Simultaneous Pancreas And Kidney Recipients Research Articles

Evolution of Pancreas Transplantation At A Single Institution-50+ Years and 2500 Transplants.

To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past 5 decades. The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care. A single-center retrospective review of 2500 pancreas transplants was performed over >50 years in bivariate and multivariable models. Transplants were divided into 6 eras; outcomes are presented for the entire cohort and by era. All measures of patient and graft survival improved progressively through the 6 transplant eras. The overall death-censored pancreas graft half-lives were >35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year death-censored pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall, graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time. Pancreas outcomes have significantly improved over time through sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss.

Outcomes of pregnancy in simultaneous pancreas and kidney transplant recipients: A single-center retrospective study.

Simultaneous pancreas and kidney (SPK) transplantation, in uremic women with insulin-dependent diabetes, increases the chance of a successful pregnancy and minimizes the risk to infants. The aim of this study was to document pregnancy and explore the challenges in this cohort of women. Retrospective analysis of women who underwent pancreas transplantation between January 1, 1998 and 8 January, 2019 was conducted. Seventeen pregnancies were identified in 13 women. Mean transplant-to-pregnancy interval was 4.6 years (range, 1.1-10.2years). Eleven pregnancies resulted in live birth (65%), and six (35%) ended in miscarriage/fetal loss at a median gestational age of 8.5weeks. Mean gestational age at delivery was 34.9weeks (SD ±3weeks). Preeclampsia and C-section rates were 77% and 67%, respectively. Adverse fetal and graft outcomes were observed in 100% of unplanned pregnancies, compared to 10% of planned pregnancies (P<.001). One kidney allograft was lost during pregnancy; one pancreas and two kidney allografts were lost within 3years of pregnancy. This is a high-risk group for grafts and offspring. Pre-pregnancy planning is vital. A multidisciplinary approach by obstetric and transplant teams is important pre-pregnancy, antenatally, and peripartum. This is the largest published series of pregnancies in SPK recipients from a single center.

One more time, emphasizing the advantage of simultaneous pancreas and kidney transplantation for patients with type 1 diabetes and end-stage renal disease.

Simultaneous pancreas and kidney (SPK) transplantation is considered the best treatment option for patients with diabetes and end-stage renal disease (ESRD). SPK recipients with a functioning pancreas graft have significantly better kidney graft survival and patient survival compared to those who received a kidney-only transplant or those with a failed pancreas graft. In addition, SPK recipients with isolated pancreas graft failure who undergo pancreas retransplant still have better kidney graft survival.

Impact of Sarcopenia on Simultaneous Pancreas and Kidney Transplantation Outcomes: A Retrospective Observational Cohort Study.

Sarcopenia has been identified as a predictive variable for surgical outcomes. We hypothesized that sarcopenia could be a key measure to identify frail patients and potentially predict poorer outcomes among recipients of simultaneous pancreas and kidney (SPK) transplants. We estimated sarcopenia by measuring psoas muscle mass index (PMI). PMI was assessed on perioperative computed tomography (CT) scans of SPK recipients. Of the 141 patients identified between 2010 and 2018, 107 had a CT scan available and were included in the study. The median follow-up was 4 years (range, 0.5-9.1 y). Twenty-three patients had a low PMI, and 84 patients had a normal PMI. Patient characteristics were similar between the 2 groups except for body mass index, which was significantly lower in low PMI group (P < 0.001). Patient and kidney graft survival were not statistically different between groups (P = 0.851 and P = 0.357, respectively). A multivariate Cox regression analysis showed that patients with a low PMI were 6 times more likely to lose their pancreas allograft (hazard ratios, 5.4; 95% confidence intervals, 1.4-20.8; P = 0.015). Three out of 6 patients lost their pancreas graft due to rejection in the low PMI group, compared with 1 out of 9 patients in the normal PMI group. Among low PMI patients who had a follow-up CT scan, 62.5% (5/8) of those with a functional pancreas graft either improved or resolved sarcopenia, whereas 75.0% (3/4) of those who lost their pancreas graft continued to lose muscle mass. Sarcopenia could represent one of the predictors of pancreas graft failure and should be evaluated and potentially optimized in SPK recipients.

