Simultaneous Pancreas-kidney Transplant Recipients Research Articles

Diabetic nephropathy alters circulating long noncoding RNA levels that normalize following simultaneous pancreas-kidney transplantation.

Simultaneous pancreas–kidney transplantation (SPKT) replaces kidney function and restores endogenous insulin secretion in patients with diabetic nephropathy (DN). Here, we aimed to identify circulating long noncoding RNAs (lncRNAs) that are associated with DN and vascular injury in the context of SPKT. Based on a pilot study and a literature‐based selection of vascular injury–related lncRNAs, we assessed 9 candidate lncRNAs in plasma samples of patients with diabetes mellitus with a kidney function >35 mL/min/1.73 m2 (DM; n = 12), DN (n = 14), SPKT (n = 35), healthy controls (n = 15), and renal transplant recipients (KTx; n = 13). DN patients were also studied longitudinally before and 1, 6, and 12 months after SPKT. Of 9 selected lncRNAs, we found MALAT1, LIPCAR, and LNC‐EPHA6 to be higher in DN compared with healthy controls. SPKT caused MALAT1, LIPCAR, and LNC‐EPHA6 to normalize to levels of healthy controls, which was confirmed in the longitudinal study. In addition, we observed a strong association between MALAT1, LNC‐EPHA6, and LIPCAR and vascular injury marker soluble thrombomodulin and a subset of angiogenic microRNAs (miR‐27a, miR‐130b, miR‐152, and miR‐340). We conclude that specific circulating lncRNAs associate with DN‐related vascular injury and normalize after SPKT, suggesting that lncRNAs may provide a promising novel monitoring strategy for vascular integrity in the context of SPKT.

P1628ASSESSING CORONARY HEART DISEASE IN SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION - IS THERE SPACE FOR A RISK SCORE MODEL?

Abstract Background and Aims Type 1 diabetes mellitus (DM1) is associated with an increased risk of coronary heart disease (CHD), which is generally more aggressive and frequently asymptomatic. This risk substantially increases for those with nephropathy. In selected patients, simultaneous pancreas-kidney transplantation (SPKT) is the renal and pancreatic replacement therapy of choice, as it increases longevity and stabilizes diabetic complications. Despite essential, universal screening protocols for silent CHD in this population are still debatable. As so, Gowdak recently developed a simple clinical risk score to determine the pre-test probability of significant CHD in single kidney transplant candidates. Our aim was to identify potential risk factors associated with the presence of significant lesions on pre-SPKT coronary angiography (CA) and test the utility of Gowdak score in SPKT candidates. Method 77 patients submitted to SPKT between 2011 and 2018 were retrospectively included in this study. All subjects underwent CA as screening method for CHD during the eligibility evaluation. Demographic, clinical, laboratory, therapeutic and imaging characteristics were studied. Continuous variables are presented as means or medians; categorical variables as frequencies. Univariate analysis (Qui2 or Fisher test) and multivariate analysis (logistic regression) were performed. Comparison between groups of patients with and without CA injury was performed using SPSS statistics version 23 and a p <0.05 was considered significant. Results In the past 8 years, 99 SPKT were performed; 78% of these patients (N=77) were submitted to preoperative CA; mean age was 36±5.9 years and 64% were male. The mean duration of DM1 was 25 years and 97% had retinopathy, 43% neuropathy, 31% dysautonomia, 19% peripheral arterial disease and 7% cerebrovascular disease. We excluded 1 due to missing data. A minority of SPKT (3%, N=2) was preemptive. The mean time on dialysis was 37 months. Only one patient had angor, wh0 was excluded of Gowdak risk score assessment. Most patients (87%, N=67) were hypertensive; 56% (N=43) were on statin; 48% (N=37) had smoking habits, and 5% (N=4) had a BMI>30 kg/m2. CA identified at least one lesion in 48% (N = 37) of the patients, of which 30% (N=11; 14% of all CA) underwent intervention; none had complaints of angor. Based on Gowdak risk score, mean probability for CHD was 30.8% and 19 patients had a risk >40% - the recommended cut off to pursuit CA as screening method - but only 2 required intervention. In a univariate analysis, we found that the only distinguishing feature between the group of patients with and without CA lesions was smoking (p=0.005). DM1 with 20 or more years of evolution was found to have a significant association with coronary artery disease development (identifiable by any diagnostic test) (p=0.048). In our population of SPKT recipients Gowdak risk score did not predicted those with significant CHD. Conclusion In our study, CA was positive for lesion in almost half of the patients, all of them asymptomatic. Despite the fact that Gowdak probability score failed to identify those with significant CHD before CA (probably because all of our patients were diabetic), in our population for every seven patients submitted to CA, one needed coronary intervention. We highlight that asymptomatic patients with long-term DM and smokers should be carefully evaluated. The task of correctly ascertaining the presence of CAD can be more overwhelming when we take into account that there is a high prevalence of asymptomatic patients with extensive CAD. Facing the importance of an unmissed diagnosis we encourage the use of CA as an initial screening method, even if it is invasive. Further studies should be encouraged to create screening algorithm for SPKT candidates. Finally, medium- and long-term follow-up studies are needed to evaluate the effects of preoperative selection on posttransplant cardiac events and survival rates.

