Tailoring cytomegalovirus prophylaxis based on T cell immunity panel assessment in kidney transplant patients at high risk of cytomegalovirus.

BACKGROUND: Valganciclovir prophylaxis against cytomegalovirus (CMV) is recommended for solid organ transplant recipients, but is associated with drawbacks, including expense and leukopenia. Our center adopted a strategy of serial assessment with a CMV-specific T cell immunity panel (CMV-TCIP) and cessation of valganciclovir prophylaxis upon demonstration of adequate CD4+ responses in kidney transplant patients at high risk of CMV disease. METHODS: We retrospectively reviewed adult recipients of a kidney or pancreas transplant between August 2019 and July 2021 undergoing serial CMV-TCIP monitoring. Included patients were considered high risk for CMV, defined by donor positive (D+)/recipient negative (R-) CMV IgG serostatus, or recipient positive (R+) patients who received induction with a lymphocyte-depleting agent. Prophylaxis was discontinued after a patient's first CMV-specific CD4+ T cell value of ≥0.20%. Risk of clinically significant CMV infection (csCMVi) in those who underwent early discontinuation of CMV prophylaxis and predictors of CMV T cell immunity were analyzed. RESULTS: Of 54 included patients, 22 stopped prophylaxis early due to CMV-specific CD4+ T cell immunity at a median of 4.7 (IQR: 3.8-5.4) months after transplant. No instances of csCMVi were observed in the 22 patients who had prophylaxis discontinued early, of whom 19/22 were CMV R+ and 3/22 were CMV D+/R-. Donor/recipient CMV serostatus was predictive of immunity (p <.001). CONCLUSION: Early discontinuation of valganciclovir prophylaxis in patients with CMV CD4+ T cellular immunity appears safe and potentially beneficial in this preliminary series, especially in R+ patients. Further study is warranted, given that truncated prophylaxis may yield patient-level benefits.

Impact of OPTN policy 3.7D providing waiting time modification for candidates affected by race-inclusive eGFR calculations: Early results from a single center.

INTRODUCTION: OPTN Policy 3.7D, implemented January 5, 2023, mandates that all kidney transplant programs modify waiting time for candidates affected by race-inclusive eGFR calculations. We report the early impact of this policy change. METHODS: Our transplant program reviewed all listed transplant candidates and identified patients potentially eligible for waiting time modification. Eligible candidates received waiting time modification after submission of supporting evidence to the OPTN. We reviewed the impact on waiting time and transplant activity through October 1, 2023. RESULTS: Forty-six adult patients on our center's active waiting list self-identified as Black/African American. 25 (54.3%) candidates qualified for waiting time modification. A median 451 (321, 1543.5) additional days of waiting time was added for qualifying patients. Of the 25 patients who qualified for waiting time modification, 11 patients received a deceased donor kidney in the early period following waiting time modification, including 5 patients transplanted within 1 month after modification. CONCLUSIONS: Policy 3.7D is one of few national mandates to address specifically structural racism within transplantation. Implementation has yielded near immediate effects with greater than 40% of time-adjusted patients at our center receiving a deceased donor kidney transplant in the initial months after policy enactment. Early assessment demonstrates great potential impact for this policy.

Improved Early Post-Transplant Outcomes and Organ Use in Kidney Transplant Using Normothermic Regional Perfusion for Donation after Circulatory Death: National Experience in the US.

BACKGROUND: Normothermic regional perfusion (NRP) is a technique that is intended to enhance organ transplant outcomes from donation circulatory death (DCD) donors. STUDY DESIGN: A retrospective analysis of data from the Scientific Registry of Transplant Recipients was performed. DCD donors were screened for inclusion based on date of donation 2020 or later, and whether the heart was also recovered for transplantation. We grouped donors as either donation after brain death or DCD. DCD donors were further divided into groups including those in which the heart was not recovered for transplant (Non-Heart DCD) and those in which it was, based on recovery technique (thoracoabdominal-NRP [TA-NRP] Heart DCD and Super Rapid Recovery Heart DCD). RESULTS: A total of 219 kidney transplant recipients receiving organs from TA-NRP Heart DCD donors were compared to 436 SRR Super Rapid Recovery DCD, 10,630 Super Rapid Recovery non-heart DCD, and 27,820 donations after brain death recipients. Kidney transplant recipients of TA-NRP DCD allografts experienced shorter length of stay, lower rates of delayed graft function, and lower serum creatinine at the time of discharge when compared with recipients of other DCD allografts. CONCLUSIONS: Our analysis demonstrates superior early kidney allograft function when TA-NRP is used for DCD organ recovery.

