Preemptive pancreas-kidney transplantation: multidisciplinary follow-up starts too late

BACKGROUND: Preemptive pancreas-kidney transplantation is increasingly considered at early stages of nephropathy in type 1 diabetics. A multidisciplinary approach is required, but referral to the nephrologist is often delayed. OBJECTIVE: To analyze the referral pattern of type 1 diabetics to a dedicated nephrology unit and to test the prevalence of indications for pancreas-kidney transplantation in this population, according to early preemptive criteria (creatinine >/= 2 mg/dL and/or nephrotic syndrome). PATIENTS AND METHODS: The setting of study was the first Italian Nephrology Outpatient Unit dedicated to diabetics during 1991 to 2002. The main biochemical and clinical parameters were analyzed at referral. RESULTS: Ninety type 1 diabetics underwent at least one nephrological visit during the period; 85 had data at referral. The referral pattern was stable: 1991 to June 1996 [22 men, 24 women of median age 36 (18 to 65) years; diabetological follow-up 18.0 (3 to 37) years] and July 1996 to March 2002 [26 men, 18 women median age 40 (18 to 65); diabetological follow-up 21.5 (11 to 36) years]. The main biochemical data at referral were superimposable: serum creatinine: 1.2 (0.6 to 3.2) versus 1.3 (0.6 to 7) mg/dL; proteinuria: 0.9 (0 to 11) versus 1.01 (0.05 to 12.3) g/24 hours. Diabetes follow-up was greater in July 1996 to March 2002 [18 (3 to 37) versus 21.5 (11 to 36) years] suggesting an effect of improvements in diabetic care. At referral 76.6% were macroproteinuric 85.6% had signs of end-organ damage other than nephropathy; and 30.6% had indications for pancreas-kidney grafting (creatinine >/= 2 mg/dL: n = 6 cases; nephrotic syndrome: n = 10; or both n = 10). CONCLUSIONS: One new frontier of transplantation is the need for early multidisciplinary evaluation of type 1 diabetic patients.     

32例胰、肾同期联合移植的近期疗效

目的报告32例胰、肾同期联合移植(SPK)的近期结果及经验。方法为合并尿毒症的27例1型糖尿病和5例2型糖尿病患者施行SPK,其中胰液膀胱引流(BD)术式2例,改进的胰液空肠引流(ED)术式30例。术后早期采用他克莫司、霉酚酸酯及皮质激素预防排斥反应,同时以抗淋巴细胞球蛋白或抗CD25单克隆抗体诱导治疗。结果32例手术均获得成功,术后随访2～12个月,1例术后9周死于肺部感染,死亡时肾功能正常,另1例术后6个月死于急性心肌梗死,死亡时移植胰、肾功能正常,其余患者目前仍存活;术后(12.7±8.1)d空腹血糖恢复正常,(8.3±4.5)d停用胰岛素,(8.4±7.8)d血肌酐恢复正常。术后发生手术相关并发症有出血、移植胰切口感染、上消化道出血、右股静脉血栓形成和淋巴漏;其它并发症有药物不良反应、肺部感染,采用BD术式者并发代谢性酸中毒和镜下血尿;4例发生移植肾急性排斥反应,均经活检证实。结论SPK治疗糖尿病并发尿毒症的近期疗效满意,ED术式更符合正常生理。     

Neoral versus prograf in simultaneous pancreas-kidney transplantation with portal venous drainage: three-year results of a single-center, open-label, prospective, randomized pilot study