Anticoagulation in simultaneous pancreas kidney transplantation - On what basis?

BACKGROUNDDespite technical refinements, early pancreas graft loss due to thrombosis continues to occur. Conventional coagulation tests (CCT) do not detect hypercoagulability and hence the hypercoagulable state due to diabetes is left untreated. Thromboelastogram (TEG) is an in-vitro diagnostic test which is used in liver transplantation, and in various intensive care settings to guide anticoagulation. TEG is better than CCT because it is dynamic and provides a global hemostatic profile including fibrinolysis.AIMTo compare the outcomes between TEG and CCT (prothrombin time, activated partial thromboplastin time and international normalized ratio) directed anticoagulation in simultaneous pancreas and kidney (SPK) transplant recipients.METHODSA single center retrospective analysis comparing the outcomes between TEG and CCT-directed anticoagulation in SPK recipients, who were matched for donor age and graft type (donors after brainstem death and donors after circulatory death). Anticoagulation consisted of intravenous (IV) heparin titrated up to a maximum of 500 IU/h based on CCT in conjunction with various clinical parameters or directed by TEG results. Graft loss due to thrombosis, anticoagulation related bleeding, radiological incidence of partial thrombi in the pancreas graft, thrombus resolution rate after anticoagulation dose escalation, length of the hospital stays and, 1-year pancreas and kidney graft survival between the two groups were compared.RESULTSSeventeen patients who received TEG-directed anticoagulation were compared against 51 contemporaneous SPK recipients (ratio of 1: 3) who were anticoagulated based on CCT. No graft losses occurred in the TEG group, whereas 11 grafts (7 pancreases and 4 kidneys) were lost due to thrombosis in the CCT group (P = 0.06, Fisher’s exact test). The overall incidence of anticoagulation related bleeding (hematoma/ gastrointestinal bleeding/ hematuria/ nose bleeding/ re-exploration for bleeding/ post-operative blood transfusion) was 17.65% in the TEG group and 45.10% in the CCT group (P = 0.05, Fisher’s exact test). The incidence of radiologically confirmed partial thrombus in pancreas allograft was 41.18% in the TEG and 25.50% in the CCT group (P = 0.23, Fisher’s exact test). All recipients with partial thrombi detected in computed tomography (CT) scan had an anticoagulation dose escalation. The thrombus resolution rates in subsequent scan were 85.71% and 63.64% in the TEG group vs the CCT group (P = 0.59, Fisher’s exact test). The TEG group had reduced blood product usage {10 packed red blood cell (PRBC) and 2 fresh frozen plasma (FFP)} compared to the CCT group (71 PRBC/ 10 FFP/ 2 cryoprecipitate and 2 platelets). The proportion of patients requiring transfusion in the TEG group was 17.65% vs 39.25% in the CCT group (P = 0.14, Fisher’s exact test). The median length of hospital stay was 18 days in the TEG group vs 31 days in the CCT group (P = 0.03, Mann Whitney test). The 1-year pancreas graft survival was 100% in the TEG group vs 82.35% in the CCT group (P = 0.07, log rank test) and, the 1-year kidney graft survival was 100% in the TEG group vs 92.15% in the CCT group (P = 0.23, log tank test).CONCLUSIONTEG is a promising tool in guiding judicious use of anticoagulation with concomitant prevention of graft loss due to thrombosis, and reduces the length of hospital stay.

Outcomes of simultaneous pancreas and kidney transplants based on preemptive transplant compared to those who were on dialysis before transplant - a retrospective study.