Current State of Multiorgan Transplantation and Implications for Future Practice and Policy.

The incidence of kidney dysfunction has increased in liver transplant and heart transplant candidates, reflecting a changing patient population and allocation policies that prioritize the most urgent candidates. A higher burden of pretransplant kidney dysfunction has resulted in a substantial rise in the utilization of multiorgan transplantation (MOT). Owing to a shortage of available deceased donor kidneys, the increased use of MOT has the potential to disadvantage kidney-alone transplant candidates, as current allocation policies generally provide priority for MOT candidates above all kidney-alone transplant candidates. In this review, the implications of kidney disease in liver transplant and heart transplant candidates is reviewed, and current policies used to allocate organs are discussed. Important ethical considerations pertaining to MOT allocation are examined, and future policy modifications that may improve both equity and utility in MOT policy are considered.

The impact of multi-organ transplant allocation priority on waitlisted kidney transplant candidates.

Kidney-alone transplant (KAT) candidates may be disadvantaged by the allocation priority given to multi-organ transplant (MOT) candidates. This study identified potential KAT candidates not receiving a given kidney offer due to its allocation for MOT. Using the Organ Procurement and Transplant Network (OPTN) database, we identified deceased donors from 2002 to 2017 who had one kidney allocated for MOT and the other kidney allocated for KAT or simultaneous pancreas-kidney transplant (SPK) (n = 7,378). Potential transplant recipient data were used to identify the "next-sequential KAT candidate" who would have received a given kidney offer had it not been allocated to a higher prioritized MOT candidate. In this analysis, next-sequential KAT candidates were younger (p < .001), more likely to be racial/ethnic minorities (p < .001), and more highly sensitized than MOT recipients (p < .001). A total of 2,113 (28.6%) next-sequential KAT candidates subsequently either died or were removed from the waiting list without receiving a transplant. In a multivariable model, despite adjacent position on the kidney match-run, mortality risk was significantly higher for next-sequential KAT candidates compared to KAT/SPK recipients (hazard ratio 1.55, 95% confidence interval 1.44, 1.66). These results highlight implications of MOT allocation prioritization, and potential consequences to KAT candidates prioritized below MOT candidates.

Zero balance ultrafiltration using dialysate during nationwide bicarbonate shortage: a retrospective analysis.

BACKGROUND: Zero balance ultrafiltration (Z-BUF) utilizing injectable 8.4% sodium bicarbonate is utilized to treat hyperkalemia and metabolic acidosis associated with cardiopulmonary bypass (CPB). The nationwide shortage of injectable 8.4% sodium bicarbonate in 2017 created a predicament for the care of cardiac surgery patients. Given the uncertainty of availability of sodium bicarbonate solutions, our center pro-actively sought a solution to the sodium bicarbonate shortage by performing Z-BUF with dialysate (Z-BUF-D) replacement fluid for patients undergoing cardiopulmonary bypass. METHODS: Single-center, retrospective observational evaluation of the first 46 patients at an academic medical center who underwent Z-BUF using dialysate over a period of 150 days with comparison of these findings to a historical group of 39 patients who underwent Z-BUF with sodium chloride (Z-BUF-S) over the preceding 150 days. The primary outcome was the change in whole blood potassium levels pre- and post-Z-BUF-D. Secondary outcomes included changes in pre- and post-Z-BUF-D serum bicarbonate levels and the amount of serum bicarbonate used in each Z-BUF cohort (Z-BUF-D and Z-BUF-S). RESULTS: Z-BUF-D and Z-BUF-S both significantly reduced potassium levels during CPB. However, Z-BUF-D resulted in a significantly decreased need for supplemental 8.4% sodium bicarbonate administration during CPB (52 mEq ± 48 vs. 159 mEq ± 85, P < 0.01). There were no complications directly attributed to the Z-BUF procedure. CONCLUSION: Z-BUF with dialysate appears to be analternative to Z-BUF with sodium chloride with marked lower utilization of intravenous sodium bicarbonate.

Donor's APOL1 Risk Genotype and "Second Hits" Associated With De Novo Collapsing Glomerulopathy in Deceased Donor Kidney Transplant Recipients: A Report of 5 Cases.