BACKGROUND: The preferential use of tacrolimus (Prograf) over cyclosporine microemulsion (Neoral) in simultaneous pancreas-kidney transplantation (SPKTx) is mainly based on historical, retrospective studies. We herein report the 3-year results of a single-center, prospective, randomized comparison of the two calcineurin inhibitors in the setting of mycophenolate mofetil (MMF)-based immunosuppression and portal drainage of pancreas allografts. METHODS: Between May 2001 and August 2004, 47 SPKTx recipients who were stratified by recipient sex, were alternatively assigned to treatment with Neoral (n = 22) or Prograf (n = 25). Concurrent immunosuppression included induction treatment with basiliximab and maintenance with MMF and steroids. RESULTS: After a median follow-up of 24.0 months, all patients remained in the study arm into which they were initially enrolled. No pancreas rejection episode was observed. One acute kidney rejection was recorded in the Neoral arm (4.5%) as compared with 7 (28.0%) including one steroid-resistant episode, in the Prograf arm (P = .03). The cumulative incidence of adverse events was 31.8% (n = 7) in the Neoral arm compared with 92.0% (n = 23) in the Prograf arm (P < .0001). One patient died in each study arm. Patient, pancreas, and kidney survivals overlapped at 1- and 3-years posttransplant, namely all 95.4% for the Neoral arm compared with 95.8%, 91.8%, and 95.8%, respectively, for the Prograf arm (P > .05). CONCLUSIONS: We conclude that in MMF-based immunosuppression there is no convincing evidence that Prograf should be preferred to Neoral in SPKTx.     

Simultaneous pancreas-kidney transplant: a single-center long-term outcome

BACKGROUND: In patients with type 1 diabetes mellitus and end-stage renal disease, simultaneous pancreas-kidney transplantation is associated with increased survival when compared with solitary deceased kidney transplant or dialysis. We consider that the analysis of our long-term program (based in a single center) of simultaneous pancreas-kidney transplantation would provide valuable information for this therapeutic approach regarding patient and organ survival. METHODS: The outcome of 57 consecutive pancreas-kidney transplants patients was analyzed. The analysis included characteristics of the donor and recipient and survival rates of patients and both grafts. We also analyzed age and modality of renal replacement treatment as possible mortality risk factors. RESULTS: Ten-year patient, kidney and pancreas graft survival rates were 75.8%, 57.2% and 42.7%, respectively. Censoring for patient death, the results for 10-year kidney and pancreas survival were 78.5% and 58%, respectively. CONCLUSION: Our results add evidence to support the notion that the double and simultaneous pancreas-kidney transplantation is in fact the treatment of choice in selected patients with end-stage renal failure due to type 1 diabetes mellitus.     

Long-term follow-up of 78 simultaneous pancreas-kidney transplants at a single-center institution in Europe

BACKGROUND: The objective of this study was to determine the long-term results after simultaneous pancreas-kidney transplantation (SPK) at a single-center institution in Europe. PATIENTS AND METHODS: Seventy-eight consecutive patients with insulin-dependent diabetes mellitus and end-stage nephropathy were followed for a median of 7 years after SPK. Immunosuppressive protocol consisted of cyclosporine A, azathioprine, prednisone, and antithymocyte globulin. Multivariate Cox proportional hazard model was used to investigate the impact of different putative risk factors on long-term patient survival. Health-related quality of life was assessed by a validated questionnaire (SF-36). RESULTS: Patient survival at 5 and 10 years was 81% and 67%, respectively. Pancreas function rate was 73% and 60% and kidney function 67% and 44%, respectively. In multivariate analysis, preexisting myocardial infarction (relative risk [RR] 5.1, 95% confidence interval [CI] 1.5-16.6) and amputation (RR 3.7, 95% CI 1.1-12.9) were strongly associated with a diminished long-term patient survival. Analysis of patients with long-term functioning pancreas and kidney grafts revealed excellent results for quality of life posttransplant that were comparable with average scores of the normal German population. CONCLUSIONS: This series representing the largest experience with long-term follow-up in Europe confirms an excellent long-term survival and an exceptional quality of life after SPK.     

Preemptive transplantation and long-term outcome in living donor kidney transplantation, single-center experience

Although preemptive transplantation of kidneys from living donors without the previous initiation of dialysis is associated with longer allograft survival in a USRDS cohort, the effect of pretransplantation dialysis on graft outcome is still controversial in Korea. The purpose of this study was to evaluate the differential effects on long-term outcomes of living donor kidney transplantation according to initiation of dialysis and its duration or no dialysis. We performed a retrospective cohort study of 494 patients who received a first kidney transplant from a living donor between 1990 and 2006. The mean duration for dialysis was 14.5+/-22.2 months. The 10-year patient survival of 98.0% in the preemptive group was not significantly higher than the dialysis group (91.2%, P>.05). However, 10-year graft survival was higher in the preemptive than the dialysis group (preemptive 94.4%, dialysis 76.5%; P<.05). The differential effect of pretransplant dialysis either by hemodialysis or peritoneal dialysis was not significant, although peritoneal dialysis as a pretransplant treatment seemed to be beneficial on long-term graft survival (5-year graft survival; peritoneal 94.8% and hemodialysis 89.2%). The duration of dialysis did not affect graft survival in our study cohort. In conclusion, we suggest that preemptive transplantation should be applied to eligible patients.     

