A. Santana

First Year Renal Function as a Predictor of Kidney Allograft Outcome

BACKGROUND Several factors are known to have detrimental effects on kidney allograft function in the first year posttransplantation, which has been reported to be an important factor influencing long-term graft survival. OBJECTIVES The objectives of this study were to evaluate risk factors for lower estimated glomerular filtration rate (eGFR) at 3 and 12 months posttransplantation and analyze the influence of first year allograft function on graft and patient survivals. PATIENTS We performed a retrospective review of the clinical data from 433 cadaveric donor kidney transplantations in adults performed in our unit from May 1989 to May 2007. RESULTS Donor female gender and nontraumatic cause of death, panel-reactive antibody (PRA) titer > or =50%, acute rejection episodes, and delayed graft function (DGF) were significant risk factors for a decreased eGFR at one year posttransplantation. Recipient and donor age showed negative correlations with eGFR at 3 and 12 months. A logistic regression model showed acute rejection episodes, DGF, donor age > or =55 years, donor female gender, and nontraumatic cause of donor death to be independent adverse risk factors for eGFR <60 mL/min at 3 and 12 months. Lower eGFRs at 3 and 12 months were associated with poorer allograft survival when data were censored for death with a functioning graft and patient survival. Multivariate analysis revealed that PRA titer > or =50%, acute rejection episodes, and eGFR <30mL/min at 12 months had adverse effects on allograft survival. CONCLUSION Several factors influence kidney allograft function in the first year after transplantation. Kidney allograft function at 12 months predicted long-term graft survival.

Influence of dialysis duration and modality on kidney transplant outcomes.

BACKGROUND The influence of pretransplantation dialysis on kidney transplant outcomes has been the subject of longstanding interest. Although increased time on dialysis prior to kidney transplantation is associated with decreased graft and patient survivals, analyses of the impact of dialysis modality on kidney allograft outcome have produced conflicting results. OBJECTIVE The objective of this study was to evaluate the influence of dialysis duration and modality on the function and survival of renal allografts. PATIENTS We retrospectively reviewed the clinical data of 421 adults who received first kidney transplantations from cadaveric heart-beating donors performed in our unit from May 1989 to May 2007. Three hundred seventy-four patients (88.8%) were on hemodialysis (HD) prior to kidney transplantation, including 247 patients (58.7%) on treatment for at least 24 months. RESULTS Patients with a dialysis duration > or =24 months were significantly older (45.9 vs 42.8 years; P = .013). Renal function at 3, 12, 60, and 96 months was similar between the 2 groups. Longer duration on dialysis was associated with poorer overall graft and patient survivals. No differences were observed in renal function or graft and patient survivals comparing HD or peritoneal dialysis (PD). Multivariate analysis confirmed the lack of correlation between dialysis duration or modality and allograft failure. CONCLUSION Longer dialysis duration influenced overall graft and patient survival. However, dialysis modality showed no influence on graft function or survival.

Teriparatide efficacy in the treatment of severe hypocalcemia after kidney transplantation in parathyroidectomized patients: a series of five case reports.

Background. Teriparatide is a recombinant human parathormone (PTH 1–34) currently approved for the treatment of osteoporosis with high risk of fracture. In this study, we analyze the efficacy and safety profile of teriparatide therapy in severe and prolonged hypocalcemia after kidney transplantation in patients previously submitted to parathyroidectomy. Methods. The authors report results from a series of five hemodialyzed patients (mean age: 50±15 years; three female) previously submitted to parathyroidectomy to control secondary hyperparathyroidism. All patients had developed severe refractory hypocalcemia (calcium minimum levels: 5±1.4 mg/dL) early after kidney transplantation. The effect of teriparatide in calcemia and phosphatemia levels was analyzed, and variations in calcium and vitamin D analog requirements were analyzed. Secondary effects and serum creatinine changes were also ascertained. Results. Teriparatide therapy was initiated 32±14 days after the development of hypocalcemia. As a result, calcemia levels increased (median±standard deviation [SD]: 6.7±0.8 vs. 8.5±0.8 mg/dL, P=0.024) allowing suspension of intravenous calcium in two patients and reduction of calcitriol doses (mean±SD: 1.1±0.38 vs. 0.55±0.27 &mgr;g/day, P=0.004). In addition, phosphatemia levels (median±SD: 5.1±1.5 vs. 3.9±0.5 mg/dL, P=0.09) and calcium carbonate requirements (mean±SD: 13.8±9.4 vs. 7.2 ±3.7 g/day, P=0.9) exhibited declining trends. No secondary effects were observed and creatinemia remained stable. Conclusions. Our data strongly suggest that refractory hypocalcemia after kidney transplantation in patients with low PTH levels can be successfully treated with teriparatide. PTH analog therapy leads to faster normalization of calcemia, permits earlier suspension of intravenous calcium supplementation, and reduces calcitriol requirements.