The presence of 2 APOL1 risk variants (G1/G1, G1/G2, or G2/G2) is an important predictor of focal segmental glomerulosclerosis (FSGS) and chronic kidney disease in individuals of African descent. Although recipient APOL1 genotype is not associated with allograft survival, kidneys from deceased African American donors with 2 APOL1 risk variants demonstrate shorter graft survival. We present a series of cases of presumed de novo collapsing FSGS in 5 transplanted kidneys from 3 deceased donors later identified as carrying 2 APOL1 risk alleles, including 2 recipients from the same donor whose kidneys were transplanted in 2 different institutions. Four of these recipients had viremia in the period preceding the diagnosis of collapsing FSGS. Cytomegalovirus and BK virus infection were present in 3 and 1 of our 5 cases, respectively, around the time that collapsing FSGS occurred. We discuss viral infections, including active cytomegalovirus infection, as possible "second hits" that may lead to glomerular injury and allograft failure in these recipients. Further studies to identify additional second hits are necessary to better understand the pathologic mechanisms of donor APOL1-associated kidney disease in the recipient.

Simultaneous Liver-Kidney Transplantation: Impact on Liver Transplant Patients and the Kidney Transplant Waiting List.

PURPOSE: The number of simultaneous liver-kidney transplants (SLKT) performed in the USA has been rising. The Organ Procurement and Transplantation Network implemented a new policy governing SLKT that specifies eligibility criteria for candidates to receive a kidney with a liver, and creates a kidney waitlist "safety net" for liver recipients with persistent renal failure after transplant. This review explores potential impacts for liver patients and the kidney waitlist. RECENT FINDINGS: Factors that have contributed to the rise in SLKT including Model for End-stage Liver Disease (MELD)-based allocation, regional sharing for high MELD candidates, and the rising incidence of non-alcoholic steatohepatitis will continue to increase the number of liver transplant candidates with concurrent renal insufficiency. The effect of center behavior based on the new policy is harder to predict, given wide historic variability in SLKT practice. SUMMARY: Continued increase in combined liver/kidney failure is likely, and SLKT and kidney after liver transplant may both increase. Impact of the new policy should be carefully monitored, but influences beyond the policy need to be accounted for.

BK viremia surveillance and outcomes in simultaneous pancreas-kidney transplant recipients.

BACKGROUND: While screening for asymptomatic BK viremia (BKV) has been well studied in isolated kidney transplant recipients, there is a paucity of published outcomes in simultaneous pancreas-kidney (SPK) transplant recipients who underwent BKV screening followed by pre-emptive reduction in immunosuppression. METHODS: This is a single-center, retrospective review of 31 consecutive SPK recipients who were transplanted over a 5-year period following the initiation of a serum BKV screening protocol. RESULTS: BK viremia developed in 11 (35.5%) patients, and all patients achieved complete viral clearance following reduction in immunosuppression. Two patients (6.5%) developed BK virus nephropathy, but both had preserved allograft function. One patient developed mild rejection of the kidney allograft following clearance of BKV, and two patients developed mild rejection of the pancreas allograft after reduction in immunosuppression, but there were no kidney or pancreas allograft losses due to rejection. The development of BK viremia did not impact overall patient survival or kidney and pancreas allograft survival. CONCLUSION: Screening asymptomatic SPK recipients for BKV followed by reduction in maintenance immunosuppression appears to be an effective strategy to prevent kidney allograft dysfunction and graft loss due to BK virus nephropathy, without compromising pancreas allograft outcomes.

A Randomized 2x2 Factorial Clinical Trial of Renal Transplantation: Steroid-Free Maintenance Immunosuppression with Calcineurin Inhibitor Withdrawal after Six Months Associates with Improved Renal Function and Reduced Chronic Histopathology.