Ten years of simultaneous pancreas-kidney transplantation: a retrospective single-center analysis of prospectively obtained data

Introduction

Simultaneous pancreas-kidney transplantation (SPK) is a standardized and life-saving procedure for a patient suffering from both insulin-dependent diabetes mellitus type 1 (IDDM 1) and end-stage diabetic nephropathy. To expand the donor pool and to determine the influence of the preprocurement pancreas suitability scoring system (P-PASS) on pancreas graft survival we retrospectively analyzed our data on SPK.

Patients and Methods

From 1999 to 2010 we performed 55 SPKs, using systemic-enteric drainage as surgical approach. The immunosuppressive therapy was induced with basiliximab; maintenance therapy was based on tacrolimus, mycophenolate mofetil, and steroids. Data were prospectively obtained, analyzed, and correlated to the P-PASS.

Results

The overall 10-year patient survival rate was 78% with a 10-year pancreas survival rate of 53%. Three patients needed retransplantation of SPK and 6 patients needed singular pancreas retransplantation. Seventeen patients showed acute rejection episodes and 14 patients suffered from cytomegalovirus (CMV) infections. We compared 43 patients receiving organs from an “ideal” donor (P-PASS <17) with 12 patients receiving grafts from “marginal” donors (P-PASS ≥17). Neither P-PASS nor donor age demonstrated significant influence on pancreas graft survival. However, the body mass index (BMI) of the donor showed a negative tendency (P = .059).

Conclusion

The P-PASS showed no significant prediction of pancreas graft survival. In view of our data, expansion of the German donor pool is possible. A multicenter study of SPK using “marginal” pancreas grafts is mandatory to define a realistic “cut-off” value for P-PASS.     

Long-term follow-up study on bone mineral density and fractures after simultaneous pancreas-kidney transplantation

BACKGROUND: In type 1 diabetic patients with end-stage renal failure, low bone mass is prevalent and the incidence of fractures high after simultaneous pancreas kidney transplantation (SPK). Data are scarce on preexisting skeletal morbidity or the long-term effects of SPK on bone mass and risk of fractures. METHODS: We conducted a prospective study addressing these issues in 19 consecutive SPK recipients before and at 3, 6, and 12 months, and 2.5 to 4 years after establishment of graft function. RESULTS: Prior to transplantation, 13 patients (68%) had hyperparathyroidism, 7 of whom had osteoporosis. Mean bone mineral density (BMD) was significantly lower at the femoral neck than at the lumbar spine (T-scores -2.0 +/- 0.89 vs. -0.66 +/- 0.84). There was a significant decrease in BMD at both lumbar spine and femoral neck at 6 months post-transplantation (-6.0 +/- 5.4% and -6.9 +/- 4.3%, respectively). No further loss was observed in the following 6 months. At 1 year post-transplantation, 9 patients had osteoporosis associated with hyperparathyroidism in 8, and none had sustained a clinical fracture. A significant albeit small increase in BMD was observed 6 months after start of alfacalcidol 0.25 microg/day. At end-evaluation, osteoporosis and hyperparathyroidism persisted in the patients in whom it was documented at 1 year. Five patients who had lower BMD at the femoral neck pretransplantation sustained a clinical fracture. CONCLUSION: Cortical osteoporosis is prevalent in SPK recipients at the time of transplantation, progresses early post-transplantation, and is associated with relatively high incidence of fractures. Reversal of persistent hyperparathyroidism with the use of alfacalcidol may contribute to a decrease in skeletal morbidity.     

