The association between MMF and risk of progressive renal dysfunction and death in adult liver transplant recipients with HCV

Abstract  The impact of a three-drug regimen including mycophenolate mofetil (MMF) vs. a two-drug (no MMF) regimen on progressive renal dysfunction (PRD) in liver transplant recipients with hepatitis C virus (HCV) infection has not been well described. Adults with HCV who received a primary liver transplant between January 1, 2000 and December. 31, 2005 and were discharged from the hospital on a three-drug regimen [CNI+MMF+steroids (S)] (n = 4 946) were compared with those discharged on two-drug regimen (CNI+S) (n = 3 884). Time to PRD (defined by a post-transplant 25% decline in estimated GFR, based on the four-variable MDRD equation) and recipient death were evaluated using Kaplan–Meier analysis. Cox proportional hazards regression was used to estimate the risk for post-transplant PRD and death after controlling for baseline characteristics and extended steroid use. The two groups were similar in baseline characteristics. The percentage of recipients on three- vs. two-drug regimen without PRD was higher, 36.8% vs. 31.9%, (p < 0.001), at three yrs post-transplant; three-drug therapy was associated with a 6% lower adjusted risk of PRD. The death rate and adjusted risk for death was lower for recipients on a three- vs. two-drug regimen. Liver transplant recipients with HCV on a MMF-containing regimen are at a lower risk for PRD and death compared with recipients on a regimen not including MMF.     

Efficacy and Safety of Everolimus and Mycophenolic Acid With Early Tacrolimus Withdrawal After Liver Transplantation: A Multicenter Randomized Trial

SIMCER was a 6‐mo, multicenter, open‐label trial. Selected de novo liver transplant recipients were randomized (week 4) to everolimus with low‐exposure tacrolimus discontinued by month 4 (n = 93) or to tacrolimus‐based therapy (n = 95), both with basiliximab induction and enteric‐coated mycophenolate sodium with or without steroids. The primary end point, change in estimated GFR (eGFR; MDRD formula) from randomization to week 24 after transplant, was superior with everolimus (mean eGFR change +1.1 vs. ?13.3 mL/min per 1.73 m² for everolimus vs. tacrolimus, respectively; difference 14.3 [95% confidence interval 7.3–21.3]; p < 0.001). Mean eGFR at week 24 was 95.8 versus 76.0 mL/min per 1.73 m² for everolimus versus tacrolimus (p < 0.001). Treatment failure (treated biopsy‐proven acute rejection [BPAR; rejection activity index score >3], graft loss, or death) from randomization to week 24 was similar (everolimus 10.0%, tacrolimus 4.3%; p = 0.134). BPAR was more frequent between randomization and month 6 with everolimus (10.0% vs. 2.2%; p = 0.026); the rate of treated BPAR was 8.9% versus 2.2% (p = 0.055). Sixteen everolimus‐treated patients (17.8%) and three tacrolimus‐treated patients (3.2%) discontinued the study drug because of adverse events. In conclusion, early introduction of everolimus at an adequate exposure level with gradual calcineurin inhibitor (CNI) withdrawal after liver transplantation, supported by induction therapy and mycophenolic acid, is associated with a significant renal benefit versus CNI‐based immunosuppression but more frequent BPAR.     

Mycophenolate mofetil vs. sirolimus in kidney transplant recipients receiving tacrolimus-based immunosuppressive regimen

Abstract:  Mycophenolate mofetil (MMF) and sirolimus (SRL) are effective immunosuppressive drugs with distinct safety profile.
Methods:  Kidney transplant recipients receiving tacrolimus (TAC)-based immunosuppressive regimen were randomized to receive fixed daily doses of MMF (2 g/d, n = 50) or SRL (one loading dose of 15 mg, 5 mg/d till day 7 and 2 mg/d thereafter, n = 50) without induction therapy.
Results:  No differences were observed in the incidence of the composite (biopsy-confirmed acute rejection, graft loss or death) end-point (18% vs. 16%, p = 1.000), biopsy confirmed acute rejection (12% vs. 14%, p = 1.000), one-yr patient (94% vs. 98%, p = 0.308), graft (92% vs. 98%, p = 0.168), and death-censored graft survival (98% vs. 100%, p = 0.317) comparing patients receiving MMF or SRL respectively. Patients receiving SRL showed worse safety outcomes, higher mean creatinine (1.6 ± 0.5 mg/dL vs. 1.4 ± 0.3 mg/dL, p = 0.007), higher proportion of patients with proteinuria (52.0% vs. 10.7%, p = 0.041), higher mean urinary protein concentrations (0.3 ± 0.5 g/L vs. 0.1 ± 0.2 g/L, p = 0.012), higher mean cholesterol concentration (217 mg/dL vs. 190 mg/dL, p = 0.030), and higher proportion of patients prematurely discontinued from randomized therapy (26% vs. 8%, p = 0.031).
Conclusion:  In patients receiving TAC, MMF produced similar efficacy but superior safety profile compared with SRL.     