INTRODUCTION: The two most significant impediments to renal allograft survival are rejection and the direct nephrotoxicity of the immunosuppressant drugs required to prevent it. Calcineurin inhibitors (CNI), a mainstay of most immunosuppression regimens, are particularly nephrotoxic. Until less toxic antirejection agents become available, the only option is to optimize our use of those at hand. AIM: To determine whether intensive rabbit anti-thymocyte globulin (rATG) induction followed by CNI withdrawal would individually or combined improve graft function and reduce graft chronic histopathology-surrogates for graft and, therefore, patient survival. As previously reported, a single large rATG dose over 24 hours was well-tolerated and associated with better renal function, fewer infections, and improved patient survival. Here we report testing whether complete CNI discontinuation would improve renal function and decrease graft pathology. METHODS: Between April 20, 2004 and 4-14-2009 we conducted a prospective, randomized, non-blinded renal transplantation trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment = 180). Subsequent maintenance immunosuppression consisted of tacrolimus, a CNI, and sirolimus, a mammalian target of rapamycin inhibitor. We report here the outcome of converting patients after six months either to minimized tacrolimus/sirolimus or mycophenolate mofetil/sirolimus. Primary endpoints were graft function and chronic histopathology from protocol kidney biopsies at 12 and 24 months. RESULTS: CNI withdrawal (on-treatment analysis) associated with better graft function (p <0.001) and lower chronic histopathology composite scores in protocol biopsies at 12 (p = 0.003) and 24 (p = 0.013) months, without affecting patient (p = 0.81) or graft (p = 0.93) survival, or rejection rate (p = 0.17). CONCLUSION: CNI (tacrolimus) withdrawal at six months may provide a strategy for decreased nephrotoxicity and improved long-term function in steroid-free low immunological risk renal transplant patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00556933.

Is bacteremic sepsis associated with higher mortality in transplant recipients than in nontransplant patients? A matched case-control propensity-adjusted study.

BACKGROUND: Sepsis is a serious complication of solid organ transplant (SOT). Evidence on survival differences between SOT recipients and non-SOT patients with sepsis is lacking. METHODS: This was a matched, case-control propensity-adjusted study. Conditional logistic regression was performed for risk factor analysis, and Cox proportional hazards regression for survival analysis. RESULTS: Three hundred sixty-nine patients (123 cases; 246 controls) diagnosed with blood culture-proven sepsis were matched 1:2 by age, sex, and hospital location. The distribution of allografts was 36.6% kidney, 34.1% liver, 13% kidney-pancreas, 7.3% small bowel/liver, 5.7% heart/lung, and 3.3% multivisceral. The conditional logistic regression showed that the following factors were significantly more frequently associated with SOT compared to non-SOT: higher number of comorbidities (odds ratio [OR] = 8.2 [95% confidence interval {CI}, 1.48-45.44], P = .016); higher Sepsis-related Organ Failure Assessment score (OR = 1.2 [95% CI, 1.07-1.32], P = .001); presence of nosocomial infection (OR = 36.3 [95% CI, 9.71-135.96], P < .0001); appropriate initial antibiotics (OR = 0.04 [95% CI, .006-.23], P < .0001); and lower white blood cell count (OR = 0.93 [95% CI, .89-.97], P < .0001). Cox proportional hazards regression showed that after all adjustments for clinical presentation, severity of illness, and types of infection, SOT recipients with sepsis had a significantly lower risk of death at 28 days (hazard ratio [HR] = 0.22 [95% CI, .09-.54], P = .001) and at 90 days (HR = 0.43 [95% CI, .20-.89], P = .025). CONCLUSIONS: The 28-day and 90-day mortality were significantly decreased for transplant recipients compared with nontransplant patients. These findings suggest that the immunosuppression associated with transplantation may provide a survival advantage to transplant recipients with sepsis through modulation of the inflammatory response.

A randomized 2×2 factorial trial, part 1: single-dose rabbit antithymocyte globulin induction may improve renal transplantation outcomes.

BACKGROUND: We conducted a randomized and unblinded 2 × 2 sequential-factorial trial, composed of an induction arm (part 1) comparing single-dose (SD) versus divided-dose rabbit antithymocyte globulin (rATG), and a maintenance arm (part 2) comparing tacrolimus minimization versus withdrawal. We report the long-term safety and efficacy of SD-rATG induction in the context of early steroid withdrawal and tacrolimus minimization or withdrawal. METHODS: Patients (n=180) received 6 mg/kg rATG, SD or four alternate-day doses (1.5 mg/kg/dose), with early steroid withdrawal and tacrolimus or sirolimus maintenance. After 6 months targeted maintenance levels were tacrolimus, 2 to 4 ng/mL and sirolimus, 4 to 6 ng/mL or, if calcineurin inhibitor-withdrawn, sirolimus 8 to 12 ng/mL with mycophenolate mofetil 2 g two times per day. Primary endpoints were renal function (abbreviated modification of diet in renal disease) and chronic graft histopathology (Banff). Secondary endpoints included patient survival, graft survival, biopsy-proven rejection, and infectious or noninfectious complications. RESULTS: Follow-up averaged longer than 4 years. Tacrolimus or sirolimus and mycophenolate mofetil exposure was identical between groups. The SD-rATG associated with improved renal function (2-36 months; P<0.001) in deceased donor recipients. The SD-rATG associated with quicker lymphocyte, CD4 T cell, and CD4-CD8 recovery and fewer infections. Cox multivariate hazard modeling showed divided-dose-rATG (P=0.019), deceased donor (P=0.003), serious infection (P=0.0.018), and lower lymphocyte count (P=0.001) associated with increased mortality. Patients with all four covariates showed a 27-fold increased likelihood of death (P=0.00002). Chronic graft histopathology, rejection rates, and death-censored graft survival were not significantly different between groups. CONCLUSION: The SD-rATG induction improves the 3-year renal function in recipients of deceased donor kidneys. This benefit, along with possibly improved patient survival and fewer infections suggest that how rATG is administered may impact its efficacy and safety.

