Acute renal failure early after heart transplantation: risk factors and clinical consequences

Gude E, Andreassen AK, Arora S, Gullestad L, Grov I, Hartmann A, Leivestad T, Fiane AE, Geiran OR, Vardal M, Simonsen S. Acute renal failure early after heart transplantation: risk factors and clinical consequences.
Clin Transplant 2010: 24: E207–E213. © 2010 John Wiley & Sons A/S. Abstract: Limited information exists about acute renal failure (ARF) early after heart transplantation (HTx). We correlated pre‐, per‐, and post‐operative patient and donor parameters to the risk of developing ARF. We also analyzed the consequences of ARF on kidney function after HTx, risk of later need for chronic dialysis or kidney transplantation, and mortality. In a retrospective study from 1983 to 2007, 145 (25%) of 585 HTx recipients developed ARF, defined as ≥26.4 micromol/L or ≥50% increase in serum creatinine from pre‐operatively to the seventh day post‐HTx and/or the need of early post‐operative dialysis. Independent risk factors for ARF were intravenous cyclosporine immediately post‐operatively (odds ratio [OR] 2.16, 95% CI 1.34–3.50, p = 0.02), donor age (OR 1.02, 95% CI 1.00–1.04, p = 0.02), and pre‐operative cardiac output (OR 1.38, 95% CI 1.12–1.71, p = 0.003). The development of ARF was a predictor for short‐term survival (≤3 months) ranging from 98% for patients who improved their creatinine after HTx vs. 79% for those in need of dialysis (p < 0.001). However, ARF did not predict subsequent end stage renal disease in need of dialysis or renal transplantation. ARF is a common complication post‐HTx. As ARF is associated with short‐term survival, post‐operative strategies of preserving renal function have the potential of reducing mortality. Of avoidable risk factors, the use of intravenous CsA should be discouraged.     

Tacrolimus as secondary intervention vs. cyclosporine continuation in patients at risk for chronic renal allograft failure

BACKGROUND: Chronic renal allograft failure (CRAF) is the leading cause of graft loss post-renal transplantation. This study evaluated the efficacy and safety of tacrolimus as secondary intervention in cyclosporine-treated kidney transplantation patients with impaired allograft function as indicated by elevated serum creatinine (SCr) levels. METHODS: Patients receiving cyclosporine-based immunosuppression who had an elevated SCr at least 3 months post-renal transplantation were enrolled. Treatment allocation was 2:1 to switch to tacrolimus or continue cyclosporine. This analysis was performed after 2 yr; patients will be followed for an additional 3 yr. RESULTS: There were 186 enrolled and evaluable patients. On baseline biopsy, 90% of patients had chronic allograft nephropathy. Baseline median SCr was 2.5 mg/dL in both treatment groups. For patients with graft function at month 24, SCr had decreased to 2.3 mg/dL in the tacrolimus-treated patients and increased to 2.6 mg/dL in the cyclosporine-treated patients (p = 0.01). Acute rejection occurred in 4.8% of tacrolimus-treated patients and 5.0% of cyclosporine-treated patients during follow-up. Two-year allograft survival was comparable between groups (tacrolimus 69%, cyclosporine 67%; p = 0.70). Tacrolimus-treated patients had significantly lower cholesterol and low-density lipoprotein levels and also had fewer new-onset infections. Cardiac conditions developed in significantly fewer tacrolimus-treated patients (5.6%) than cyclosporine-treated patients (24.3%; p = 0.004). Glucose levels and the incidences of new-onset diabetes and new-onset hyperglycemia did not differ between treatment groups. CONCLUSIONS: Conversion from cyclosporine to tacrolimus results in improved renal function and lipid profiles, and significantly fewer cardiovascular events with no differences in the incidence of acute rejection or new-onset hyperglycemia.     

Acute Renal Disease, as Defined by the RIFLE Criteria, Post-Liver Transplantation

Acute renal failure (ARF) can complicate up to 60% of orthotopic liver transplants (OLT). The RIFLE criteria were developed to provide a consensus definition for acute renal disease in critically ill patients. Using the RIFLE criteria, we aimed to determine the incidence and risk factors for ARF and acute renal injury (ARI), and to evaluate the link with the outcomes, patient survival and length of hospital stay. Three hundred patients, who received 359 OLTs, were retrospectively analyzed. ARI and ARF occurred post 11.1 and 25.7% of OLTs, respectively. By multivariate analysis, ARI was associated with pre-OLT hypertension and alcoholic liver disease and ARF with higher pre-OLT creatinine, inotrope and aminoglycoside use. ARF, but not ARI, had an impact on 30-day and 1-year patient survival and longer length of hospital stay. ARI and ARF, as defined by the RIFLE criteria, are common complications of OLT, with distinct risk factors and ARF has serious clinical consequences. The development of a consensus definition is a welcome advance, however these criteria do need to be validated in large studies in a wide variety of patient populations.     

