Rossana Caldara

Incidence of cancer after kidney transplant: Results from the north italy transplant program

Background. Patients undergoing kidney transplantation demonstrate a higher risk of developing cancer as the result of immunosuppressive treatment and concurrent infections. Methods. The incidence of cancer in a cohort of patients who underwent kidney transplantation between 1990 and 2000, and who survived the acute phase (10 days), was analyzed as part of the North Italy Transplant program. Results. A total of 3,521 patients underwent transplantation during a 10-year period in 10 of 13 participating centers; the length of follow-up after kidney transplant was 67.7±36.0 months. During the follow-up, 172 patients developed cancer (39 with Kaposi sarcoma, 38 with lymphoproliferative diseases, and 95 with carcinomas [17 kidney, 11 non-basal cell carcinoma of the skin, 10 colorectal, 8 breast, 7 gastric, 7 lung, 6 bladder, and 3 mesothelioma]). The average time to cancer development after transplant was 40.1±33.4 months (range 0–134 months). Twenty-four patients developed cancer within 6 months from the transplant (10 with carcinomas, 7 with Kaposi sarcoma, and 7 with lymphoproliferative diseases). Three patients demonstrated a second primary cancer. The average cancer incidence was 4.9%. The incidence of cancer was 0.01 per year. Independent determinants of cancer development were age, gender, and immunosuppressive protocol including induction. Ten-year mortality was significantly higher in patients with cancer (33.1%) than among patients without cancer (5.3%). The relative risk of death in subjects with cancer was 5.5 (confidence interval 4.1–7.4). Conclusions. These preliminary data underline the importance of long-term surveillance of transplant recipients, choice of immunosuppressive treatment, and careful donor selection.

Cephalic-phase insulin and glucagon release in normal subjects and in patients receiving pancreas transplantation

The aim of the study was to evaluate whether the cephalic phase of insulin release is still present in patients submitted to simultaneous kidney and pancreas transplantation. Subjects were five kidney-pancreas-transplanted patients (group P) and five control (group C). The experimental protocol lasted 30 minutes, and blood samples were collected at 1-minute intervals. After a 20-minute period of steady-state fasting (premeal period), subjects received a palatable standard meal (pizza). Samples were collected over the subsequent 10 minutes (meal period). No evidence of an increase in serum free insulin, serum C-peptide, and plasma glucagon during food ingestion was observed in group P whereas the test was effective in eliciting cephalic-phase insulin and glucagon release in group C. Gastric inhibitory polypeptide and somatostatin did not show any variation during the test in both groups. In conclusion, the absence of cephalic-phase insulin and glucagon release in group P could be explained by denervation of the grafted pancreas. This early alteration could contribute to the impairment in glucose tolerance frequently observed in successfully pancreas-transplanted patients.

Risks and benefits of transplantation in the cure of type 1 diabetes: whole pancreas versus islet transplantation. A single center study.

BACKGROUND Pancreas and islet transplantation are the only available options to replace beta-cell function in patients with type 1 diabetes. Great variability in terms of rate of success for both approaches is reported in the literature and it is difficult to compare the respective risks and benefits. OBJECTIVES The aim of this study was to analyze risks and benefits of pancreas transplantation alone (PTA) and islet transplantation alone (ITA) by making use of the long-term experience of a single center where both transplantations are performed. We focused on the risks and benefits of both procedures, with the objective of better defining indications and providing evidence to support the decision-making process. The outcomes of 33 PTA and 33 ITA were analyzed, and pancreas and islet function (i.e., insulin independence), perioperative events, and long-term adverse events were recorded. RESULTS We observed a higher rate of insulin independence in PTA (75%) versus ITA (59%), with the longer insulin independence among PTA patients receiving tacrolimus. The occurrence of adverse events was higher for PTA patients in terms of hospitalization length and frequency, re-intervention for surgical and immunological acute complications, CMV reactivation, and other infections. CONCLUSIONS In conclusion, these results support the practice of listing patients for PTA when the metabolic control and the progression of chronic complications require a rapid normalization of glucose levels, with the exception of patients with cardiovascular disease, because of the high surgical risks. ITA is indicated when replacement of beta-cell mass is needed in patients with a high surgical risk.

Near Normalization of Metabolic and Functional Features of the Central Nervous System in Type 1 Diabetic Patients With End-Stage Renal Disease After Kidney-Pancreas Transplantation

OBJECTIVE The pathogenesis of brain disorders in type 1 diabetes (T1D) is multifactorial and involves the adverse effects of chronic hyperglycemia and of recurrent hypoglycemia. Kidney-pancreas (KP), but not kidney alone (KD), transplantation is associated with sustained normoglycemia, improvement in quality of life, and reduction of morbidity/mortality in diabetic patients with end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS The aim of our study was to evaluate with magnetic resonance imaging and nuclear magnetic resonance spectroscopy (1H MRS) the cerebral morphology and metabolism of 15 ESRD plus T1D patients, 23 patients with ESRD plus T1D after KD (n = 9) and KP (n = 14) transplantation, and 8 age-matched control subjects. RESULTS Magnetic resonance imaging showed a higher prevalence of cerebrovascular disease in ESRD plus T1D patients (53% [95% CI 36–69]) compared with healthy subjects (25% [3–6], P = 0.04). Brain 1H MRS showed lower levels of N-acetyl aspartate (NAA)-to-choline ratio in ESRD plus T1D, KD, and KP patients compared with control subjects (control subjects vs. all, P < 0.05) and of NAA-to-creatine ratio in ESRD plus T1D compared with KP and control subjects (ESRD plus T1D vs. control and KP subjects, P ≤ 0.01). The evaluation of the most common scores of psychological and neuropsychological function showed a generally better intellectual profile in control and KP subjects compared with ESRD plus T1D and KD patients. CONCLUSIONS Diabetes and ESRD are associated with a precocious form of brain impairment, chronic cerebrovascular disease, and cognitive decline. In KP-transplanted patients, most of these features appeared to be near normalized after a 5-year follow-up period of sustained normoglycemia.