Conversion to sirolimus with calcineurin inhibitor elimination vs. dose minimization and renal outcome in heart and lung transplant recipients

Abstract:  Sirolimus (SRL) has been used as an alternative immunosuppressant strategy to allow either dose minimization or complete withdrawal of calcineurin inhibitors (CNI) therapy to improve renal outcome. One hundred thirty-one heart and 55 lung transplant patients were converted from a CNI to SRL based immunosuppression, with CNI elimination in 25 patients, and dose reduction in 161 patients. Fifty-six (28%) patients died and 65 (33%) patients had a 25% or more decline in estimated glomerular filtration rate (eGFR) during a median follow-up of 18 months. The three groups (SRL only group n = 25; SRL + tacrolimus n = 94; SRL + cyclosporine n = 67) had an initial improvement in estimated glomerular filtration rate (p = 0.05), with subsequent similar slow decline in mean eGFR (repeated measures ANOVA, p = 0.96). After controlling for important potential confounding variables, the three groups had similar renal outcome (p = 0.40) and overall survival (p = 0.45). In conclusion, the benefits of CNI withdrawal vs. minimization as part of SRL-based regimens are similar with regard to renal outcomes and patient survival.     

Long-term outcomes of dual kidney transplantation—a single center experience

Abstract:  The shortage of kidney donors has led to broadening of the acceptance criteria for deceased donor organs beyond the traditional use of young donors. We determined long-term post-transplant outcomes in recipients of dual expanded criteria donor kidneys (dECD, n = 44) and compared them to recipients of standard criteria donor kidneys (SCD, n = 194) and single expanded criteria donor kidneys (sECD, n = 62). We retrospectively reviewed these 300 deceased donor kidney transplants without primary non-function (PNF) or death in the first two wk, at our center from 1996 to 2003. The three groups were similar in baseline characteristics. Kidney allograft survival and patient survival (nine yr) were similar in the three respective donor groups, SCD, sECD and dECD (60% vs. 59% vs. 64% and 82% vs. 73% vs. 73%). Acute rejection in the first three months was 23.2%, 16.1%, and 22.7% in SCD, sECD and dECD, respectively (p = 0.49) and delayed graft function was 25.2%, 31.9% and 17.1% in the three groups, respectively (p = 0.28). When PNF and death within the first two wk was included, there was no significant difference in graft survival between the three groups. In our population, recipients of dECD transplants have acceptable patient and graft survival with kidneys that would have usually been discarded.     

Microalbuminuria post-renal transplantation: relation to cardiovascular risk factors and C-reactive protein

Abstract:  Microalbuminuria predicts graft loss and all-cause mortality in renal transplant recipients. In the general population, it clusters with both traditional cardiovascular risk factors and elevated C-reactive protein (CRP). Our objective was to define the relationship between microalbuminuria and these risk factors in stable renal transplant recipients. We identified 222 stable recipients who were minimum two months post-transplant and provided three urine albumin-to-creatinine ratio (ACR) measurements, excluding those with recent illness and proteinuria. Microalbuminuria was defined as averaged ACR ≥ 2.0 in men and 2.8 mg/mmol in women (Canadian Diabetes Association 2003). Risk factors associated with microalbuminuria were determined by multivariate logistic regression analysis. Averaged ACR correlated to CRP (R = 0.21, p = 0.001). Prevalence of microalbuminuria was 48% (108/222). Patients with microalbuminuria had higher CRP (7.01 ± 8 vs. 3.21 ± 3 mg/L, p < 0.0001) and systolic BP (129 ± 17 vs. 123 ± 12 mmHg, p = 0.004). Microalbuminuria was associated with increasing CRP [odds ratio 1.129 per 1 mg/L (95% CI 1.058–1.204), p = 0.0002], SBP [1.248 per 10 mmHg (1.023–1.522), p = 0.029] and smoking [1.938 (1.023–3.672), p = 0.042]. Post-transplant microalbuminuria is prevalent and is associated with elevated CRP, elevated BP, and smoking. Its relationship to these factors suggests it may be an indicator of graft and patient health.     