Delayed kidney graft function in simultaneous pancreas-kidney transplant recipients is associated with early pancreas allograft failure.

Delayed graft function (DGF) is a common complication associated with significant untoward effects in kidney-alone transplantation. The incidence and outcomes following kidney delayed graft function (K-DGF) among patients undergoing simultaneous pancreas-kidney (SPK) transplantation are less certain. We analyzed SPK recipients transplanted at our center between January 1994 and December 2017. A total of 632 recipients fulfilled the selection criteria, including 69 (11%) with K-DGF and 563 without. The incidence of K-DGF was significantly higher in recipients of organs from older donors and donation after circulatory death (DCD). The presence of K-DGF was significantly associated with an increased risk of pancreas graft failure during the first 90days (n=9, incidence rate [IR] 2.45/100 person-months), but not with late pancreas failure (n=32, IR0.84/100 person-months), kidney graft failure, or patient death. Although DCD was associated with K-DGF, it was not associated with either pancreas (hazard ratio [HR] 0.91, 95% CI 0.58-1.44, P=.69) or kidney (HR 1.09, 95% CI 0.66-1.82, P=.74) graft failure after adjustment for potential confounders. We found K-DGF to be a significant risk factor for pancreas graft failure but not kidney graft failure, with the major risk period being early (<90days) posttransplant, and the major donor risk factor being older donor age.

Enteric Conversion of Bladder-drained Pancreas as a Predictor of Outcomes in Almost 600 Recipients at a Single Center.

Background.Complications associated with bladder-drained pancreata necessitating enteric conversion are common. Data on the outcomes after enteric conversion are conflicting. We studied the association between enteric conversion and the pancreas graft rejection, loss, and mortality.Methods.At our center, 1117 pancreas transplants were performed between 2000 and 2016. We analyzed 593 recipients with bladder-drained pancreata, of which 523 received solitary transplants and 70 received simultaneous pancreas-kidney transplants. Kaplan-Meier function was used to estimate time to conversion by transplant type. Cox proportional hazards models were utilized to evaluate patient survival, death-censored graft survival, and acute rejection-free survival while treating conversion as a time-dependent covariate. Subsequently, we examined the association between timing of conversion and the same outcomes in the conversion cohort.Results.At 10 y posttransplant, 48.8% of the solitary pancreas recipients and 44.3% of simultaneous pancreas-kidney transplant recipients had undergone enteric conversion. The enteric conversion was associated with 85% increased risk of acute rejection (hazard ratio [HR] = 1.85; 95% confidence interval [CI] = 1.37-2.49; P < 0.001). However, the conversion was not associated with graft loss or mortality. In the conversion cohort, a longer interval from engraftment to conversion was associated with an 18% lower rejection rate (HR = 0.82; 95% CI = 0.708-0.960; P = 0.013) and a 22% better graft survival (HR = 0.78; 95% CI = 0.646-0.946; P = 0.01).Conclusions.Enteric conversion was associated with increased risk of rejection, but not increased risks of graft loss or mortality. The decision to convert should consider the increased rejection risk. A longer interval from engraftment to conversion appears favorable.

The Prevalence and Treatment of Erectile Dysfunction in Male Solid Organ Transplant Recipients.