End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.

BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.     

Acute renal failure in liver transplant recipients: role of pretransplantation renal function and 1-year follow-up

Chronic renal failure and acute renal failure (CRF and ARF) are common complications after orthotopic liver transplantation (OLT) that adversely affect patient survival. Many factors influence the development of ARF in the OLT setting. In a previous study we reported an association between ARF and the development of CRF at 1 month after OLT. The aims of our study were to evaluate the influence of ARF on short-, middle-, and long-term renal function after OLT and its influence on 1-year survival of patients and grafts.Fourty-four patients who underwent deceased donor OLT between August 2008 and August 2010 were evaluated pretransplantation, in the perioperative period, and at 1, 6, and 12 months posttransplantation. ARF was associated with CRF at 1 month post-OLT, whereas no association was observed at 6 and 12 months post-OLT. The development of CRF at 6 months post-OLT was associated with pre-OLT renal dysfunction and 1 month post-OLT CRF. Four patients died in the ARF group, whereas 3 patients died in the group without ARF. We confirmed ARF to be a predictive event for short-term renal dysfunction. The majority of patients recovered renal function after the first month. Although many pre-, peri-, and post-OLT factors may contribute to the development of posttransplantation CRF, pre-OLT CRF seemed to be the most important risk factor.     

Occurrence of chronic renal failure in liver transplantation: monitoring of pre- and posttransplantation renal function

The aim of our study was to evaluate the occurrence of middle and long-term chronic renal failure (CRF) after orthotopic liver transplantation (OLT) in relation to acute renal failure (ARF). We prospectively monitored 75 patients, studying renal function on the basis of serum creatinine and glomerular filtration rate as estimated using the Modification of Diet in Renal Disease formula before as well as 1,6, and 12 months after OLT. The prevalence of ARF was 56% classified by the Acute Kidney injury Network criteria (52% stage 1, 29% stage 2, and 19% stage 3). The occurrences of CRF were 18.6% (11/59), 11.5% (6/52), and 14% (6/43) at 1, 6, and 12 months after OLT, respectively. The occurrence of CRF before OLT was 14.7%. We did not find any association between ARF and post-OLT CRF. The most relevant result of our study was the association between CRF at 6 and 12 months after transplantation with pre-OLT CRF on univariate and multivariate analysis. We suggest that evaluation of pre-OLT renal function should always be considered in the follow-up of liver transplant patients. Pre-OLT renal dysfunction must be recognized to be a risk factor for post-OLT CRF, representing important criterion to define specific therapeutic interventions to reduce patient morbidity and mortality.     

Decreased survival in liver transplant patients requiring chronic dialysis: a Canadian experience

BACKGROUND: Chronic kidney disease is associated with increased mortality among nonrenal organ transplant recipients. End-stage renal disease (ESRD) is a serious complication after orthotopic liver transplantation (OLT). It is unclear if the outcomes of these individuals are different from nontransplant patients requiring dialysis or a kidney transplant. METHODS: We report the incidence of ESRD in OLT recipients and compare their outcomes to matched dialysis controls. We analyzed 4186 patients who received an OLT in Canada between January 1981 and December 2002 and 228 matched, nontransplant, chronic dialysis controls. RESULTS: The incidence of ESRD after OLT was 2.9% (n=120). The unadjusted mortality rate for those who required chronic dialysis was 49.2% compared with 26.8% in those who did not develop kidney failure (P<0.0001). The survival of OLT recipients on dialysis was lower than the matched chronic dialysis cohort (log-rank test, P=0.01). A kidney transplant was performed in 24% of the OLT recipients and 21% of the matched dialysis cohort, and their overall survival was similar. The OLT patients who remained on dialysis had a significantly lower survival when compared with matched dialysis patients who did not receive a kidney transplant (log-rank test, P=0.0002). CONCLUSIONS: Mortality was greater for OLT recipients on dialysis than would be expected from a matched, nontransplant, dialysis cohort. Kidney transplantation may abrogate some of this increased mortality risk.     