Simultaneous pancreas-kidney transplantation: Early complications and long-term outcomes — a single-center experience

IntroductionThis study aimed to assess the prevalence and severity of complications after simultaneous pancreas-kidney transplantation (SPKT) and to evaluate its influence on both grafts’ long-term results.MethodsThis was an observational, retrospective study including 39 consecutive SPKT cases from 2000–2018. Complications were classified into kidney-related and pancreas-related. The severity of complications was assessed using the modified Clavien-Dindo scale. Kaplan-Meier curve analysis and log-rank tests were used. Cox regression was performed for the multivariate analysis.ResultsAll 39 recipients had long-term type I diabetes. Twenty-one (53.8%) patients suffered a Clavien-Dindo ≥IIIa complication. Most complications were pancreas-related, with 17 (43.6%) patients suffering from one. Kidney-related major complications were seen in 11 (28.2%) patients. Patient survival at one, five, and 15 years was 89.7%, 87.1%, and 83.9%, respectively; kidney survival was 87.1%, 81.4%, and 73.6%, respectively; and pancreas survival was 76.9%, 71.3%, and 72%, respectively. Pancreas graft survival was influenced by the presence of major postoperative complications; patients and kidney graft survival were not.ConclusionsComplications after SPKT influence pancreas graft survival. Despite the high rate of complications, our results suggest that patient and kidney graft survival may not be affected by complications.     

Changes in bone mineral density following long-term simultaneous pancreas-kidney transplantation

The symptoms of chronic renal disease-related mineral and bone disease improve significantly in patients after successful simultaneous pancreas-kidney transplantation (SPKT); however, bone pathology is still present even after many post-transplant years. The aim of this study was to analyze the bone densitometry in different periods after SPKT. Three-point densitometry was performed with the dual-energy X-ray absorptiometry (DXA) technique. Serum levels of alkaline phosphatase (ALP), total serum calcium, phosphate and parathyroid hormone were analyzed as markers of mineral metabolism. The study population consisted of 48 patients (28 females, 20 males) with a mean age of 35 ± 6 years and mean 24 ± 6 years of prior diabetes. Mean period of maintenance dialysis was 36 ± 26 months. The median time from SPKT and DXA measurement was 0.53, 26.2 and 41.9 months, respectively. Based on the DXA technique, 35.4 % of patients were categorized as having osteoporosis at the lumbar spine and 39.6 % at the femoral neck. Patients with diagnosed osteoporosis had significantly higher levels of ALP (OR = 1.5; 95 % CI = 1.1–2.2; p < 0.05 at the lumbar spine; OR = 1.4; 95 % CI = 1.0–1.9; p < 0.05 at the femoral neck). In addition, subjects with lumbar osteoporosis were characterized by a significantly lower body mass index (BMI) (OR = 0.5; 95 % CI = 0.3–0.9; p < 0.05). In the long-term follow-up, BMD increased significantly at the lumbar spine (T-score ?1.86 ± 1.07 to ?1.08 ± 0.89) and femoral neck (T-score ?2.12 ± 0.78 to ?1.63 ± 0.65). A multivariate linear model identified a BMI increase as a significant factor associated with improvement in BMD. Results of our study led us to conclude that, according to three-point densitometry, BMD among patients with functioning kidney and pancreas grafts improved. Increased serum levels of ALP were significantly associated with a decrease in BMD, suggesting a higher risk of osteoporosis. BMI gain was predictive of BMD improvement.     

The impact of simultaneous pancreas-kidney transplantation on long-term patient survival

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) ameliorates the progression of microvascular diabetic complications but the procedure is associated with excess initial morbidity and an uncertain effect on patient survival when compared with solitary cadaveric or living donor renal transplantation. We evaluated mortality risks associated with SPK, solitary renal transplantation, and dialysis treatment in a national cohort of type 1 diabetics with end-stage nephropathy. METHODS: A total of 13,467 adult-type 1 diabetics enrolled on the renal and renal-pancreas transplant waiting list between 10/01/88 and 06/30/97 were followed until 06/30/98. Time-dependent mortality risks and life expectancy were calculated according to the treatment received subsequent to wait-list registration: SPK; cadaveric kidney only (CAD); living donor kidney only (LKD) transplantation; and dialysis [wait-listed, maintenance dialysis treatment (WLD)]. RESULTS: Adjusted 10-year patient survival was 67% for SPK vs. 65% for LKD recipients (P=0.19) and 46% for CAD recipients (P<0.001). The excess initial mortality normally associated with renal transplantation and the risk of early infectious death was 2-fold higher in SPK recipients. The time to achieve equal proportion of survivors as the WLD patients was 170, 95, and 72 days for SPK, CAD, and LKD recipients, respectively (P<0.001). However, the adjusted 5-year morality risk (RR) using WLD as the reference and the expected remaining life years were 0.40, 0.45, and 0.75 and 23.4, 20.9, and 12.6 years for SPK, LKD, and CAD, respectively. There was no survival benefit in SPK recipients > or =50 years old (RR=1.38, P=0.81). CONCLUSIONS: Among patients with type 1 DM with end-stage nephropathy, SPK transplantation before the age of 50 years was associated with long-term improvement in survival compared to solitary cadaveric renal transplantation or dialysis.     