Erectile dysfunction (ED) is a prevalent and under-recognized complaint among male solid organ transplant recipients. Most research on this topic has focused on kidney transplant recipients alone. In this review, we integrate current research on ED across all types of solid organ transplant recipients and assess the success of current methods of ED treatment in transplant populations. To review the current literature addressing the prevalence and treatment of ED in the male solid organ transplant population. A literature search was conducted using PubMed to identify relevant studies. Search terms included "organ transplant" and "erectile dysfunction." Titles and abstracts were reviewed for relevance. References from identified articles were also searched and included, if appropriate. Review of peer-reviewed literature. The prevalence of ED among transplant recipients is higher than that in the general population: 39.8-86.2% in liver transplant recipients, 54-66% in renal transplant recipients, 71-78% in heart transplant recipients, and 79% in simultaneous pancreas-kidney transplant recipients. Phosphodiesterase-5 inhibitors have up to 80% efficacy in treating ED in kidney transplant recipients. Intracavernosal injections have been used with success rates of 60-70% in cardiac and renal transplant recipients. Penile prostheses have also been shown to be safe and effective across transplant types. A low incidence of infection has been reported in several case series, although there is concern for an increased rate of mechanical complications in pelvic organ transplant recipients. Accordingly, placement of a two-piece or malleable prosthesis or ectopic reservoir placement with a three-piece inflatable prosthesis is suggested in this population. ED is highly prevalent among male solid organ transplant recipients and should be routinely screened in this population. Current modalities of ED treatment used in the general population are safe and effective in solid organ transplant recipients, although success rates are often lower than those in the general population. Payne K, Popat S, Lipshultz LI, etal. The Prevalence and Treatment of Erectile Dysfunction in Male Solid Organ Transplant Recipients. Sex Med Rev 2021;9:331-339.

Superior Long-term Survival for Simultaneous Pancreas-Kidney Transplantation as Renal Replacement Therapy: 30-Year Follow-up of a Nationwide Cohort.

In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients. We included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy between 1986 and 2016. We used multivariable Cox regression analyses adjusted for recipient age and sex, dialysis modality and vintage, transplantation era, and donor age to compare all-cause mortality between deceased- or living-donor kidney and SPK transplant recipients. Separately, we analyzed mortality between regions where SPK transplant was the preferred intervention (80% SPK) versus regions where a kidney transplant alone was favored (30% SPK). Of 996 transplanted patients, 42%, 16%, and 42% received a deceased- or living-donor kidney or SPK transplant, respectively. Mean (SD) age at transplantation was 50 (11), 48 (11), and 42 (8) years, respectively. Median (95% CI) survival time was 7.3 (6.2; 8.3), 10.5 (7.2; 13.7), and 16.5 (15.1; 17.9) years, respectively. SPK recipients with a functioning pancreas graft at 1 year (91%) had the highest survival (median 17.4 years). Compared with deceased-donor kidney transplant recipients, adjusted hazard ratios (95% CI) for 10- and 20-year all-cause mortality were 0.79 (0.49; 1.29) and 0.98 (0.69; 1.39) for living-donor kidney and 0.67 (0.46; 0.98) and 0.79 (0.60; 1.05) for SPK recipients, respectively. A treatment strategy favoring SPK over kidney transplantation alone showed 10- and 20-year mortality hazard ratios of 0.56 (0.40; 0.78) and 0.69 (0.52; 0.90), respectively. Compared with living- or deceased-donor kidney transplantation, SPK transplant was associated with improved patient survival, especially in recipients with a long-term functioning pancreatic graft, and resulted in an almost twofold lower 10-year mortality rate.

Association between Aortic Calcification, Cardiovascular Events, and Mortality in Kidney and Pancreas-Kidney Transplant Recipients