Survival after liver transplantation in patients who develop renal insufficiency

Background

Renal insufficiency (RI) after liver transplantation (OLT) is associated with worse outcomes but the actual survival after RI ensues is not well described. We examined the survival of OLT recipients who developed moderate or severe RI or end-stage renal disease (ESRD), seeking to identify variables associated with these outcomes.

Methods

Between 1993 and 2007, 731 patients underwent OLT. After excluding patients undergoing retransplantation, combined kidney-liver grafts, and those who died within 1 year, we had a cohort of 527 subjects whose basic demographic data were obtained. Glomerular filtration rate (GFR) calculated (by MDRD4–Modification of Diet in Renal Disease 4–formula) at 3-month intervals in the first year and then at 6-month intervals. Moderate RI was defined as a GFR < 60 mL/min/1.73 m²; severe RI, GFR < 30; and ESRD by need for dialysis or renal transplantation. We determined survival from the point of developing RI. An analysis determined factors associated with survival.

Results

Among 527 patients, 251 developed moderate (47.6%) and 40 (7.6%) severe RI as well as 40 (7.6%) with ESRD. Once RI ensued, the 5-year survivals for patients with moderate RI, severe RI or ESRD were 84.0%, 67.7%, and 48.5%, respectively. Five-year survival, for patients receiving a renal transplant was 100%. On multivariate Cox regression analysis, the only variables associated with time to death for patients with any RI were higher age at transplant (hazard ratio [HR] = 1.04, P = .02), higher creatinine at transplant (HR = 1.25, P = .01), pretransplant diabetes (HR = 2.34, P = .008), and transplantation in the Model for End-stage Liver Disease (MELD) era (HR = 0.15, P = .002).

Conclusion

Development of severe RI or ESRD correlated with diminished survival. For patients with RI, age and creatinine at transplant, pretransplant diabetes, and transplantation in the pre-MELD era were associated with lower survival rates. Five-year survival for dialysis patients was somewhat higher than that previously reported but worse than that of subjects treated by renal transplantation.     

The incidence of end-stage renal failure in 17 years of heart transplantation: a single center experience.

BACKGROUND: Predictions of the incidence of renal failure within a heart transplant population are based on the early experiences of cyclosporine (CsA)-based immunosuppression. We report a single-center experience of end-stage renal failure (ESRF) during a 17-year period encompassing current lower dose CsA regimens. METHOD: Prospectively collected data were analyzed on all patients who underwent first heart transplants between April 1982 and February 1999 (n = 697). We further categorized patients by the date of transplantation into a higher and lower dosage maintenance CsA group. RESULTS: End-stage renal failure developed in 44 patients. The median time to dialysis was 87 months after transplantation and was independent of the initial CsA regimens used (p = 0.798). In the ESRF group, 14 underwent hemodialysis, 28 underwent peritoneal dialysis, and 9 underwent renal transplantation. One- and 5-year survival rates after dialysis were 82% and 62% respectively. The incidence of ESRF at our institution was 5.8%. It increased with post-operative survival and was independent of the initial CsA regimen used. We found no difference in pre-transplant age, sex, diagnosis, immediate post-operative creatinine, or the development of diabetes between the ESRF group and controls. The ESRF group received higher dosages of CsA within the first post-transplant year, although this did not reach significance (CsA dosage, 5.9 microg/kg/day vs 5.1 microg/kg/day, respectively p = 0.075). CONCLUSIONS: Lower dosage CsA regimes have not altered the incidence of ESRF at our institution, suggesting an individual predisposition to nephropathy. Therefore, reduction in the future incidence of ESRF may rely on extremely low-dose or calcineurin-free immunosuppression regimes.     