Among kidney transplant recipients, the duration of pretransplant dialysis is significantly associated with worse post-transplant outcomes. However, data on the outcomes of preemptive simultaneous pancreas and kidney (SPK) are limited. We analyzed primary SPK recipients transplanted between January 2000 and December 2017. Patients were divided into two groups based on pretransplant dialysis history of preemptive versus non-preemptive. Patient and survival of grafts were outcomes of interest. Of the 644 recipients, 174 (27%) were preemptive and 470 (73%) were not. Most of the baseline characteristics were similar between the groups. In the univariable analysis, the non-preemptive transplant was associated with 54% increased risk for kidney death-censored graft failure (DCGF; HR: 1.54; 95% CI: 1.01-2.35; P=0.05). There was a 29% increased risk after adjustment for confounding factors (HR: 1.29; 95% CI: 0.83-2.02; P=0.26), although this association was not statistically significant. Similarly, there was a 16% increased risk of pancreas DCGF in univariable analysis and 1% after adjustment, which was also not statistically significant. When outcomes were based on the duration of pretransplant dialysis, the duration was not associated with either patient survival or survival of either graft in K-M analysis. In SPK recipients, with pretransplant dialysis history, there was a tendency toward inferior graft survival, mainly for the kidney more than the pancreas.

Polyomavirus and cytomegalovirus infections are risk factors for grafts loss in simultaneous pancreas and kidney transplant.

Published literature on predictors of polyomavirus (BKV) and cytomegalovirus (CMV) infections in simultaneous pancreas and kidney (SPK) transplant and their impact on allograft outcomes remain sparse. We hypothesize that BKV and CMV viremia infections decrease allograft survival in SPK. Identifying modifiable predictors of BKV and CMV may help tailor immunosuppression and improve allograft survival. All SPK recipients at our institution between January 2000 and April 2016 were included (n=757). Thirty-nine recipients had BKV only and 25 had CMV only, and infection occurred at median follow-up times of 217 and 163days, respectively. Event density sampling was used to match recipients with BKV or CMV to up to 10 recipients without infection by age, sex, and HLA mismatch status, and these were followed for a median of 4.3years after infection. Older age (HR 1.49 for each decade; 95% CI: 0.95, 2.35; P=.083) and tacrolimus use (HR 20.6; 95% CI: 2.37, 179.53; P=.006) were associated with increased incidence of BKV, but not CMV, infection. Both BKV and CMV infections were associated with increased risk of allograft failure for both pancreas (BKV [HR 2.17; 95% CI 1.47, 3.208; P=.000], CMV [HR 1.7; 95% CI 1.077, 2.687; P=.023]) and kidney (BKV [HR 2.65; 95% CI 1.765, 3.984; P=.000], CMV [HR 2.07; 95% CI 1.295, 3.308; P=.002]). Older age at time of transplant and tacrolimus may help predict BKV infection in SPK recipients.

The use of LCP-Tacrolimus (Envarsus XR) in simultaneous pancreas and kidney (SPK) transplant recipients

BackgroundExtended release LCP-tacrolimus (LCPT) allows once-daily dosing in transplant recipients. The improved bioavailability may be beneficial for simultaneous pancreas-kidney recipients (SPK). MethodsThis is a study of 39 SPK recipients on standard immediate-release tacrolimus (IR-TAC, n = 21) or LCPT (n = 18). Coefficient of variability (CV = 100∗standard deviation/mean) was calculated to assess drug levels. Hemoglobin A1c (HbA1c), tacrolimus and creatinine levels were measured postoperatively. ResultsThere was no difference in tacrolimus CV in the IR-TAC and LCPT groups at 1 month or 3 months postoperatively; however, a greater difference was observed at 1 year (41.0 vs. 33.1%; p = 0.19). There were six episodes of acute rejection in the IR-TAC group compared to zero episodes in the LCPT group (p = 0.01). HbA1c was significantly higher in the IR-TAC group compared to LCPT at 3 (5.5 vs. 4.9%, p = 0.01), 6 (5.6 vs. 4.9%, p = 0.01) and 12 months (5.8 vs. 5.1%, p = 0.07). ConclusionsSignificantly lower rates of rejection were observed in patients receiving LCPT. The once daily dosing may facilitate medication adherence and result in improved long-term outcomes.

