N and 93% in the P/P recipient groups (P = 0.009). LRKT recipients developing de novo Abs, especially those with DSA, showed a much higher incidence of AMR and a worse prognosis. Cautious monitoring for the appearance of anti-HLA Abs should be adopted after transplantation, even in patients without anti-HLA Abs prior to the transplantation.     

Monitoring anti-HLA Class I IgG antibodies in renal transplant recipients

Anti-HLA class I IgG antibodies play an important role in hyperacute rejection but the significance of its de novo appearance or increase in levels during the posttransplant period remains controversial. The purpose of this study was to determine the correlation between the anti-HLA class I IgG antibodies and posttransplant events during the first 4 months after renal transplantation. From 200 renal allograft recipients, 549 serum samples were retrospectively evaluated. Patients who experienced graft dysfunction confirmed by biopsy had three serum samples tested: before, during (within 24 hours), and after the event. The presence of anti-HLA antibodies was observed in recipients with chronic allograft nephropathy (60%); acute rejection (clinical criteria without biopsy 57.1%); rejection types IIA (7.1%), IIB (40%), and III (50%); borderline changes (42.8%); acute tubular necrosis (34.4%); infarction (25%); and no rejection (12.5%). We observed a high incidence of anti-HLA class I IgG antibodies during acute tubular necrosis, borderline changes, acute rejection types IIB and III, and chronic allograft nephropathy.     

Hepatic dysfunction in kidney transplant recipients: prevalence and impact on graft and patient survival

Background Liver disease has emerged as an important cause of morbidity and mortality in renal transplant recipients. Liver insufficiency is the cause of death in up to 28% of long-term survivors after renal transplantation. The aim of this work was to evaluate the prevalence and causes of hepatic dysfunction in renal transplant recipients in Egypt, and its impact on both renal graft function and patient survival. Methods This study comprised 447 kidney transplant recipients who received their grafts between January 1999 and December 2003 at Mansoura Urology and Nephrology Center. Among these recipients, 104 patients showed persistent hepatic dysfunction, while the remaining 343 had normal liver function or transient hepatic dysfunction of less than 6 months’ duration. Results We found that the prevalence of persistent hepatic dysfunction in our recipients was 23.3%. Infections such as hepatitis C virus (HCV;, with longer dialysis duration and blood transfusion as risk factors), HBV, and cytomegalovirus (CMV), were the main causes of persistent hepatic dysfunction. Drugs (e.g., the sirolimus and tacrolimus; cyclosporine; and azathioprine) were also associated with hepatic dysfunction. We did not find a significant impact of hepatic dysfunction on either patient or graft survival. Conclusions Viral infections–especially HCV and CMV–were more prevalent in the group of patients with persistent hepatic dysfunction, with duration of dialysis as an important risk factor for HCV infection. Dose-dependent cyclosporine-induced hepatic dysfunction was observed early post-transplant. Neither tacrolimus- nor sirolimus-associated hepatic dysfunction was dose-dependent. Hepatic dysfunction had no significant impact on either patient or graft survival; however, this finding may be due to the relatively short duration of follow up.     

Influence of hypercholesterolemia on patient and graft survival in recipients of kidney transplants

AIM: The aim of this retrospective, single centre study, was to study the effect of pre- and post-transplant serum total cholesterol (TC) on patient and graft survival. We also sought to see whether patients who had very high TC (>8 mmol/L) had a higher incidence of graft failure and patient mortality compared with those whose cholesterol was only moderately elevated. METHODS: Records of 935 cadaver kidney transplants between 1984 and 1998 were examined. Patients were placed into three groups based on TC level: <5.5 mmol/L (group 1), 5.5-8 mmol/L (group 2) and >8 mmol/L (group 3). The mean TC value from the first five post-transplant years was taken to seek a correlation between TC and post-transplant events. RESULTS: The mean graft follow-up was 66.9 +/- 50.1 months, ranging from 0.1 to 191 months, while mean patient follow-up was 83.8 +/- 50.1 months, ranging from 0.5 to 191.6 months. Pre-transplant TC was available in 201 patients (21.5%), and post-transplant data was available (for first 5 yr) in 655 patients (70%). During the study period, 220 patients (23.5%) had died, 285 (30.5%) of the grafts had failed during the follow-up, while 129 (13.8%) of the patients died with a functioning graft. We found significantly longer survival of patients having a pre-transplant TC below 5.5 mmol/L vs. patients whose pre-transplant TC was above 5.6 mmol/L (p = 0.02). We also compared patients who had very high pre-transplant TC (>8 mmol/L) level with those whose TC was moderately elevated (5.5-8 mmol/L) and found that there was no higher incidence of graft failure (p = 0.77) nor patient mortality (p = 0.83). No difference could be found in graft survival based on pre-transplant TC. We also did not find a detrimental influence of post-transplant TC on the patient or graft survival. Diabetes mellitus (p = 0.006) and age over 50 yr (p = 0.007) affected patient survival, while low cyclosporine levels (p = 0.02) and acute rejection episodes (p = 0.009) affected graft survival. The mode of dialysis and time on dialysis prior to transplantation did not affect patient and graft survival. CONCLUSIONS: We found significantly greater survival of patients having a pre-transplant TC below 5.5 mmol/L. No difference could be found in graft survival based on pre-transplant TC. Post-transplant TC did not adversely affect patient or graft survival.     