Impact of Donor Age on Renal Allograft Function and Survival

BACKGROUND The lack of cadaveric donors coupled with a rapidly growing number of potential recipients have stimulated the implementation of several strategies, including the acceptance of older donors, to increase the organ pool and reduce the waiting list for kidney transplantation. However several studies have demonstrated higher incidences of delayed graft function and poor graft outcomes among kidneys harvested from older donors. OBJECTIVE The objective of this study was to evaluate the influence of donor age on the function and long-term survival of renal allografts. PATIENTS We performed a retrospective review of the clinical data from 441 adult kidney transplantation from cadaveric heart-beating donors performed in our unit from May 1989 to May 2007. RESULTS Recipients of kidney allografts from older donors were significantly older (49.2 vs 43.7 years; P < .0001) and had a higher incidence of delayed graft function (15.1% vs 5.4%; P = .005). Renal function was superior following kidney transplantation using younger donors not only at 3 months (P < .0001) and 12 months (P < .0001) posttransplantation, but also upon long-term follow-up at 60 months (P < .0001) and 96 months (P = .030). Allograft survival censored for death with a functioning graft and patient survival were not different when comparing older versus younger donors. Multivariate analysis confirmed the lack of correlation between donor age and allograft failure. CONCLUSION Donor age showed no influence on allograft survival. However, kidney allografts from older donors displayed lower first year and long-term renal function.

Mycophenolate Mofetil: Ten Years' Experience of a Renal Transplant Unit

Mycophenolate mofetil (MMF) use in renal transplantation has allowed a significant decrease in early acute rejection rates. We retrospectively evaluated the incidence of acute rejection episodes, renal function at the first year posttransplant, patient and graft survivals, cytomegalovirus (CMV) infection rate, influence of the degree of sensitization, and number of MHC antigen mismatches on graft survival in two groups of patients receiving either MMF or azathioprine. Group 1 included 149 patients receiving cyclosporine, MMF, and prednisolone; group 2 included 191 patients receiving cyclosporine, azathioprine, and prednisolone. The two groups did not differ in terms of age, sex, degree of sensitization (expressed as percentage of antibodies reactive to panel), MHC mismatch number, cold ischemia time, donor age, or anti-thymocyte globulin induction. In group 1 (MMF) there was a significant decrease in early acute rejection rate (19% vs 57%, P < .0001), longer graft survival at 10 years (92% vs 75%, P = .006), and higher rate of CMV infection (22% vs 12%, P = .004). Renal function at the first year posttransplant and patient survival during follow-up did not differ between the groups. The degree of sensitization influenced graft survival in group 2. The number of MHC mismatches did not influence graft survival in either group. With MMF, there was a significant reduction in early acute rejection rate, a significant increase in graft survival at 10-year follow-up, and diminished impact of the degree of sensitization on graft survival.