Background: Cardiovascular (CV) disease is the leading cause of death in kidney and simultaneous pancreas-kidney (SPK) transplant recipients. Assessing abdominal aortic calcification (AAC), using lateral spine x-rays and the Kaupilla 24-point AAC (0–24) score, may identify transplant recipients at higher CV risk. Methods: Between the years 2000 and 2015, 413 kidney and 213 SPK first transplant recipients were scored for AAC at time of transplant and then followed for CV events (coronary heart, cerebrovascular, or peripheral vascular disease), graft-loss, and all-cause mortality. Results: The mean age was 44 ± 12 years (SD) with 275 (44%) having AAC (26% moderate: 1–7 and 18% high: ≥8). After a median of 65 months (IQR 29–107 months), 46 recipients experienced CV events, 59 died, and 80 suffered graft loss. For each point increase in AAC, the unadjusted hazard ratios (HR) for CV events and mortality were 1.11 (95% CI 1.07–1.15) and 1.11 (1.08–1.15). These were similar after adjusting for age, gender, smoking, transplant type, dialysis vintage, and diabetes: aHR 1.07 (95% CI 1.02–1.12) and 1.09 (1.04–1.13). For recipients with high versus no AAC, the unadjusted and fully-adjusted HRs for CV events were 5.90 (2.90–12.02) and 3.51 (1.54–8.00), for deaths 5.39 (3.00–9.68) and 3.38 (1.71–6.70), and for graft loss 1.30 (0.75–2.28) and 1.94 (1.04–3.27) in age and smoking history-adjusted analyses. Conclusion: Kidney and SPK transplant recipients with high AAC have 3-fold higher CV and mortality risk and poorer graft outcomes than recipients without AAC. AAC scoring may be useful in assessing and targeted risk-lowering strategies.

Effect of Pretransplant Dialysis Modality on Outcomes After Simultaneous Pancreas-Kidney Transplantation.

BackgroundPretransplant dialysis modality may affect outcome after simultaneous pancreas-kidney transplantation (SPKT), and it has been suspected that peritoneal dialysis (PD) is associated with more postoperative complications compared to hemodialysis (HD). The aim of this study was to evaluate whether pretransplant dialysis modality affects the risk for postoperative complications in SPKT recipients.Material/MethodsThis was a retrospective longitudinal cohort study of all patients undergoing SPKT from 2010 to 2017, during which 99 simultaneous pancreas-kidney transplantations were performed. Three pre-emptive transplantations were excluded. Patient groups receiving PD (n=59) or HD (n=37) were similar regarding baseline characteristics. All complications occurring during the first 3 months after transplantation, as well as patient and graft survival, were analyzed.ResultsThere were no significant differences in postoperative complications between groups, with similar rates of intra-abdominal infections (8% in HD vs. 10% in PD), pancreatitis (16% in HD vs. 17% in PD), gastrointestinal bleedings (22% in HD vs. 10% in PD), and relaparotomies (27% in HD vs. 24% in PD). None of the patients had venous graft thrombosis. Past peritonitis was not associated with increased risk for postoperative complications in PD patients. Patient and graft survival were similar between PD and HD groups.ConclusionsPeritoneal dialysis is not a risk factor for postoperative complications after SPKT.

Pneumocystis jiroveci pneumonia in kidney and simultaneous pancreas kidney transplant recipients in the present era of routine post-transplant prophylaxis: risk factors and outcomes

BackgroundThe goal of this study was to identify predictors for development of Pneumocystis jirovecii pneumonia (PJP) in kidney and simultaneous kidney and pancreas transplant recipients in the present era of universal primary prophylaxis.MethodsWe reviewed adult recipients of kidney transplant or simultaneous pancreas and kidney transplant at the University of Wisconsin between January 1, 1994 and December 31, 2016. Patients diagnosed with PJP during this time frame were included. Controls were randomly selected from among those whose post-transplant course was not complicated by PJP, matched on time since transplant through incidence density sampling with a 3:1 ratio.Results28 (0.45%) of 6270 recipients developed PJP between 1994 and 2016. Median time since transplant was 4.6 years (interquartile range (IQR): 1.4–9.6 years). Affected recipients were older, had more HLA mismatches, and were more likely to have had BK viremia, CMV viremia and invasive fungal infections than matched controls. CMV viremia remained the only significant risk factor in multivariate analysis, and was a strong predictor (OR 6.27; p = 0.002). Ninety percent of the cases with prior CMV viremia had been diagnosed in the year preceding the diagnosis of PJP; among these, median time from diagnosis of CMV to diagnosis of PJP was 3.4 months (IQR: 1.74–11.5 months) and median peak CMV viral load prior to diagnosis of PJP was 3684.5 IU/mL (IQR: 1034–93,300 IU/mL). Additionally, 88.9% of patients with CMV in the preceding year had active infection at time of PJP diagnosis. Patient and graft survival were significantly worse at 2 years in recipients with PJP than our control group (42.4% vs. 88.5, and 37.9% vs. 79.9%; p < 0.001).ConclusionsDespite the low overall incidence of PJP in the era of universal prophylaxis, outcomes are poor. We suggest extending or re-initiating PJP prophylaxis for at least 6 months in the setting of CMV viremia due to the relatively low risk of therapy and potential significant impact on disease prevention.