Impact of pretransplant dialysis on early graft function in pediatric kidney recipients.

Delayed graft function (DGF) is a frequent complication of kidney transplantation (KT) that may affect both short- and long-term graft outcome. It has been reported that pretransplantation peritoneal dialysis was correlated with a better recovery of graft function than hemodialysis in adult kidney recipients. However, the effect of pretransplantation dialysis mode (PDM) seemed to be unclear on the early outcome of KT in pediatric recipients. In this study, the potential impact of PDM on early graft function was evaluated in 174 pediatric patients who underwent KT by using cadaveric donors. The primary outcome parameter was the time to reach a serum creatinine (SCr) level 50% of the pretransplantation value [T(1/2(SCr))], while DGF was defined as a T(1/2(SCr)) >3 days after KT (n = 40). By stratifying kidney recipients for normal function graft or DGF, this latter group showed a significantly higher body weight (BW) on the day of KT (P = 0.014), body surface area (BSA) (P = 0.005), warm ischemia time (WIT) (P = 0.022), early SCr on the day 1 after KT (P < 0.001), and T(1/2(SCr)) (P < 0.001), whereas lower urine volume (UV) collected in the first 24 h after KT (P < 0.001) and fluid load (P < 0.001) occurred. Univariate exponential correlation that was carried out between T(1/2(SCr)) and all the other variables had shown a better value than the linear correlation for BW (R(2) = 0.28 vs. R(2) = 0.04), BSA (R(2) = 0.29 vs. R(2) = 0.03), and SCr (R(2) = 0.51 vs. R(2) = 0.28). In a multivariate regression analysis performed by entering T(1/2(SCr)) as dependent variable and following a forward stepwise method, cold ischemia time (CIT) (P = 0.027) but not PDM (P = 0.195) reached significance. In a Cox regression analysis carried out with T(1/2(SCr)) as dependent variable, neither CIT nor PDM gained significance. This study suggests that PDM does not affect early graft function in pediatric kidney recipients.     

Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation

AIMS: To investigate the outcomes in patients who have pre-existing diabetes and those who develop post-transplant diabetes mellitus (PTDM). METHODS. We retrospectively reviewed the charts of 939 patients who received a first functioning renal transplant in the cyclosporine (CyA) era between 1984 and 1999. RESULTS. Sixty-six (7%) patients had renal failure due to insulin-dependent diabetes mellitus (IDDM) and 7 (0.8%) patients due to non-insulin-dependent diabetes mellitus (NIDDM). Ten (1.1%) patients had coexistent diabetes and 48 (5.1%) recipients developed PTDM. The mean graft survival for the patients with PTDM was 9.7 yr versus 11.3 yr for the non-diabetic patients, while mean graft survival was 10.1 yr for patients with IDDM and 2.9 yr with NIDDM and 8.3 yr for those with coexistent diabetes (p=ns). However, there was a statistically significant difference in patient survival between patients who developed PTDM and in those who did not develop this complication. The mean survivals of patients with IDDM, NIDDM, coexistent diabetics and PTDM were 8.4, 3.7, 8.6 and 10.3 yr, respectively. The mean survival of the patients without pre-existing diabetes or PTDM was 12.8 yr (p<0.001). The survival of patients older than 55 yr with PTDM was no different to the control group. However, in those younger than 55 yr, PTDM was associated with a higher risk of death (relative risk of 2.54, p<0.001). Fifty percent of patients with IDDM developed acute rejection episodes, whereas rejection rate was 57.1% in NIDDM group, 50.0% in the PTDM group, 20.0% in the coexistent diabetes group and 44.3% in the control group (p=ns). CONCLUSION. Patient survival, but not graft survival, was adversely affected by both pre-existing diabetes and by PTDM, particularly in those with an age less than 55 yr.     

Frailty and delayed graft function in kidney transplant recipients

The ability to predict outcomes following a kidney transplant is limited by the complex physiologic decline of kidney failure, a latent factor that is difficult to capture using conventional comorbidity assessment. The frailty phenotype is a recently described inflammatory state of increased vulnerability to stressors resulting from decreased physiologic reserve and dysregulation of multiple physiologic systems. We hypothesized that frailty would be associated with delayed graft function, based on putative associations between inflammatory cytokines and graft dysfunction. We prospectively measured frailty in 183 kidney transplant recipients between December 2008 and April 2010. Independent associations between frailty and delayed graft function were analyzed using modified Poisson regression. Preoperative frailty was independently associated with a 1.94-fold increased risk for delayed graft function (95% CI, 1.13-3.36; P = .02). The assessment of frailty may provide further insights into the pathophysiology of allograft dysfunction and may improve our ability to preoperatively risk-stratify kidney transplant recipients.     