Simultaneous pancreas-kidney transplantation: a single-center experience and prospective analysis

In patients with end-stage chronic kidney disease (CKD) and type 1 diabetes mellitus (DM 1), simultaneous pancreas-kidney (SPK) transplantation is currently considered the gold standard therapy. The aim of this study was to analyze and report the long-term clinical outcomes of the 23 SPK transplantations performed at our institution over an 84-month period (January 1, 2000 to December 31, 2006). A prospective analysis of these patients included donor, recipient, and transplantation characteristics. The only requirements for transplantation were blood group compatibility and a negative cross-match. Bladder drainage via pancreaticoduodenocystostomy was performed in all of the patients. Due to a pulmonary embolus 1 patient (4.3%) died at 2 months. The actuarial patient survival rates at 3 months and 1, 3, and 5 years were 95.6%. Causes for the renal graft loss were chronic allograft nephropathy in 3 cases (13%) and death of the patient in 1 case (4.3%). The actuarial censored renal allograft survival rates at 3 months and at 1 year were 100%, and at 3 and 5 years were 91.3%. Causes for the renal graft loss were chronic rejection in 1 case (4.3%) and patient death in 1 case (4.3%). The actuarial censored pancreatic allograft survival rates at 3 months and at 1 and 3 years were 100%, and at 5 years was 95.6%. The results of this work add further evidence that SPK is the gold standard therapy for selected patients with end-stage CKD due to DM 1.     

Single-center, open, prospective, randomized pilot study comparing cyclosporine versus tacrolimus in simultaneous pancreas-kidney transplantation

BACKGROUND: Although tacrolimus (Prograf) is the calcineurin inhibitor usually employed in simultaneous pancreas-kidney transplantation (SPKTx), no prospective randomized studies have compared its efficacy to cyclosporine (Neoral), when either drug is used in combination with mycophenolate mofetil (MMF) and the pancreas is drained into the portal vein. METHODS: Between May 2001 and June 2003, 16 SPKTx recipients were randomized to be prescribed Neoral and 17 Prograf in addition to basiliximab, steroids, and MMF. All pancreata were drained into the portal vein. RESULTS: After a median follow-up of 15.6 months, six kidney acute rejection episodes were observed with Prograf (36.5%; one steroid-resistant) and one Neoral (n = 1, 6.2%; P =.04). No pancreas rejection episode was recorded. Two infections occurred in two recipients from each group. No major adverse events were noted other than a severe hematological toxicity (Prograf). Metabolic parameters were equivalent in the two groups, save for higher total cholesterol (212 +/- 39 mg/dL vs 173 +/- 23 mg/dL; P =.008), LDL (129 +/- 33 mg/dL vs 101 +/- 21 mg/dL; P =.029), and triglyceride (191 +/- 86 mg/dL vs 126 +/- 40 mg/dL; P =.028), values with Neoral, although the same differences were already present at baseline. One recipient (Neoral) died with functioning grafts. Patient, pancreas, and kidney survival rates were all 94% for Neoral versus 100% for Prograf. CONCLUSIONS: Although a larger series and a longer follow-up are needed, Neoral and Prograf used in combination with MMF seem to achieve equivalent success rates among primary SPKTx when the pancreas is drained into the portal vein.     