Evidence for IFN-gamma up- and IL-4 downregulation late post-transplant in patients with good kidney graft outcome

Abstract:  We found recently that patients with good graft outcome showed higher IFN-γ and IL-2, and lower IL-10 plasma levels late post-transplant than early post-transplant. In this retrospective study, we compared cytokine plasma levels in 33 symptom-free outpatients with those of 33 renal transplant recipients with early acute rejection (EAR), 29 with chronic rejection (CR), and 34 healthy controls (HC) to assess whether there is evidence for Th1 activation late post-transplant in patients with good graft outcome. Cytokines were measured pre-transplant, one wk, one month, six months, one yr, and two yr after transplantation. Twelve and 24 months post-transplant, IFN-γ plasma levels were significantly higher (p = 0.001; p = 0.001, respectively) and IL-4 plasma levels significantly lower (p = 0.028; p = 0.003, respectively) in patients with stable graft function than those in controls. Six, 12, and 24 months post-transplant, patients with stable graft function had similar IFN-γ and IL-4 plasma levels as patients with successfully treated EAR (p = n.s.), and higher IFN-γ (p = 0.013; p = 0.001; p = 0.0005, respectively) and lower IL-4 (p = 0.007; p = 0.417; p = 0.0001, respectively) plasma levels than patients with CR. These data suggest that increased plasma IFN-γ and decreased plasma IL-4 late post-transplant might be involved in the induction of mechanisms that facilitate good long-term graft outcome.     

What happens to the kidney in an SPK transplant when the pancreas fails due to a technical complication?

Abstract:  We examined a group of SPK recipients that had early (<90 d post-transplant) pancreas graft failure caused by a technical complication, and looked at outcomes of the kidney graft in these recipients. Of 289 SPK transplants, 36 (12.5%) had early pancreas graft failure because of a technical complication: thrombosis (n = 16), leak (n = 5), infection (n = 14), and pancreatitis (n = 1). Once the pancreas was lost, there was a high incidence of subsequent kidney graft failure. Kidney graft survival in these 36 recipients was 71.4% at one yr and 59.5% at three yr, significantly inferior compared to recipients that did not have early failure of the pancreas (86% at one yr and 82% at three yr, p < 0.001). Of the 36 recipients with early pancreas loss, 18 have gone on to failure of the kidney graft. Causes included thrombosis (n = 3), infection (n = 1), death with function (n = 6), chronic rejection (n = 4), ischemia (n = 1), and other (n = 3). Of the 18 kidney graft failures, nine occurred within three months after loss of the pancreas graft, usually either because of graft thrombosis, or patient death (usually from systemic sepsis). Multivariate analysis showed technical failure of the pancreas to be the most significant risk factor for kidney graft loss (HR = 2.08, p = 0.006).     

Post-transplant diabetes mellitus in lung transplant recipients: incidence and risk factors

Objective: Post-transplant diabetes mellitus (PTDM) is a common and potentially serious complication after solid organ transplantation. There are only a few data, however, about the incidence of DM in patients undergoing lung transplantation. Patients and methods: The medical records of 119 consecutive patients who underwent lung transplantation from 1998 to September 2004 were reviewed. Patients were divided in three groups according to their diabetes status, including pre-transplant DM, the PTDM group and those without DM. Patient records and all laboratory data were reviewed and the clinical course of diabetes was monitored. All recipients were treated with tacrolimus based regimen. Results: Mean follow-up for all patients was 25 ± 10. Twenty-three patients had DM in the pre-lung transplantation (LTX) DM group. PTDM developed in 34 of the remaining 96 patients (35.4%) with an incidence of 20%, 23% after 6 months and 12 months post-transplant. No significant difference was noted between 12 and 24 months post-LTX. The patients who developed DM were older (57 ± 15 vs 53 ± 13 years, p = 0.009), had increased BMI (26 ± 5 vs 24 ± 4, p = 0.0001), shorter time from diagnosis to LTX (21 ± 13 vs 28 ± 18 months, p = 0.007) more cytomegalovirus infection and more acute rejection and hyperglycemia in the first month after LTX. Four patients died in the PTDM group compared to nine patients in the no-DM group (12% vs 14%; p = 0.72). Conclusions: Post-transplant diabetes is a common complication in lung transplant patients receiving tacrolimus-based immunosuppression. The risk for developing PTDM is greatest among older recipients, those obese, and among recipients with more rejections episodes.     