Acute renal failure in patients with pre-existing renal dysfunction following coronary artery bypass grafting

BACKGROUND: Pre-existing renal dysfunction predisposes to acute renal failure (ARF) in patients undergoing coronary artery bypass grafting. We assessed the incidence and impact of the development of ARF in this patient population in our unit. METHODS: One-hundred and six patients had a preoperative serum creatinine of >or=0.13 mmol/L and underwent coronary artery bypass grafting in the year 2000. The incidence of ARF (as defined by a >or=50% rise in postoperative serum creatinine), hospitalization days, dialysis requirement, in-hospital and 1-year mortality, and potential risk factors for ARF were recorded. RESULTS: Of the patients recorded, 43/104 (41.35%) developed ARF following coronary artery bypass grafting. Patients with ARF stayed in hospital longer (P < 0.02). Ten out of forty-three patients required some form of dialysis and the in-hospital mortality of the renal failure group was 23% compared to 3.1% in the other group (P < 0.002). One year postoperatively, the group with renal failure had significantly worse survival (71.8% vs 98%P < 0.0001). CONCLUSION: For patients undergoing coronary artery bypass grafting, pre-existing renal dysfunction predisposes to the development of ARF, this is associated with prolonged hospitalization and increased mortality.     

RIFLE Criteria and Hepatic Function in the Assessment of Acute Renal Failure in Liver Transplantation

Renal dysfunction in cirrhotic patients is primary related to disturbances of circulatory function, triggered by portal hypertension with chronic intrarenal vasoconstriction and hypoperfusion. Pretransplant renal function is an important factor implicated in the development of acute renal failure (ARF) after liver transplantation (OLT), but other factors mostly related to liver function seem to influence the development of ARF.The Acute Dialysis Quality Initiative workgroup developed the RIFLE classification to define ARF. We sought to evaluate the incidence of ARF among patients undergoing OLT, to evaluate the association of ARF with pre-OLT renal and hepatic functions, and to evaluate the influence of ARF on chronic kidney disease (CKD) at 1 month post-OLT.Clinical, renal, hepatic function, and donor risk index data of 24 patients who underwent deceased donor OLT were collected before transplantation, in the perioperative period and in the first month post-OLT. ARF occurred in 37.5% of patients with 56% developing the R grade and 44% the I grade; no patient showed the F grade.An association was observed between ARF and a higher Model for End-Stage Liver Disease (MELD) score and between ARF and a reduced pre-OLT serum albumin. No association was noted between ARF and other pre-OLT parameters. In cirrhotic patients serum creatinine is a bias for renal function assessment and the Modification of Diet in Renal Disease formula overestimates GFR. Post-OLT CKD was present in 6.7% of patients without ARF and in 44.4% of patients with ARF. The R grade developed more frequently among patients with viral cirrhosis.The association of ARF with MELD and hypoalbuminemia may be the result of a close relationship between renal and hepatic functions among cirrhotic patients. Post-OLT CKD may be the result of unrecognized, preexisting CKD and/or the effects of not fully resolved acute damage to an injured kidney.     

Impact of renal failure on liver transplantation survival

Renal failure after orthotopic liver transplantation (OLT) is a common complication (ranging from 12% to 70%) associated with worse outcomes, particularly when it requires renal replacement therapy (RRT). Renal dysfunction is a common scenario among waiting list patients. It can lead to a worse prognosis after OLT, due to an increased incidence of postoperative renal failure. The aim of this study was to analyze the incidence of renal failure after OLT, its relationship to pretransplant renal dysfunction, and its impact on outcomes. We analyzed data collected prospectively from 152 consecutive OLTs in 139 patients performed by the same team from March 2003 to November 2007. Exclusion criteria for 34 cases included transplantation due to acute liver failure, combined liver-kidney transplantation, retransplantation, and patients who died up to 2 days posttransplantation. Based on creatinine clearance (CCr) calculated at the time of OLT, the 118 patients were classified in two groups: group I, normal pre-OLT renal function (CCr > or = 70 mL/min) versus group II, pre-OLT renal failure (CCr < 70 mL/min). Each group was analyzed according to the development of post-OLT renal failure, being classified as subgroup A (normal renal function post-OLT), subgroup B (mild renal impairment post-OLT-serum creatinine level between 2.0 and 3.0 mg/dL or doubled basal value up to 3.0 mg/dL) versus subgroup C (severe renal impairment post-OLT-serum creatinine level > or = 3.0 mg/dL or utilization of RRT). The overall incidence of post-OLT renal impairment was 41.52% with RRT in 22 patients (18.64%). Group II patients showed a greater incidence of post-OLT renal failure when compared with other patients (P < .05), but without a statistical difference when compared according to RRT requirement. Comparison of average hospital stay was similar between groups I and II, and also among its subgroups (A, B, and C, respectively). There was no statistical difference in early (30-day) and 1-year survival rates between groups I and II. Comparing all subgroups for early and 1-year survival, we observed that patients who developed severe renal failure post-OLT (subgroups I-C and II-C) showed worse outcomes compared with other patients (subgroups I-A, I-B, II-A, and II-B), respectively 95.29% versus 69.69% and 86.95% versus 41.66% for early and 1-year survivals (P < .001). In conclusion, our findings suggested that patients who developed severe renal failure post-OLT, independent of pretransplant renal function, showed worse outcomes.     