Type 1 Diabetes Recurrence After Simultaneous Pancreas-Kidney Transplantation

Simultaneous pancreas-kidney transplantation (SPKT) is an important option for patients with type 1 diabetes (T1D) and end-stage renal disease. While most SPKT recipients experience long-term euglycemia, about 5% return to insulin therapy, 5–20 years after transplantation due to T1D recurrence (T1DR). Over the last two decades, we have assessed autoimmunity in our patients, evaluating autoantibodies (GAD65, IA2, and ZnT8), autoreactive T cells, and pancreas transplant biopsies. Most patients demonstrate seroconversion for multiple autoantibodies. Autoreactive memory T cells have been identified in the peripheral blood, pancreas transplant, and peri-pancreas transplant tissues. Biopsies generally exhibit insulitis, the typical lesion of T1D, affecting pancreatic islets in the pancreas transplant, and lack of rejection in the pancreas and kidney transplants. In addition to membrane expression of memory markers, we have identified other biomarkers, including CXCR3, on circulating and infiltrating autoreactive memory T cells. We hope that this work will lead to therapeutic intervention in our patients with T1DR, and that this will translate to effective treatment for T1D.

Performances of creatinine-based glomerular filtration rate estimating equations in simultaneous pancreas-kidney transplant recipients: a single center cohort study.

Estimating glomerular filtration rate (GFR) is important for clinical management and research studies in simultaneous pancreas-kidney transplantation (SPK) recipients. No study has specifically investigated the reliability of recent creatinine-based GFR estimating equations in this singular population. We assessed the performances of CKD-EPI, MDRD, Schwartz-2009, Schwartz-Lyon, Lund-Malmo and Full Age Spectrum equations for estimating GFR after SPK. 126 patients were included. GFR was measured by a reference method (mGFR) one year after SPK and estimated with the different equations from a standardized measure of serum creatinine. Relative bias, precisions, 10% and 30% accuracies (P30) were used to determine equations reliability. Ages ranged from 29 to 58. Mean mGFR was 56.3 ± 13.3 [23.6-92.5] ml/min/1.73 m2 . In the whole population, P30 of the CKD-EPI and MDRD equations were 42% (38.0; 46.0) and 65% (61.5; 69) respectively. As compared to the other equations, the Schwartz-Lyon equation was significantly more accurate (P30 = 86.0% [83.5-88.0], P < 0.01) and less biased (1.13 [1.06-1.19], P < 0.01). Conclusions were similar whatever the age class (<40 or ≥40) and mGFR level (<60 or ≥60 ml/min/1.73 m2 ). This study suggests that the CKD-EPI and MDRD equations have poor performances in SPK recipients and that the Schwartz-Lyon equation is a reliable alternative.

Graft dysfunction in simultaneous pancreas kidney transplantation (SPK): Results of concurrent kidney and pancreas allograft biopsies.

Simultaneous pancreas and kidney transplants offer significant therapeutic advantages but present a diagnostic approach dilemma in the diagnosis of rejection. Because both organs are from the same donor, the kidney has been treated traditionally as the "sentinel" organ to biopsy, presumably representing the status of both allografts. Truly concurrent biopsy studies, however, are needed to confirm this hypothesis. We examined 101 concurrent biopsies from 70 patients with dysfunction in either or both organs. Results showed concurrent rejection in 23 of 57 (40%) of cases with rejection; 19 of 57 (33.5%) and 15 of 57 (26.5%) showed kidney or pancreas only rejection, respectively. The degree and type of rejection differed in the majority (13 of 23, 56.5%) of cases with concurrent rejection, with the pancreas more often showing higher rejection grade. Taking into account pancreas dysfunction, a positive kidney biopsy should correctly predict pancreas rejection in 86% of the instances. However, the lack of complete concordance between the 2 organs, the discrepancies in grade and type of rejection, and the tendency for higher rejection grades in concurrent or pancreas only rejections, all support the rationale for pancreas biopsies. The latter provide additional data on the overall status of the organ, as well as information on nonrejection-related pathologies.