Outcomes after simultaneous kidney‐pancreas versus pancreas after kidney transplantation in the current era

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1year. Similarly, 1-year graft survival for both organs was not different. At last follow-up, uncensored and death-censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times.

Risk factors for surgical site infection after kidney and pancreas transplantation.

To evaluate the incidence of surgical site infection (SSI) in a cohort of pancreas transplant recipients and assess predisposing risk factors for SSI DESIGN: Retrospective cohort study SETTING: Single transplant center in CanadaPatientsPatients who underwent any simultaneous pancreas and kidney (SPK) or pancreas after kidney (PAK) transplant procedures between January 2000 and December 2015 METHODS: In this retrospective cohort evaluation of SPK or PAK recipients, we assessed the incidence of SSI and risk factors associated with superficial, deep, and organ/space SSI. Multivariate logistic regression was used to identify independent risk factors for SSI in SPK and PAK recipients. In total, 445 adult transplant recipients were enrolled. The median age of these patients was 51 years (range, 19-71 years), and 64.9% were men. SSIs were documented in 108 patients (24.3%). Organ/space SSIs predominated (59 patients, 54.6%), followed by superficial SSIs (47 patients, 43.5%) and deep SSIs (3 patients, 2.8%). Factors predictive of SSIs in the multivariate analysis were cold pancreas ischemic time (odds ratio [OR], 1.002; P=.019) and SPK transplant (compared to PAK transplant recipients; OR, 2.38; P=.038). Patients with SSIs developed graft loss more frequently (OR, 16.99; P<.001). Organ/space SSIs remain a serious and common complication after SPK and PAK. Prolonged cold ischemic time and SPK transplant were the risk factors predictive of SSIs. Appropriate perioperative prophylaxis in high-risk patients targeting the potential pathogens producing SSIs in kidney and/or pancreas transplant recipients and a reduction in cold ischemia may prove beneficial in reducing these SSIs.

An audit of pregnancy outcomes in solid organ transplant recipients at a metropolitan hospital.

Pregnancies in patients with solid organ transplants have higher rates of complications and caesarean sections (CS). To perform an audit of the pregnancy outcomes in transplant recipients, to determine the rate of CS in our cohort, the appropriate skin incision for CS in these patients and to formulate recommendations for preoperative planning. This is a retrospective cohort study. All patients who had a solid organ transplant were identified from the obstetrics database. The operation records of the transplant recipients who delivered by CS were reviewed and the de-identified data were evaluated for pregnancy outcomes. This cohort consisted of 22 women: six had simultaneous pancreas and kidney (SPK) transplants and 16 had kidney transplants. Over a ten-year period, four women had two pregnancies and one had a twin pregnancy, thus 27 babies were born. The rate of CS was 58% (n=15) and the surgical approach in 13 of these patients was by Pfannenstiel incision. One patient had an elective midline incision at the first CS, which was repeated in the next pregnancy. Two CS were complicated by bladder injury, both occurring in SPK recipients. Patients with solid organ transplants have a higher rate of CS and SPK patients may be at a higher risk of bladder injuries during CS. Our data suggest that Pfannenstiel skin incision is still suitable for these patients. We recommend reviewing the operative details of the transplant operation and a pelvic magnetic resonance imaging for pre-operative planning.

Concurrent biopsies of both grafts in recipients of simultaneous pancreas and kidney demonstrate high rates of discordance for rejection as well as discordance in type of rejection - a retrospective study.