Higher tacrolimus trough levels on days 2–5 post-renal transplant are associated with reduced rates of acute rejection

Abstract:  We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng/mL (n = 122, range 2–13.5 ng/mL), Group 2: median 17 ng/mL (n = 123, range 14–20 ng/mL), Group 3: median 24 ng/mL (n = 108, range 20.5–27 ng/mL) and Group 4: median 33.5 ng/mL (n = 116, range 27.5–77.5 ng/mL). A graded reduction in the rates of ACR was observed for each incremental days 2–5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26–32.88), 22.20% (95% CI 15.78–30.70), 13.41% (95% CI 8.15–21.63) and 8.69% (95% CI 4.77–15.55) for Groups 1–4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.     

Renal Transplantation With Final Allocation Based on the Virtual Crossmatch

Solid phase immunoassays (SPI) are now routinely used to detect HLA antibodies. However, the flow cytometric crossmatch (FCXM) remains the established method for assessing final donor–recipient compatibility. Since 2005 we have followed a protocol whereby the final allocation decision for renal transplantation is based on SPI (not the FCXM). Here we report long‐term graft outcomes for 508 consecutive kidney transplants using this protocol. All recipients were negative for donor‐specific antibody by SPI. Primary outcomes are graft survival and incidence of acute rejection within 1 year (AR <1 year) for FCXM+ (n = 54) and FCXM? (n = 454) recipients. Median follow‐up is 7.1 years. FCXM+ recipients were significantly different from FCXM? recipients for the following risk factors: living donor (24% vs. 39%, p = 0.03), duration of dialysis (31.0 months vs. 13.5 months, p = 0.008), retransplants (17% vs. 7.3%, p = 0.04), % sensitized (63% vs. 19%, p = 0.001), and PRA >80% (20% vs. 4.8%, p = 0.001). Despite these differences, 5‐year actual graft survival rates are 87% and 84%, respectively. AR <1 year occurred in 13% FCXM+ and 12% FCXM? recipients. Crossmatch status was not associated with graft outcomes in any univariate or multivariate model. Renal transplantation can be performed successfully, using SPI as the definitive test for donor–recipient compatibility.     

Renal insufficiency after liver transplantation in the MELD era compared to the pre-MELD era

Abstract:  Because the model for end-stage liver disease (MELD) system for liver allocation gives priority to patients with a higher creatinine, and because pre-transplant renal function is one determinant of post-transplant renal function, this study compares the burden of renal insufficiency in the pre-MELD and MELD eras. Two hundred and elven patients, at our institution, transplanted in the pre-MELD era, were compared to 143 in the MELD era. The GFR (mL/min/1.73 m²) was significantly higher in the MELD cohort than the pre-MELD cohort at time of transplant, discharge, and 12 months post-transplant (95.5 vs. 85.3, p = 0.039; 90.4 vs. 77.4, p = 0.002; 66.8 vs. 60.3, p = 0.026). There was no difference between the two groups in time to renal failure. There was a higher rate of sirolimus use in the MELD era (27% vs. 18%: p = 0.042) and a slightly higher use of kidney–liver transplant in the MELD era (p = 0.056). We did not identify greater renal insufficiency in the MELD era. There was greater renal function in the MELD era at time of transplant, discharge and month 12. Potential explanations include: absence of an increase in renal insufficiency prior to transplant in the MELD era, greater use of renal sparing immunotherapy and growing use of kidney–liver transplant.     

The impact of employment status on recipient and renal allograft survival

Abstract: Background:  With the improved median survival of kidney transplant recipients, there has been an increased focus on quality of life after transplantation. Employment is a widely recognized component of quality of life. To date, no study has demonstrated a link between post-transplant employment status and recipient and allograft survival after transplant.
Methods:  The records from the United States Renal Data System (USRDS) and the United Network for Organ Sharing (UNOS) from January 1, 1995, through December 31, 2002, were examined in this retrospective study. Two outcomes, allograft survival time (time between the transplantation and allograft failure or censor) and recipient survival time (time between the transplantation and recipient death or censor), were analyzed using Cox models adjusted for potential confounding factors.
Results:  Compared to patients working full time at the time of transplantation, those not working by choice have a greater risk to graft [hazard ratio (HR) 1.27, p < 0.001] but not to recipient survival. A similar trend was observed in patients not working at 12 months post-transplant (HR 1.30, p < 0.001 for graft survival but not for recipient survival). However, at five-yr post-transplant not working by choice was protective to the graft (HR 0.47, p < 0.01) as compared to working full time. Results of the analysis in the patient subgroups based on the comorbidities and the overall health status were similar.
Conclusion:  Employment status at the time of transplantation and in post-transplant period has a strong and independent association with the graft and recipient survival. Full time employment at the time of transplant and at one-yr post-transplant is associated with lower risk for graft failure and recipient mortality. However, working beyond the time covered by Medicare might be associated with potential risk for graft survival.     