Unexplained fever after pancreas transplantation.

Fever occurs frequently early after pancreas transplant, however, the exact cause is often undetermined. Limited data are available on pancreas recipients experiencing unexplained, noninfectious fever. This study aims to characterize unexplained fever (UF) in pancreas recipients and its effect on patient and graft outcomes. We performed a retrospective cohort study of UF among consecutive pancreas or simultaneous pancreas-kidney transplant recipients from 1 January 2011 to 31 August 2015. Classification of UF was based on the absence of positive cultures, radiologic findings, and other diagnostic features of infection or rejection. Twenty-three of 92 (25%) patients experienced UF. The UF episode first occurred at a mean of 31±17days post-transplant and accounted for 34 admissions with an average length of stay of 5.1±3.4days. Intravenous corticosteroid was administered following confirmation of negative diagnostic tests in 77% of patients, with fever resolution occurring in all. No differences were seen in rates of biopsy-proven rejection, graft loss, death, or documented infections compared to UF-free patients during the first-year post-transplant. UF is a common cause for readmission following pancreas transplantation. While the etiology of UF remains difficult to identify, UF occurrence was not associated with adverse outcomes during the first-year post-transplant.

Clinical characteristics and outcomes of late-onset BK virus nephropathy in kidney and kidney-pancreas transplant recipients.

BK virus nephropathy (BKPyVAN) is a major complication in kidney transplant recipients (KTR) and typically occurs within 1year of transplant. Guidelines vary in recommendations for BKPyV screening beyond 1year. A systematic characterization of risk factors and outcomes of late-onset (>1year) BKPyVAN has not previously been reported. We retrospectively compared characteristics and outcomes of early- (<1year) and late-onset BKPyVAN (definitive [biopsy-confirmed] or presumptive [plasma BKPyV >10000copies/mL]) in a cohort of 671 KTR and simultaneous kidney-pancreas transplant (SPK) recipients between 2008 and 2013 at a single US transplant center. Proportions were compared using Chi-square or Fisher's exact test with P<.05 considered significant. BKPyVAN was diagnosed in 96 (14.3%) patients (proven 16.7%, presumptive 83.3%): 79 (82.3%) early- and 17 (17.7%) late-onset. The proportion with late-onset BKPyVAN was significantly higher among SPK than KTR (4 of 7 [57.1%] vs 13 of 89 [14.6%], P=.017). Late-onset represented "de novo" infection (no BKPyV detection within the first year) in 14 (82.4%) and progression of earlier lower grade BKPyV reactivation in 3 (17.6%). Clinical outcomes were similar for early- and late-onset BKPyVAN (P>.05 all comparisons). In a pooled analysis of prior studies of BKPyVAN in SPK recipients, 62.9% (17 of 27) were late-onset. A significant proportion of BKPyVAN is late-onset, especially among SPK recipients, and supports a longer duration of BKPyV monitoring for SPK recipients than recommended in some guidelines.

Long-term Outcomes in Simultaneous Pancreas-Kidney Transplant Recipients: Single-center Experience From Poland

BackgroundSimultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with end-stage renal disease (ESRD) due to type 1 diabetes mellitus (DM1). Since the 1980s, pancreas transplantation has become the most effective strategy to restore normoglycemia in patients with DM1. The aim of this study was to present long-term outcomes data for SPKT. MethodsWe performed a retrospective analysis of 73 SPKT recipients followed in our outpatient center who underwent transplantation between 1988 and 2015. ResultsA total of 50.7% of the patients were male. At the time of surgery, patients' mean age was 37.38 ± 7.44 years. Patients were diagnosed with DM1 at an average of 25 ± 6.08 years before SPKT. For 21.9% of patients, the transplant was done preemptively. Most (91.8%) had enteric drainage. All patients received induction of immunosuppression (either polyclonal immunoglobulins anti-thymocyte globulin or thymoglobulin [64.4%] or monoclonal globulins daclizumab or basiliximab [35.6%]). Patient survival at 1, 5, 10, 15 years was 99%, 97%, 89%, and 75%; kidney survival was 99%, 96%, 84%, and 67%; and pancreas survival was 95%, 92%, 84%, and 64%, respectively. There was a notable tendency toward increased creatinine level (from 1.18 at 1 year to 1.78 at 15 years) and decreased hemoglobin level (from 13.84 at 1 year to 12.65 at 15 years). ConclusionDiabetic patients with ESRD have a poor prognosis without transplantation. SPKT provides marked prolongation of the patient's life and freedom from insulin injections. Enteric drainage is currently the surgical technique of choice. SPKT should remain as the treatment of choice in this patient population.