It is commonly assumed that in simultaneous pancreas and kidney (SPK) recipients, rejection of the two organs is concordant. As a result, concurrent biopsies of both organs are rarely performed and there are limited histological data on how often rejection is in fact discordant. We reviewed all SPK recipients transplanted at the University of Wisconsin between January 01, 2001, and December 31, 2016, that underwent biopsy of both organs. We included all patients whose biopsies were within 30 days. If patients were treated for rejection between biopsies, they were excluded if the biopsies were more than 4 days apart. Ninety-one simultaneous biopsies were performed within 30 days of each other, and 40 met our inclusion criteria. A total of 25 (62.5%) patients had concordance of biopsy findings: 11 had rejection of both organs, and 14 had no rejection of either organ. The other 15 (37.5%) were discordant for rejection, with 10 having pancreas-only rejection and five kidney-only rejection. It was striking to find that four of the 11 patients with concordance for rejection (36%) had different types (AMR, ACR, or mixed) of rejection in the two organs. This large series of simultaneous pancreas and kidney biopsies demonstrates the continued utility of performing biopsies of both organs.

Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation

AimsPatients with type 1 diabetes and end-stage renal disease with simultaneous pancreas and kidney (SPK) or kidney transplants alone (KA) were recruited 9–12 years post transplantation. We investigated differences between these groups with regard to inflammatory parameters and long-term structural changes in kidneys. MethodsBlood samples were analyzed by ELISA and multiplex for chemokines, cytokines, growth factors, cell adhesion molecules and matrix metalloproteinases. Kidney graft biopsies were analyzed by electron microscopy for glomerular basement membrane thickness. Heparan- and chondroitin sulfate disaccharide structures were determined by size exclusion chromatography mass–spectrometry. ResultsThe SPK and the KA group had average glycated hemoglobin A1c (HbA1c) of 5.8% (40mmol/mol) and 8.6% (70mmol/mol) respectively. SPK recipients also had 16.2% lower body mass index (BMI) and 46.4% lower triglyceride levels compared with KA recipients, compatible with an improved metabolic profile in the SPK group. Plasminogen activator inhibitor (PAI-1), C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) were lower in the SPK group. In kidney graft biopsies of the KA-patients an 81.2% increase in average glomerular basement membrane thickness was observed, accompanied by alterations in heparan sulfate proteoglycan structure. In addition to a decrease in 6-O-sulfated disaccharides, an increase in non-N-sulfated disaccharides with a corresponding slight decrease in N-sulfation was found in kidney biopsies from hyperglycemic patients. ConclusionsPatients with end stage renal disease subjected to KA transplantation showed impaired inflammatory profile, increased thickness of basement membranes and distinct changes in heparan sulfate structures compared with SPK recipients.

Simultaneous pancreas and kidney (SPK) retransplantation in prior SPK recipients

We have performed 113 renal and 28 isolated pancreas retransplants in our cohort of more than 1200 prior simultaneous pancreas and kidney (SPK) recipients. On the basis of these experiences, we began performing repeat SPK in prior SPK recipients (n = 9). This retrospective review summarizes our experience with repeat SPK transplantation in prior SPK recipients. Mean age at retransplant was 39 yr; mean interval to retransplant was 7.8 yr. Thirty-three percent were pre-dialysis. Eighty-nine percent of patients underwent transplant nephrectomy (five during the repeat SPK and three prior to it), and 78% underwent transplant pancreatectomy (four during the repeat SPK and three prior to it). Enteric drainage was performed in all repeat SPKs. Median length of stay was 11 d. Perioperative complications included the following: renal artery thrombosis (1), pancreatic portal venous thrombosis (1), enteric leak (1), and hematoma (2). Overall pancreatic allograft survival was 78% at one yr and 67% at two yr. Overall renal allograft survival was 89% at one yr and 78% at two yr. Patient survival at one and three yr was 100%. Survival of repeat SPK allografts is acceptable despite the increased technical and immunologic demands of retransplantation. Graftectomy prior to or at the time of retransplantation is often necessary.