B cell positive cross-match not due to anti-HLA Class I antibodies and first kidney graft outcome

The effect of B cell cross-match (XM) was investigated in 680 first deceased-donor kidney transplants in a single centre from 1990 to 1999: 74 transplants presented a B-positive XM (Group 1) 606 had a B-negative XM (Group 2). The absence in Group 1 of weak/low-titre anti-HLA Class I antibodies was assured blocking anti-Class I reactivity by treating B cells with non-cytotoxic anti-beta2 microglobulin (alphabeta2 M) serum before XM. Graft survivals up to 5 years were not significantly different; some differences were nevertheless observed: HLA-A,B,DR mismatches influenced graft outcome in Group 1: patients with 0-2 mismatches had better survival than patients with 3-4. When analysed according DR mismatch, patients with 1 mismatch had worse graft survival than well matched patients (p<0.05). No significant difference depending on HLA match was observed in Group 2. Early acute rejection rate was similar in the Groups except the rejection episodes after one year: Group 1 had significantly more. 61/74 patients of Group 1 were retrospectively analysed for anti-HLA-DR,DQ reactivity: only 11/61 had anti-HLA-DR or DQ antibodies (3/11 were donor specific); graft survival and rejections were not significantly different in the patients with and without anti-HLA Class II antibodies. Anti-donor B cell reactivity, at XM, once excluded the presence of weak/low-titre anti-HLA Class I antibodies, did not influence first kidney graft survival.     

Identification of highly responsive kidney transplant recipients using pretransplant soluble CD30

The identification of high immunologic responders is desirable for the selection of appropriate immunosuppressive regimens. With the collaboration of 29 transplant centers in 15 countries, we investigated whether the pretransplant serum content of soluble CD30 (sCD30), a marker for the activation state of Th2-type cytokine producing T cells, is a useful predictor of kidney graft outcome. Pretransplant sera of 3899 cadaver kidney recipients were tested for serum sCD30 concentration using a commercially available enzyme-linked immunosorbent assay kit. Subsequent kidney graft survival was analyzed. The 5-yr graft survival rate in 901 recipients with a high pretransplant serum sCD30 (> or =100 U/ml) was 64 +/- 2%, significantly lower than the 75 +/- 1% rate in 2998 recipients with low sCD30 (<100 U/ml) (P < 0.0001). High sCD30 was associated primarily with graft loss and not with patient death. The sCD30 effect on graft survival was evident in first transplants as well as in retransplants, in presensitized patients with lymphocytotoxic antibodies as well as in nonsensitized patients, and in patients who received HLA well-matched kidneys as well as in patients who received poorly matched grafts. Recipients with a high pretransplant sCD30 needed significantly more rejection treatment after the first posttransplant year and continued to lose grafts at a higher rate during the 5-yr follow-up period, indicating that pretransplant sCD30 predicts not only the risk of acute rejection but also of chronic allograft nephropathy.     

Impact of pretransplant human leukocyte antigen-C and -DP antibodies on kidney graft outcome

The aim of our study was to determine whether the presence of specific human leukocyte antigen (HLA)-C and -DP antibodies before transplantation influenced graft outcomes in immunized recipients. Two groups of pretransplant immunized recipients were studied: patients with only classical HLA-A, -B, -DR, -DQ antibodies (n = 176) and those with classical plus HLA-C and/or -DP antibodies (n = 27). Acute antibody-mediated rejection was preferentially associated with the presence of pretransplant anti-HLA-C and -DP antibodies (5/6 cases). In four cases, acute rejection episodes were followed by graft loss within 15 months after transplantation. There was a significant increase in the number of acute rejection episodes especially antibody-mediated acute rejections (P = .036) and in the number of graft losses for immunologic reasons (P < .001) among the group with pretransplant anti-C and -DP antibodies. Pretransplant anti-DP antibodies seemed to be involved more frequently in poor graft outcomes as shown in several recent published cases. We need to investigate their specific role among a larger cohort, taking into account an epitope analysis.     

Hyperuricemia in kidney transplant recipients with intact graft function

Objectives

The aim of this study was to investigate the prevalence of hyperuricemia and factors predicting its occurrence, and to establish the relationship over time between serial changes in estimated glomerular filtration rate (eGFR) and uric acid (UR) concentration in kidney transplant (KT) recipients with eGFR >60 mL/min/1.73 m².

Methods

Adult patients who underwent KT at the Asan Medical Center between 1990 and 2008 and maintained eGFR >60 mL/min/1.73 m² were retrospectively assessed. Clinical and laboratory data were obtained from inpatient and outpatient charts and from the hospital electronic database.

Results

Of 356 patients, 301 (84.55%) had normal UR levels and 55 (15.45%) had hyperuricemia. After multivariate adjustment, transplant duration, male gender, eGFR, diabetes mellitus (DM), and calcium level were associated with higher mean UR levels. Mean UR level increased significantly and mean eGFR decreased significantly during the first year after transplantation, but there were no significant differences over the next 4 years. Serial UR and eGFR levels changed almost simultaneously.

Conclusions

Transplantation duration, male gender, eGFR level, DM, and serum calcium level were risk factors for hyperuricemia in kidney recipients with intact graft function. Increased uric acid after KT did not significantly affect graft function.