Analysis of Hospitalizations in Simultaneous Pancreas-Kidney Transplant Recipients: A Single-center Experience in Poland

BackgroundEnd-stage renal disease due to type 1 diabetes mellitus appears to be a regular indication for simultaneous pancreas and kidney transplantation (SPKT). Although transplantation improves a patient's health condition, it does not mean that all complications will be eliminated. MethodsWe performed a retrospective analysis of 73 patients who underwent SPKT and follow-up between 1988 and 2015 at our institute. The number, duration, and reasons for hospitalization at 1, 5, 10, and 15 years after SPKT were analyzed. ResultsThe average number of hospitalizations at 1, 5, 10, 15 years after SPKT were 1.66, 0.39, 0.36, and 0.33, respectively. The main reason for hospitalization over the 15-year period was infections, at 32.4% (SD, 6.8%). Within the first year after SPKT, 6.8% of hospital admissions were caused by cytomegalovirus (CMV) infection. Over time, the percentage of hospitalizations for cardiovascular complications increased from 0.6% at 1 year to 29% at 12–15 years. Incidence of hospitalization due to cardiovascular complications correlated with a longer period of dialysis and a diagnosis of ischemic heart disease before transplant (r = 0.56, P = .004; r = 0.54, P < .0001, respectively). At 12–15 years after transplantation, 18.2% of hospitalizations were caused by secondary complications of diabetes. ConclusionThe most common reason for hospitalization after SPKT is infectious complications. In the first year posttransplant, there is a high percentage of CMV infections. Hospitalization associated with cardiovascular complications was found to be most common in the latter follow-up period and showed a correlation with longer dialysis period.

Factors and outcomes in association with sepsis differ between simultaneous pancreas/kidney and single kidney transplant recipients.

As immunosuppressive therapy has improved in simultaneous pancreas/kidney transplant recipients (SPKTRs), infection has become the major limitation of disease-free survival. We studied all SPKTRs and deceased-donor kidney transplant recipients (KTRs) between 2003 and 2015. Thirty-six of 134 SPKTRs (26.9%) were diagnosed with sepsis among which 13/36 SPKTRs (36.1%) developed severe sepsis/septic shock. A control group of 98 SPKTRs without sepsis and 61/538 KTRs (11.3%) with sepsis were used for comparison. Among SPKTRs, female sex, low BMI, CMV seronegativity, CMV disease, and acute cellular rejection increased the risk for sepsis (P < .05). Patient and allograft survival was comparable among SPKTRs with and without sepsis (P > .05), but showed inferior kidney allograft function (P < .05). While urosepsis was less common among SPKTRs (45%), pneumonia (33%) and peritonitis (15%) as site of infections were more frequent (P < .05). Here, gram-positive and fungal sepsis were more common among SPKTRs compared to KTRs (P < .05). SPKTRs showed a higher incidence and an earlier onset of sepsis compared to KTRs (P < .001). SPKTRs with severe sepsis/septic shock were more likely to show pneumonia as site of infection with gram-positive/polymicrobial bacteremia (P < .05). Mortality from severe sepsis was 29% among SPKTRs compared to 58% among KTRs (P < .05). Differences in incidence, site, causative pathogens, and onset of sepsis between SPKTRs and KTRs may be attributed to more intense immunosuppression, major surgery, and complications of diabetes among SPKTRs. Lower sepsis-related mortality may reflect younger age and more timely diagnosis, but also supports recent findings of less sepsis-related mortality among recipients of solid organ transplantation.

Intraoperative Heparinization During Simultaneous Pancreas-Kidney Transplantation: Is It Really Necessary?