Early Pancreas Graft Failure Is Associated With Inferior Late Clinical Outcomes After Simultaneous Kidney-Pancreas Transplantation

Early pancreas graft failure after simultaneous pancreas and kidney (SPK) transplantation is common. We studied the impact of early pancreas graft failure on long-term kidney and patient survival. We included all primary SPK transplants performed in the United States between January 1, 2000, and December 31, 2007, who had maintained kidney graft function at 90 days posttransplantation. Kaplan-Meier and Cox multivariate analyses were performed. The causes of death between the two cohorts were compared. A total of 6282 SPK recipients were included in the analyses. Of those, 470 had lost pancreas graft within the first 90 days largely related to pancreas graft thrombosis. Early pancreas graft failure was associated with lower subsequent kidney graft and patient survival (log-rank, P=0.02 and P<0.001, respectively). Multivariate regression analyses demonstrated a 70% higher risk of kidney graft failure after 3 years (adjusted hazard ratio 1.69; 95% CI 1.08, 2.66; P=0.022) and more than doubled the risk for death (adjusted hazard ratio 2.18; 95% CI 1.67, 2.85; P<0.001) among SPK recipients with early pancreas graft failure. The causes of death were similar between the two cohorts. Early pancreas graft failure in SPK transplant recipients is associated with an increased risk for subsequent kidney failure and death. Optimization of therapeutic interventions after early pancreas graft failure is needed.

The case for pancreas after kidney transplantation

Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti-thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One-yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus-based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.

The long‐term survival of simultaneous pancreas and kidney transplant with basiliximab induction therapy

Interleukin-2 receptor (IL2R) antibody has emerged as an attractive induction therapy for organ transplant. However, the long-term outcome of basiliximab induction in simultaneous pancreas and kidney (SPK) transplant remains speculative. We retrospectively analyzed the long-term survivals of 91 consecutive SPK recipients with basiliximab as induction, combination of steroid, tacrolimus (TAC) and mycophenolate acid (MFA)--either mycophenolate mofetil (MMF) or sodium mycophenolate (myfortic) as maintenance. At one, three, five, and seven-yr, the actual patient survival rate were 91.2%, 90.3%, 88.1%, and 88.2%, respectively; kidney graft survivals were 90.1%, 84.7%, 78.6%, and 70.6%, respectively; and pancreas graft survivals were 86.8%, 80.6%, 71.4%, and 58.8% respectively. There was a low incidence of rejection and CMV infection. Basiliximab induction with TAC, MFA, and steroid maintenance therapy can provide excellent long-term outcome for SPK recipients.

Long-term renal allograft outcome after simultaneous kidney and pancreas transplantation.

In selected young patients with type 1 diabetes mellitus and end-stage renal failure, simultaneous pancreas and kidney (SPK) transplantation is the treatment of choice. We conducted a retrospective, case-controlled study to compare the function, survival and pathology of renal allografts after SPK and kidney-alone (KA) transplantations. We studied 26 consecutive SPK patients and 67 KA controls matched for time of transplantation. Renal function was assessed by routine evaluation of serum creatinine and its course by the 1/serum creatinine vs time curve. Histologic evaluation of early biopsies (0-3 months post-transplantation, n=63), intermediate biopsies (3 months-1 year, n=75) and late biopsies (after 1 year, n=35) were performed by two independent reviewers. SPK and KA recipients differed significantly with regard to donor and recipient age, time on the waiting list, HLA sensitization, renal cold ischaemia time (CIT) and the incidence of delayed graft function. Acute rejection was more frequent after SPK than KA (54 vs 27%; P=0.01), despite higher trough levels of calcineurin inhibitors. After SPK and KA, actuarial patient and renal allograft survival and renal function were comparable at 1 and 4 years. Severe chronic lesions, especially vascular lesions, and calcineurin-inhibitor nephrotoxicity were more frequent in intermediate and late biopsies in the SPK group. We confirmed that patient and graft survival is comparable between SPK and KA recipients. Despite the use of optimal organs and shorter CIT in SPK, renal graft function was not different in the two groups. Histologic chronic lesions were more severe in SPK than in KA recipients. This might be caused by acute rejection episodes or be due to more severe nephrotoxicity after SPK, because of higher doses of calcineurin inhibitors, or higher sensitivity to calcineurin-inhibitor nephrotoxicity.