A long-term study on hyperlipidemia in stable renal transplant recipients

OBJECTIVES: Hyperlipidemia is a common and important risk factor after renal transplantation, but there is little long-term data on its incidence, pattern, and evolution in stable renal allograft recipients on low dose maintenance immunosuppression. PATIENTS AND METHODS: A retrospective study was conducted on all patients who received kidney transplants from April 1, 1990 to March 31, 2000 at a single center, on their serial lipid profile during the first 3 yr after kidney transplantation. RESULTS: A total of 221 (122 male, 99 female; mean age 37.8 +/- 10.0 yr at the time of transplantation) Chinese adult renal allograft recipients were included. A 95.3% of patients were on cyclosporine and prednisolone based immunosuppression. Increases in total cholesterol (TC), low density lipoprotein (LDL), and high density lipoprotein (HDL) were noted, while the level of triglyceride (TG) decreased after renal transplant. The incidence of hypercholesterolemia (defined as TC >/= 6.3 mmol/L or LDL >/= 4.2 mmol/L) within the first year was 28.2 and 20.3%, respectively. The incidence rate decreased significantly in the second (5.4%, p = 0.000 and 6.4%, p = 0.003) and third year (9.5%, p = 0.003 and 4.9%, p = 0.021), but the incidence of patients having a high risk-ratio (defined as TC/HDL >/= 5) remained unchanged (6.9, 4.9 and 10.3% within the first, second, and third year, respectively). Treatment with statin was necessitated in 6.8, 13.6 and 21.7% of the patients at 1, 2, and 3 yr after transplantation, respectively. The prevalence rates of elevated TC and LDL were 18.3 and 18.9% at baseline, 40.6 and 33.3% after 1 yr, 32.8 and 27.3% after 2 yr, and 24.8 and 19.0% after 3 yr, despite treatment. The prevalence of patients with a high risk-ratio was 45.0% at baseline, 30.5% after 1 yr (p = 0.002), 22.6% after 2 yr (p = 0.000) and 21.8% after 3 yr (p = 0.000). Hypercholesterolemia at the time of transplantation was an independent predictor for post-transplant hypercholesterolemia (odds ratio 3.76, 95% confidence interval 1.47-9.62, p = 0.006). CONCLUSION: Renal transplantation is associated with a characteristic pattern of dyslipidemia, with increased TC, LDL and HDL, and a decrease in TG. Patients with pre-existing hypercholesterolemia were at higher risk for post-transplant hypercholesterolemia. Although the incidence of hypercholesterolemia peaks within the first year after transplantation, this remains a long-term complication in a significant proportion of patients on low dose immunosuppressive medications.     

Acute renal failure after nonmyeloablative hematopoietic cell transplantation

Acute renal failure (ARF) is a common life-threatening complication after myeloablative allogeneic hematopoietic cell transplantation (HCT). Nonmyeloablative HCT aims to eradicate the malignancy with graft-versus-tumor effect, rather than with high doses of chemoradiotherapy. It may be anticipated that a lower risk of ARF exists in nonmyeloablative HCT as a result of the milder preconditioning regimen. However, the patients who receive the nonmyeloablative HCT are older individuals who are not eligible for the more toxic allogeneic myeloablative procedure. The goal of this study was to evaluate ARF in a large group of patients who received nonmyeloablative HCT. This cohort study enrolled patients who were undergoing nonmyeloablative HCT at four major centers from 1998 to 2001. Conditioning therapy involved total body irradiation 2 Gy +/- fludarabine 30 mg/m2. Posttransplantation immunosuppression consisted of cyclosporine or tacrolimus and mycophenolate mofetil. ARF was classified into four grades, similar to previous studies in the literature. Collectively, 253 patients were recruited into this study. ARF (>50% decrease in GFR) occurred in 40.4% of patients over a 3-mo period, with 4.4% of patients requiring dialysis. The overall mortality in the study population was 34% at 1 yr. The mortality increased with worsening grade of ARF. The combined need for dialysis and artificial ventilation was associated with a mortality exceeding 80%. Although the number of patients who develop ARF is significant, the risk of developing ARF that requires dialysis after nonmyeloablative HCT is infrequent despite the older age of the patients. The data are also suggestive that ARF may contribute to mortality after nonmyeloablative HCT.     