IntroductionThe use of intraoperative sodium heparin during simultaneous pancreas-kidney transplantation (SPKT) remains as a routine practice in some referral centers to minimize pancreatic graft thrombosis rate. One of its disadvantages is the theoretical increased risk of postoperative bleeding. In our center, we have abandoned its use since 2011. Materials and methodsWe performed a retrospective analysis among 198 SPKTs performed in our center between the years 1989 and 2017. The variables of our study were vascular thrombosis of the pancreatic graft and hemoperitoneum and upper gastrointestinal bleeding in the mediate postoperative period (up to 2 months after the transplant). We compared these results between SPKT recipients who had undergone intraoperative heparinization (n = 157) and those who had not (n = 51). To avoid bias, a second comparison was performed using propensity score matching on the following characteristics: sex, recipient age, recipient body mass index, cold ischemia time, preoperative hemodialysis or peritoneal dialysis, time of diabetes, and Pancreas Donor Risk Index. Student t test or Mann-Whitney U test was used for intergroup comparisons of quantitative variables where appropriate, whereas χ2 or Fisher exact test was used to compare categorical data. ResultsNo statistically significant differences were found when comparing the use of intraoperative heparin, even after the homogenization of both groups. ConclusionsIn our experience, intraoperative heparinization during SPKT surgery was not useful because it did not significantly decrease the graft thrombosis rate, and its withdrawal did not enhance hemoperitoneum or upper gastrointestinal bleeding postoperative rates.

Pancreas Donor Hypernatremia: Is it Really a Risk Factor for Simultaneous Pancreas-kidney Transplantation?

IntroductionSolid organ donor hypernatremia has been classically reported to be a risk factor for cell lysis and graft damage. National criteria for pancreatic donation consider severe hypernatremia (sodium level more than 160 mEq/L) to be relative exclusion criteria. The aim of our study is to review the postoperative outcomes of our simultaneous pancreas-kidney transplantation (SPKT) sample in terms of pancreatic fistula, intra-abdominal abscesses, pancreatitis, pancreas graft thrombosis, early pancreatectomy, and reoperation rates regarding different ranges of donor sodium levels. Material and MethodsWe performed a retrospective analysis among 161 SPKTs performed in our center between the years 2001 and 2017. We compared the aforementioned postoperative variables in two situations: 1) Whether the donor pancreas sodium levels were inferior to 149 mEq/L, or equal to or greater than 150 mEq/L; and 2) If they had severe hypernatremia (considering sodium levels greater than or equal to 160 mEq/L as threshold) or not. To ensure the comparability of the groups, a second comparison was performed on new samples after using propensity score matching. A Student t test or Mann-Whitney U test was used for intergroup comparisons of quantitative variables where appropriate, whereas a χ2 test or Fisher's exact test was used to compare categorical data. ResultsNo statistically significant differences were found between the groups that relate high donor serum sodium levels with the morbidity variables included in our study or with early pancreatic graft loss. ConclusionsIn our cohort, early postoperative main morbidity and pancreas graft loss of SPKT recipients do not differ significantly regarding donor serum sodium levels.

Association between the pancreas transplantation and survival of patients with diabetes: A single center experience.

Pancreas transplantation is considered a therapeutic option for patients with complicated diabetes mellitus. In this study, we compared survival rate between patients on the waiting list for pancreas transplant alone(PTA), simultaneous pancreas–kidney(SPK) transplant, and pancreas after kidney(PAK) transplant and transplant recipients. A total of 503 patients (PTA:n = 116; SPK:n = 303; PAK:n = 84) and 280 PT recipients (PTA:n = 89; SPK:n = 155; PAK:n = 36) were retrospectively analyzed at our center between February 2000 and December 2015; 11.9%(60/503) of the patients on the waiting list and 4.3%(12/280) of the PT recipients died. The overall survival rate was higher in the waiting list group for the first year (99.3% vs. 97.8%), after which it was significantly higher in PT group (p = 0.039). The overall relative risk of all-cause mortality for transplant recipients was 2.145(p = 0.285) for PTA, 0.688(p = 0.735) for PAK, however,0.361 (p = 0.012) for SPK compared with that for the waiting list patients. SPK transplant recipients had considerable higher survival benefits, despite the relatively long waiting period, especially after 1 year. In addition, PTA and PAK can also be considered as a treatment option as patient survival was not poor.