Efficacy and safety of sitagliptin for the treatment of new-onset diabetes after renal transplantation.

New-onset diabetes after transplantation (NODAT) is a common comorbidity after renal transplantation. Though metformin is the first-line agent for the treatment of type 2 diabetes, in renal transplant recipients, metformin is frequently avoided due to concerns about renal dysfunction and risk for lactic acidosis. Therefore, alternative first-line agents for the treatment of NODAT in renal transplant recipients are needed. Sitagliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, has a low incidence of hypoglycemia, is weight neutral, and, in a small study, did not affect immunosuppressant levels. However, long-term sitagliptin use for the treatment of NODAT in kidney transplant recipients has not been studied. We retrospectively analyzed renal transplant recipients diagnosed with NODAT and treated with sitagliptin to assess safety and efficacy. Twenty-two patients were started on sitagliptin alone. After 12 months of followup, 19/22 patients remained on sitagliptin alone with a significant improvement in hemoglobin A1c. Renal function and immunosuppressant levels remained stable. Analysis of long-term followup (32.5 ± 17.8 months) revealed that 17/22 patients remained on sitagliptin (mean hemoglobin A1c < 7%) with 9/17 patients remaining on sitagliptin alone. Transplant-specific adverse events were rare. Sitagliptin appears safe and efficacious for the treatment of NODAT in kidney transplant recipients.

What do we know about adenovirus in renal transplantation?

Adenoviruses are common pathogens that have the potential to cause opportunistic infections with significant morbidity and mortality in immunocompromised hosts. The significance of adenoviral infection and disease is incompletely known in the setting of kidney transplantation. Reported adenovirus infections in renal transplant recipients have typically manifested as hemorrhagic cystitis and tubulointerstitial nephritis, less severe diseases than often seen in other solid organ transplant recipients (i.e. pneumonia, hepatitis and enteritis). The prevalent adenovirus subgroups associated with cystitis and nephritis are B1 and B2 with the serotypes 7, 11, 34, 35. However, disseminated or severe adenovirus infections, including fatal cases, have been described in renal transplant recipients. There is uncertainty regarding monitoring of and treatment of this virus. Although not supported by randomized clinical trials, cidofovir is used for the treatment of adenovirus disease not responding to reduction of immunosuppression.

Single-dose rATG induction at renal transplantation: superior renal function and glucoregulation with less hypomagnesemia.

BACKGROUND: Rabbit anti-thymocyte globulin (rATG) induction reduces reperfusion injury and improves renal function in kidney recipients by means of properties unrelated to T-cell lysis. Here, we analyze intensive rATG induction (single dose, rATG(S) , vs. divided dose, rATG(D) ) for improved renal function and protection against hyperglycemia. METHODS: Patients without diabetes (n = 98 of 180) in a prospective randomized trial of intensive rATG induction were followed for six months for the major secondary composite end point of impaired glucose regulation (hyperglycemia and new-onset diabetes after transplantation, NODAT). Prospectively collected data included fasting blood glucose and HbA(1c). Serum Mg(++) was routinely collected and retrospectively analyzed. RESULTS: Induction with rATG(S) produced less impaired glucose regulation (p = 0.05), delayed NODAT development (p = 0.02), less hyperglycemia (p = 0.02), better renal function (p = 0.04), and less hypomagnesemia (p = 0.02), a factor associated with a lower incidence of NODAT. Generalized linear modeling confirmed that rATG(S) protects against a synergistic interaction between tacrolimus and sirolimus that otherwise increased hypomagnesemia (p = 0.008) and hyperglycemia (p = 0.03). CONCLUSIONS: rATG(S) initiated before renal reperfusion improved early renal function and reduced impaired glucose regulation, an injury by diabetogenic maintenance agents (tacrolimus and sirolimus).