Cardiovascular risk, cardiovascular events, and metabolic syndrome in renal transplantation: comparison of early steroid withdrawal and chronic steroids

Abstract: Background:  Cardiovascular disease (CVD) is the leading cause of death with a functioning graft in renal transplant recipients. The purpose of this study was to compare Framingham Risk Score (FRS), metabolic syndrome (MS), and cardiovascular events (CVE) in patients receiving early corticosteroid withdrawal (ECSWD), or chronic corticosteroid therapy (CCS).
Methods:  In all, 251 ECSWD and 146 CCS patients were evaluated. FRS and MS were identified at baseline, six, 12, and 24 months post-transplant. A total of 124 patients with diabetes mellitus prior to transplantation were excluded from MS analysis. CVE were defined as sudden-death, MI, angina, or CVA/TIA. Repeat-measure logistic regression was used for statistical analysis.
Results:  Fifty-four patients experienced 72 CVE. Mean follow-up was 755 ± 312 d and time to CVE was 14.8 ± 8.3 months. Demographics were similar between groups. FRS was not different between groups. CVE were significantly greater in CCS patients then ECSWD (20% vs. 10%, p = 0.024). New-onset MS occurred more frequently in patients receiving CCS then ECSWD (45% vs. 22%, p < 0.001) and was associated with more CVE (p < 0.015).
Conclusions:  Patients receiving ECSWD regimens have significantly decreased CVE and new onset MS compared with CCS. MS is associated with increased CV risk and CVE.     

The role of the economic environment in kidney transplant outcomes

Abstract:  The relationship between global economic indicators and kidney allograft and patient survival is unknown. To investigate possible relationships between the two, we analyzed kidney transplant recipients receiving transplants between January of 1995 and December of 2002 (n = 105 181) in the USA using Cox regression models. We found that: The Dow Jones Industrial Average had a negative association with outcome at one year post-transplant (HR 1.03 and 1.06, p < 0.001 for graft and recipient survival, respectively) but changed to a protective effect in the late period (HR 0.77, p < 0.001, and HR 0.83, p < 0.001 for graft and recipient survival, respectively, five yr after transplantation). Unemployment rate had a protective effect at the time of transplantation (HR 0.97, p < 0.005) and at one year after transplantation (HR 0.95, p < 0.005) but changed to the opposite in the late period at the fifth post-transplant year (HR 1.35, p < 0.001, and HR 1.20, p < 0.001, for graft and recipient survival respectively). The Consumer Price Index measured at different post-transplant time points seems to have had a protective effect on the graft (HR 0.77, p < 0.001 at five yr) and recipient (HR 0.83, p < 0.001 at five yr) survival. Beyond three yr after transplantation, when some of the recipients lose Medicare benefits, economic downturns might have a negative association with the kidney graft and recipient survival.     

A randomized trial of basiliximab with three different patterns of cyclosporin A initiation in renal transplant from expanded criteria donors and at high risk of delayed graft function

Abstract:  This study assays therapy with basiliximab and different patterns of cyclosporin A (CsA) initiation in renal transplant (RT) recipients from expanded criteria donors (ECD) and at high risk of delayed graft function (DGF). A multicentre six-month open-label randomized trial with three parallel groups treated with basiliximab plus steroids, mycophenolate mofetil and different patterns of CsA initiation: early within 24 h post-RT at 3 mg/kg/d (Group 1; n = 38), and at 5 mg/kg/d (Group 2; n = 40), or delayed after 7–10 d at 5 mg/kg/d (Group 3; n = 36). There were no differences among groups in six months GFR (43.1 ± 12, 48.0 ± 14 and 47.2 ± 17 mL/min, respectively), DGF (Group 1: 31%, Group 2: 37%, Group 3: 42%), nor biopsy-proven acute rejection, although clinically treated and biopsy-proven acute rejection was significantly higher in Group 3 (25%) vs. Group 1 (5.3%, p < 0.05). At six months no differences were observed in death-censored graft survival or patient survival. Induction therapy with basiliximab and three CsA-ME initiation patterns in RT recipients from ECD and at high risk of DGF presented good renal function and graft survival at six months. Late onset group did not achieve improvement in DGF rate and showed a higher incidence of clinically treated and biopsy-proven acute rejection.     