Intermediate Early Graft Function Is Associated With Increased Incidence of Graft Loss and Worse Long-Term Graft Function in Kidney Transplantation

INTRODUCTION Intermediate early graft function is associated with increased incidence of graft loss and worse long-term graft function in kidney transplantation. BACKGROUND Delayed graft function (DGF) is associated with premature graft loss, increased rate of allograft function decline, and greater incidence of acute rejection episodes (ARE). Regarding early intermediate graft function (IGF), these prognostic observations have not been clearly made. Our objective was to investigate the impact of IGF as compared with excellent graft function (EGF) on these outcomes. METHODS Retrospective analysis included all patients who underwent transplantation in a tertiary care center between 1989 and 2009. Definitions are as follows: DGF, need for dialysis in the first 7 days posttransplantation; EGF, serum creatinine (sCr) <3 mg/dL at 5 days posttransplantation; IGF, absence of dialysis need but with a sCr >3 mg/dL at 5 days posttransplantation. For univariate analysis we performed Student t test, Mann- Whitney test, or Chi-square test, as appropriate. For survival analysis we performed Kaplan-Meier method to determine survival curves and we used the log-rank test for comparison. Multivariate logistic regression analysis was used to determine independent predictors of IGF and of graft survival. RESULTS Five hundred seventy patients were included: 69.0% had EGF, 22.6% had IGF, and 8.4% had DGF. Patients with IGF had worse graft survival at 5 and 10 years posttransplantation (75% vs 92% and 69% vs 85%, respectively; P < .001 for both comparisons) and higher incidence of ARE (41% vs 27%; P = .001), compared with EGF. In multivariate analysis, IGF was independently associated with an increased risk of graft loss compared with EGF (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.32-4.35; P = .004]. Donor age (OR, 1.03 per year; 95% CI, 1.02-1.05; P < .001) was the strongest predictor of the occurrence of IGF. IGF was also associated with worse long-term graft function until 7 years posttransplantation (mean glomerular filtration rate [GFR] 48.3 ± 18.9 vs 57.4 ± 20.4 mL/min/1.73 m(2); P = .008). CONCLUSIONS IGF, as DGF, is associated with increased rates of graft loss and ARE, as well as worse long- term graft function. Donor age was the strongest risk factor for the occurrence of IGF. This is especially relevant regarding the increasing use of extended criteria donors.

Autosomal-dominant polycystic kidney disease and kidney transplantation: experience of a single center.

BACKGROUND Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease that frequently leads to end-stage renal disease and is a common indication for kidney transplantation. We sought to evaluate the demographic characteristics, graft and patient survival, and some posttransplantation complications among ADPKD recipients. METHODS This retrospective study included 445 renal transplant recipients, among whom 48 had ADPKD. We excluded patients with pretransplantation diabetes mellitus. We evaluated patient and graft survivals as well as posttransplantation complications. RESULTS There was no difference between the 2 groups with respect to demographic or transplant characteristics, except for older age among the ADPKD group (51.2 +/- 8.6 years vs 44 +/- 13.1 years; P < .001). We also observed no significant difference with regard to immediate graft function, immunological graft, or patient survival. Although not significant, there was a lower incidence of proteinuria and a greater number of acute rejections among ADPKD patients. As for posttransplantation complications, there was no difference regarding the prevalence of hypertension, but there was more erythrocytosis among the ADPKD group. The incidence of posttransplantation diabetes mellitus was significantly greater in ADPKD patients (33.3% vs 17.1%; P = .009), and remained significant after adjusting for confounding variables by multivariate analysis with an adjusted odds ratio of 2.3 (95% confidence interval, 1.008-5.136; P = .048). CONCLUSION Our results suggested that ADPKD patients display a greater incidence of diabetes mellitus posttransplantation; ADPKD emerged as an independent predictor for this complication.

Induction Immunosuppressive Therapy in Renal Transplantation: Does Basiliximab Make the Difference?

The optimal prophylactic induction immunosuppressive therapy to prevent renal transplant rejection remains controversial. Recently, basiliximab efficiency has been reported in several studies. We sought to evaluate the efficiency of induction immunosuppressive therapy with basiliximab in renal transplantation in our unit based upon the acute rejection rate, patient and graft survivals, first hospital admission length, and incidence of infectious or malignant complications during 4 years of follow-up. We retrospectively evaluated the outcome of two groups of renal transplant recipients treated with triple immunosuppressive therapy (cyclosporine, mycophenolate mofetil, and prednisolone) without (group 1, 149 patients) or with (group 2, 104 patients) induction immunosuppression with basiliximab. The two groups did not differ in demographic characteristics, number of hypersensitized patients, cold ischemia time, or donor age. The group receiving basiliximab displayed a significantly lower acute rejection rate (7.6% vs 24%, P = .001) and shorter first hospital admission (14.4 +/- 8 vs 19.5 +/- 11 days). There was no difference in graft or patient survival, death due to sepsis, or incidence of posttransplant malignancies. Although there was no difference in graft or patient survival, immunosuppressive induction therapy with basiliximab yielded a significant reduction in the acute rejection rate.