Factors contributing to long graft survival in non-heart-beating cadaveric renal transplantation in Japan: a single-center study at Kitasato University

A total of 107 cadaveric kidneys from non-heart-beating donors (NHBDs) have been transplanted between 1974 and 2000 at Kitasato University Hospital, Sagamihara, Japan. The patient survival of the 107 recipients of cadaveric renal transplants at 1, 5 and 10 yr was 0.857, 0.770 and 0.746, respectively. The 50% graft survival was 3.8 yr. The 5 and 10-yr graft survival was 0.457 and 0.337, respectively. Twenty of the 107 recipients of non-heart-beating cadaveric renal transplantation had graft survival longer than 10 yr. Of these 20 patients, 14 survivors still maintain functioning renal grafts and two died with functioning graft, although the remaining four reverted to dialysis because of chronic rejection and nephropathy. The average graft survival of these 20 patients at the time of study was 13.3 yr and the longest was 21.4 yr. The average serum creatinine level at 10 yr after transplantation was 1.63 mg/dL, almost identical to that at 5 yr post-transplant. The donors aged on average 40.2 yr; 13 were male and seven were female. The youngest donor was 9-yr-old and the oldest was 66. The graft survival was significantly better in the group with donor age younger than 55 yr (Log-rank: p=0.007). The average weight of the renal graft was not different between the long and shorter graft survival groups. The average warm ischemic time and total ischemic time were 9.7 and 539.7 min, respectively. The duration of post-transplant acute tubular necrosis averaged 9.2 days. These parameters tended to be shorter than those in recipients with graft survival >10 yr, but with no statistical significance. The mean numbers of acute rejection (AR) episode within 3 months after transplantation were 0.25 +/- 0.66 and 0.92 +/- 0.90 (p=0.020) in long survival and shorter survival groups, respectively. Long survivors had a significantly lower incidence of AR. Two of 20 cases received conventional immunosuppression with prednisolone, azathioprine and mizoribin, and 18 had prednisolone and calcineurin inhibitor (CNI). Kaplan-Meier analysis showed a significant contribution of CNI to graft survival (p=0.036). However, the graft survival reduction rate after 1 yr post-transplant did not differ between conventional and CNI immunosuppression. These data suggest that renal grafts retrieved with proper organ procurement procedures from NHBDs may survive long-term and help to overcome donor shortage.     

The clinical status of cadaveric renal transplant patients treated for 10 year with cyclosporine therapy

In this paper we assessed the clinical status of 150 cadaveric renal transplant patients who received cyclosporine without interruption for 10 yr. The mean creatinine clearance was 59.2 +/- 15.71 at 1 yr and 55.6 +/- 24.91 mL/min at 10 yr (p = 0.039). Patients were subdivided into four quartiles according to the mean creatinine clearance at 1 yr. The 14 patients with the lowest quartile showed a significant decrease of creatinine clearance from the 1st to 10th year (from 31.5 +/- 5.83 to 24.8 +/- 14.00 mL/min; p = 0.038) while no difference between the mean creatinine clearance at 1 and at 10 yr was found in the other three quartiles. At 10 yr, 84.6% patients needed antihypertensive therapy, a rate similar to that seen at 1 yr (81.4%). The mean plasma cholesterol (253 +/- 57.8 mg/dL) and triglyceride (197 +/- 113.1 mg/dL) at 10 yr were similar to those found at +/- yr (243 +/- 48.2 and 201 +/- 143.0 mg/dL, respectively). Most patients have a high degree of rehabilitation 10 yr after uninterrupted cyclosporine therapy and all patients but 3 were able to work.     