Urodynamic testing predicts long-term urological complications following simultaneous pancreas-kidney transplantation

INTRODUCTION: Combined pancreas-kidney transplantation is the treatment of choice for patients with type I diabetes mellitus associated with chronic renal failure. The introduction of the bladder drainage technique constituted a marked improvement of the surgical technique with a reduction of life-threatening complications. However, drainage of pancreatic secretions via the urinary bladder causes urological complications leading, in some cases, to cystoenteric conversion. We retrospectively analysed whether pre-operative urodynamic findings may predict the subsequent development of urological complications and influence the choice of exocrine secretion drainage. PATIENTS AND METHODS: From 1987 to 1997, 39 bladder-drained simultaneous pancreas-kidney transplantations were performed in 16 men and 23 women with a mean age of 38.5 yr. All patients underwent a complete urological assessment prior to surgery, including medical history, physical examination, urethrocystography and urodynamic assessment. RESULTS: Twenty-eight patients are alive with a mean follow-up of 62 +/- 8 months. In 60% of cases, both kidney and pancreas remain functional. Seven patients experienced recurrent lower urinary tract infections. Six patients suffered from chemical urethritis (four men and two women) and six suffered from recurrent haematuria (blood transfusions were required in two patients). One patient had incrusted stones at the site of duodenal staples. Urological complications were mostly observed in the 22 patients (79%) with abnormal urodynamic characteristics (Relative risk: 5.1). Intravenous Somatostatin failed to definitively cure these complications in most cases. Seven patients (17%) (five with urethritis, two with haematuria) required cystoenteric conversion. Two patients developed post-operative ileal fistula, one cutaneous and one into the bladder. All urinary symptoms resolved in these seven patients. CONCLUSION: The frequency of specific urinary complications is high (28%) in bladder-drained simultaneous pancreas-kidney transplantation patients. These complications are statistically more frequent in the case of an abnormal pre-transplant urodynamic assessment.     

胰肾联合移植的排斥反应

目的　探讨胰肾联合移植术后的排斥反应。方法　对我院施行的 3例胰肾联合移植的病人 ,采用FK5 0 6 MMF Perid Zenapax四联免疫治疗方案 ,通过床边彩超及Cr、BUN、血糖等来监测移植物的排斥反应。对排斥反应采用激素冲击疗法 ,对激素不敏感者采用OKT3治疗。结果　3例患者中有 2例出现排斥反应 ,其发生率达 6 6 % ;在出现排斥反应时 ,首先表现为低热、全身不适 ,尿量减少 ,血Cr、BUN升高 ,彩超示移植物血流阻抗升高 ,之后才是血糖升高。结论　胰肾联合移植中 ,排斥反应与多种因素有关 ,移植肾对移植胰具有保护作用 ,肾脏可以作为监测胰腺排异的窗口 ,彩超检查可以作为筛选移植物排异反应的手段。     

Cytomegalovirus infection in simultaneous pancreas-kidney transplantation

INTRODUCTION: In this open-label multicenter study, 205 simultaneous pancreas-kidney (SPK) transplant recipients between 1998 and 2000 were randomly assigned to tacrolimus or cyclosporine-microemulsion (ME). All patients received concomitant rATG induction therapy, mycophenolate mofetil and short-term corticosteroids. We report the 3-year data related to the occurrence, severity and effect of cytomegalovirus (CMV) infections. The type of CMV prophylaxis and treatment was at the discretion of the investigator. RESULTS: The overall incidence of CMV infection was 34% with no difference in incidence between the tacrolimus and cyclosporine-ME treatment arms. Statistically significant fewer CMV infections occurred among patients who received ganciclovir (22%) than those who did not receive prophylaxis (42%; P = .0075) or were treated with acyclovir (43%; P = .0066). The CMV infection rate according to donor recipient CMV serological status was: D-/R- group 11%, which was lower than the D-/R+ group at 40% (P = .0035), the D+/R+ group at 37% (P = .0024), or the D+/R- group at 52% (P = .00001). Among the last three groups, the infection rate was lower in patients on ganciclovir than those with no prophylaxis or on acyclovir (22% vs 64%; P = .00001). The incidence of acute rejection episodes was higher among patients without ganciclovir prophylaxis. No difference was observed in actuarial patient, kidney, or pancreas survival rates between patients with versus without infection. CONCLUSIONS: Ganciclovir prophylaxis effectively prevented CMV infection in SPK transplant recipients, especially in higher risk groups. An effect of CMV prophylaxis on the incidence of rejection is possible.