Factors that may influence estimated glomerular filtration rate in patients with excellent graft function 10 years posttransplant.

BACKGROUND Donor age, cold ischemia time, delayed graft function (DGF), prior sensitization, HLA mismatches, acute rejection episodes, glomerular disease and viral nephropathy are some factors that shorten graft survival. Patients with excellent graft function at 10 years posttransplant have probably successfully overcome these detrimental factors. The effect of initial functional renal mass is probably associated with this outcome. The objective of the present study was to identify factors that show predictive value for the population of patients with excellent graft function at 10 years posttransplantation. PATIENTS AND METHODS This retrospective observational study included 117 patients transplanted from deceased donors. They all presented glomerular filtration rates (GFR) ≥ 40 mL/min. They were stratified as group I (n = 56) estimated GFR ≥ 40 <60 mL/min versus group II (n = 61) estimated GFR ≥ 60 mL/min. We analyzed the variables of donor age, recipient age and gender, DGF, immunosuppression, obesity, acute rejection episodes, HLA mismatches, panel-reactive antibodies and the mean estimated GFR at 1, 5, and 10 years posttransplant. RESULTS Donor age and patients with DGF were significantly different between the two groups upon univariate analysis. Multivariate logistic regression analysis showed only donor age to be independently associated with an eGFR < 60 mL/min at 10 years. In both groups a decrease of eGFR > 10 mL/min between the 1st and the 10th year correlated significantly with donor age (P = .04). The deterioration of graft function was greater among group I than group II (6.7 vs 0.23 mL/min; P = .007). CONCLUSION Donor age was the most significant predictive factor for graft function at 10 years.

Are There Real Advantages of Induction Therapy With Basiliximab in Renal Transplantation

BACKGROUND Randomized clinical trials have supported the use of interleukin-2 receptor (IL-2R) antagonists as induction therapy in renal transplantation. This strategy has reduced the incidence of acute rejection episodes (ARE) but not improved graft survival. Our objective was to investigate the impact of induction therapy using the IL-2R antagonist basiliximab, as compared with no induction therapy, on relevant clinical outcomes-initial length of stay, incidence of ARE, long-term graft function, and graft survival. METHODS We retrospectively reviewed the medical records of patients transplanted in a tertiary care center between 1996 and 2011. We selected patients who received cyclosporine, mycophenolate mofetil, and prednisolone (n = 334) to classify as: no induction therapy (n = 131; group 1); induction therapy with basiliximab (n = 203; group 2). Estimated glomerular filtration rate (eGFR) was assessed with the 4-variable Modification of Diet in Renal Disease (MDRD) equation. RESULTS Mean follow-up was 72.7 ± 35.4 months. Patients who received basiliximab had a shorter mean hospital stay (19.2 versus 22.5 days; P = .02), lower incidence of ARE (10.8% versus 23.7%; P = .02) and better graft function post transplantation at 12 months (mean eGFR 59.4 ± 18.4 versus 54.8 ± 18.7 mL/min/1.73 m(2); P = .015) and 5 years (mean eGFR 64.1 ± 21.5 versus 55.4 ± 19.6 mL/min/1.73 m(2); P = .009). On multivariate analysis, induction therapy with basiliximab was independently associated with a lower incidence of ARE and better graft function at 1 and 5 years after transplantation. There was no difference in 5-year graft survival between the two groups (log-rank: P = .54). CONCLUSIONS Induction therapy with basiliximab was associated with a reduced incidence of ARE and better long-term graft function but no difference in 5-year graft survival.