Impact of tacrolimus and mycophenolate mofetil regimen vs. a conventional therapy with steroids on cardiovascular risk in liver transplant patients

The aim of this study was to evaluate the impact of a steroid‐free regimen with tacrolimus and mycophenolate mofetil (modified therapy) vs. a standard regimen of tacrolimus and steroids on the cardiovascular risk score of liver transplant recipients. Patients who received a liver transplant were randomized to a modified therapy (n = 58) or a standard regimen (n = 59). Both groups were balanced at baseline, except for a higher prevalence of diabetes mellitus (DM) (p < 0.01) and a higher serum creatinine concentration (p < 0.05) in the modified therapy group. After 12 months, the prevalence of new‐onset DM, arterial hypertension, hypercholesterolemia, hypertriglyceridemia, and changes in cardiovascular risk factors was similar in both groups. The increase in serum creatinine (mg/dL) compared to baseline at one yr post‐transplantation was numerically lower in the modified therapy group (0.22 ± 0.42) than in the standard regimen group (0.41 ± 0.67) (p = 0.068). Although estimated cardiovascular risk score did not vary significantly compared to baseline in either group, there was a slight reduction in the modified regimen (?0.27 ± 2.87) vs. a mild increase (0.17 ± 2.94) in the standard regimen (p = 0.566). In conclusion, a steroid‐free regimen with tacrolimus and mycophenolate mofetil was associated with a trend toward better preservation of kidney function and reduction of cardiovascular risk score.     

Technical failure of the pancreas after SPK transplant: are these patients good candidates for later pancreas retransplant?

Abstract:  Technical failure of the pancreas graft after a simultaneous pancreas–kidney (SPK) transplant is not uncommon, affecting roughly 10% of SPK recipients. These patients often recover with good kidney function, but have persistent issues related to their diabetes. The aim of this study was to determine if these patients were good candidates for a later pancreas retransplant. Outcomes were compared between 21 PASPK (pancreas after SPK) recipients and 361 recipients of a primary pancreas after kidney (PAK) transplant. Except for kidney graft source, there was no significant difference in the demographic characteristics between these two groups. In general, early surgical complications were more common in PASPK than PAK recipients (47.6% vs. 35.5%, p = 0.15), although the difference was not statistically significant. The incidence of acute rejection was no different between these two groups (28% vs. 33%, p = NS). At three yr post-transplant, patient and pancreas graft survival rates were also no different between the two groups (p = NS). The most common cause for graft loss in both groups was acute or chronic rejection. In conclusion, pancreas retransplant is a viable option for SPK recipients experiencing early technical failure of the pancreas graft. These recipients are not at higher immunologic risk vs. primary PAK recipients.     

Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function

Abstract:  In this single-institution study, we compared outcomes in diabetic recipients of living donor (LD) kidney transplants that did vs. did not undergo a subsequent pancreas transplant. Of 307 diabetic recipients who underwent LD kidney transplants from January 1, 1995, through December 31, 2003, a total of 175 underwent a subsequent pancreas after kidney (PAK) transplant; 75 were deemed eligible (E) for, but did not receive (for personal or financial reasons), a PAK, and thus had a kidney transplant alone (KTA); and 57 deemed ineligible (I) for a PAK because of comorbidity also had just a KTA. We analyzed the three groups (PAK, KTA-E, KTA-I) for differences in patient characteristics, glycemic control, renal function, patient and kidney graft survival rates, and causes of death. Kidney graft survival rates (actuarial) were similar in the PAK vs. KTA-E groups at one, five, and 10 yr post-transplant: 98%, 82%, and 67% (PAK) vs. 100%, 84%, and 62% (KTA-E) (p = 0.9). The long-term (greater than four yr post-transplant) estimated glomerular filtration rate (GFR) was higher in the PAK than in the KTA-E group: 53 ± 20 mL/min (PAK) vs. 43 ± 16 mL/min (KTA-E) (p = 0.016). The patient survival rates were also similar for the PAK and KTA-E groups. We conclude that the subsequent transplant of a pancreas after an LD kidney transplant does not adversely affect patient or kidney graft survival rates; in fact, it is associated with better long-term kidney graft function.