Effects of sirolimus vs. calcineurin inhibitors on renal dysfunction after orthotopic liver transplantation

Small uncontrolled series have suggested that sirolimus favorably impacts renal function after orthotopic liver transplantation (OLT). We sought to retrospectively compare renal dysfunction between cohorts exposed to sirolimus-based and calcineurin inhibitor-based immunosuppression. We retrospectively studied 79 patients converted to sirolimus-based immunosuppression and 100 control subjects continued on calcineurin inhibitor-based immunosuppression after OLT at our institution from 2000 to 2005. We collected clinical, demographic, and medication history. Renal dysfunction was defined as two or more wk of creatinine > or =2.0 mg/dL. Cohorts were compared using Kaplan-Meier survival analysis and Cox proportional hazards modeling. Patients began sirolimus a median 83 d post-OLT and were followed on the medication for median 359 d. Patients in both the sirolimus and calcineurin inhibitor cohorts had median creatinine 1.2 mg/dL at study entry. Sirolimus-based immunosuppression was associated with a 1.8 (0.8-4.3, p = 0.17) hazards ratio for renal dysfunction. Adjusting for presence of hepatocellular carcinoma, combined kidney/liver transplantation, and age, the hazards ratio was 2.0 (0.8-4.8, p = 0.13). These point estimates were not substantially altered after subgroup analysis of sirolimus as the lone immunosuppressant, duration of exposure, and time between OLT and sirolimus conversion. In conclusion, our retrospective, controlled study showed that conversion to sirolimus after OLT did not protect against renal dysfunction. The effect of sirolimus on renal function will need to be prospectively evaluated in a prospective, randomized trial.     

Immunosuppression for delayed or slow graft function in primary cadaveric renal transplantation: use of low dose tacrolimus therapy with post-operative administration of anti-CD25 monoclonal antibody

BACKGROUND: Patients who develop delayed graft function (DGF) following cadaveric renal transplantation have inferior survival to those who do not. Calcineurin inhibitors (CNI) may prolong recovery from DGF. Patients with DGF are therefore routinely treated with either polyclonal antilymphocyte preparations or monoclonal anti-CD3 monoclonal antibodies and delayed introduction of CNI. The purpose of this study was to evaluate the efficacy of the anti-CD25 monoclonal antibody basiliximab (BSLIX) started post-operatively in patients at high risk for DGF combined with low dose tacrolimus (TAC). METHODS: Patients who received a primary cadaveric renal transplant only after August 1998 were included in this retrospective study (n = 143). All patients received TAC and mycophenolate Mofetil (MMF) pre-operatively. At 6 h post-operatively, graft function was assessed clinically by urine output and serum creatinine. Those patients who had a urine output < 300 cc/6 h or a rising serum creatinine were presumed to be at risk for DGF (n = 46). These patients were treated with 20 mg BSLIX and had TAC dose reduced to maintain a trough blood level of < 5 ng/mL. Basiliximab was repeated at day 5. Patients not felt to be at risk for DGF were treated with standard TAC dose with trough level target of 9-12 ng/mL. Patients at risk were classified as DGF if they needed dialysis or as slow graft function (SGF) if they did not. The combined group (SGF/DGF) were analysed together. Patients with SGF/DGF had their TAC dose increased to achieve trough levels of 9-12 ng/mL when renal function improved. Patient groups were compared for demographics, need for dialysis, serum creatinine, glomerular filtration rate (GFR), TAC trough levels, MMF dosage, complications and 1- and 2-yr actuarial graft survival. RESULTS: Patients with SGF/DGF had a longer length of stay (8 vs. 5.7 d), were more likely to be black (41.3 vs. 25.7%), and required more post-operative haemodialysis (HD) (52.2 vs. 4.1%). SGF/DGF and non-SGF/DGF patients had similar rates of rejection (28.2 vs. 19.6%, p = 0.28) and steroid resistant rejection (SRR) (6.5 vs. 2.1%, p = 0.32). There were no differences in the rate of cytomegalovirus (CMV) infection (4.3 vs. 6.1%). Serum creatinine was higher and GFR lower at all time points in the SGF/DGF patients. The 1 and 2 yr actuarial survival in the non-SGF/DGF patients was 97.6 and 97.6% compared with 1 and 2 yrs actuarial survival of 94.1% and 80.0% in the SGF/DGF patients, p = 0.04. There were no differences in patient survival. There were no differences in actuarial survival for the SGF/DGF patients who received dialysis compared with those who did not receive dialysis. Comparison of patients who received HD (n = 28) to those who did not (n = 115), regardless of group demonstrated no difference in 1 and 2 yrs actuarial survival, 100 and 94.1% in HD patients vs. 98.2 and 92.5% in non-HD patients. CONCLUSIONS: The clinical diagnosis of SGF/DGF can be made 6 h post-operatively based on urine output and serum creatinine. Basiliximab can be started post-operatively in these patients and decreased levels of TAC can be used to achieve acceptably low rates of rejection in these patients. However, SGF/DGF patients, regardless of their need for dialysis, have worse function at 1 yr and lower 2-yr actuarial graft survival compared with non-SGF/DGF patients. Most of the poor survival can be attributed to the SGF group. Further strategies to either prevent SGF/DGF or to optimize treatment in these patients are needed.     