Albuminuria after renal transplantation: maintenance with sirolimus/low-dose tacrolimus vs. mycophenolate mofetil/high-dose tacrolimus.

Maintenance immunosuppression with sirolimus (SRL) in renal transplantation has been associated with proteinuria. We report long-term outcomes of kidney transplant recipients maintained on steroid-free regimens, either SRL with low-dose tacrolimus (SRL/L-Tac) or mycophenolate mofetil (MMF) with high-dose tacrolimus (MMF/H-Tac). We conducted a case-matched study of 50 patients receiving MMF/H-Tac, matched 1:2 with 100 patients maintained on SRL/L-Tac. All patients were induced with rabbit antithymocyte globulin followed by early steroid withdrawal. Comparisons were made of patient and graft survival, graft function, acute rejection, and albuminuria. There were no significant differences between the SRL/L-Tac and MMF/H-Tac groups for patient survival, graft survival, occurrence of acute rejection, or graft function. There was no difference in the proportion of patients with albumin/creatinine ratio (ACR) ≥300 µg/mg (19% vs. 20%), but more patients in the SRL group were receiving renin-angiotensin system blocking agents (72% vs. 53%, p = 0.04). Only flushing the donor kidney with histidine-tryptophan-ketoglutarate solution (vs. UW solution) was predictive of albuminuria. Long-term outcomes are similar at our center for kidney transplant patients receiving either SRL/L-Tac or MMF/H-Tac. Although the occurrence of albuminuria was not different, significantly more SRL-treated patients were receiving antiproteinuric medications.

The role of donor-recipient relationship in long-term outcomes of living donor renal transplantation.

BACKGROUND: Graft failure related to acute and chronic rejection remains an important problem in transplantation. An association has been reported between microchimerism and the development of tolerance. Since it has been established that cells of fetal origin can be found in maternal tissues long after parturition, and cells of maternal origin may persist for years in offspring, we hypothesized that this fetal-maternal microchimerism may confer tolerance and thus less graft loss for kidneys transplanted between mothers and their offspring. METHODS: We used data from the Scientific Registry of Transplant Recipients to compare death-censored graft survival among recipients of living-related renal transplants sharing at least one human leukocyte antigen (HLA) haplotype with their donor. A total of 23,064 such transplants were reported from 1995 to 2004. A Cox proportional hazards model was constructed to compare death-censored graft survival among the following donor-recipient pairings: child-to-mother, child-to-father, mother-to-child, father-to-child, 1-haplotype matched siblings, and HLA-identical siblings. RESULTS: HLA-identical sibling recipients had the best survival, but results for the child-to-father group were not significantly worse (hazard ratio=1.07, P=0.47). Mother-to-child transplants had the poorest graft survival (hazard ratio=2.61, P<0.0001). We found no evidence of tolerance to kidneys transplanted between mothers and offspring. CONCLUSIONS: Our analysis of 1-haplotype matched living-related renal transplants argues against tolerance to organs based on fetal-maternal microchimerism. Mechanistic studies examining the relationship between chimerism and immune sensitization would be useful to explore our results, and may contribute to a better understanding of tolerance.

Impact of simultaneous pancreas and kidney transplantation on cardiovascular risk factors in patients with type 1 diabetes mellitus.

We retrospectively investigated the impact of pancreas transplantation on cardiovascular disease risk factors in patients with type 1 diabetic end-stage renal disease (ESRD). Two cohorts of patients, 44 simultaneous pancreas and kidney transplant patients (SPK) and 30 kidney transplant-alone patients (KTA), were included. Univariate and multivariate analyses were performed. Compared with KTA patients, SPK patients had significantly lower mean arterial pressure (88.5+/-12.7 vs. 98.2+/-13.0 mmHg, P=0.002), lower pulse pressure (51.6+/-15.1 vs. 61.4+/-15.6 mmHg, P=0.008), lower low-density lipoprotein cholesterol (83.5+/-20.6 vs. 99.2+/-32.5 mg/dl, P=0.02), and required fewer lipid-lowering medications (31.8% vs. 60.0%, P=0.02). Compared with pretransplant values, only SPK patients showed significant improvement in both blood pressure and total cholesterol. We conclude that SPK significantly improves blood pressure and dyslipidemia compared with KTA in type 1 diabetic ESRD patients.