Evaluation of renal grafts in patients with lupus nephritis as cause of end-stage renal disease

INTRODUCTION: Kidney transplantation is the best option in end-stage renal disease (ESRD). For many years patients affected with lupus nephritis have had poor graft results. However, this has been changing over recent years with the development of new immunosuppressive drugs and a better comprehension of the natural evolution of the entity. METHODS: We studied 20 patients with lupus nephritis who received 22 kidney grafts: 15 women and five men (n = 11) who were treated with cyclosporine or with tacrolimus (n = 11). Secondary immunosuppression included mycophenolate match (MMF) (n = 13) or azathioprine (n = 9). We analyzed human leukocyte antigen, cold ischemia time, acute tubular necrosis, creatinine, cholesterol, triglycerides, glucose, blood pressure, acute rejection episodes, immunosuppression, infections, disease recurrences, as well as graft and patient survival. RESULTS: After a mean cold ischemia time of 22 +/- 4 hours, nine patients displayed delayed graft function of an average duration 9 +/- 4 days. At 36 +/- 35 months nine grafts were lost: two due to acute rejection; five to chronic allograft nephropathy; and two to venous thrombosis. One patient died of hemorrhagic shock. There were five cytomegalovirus infections. Graft survival was dependent on the type of secondary immunosuppression, incidence of acute rejection episodes and occurrence of delayed graft function. CONCLUSIONS: We found no clinical recurrence of lupus nephritis after transplantation and a low incidence of complications, although there was a trend toward thrombosis. The presence of delayed graft function, episodes of acute rejection, and receiving azathioprine instead of MMF as secondary immunosuppression were associated with poorer graft survival.     

Acute renal failure following liver transplantation with induction therapy

AIMS: To identify the predictive factors for acute renal failure (ARF) in a retrospective study of 100 orthotopic liver transplantations (OLT) performed in 94 patients between 2000 and 2003. METHODS: Acute renal failure (ARF) was defined using the RIFLE criteria, i.e. injury when creatinine doubles or GFR halves, and failure when creatinine trebles or GFR decreases by > 75%. Patients on dialysis pre OLT (n = 3) were excluded from the study. Immunosuppression included steroids, calcineurin inhibitors (CNIs), with (n = 32) or without mycophenolate mofetil. A total of 85% of patients also received induction therapy with antithymocyte globulins (29%) or anti-CD25 monoclonal antibodies (56%). RESULTS: 39 patients (41.5%) and 21 (22.3%) patients developed injury, and failure, respectively. Of these, 10 (10.6%) underwent dialysis. Univariate analysis revealed that acute renal dysfunction with a RIFLE score > or = 3 was significantly associated with a pre-operative serum creatinine level of > 100 micromol/l, pre-operative creatinine clearance of < 75 ml/mn, need for a transfusion (> 10 red packed units), post-operative diuresis of < 100 ml/h, use of vasopressive drugs, times to aspartate (AST) and alanine (ALT) aminotransferase peaks of > 20 and > 24 hours, respectively, relaparotomy, CNIs transient discontinuation, and the use of lower daily dosage of CNIs at post-OLT Days 3, 5, 7 and 15. In multivariate analysis, failure was significantly associated with time to AST peak (> 20 h) (OR 6.35 (1.2 - 33.6), p = 0.029), post-operative diuresis (< 100 ml/h) (OR 9.8 (2.03 47.3), p = 0.004), post-operative use of vasopressive drugs (OR 9.91 (2.02 - 48.7), p = 0.004), and transient CNIs withdrawal (OR 51.08 (7.58-344.1), p < 0.0001). Finally, the occurrence of ARF was significantly associated with an increased number of days on mechanical ventilation, on stay-in intensive care unit (ICU), and on overall hospitalization time. CONCLUSION: ARF is quite common after OLT and significantly increases the post-operative time at the hospital, thereby increasing the OLT cost. Its independent predictive factors are mainly related to perioperative events.