Effect of pancreas transplantation on diabetic retinopathy : a 20-case report

SummaryIn order to study the effects of normoglycaemia on diabetic retinopathy, 20 diabetic uraemic patients who underwent a kidney-pancreas transplantation were evaluated before and after surgery (6,9 months and once a year). The control group consisted of 12 uraemic patients who underwent kidney transplantation alone. At each follow-up examination a complete clinical examination and a retinal fluorescein angiography were performed. The eyes with end-stage retinopathy at baseline were excluded from the study. The analysis of the results showed no significant differences in the two groups. The diabetic retinopathy at the moment of the transplantation was already too advanced to benefit from the better glycaemic control.

Effect of pancreas transplantation on life expectancy, kidney function and quality of life in uraemic Type 1 (insulin-dependent) diabetic patients

SummaryThe aim of our study was to evaluate the effects of haemodialysis, kidney transplantation and simultaneous kidney and pancreas transplantation on survival of diabetic subjects and on kidney function. 40 Type 1 (insulin-dependent) diabetic patients received a kidney transplantation: in 31 cases the kidney was transplanted simultaneously to a pancreas graft from the same donor (KP group), while in 9 cases the pancreas was not available (K group). 44 uraemic Type 1(insulin-dependent) diabetic patients on dialysis and in waiting list for kidney transplantation, constituted the control group (HD group). Patient survival rate 1, 3 and 5 years following transplantation was better in KP group (93%, 89%, 89%, respectively) than in K group (88%, 88%, 73%, respectively) and in HD group (88%, 62%, 51%, respectively). Kidney graft survival at 1, 3 and 5 years post-transplant was better in KP group (93%, 72%, 72%, respectively) than in K group (76%, 61%, 31%, respectively). 1 year after transplantation, patients of the KP group who had lost the pancreas for technical reasons (thrombosis) were included in the K group so as to evaluate the effect of the transplanted pancreas on long-term patient and kidney survival. Patient survival rate in the KP group (17 patients) at 2 and 4 years was 100%, while at the same intervals it was 78% in the K group (13 patients). Kidney graft function rate at 2 and 4 years was 93% in the KP group (17 grafts) and 54% and 27% respectively in the K group (14 grafts). Evaluation of quality of life in patients receiving a kidney and pancreas transplantation showed an improvement in psychological well-being, when compared to patients receiving a kidney transplantation alone. Physical well-being was similar in patients transplanted with kidney and pancreas or with kidney alone.

Prediction of the long-term metabolic success of the pancreatic graft function

Background. Strategies to prevent the return to the diabetic state for graft loss or failure or any other cause after pancreas transplantation require the identification of the subjects at risk. This study evaluated whether daily glucose, insulin, and c-peptide profiles and studies of insulin sensitivity and secretion after transplantation predict pancreatic graft failure. Methods. Fifty-three subjects with type 1 diabetes with end-stage renal failure who received a combined pancreas and kidney transplant underwent the following procedures 1 year after transplantation: 1-day metabolic profiles, sampling every 2 hours for plasma glucose, serum insulin, and c-peptide (n=51); an intravenous glucose tolerance test (IVGTT) to evaluate insulin secretion (n=48); and an euglycemic insulin clamp to evaluate insulin sensitivity (M value, n=14). The recipients were then followed up to 8 years (mean follow-up 4.8±0.3 years) to evaluate the return to the diabetic state. Results. Survival analysis showed that plasma glucose in the profiles and insulin secretion in IVGTT were strongly related to the risk of returning to the diabetic state. A cutoff value of mean daily plasma glucose >127 mg/dL, corresponding to the top quartile of the mean plasma glucose distribution in the profiles, predicted the return to the diabetic state within 4 years from transplantation with a 93% specificity and a 100% sensitivity. A cutoff value of insulin delta peak <32 &mgr;U/ml in the IVGTT predicted the return to the diabetic state within 4 years from transplantation with a 75% specificity and a 75% sensitivity. In contrast, the M value in the clamp was devoid of predictive value. Conclusions. This study indicates that the mean 24-h plasma glucose 1 year after transplantation is the strongest predictor of the return to the diabetic state. The risk is related to defects in insulin secretion and not to insulin resistance. Metabolic profiles can be used to screen the subjects at risk to strictly monitor the graft function and to investigate early determinants of graft failure.

Epidemiologic study on the origin of cancer after kidney transplantation.

Background. Subjects who underwent solid organ transplantation are at higher risk for a wide variety of cancers. Methods. The authors investigated the origin of cancer in a cohort of 2,526 patients followed up for 60.7±35.6 months after kidney transplantation between 1990 and 2000 in seven transplant centers. Results. One hundred four of them developed cancer. All subjects who developed solid cancer within 6 months after transplantation (n=10) and a group of subjects who developed solid cancer after 6 months posttransplant (n=10) were selected. Short tandem repeat analysis was performed on paraffin-embedded biopsy specimens of tumors and on both donor and recipient pretransplant peripheral blood. Biologic material was obtained in 17 of the 20 selected patients (85.0%). The analysis showed that 16 of 17 tumors were genetically identical to the recipient. Conclusions. The authors’ results suggest that donor transmission of solid cancer is an unlikely event in their population.

Successful surgical salvage of pancreas allograft.

Background. Early and late complications related to the pancreas after simultaneous kidney-pancreas transplantation (SKPT) frequently result in graft loss. The authors describe a surgical rescue technique that allows salvage of the pancreatic graft when surgical complications appear after the transplant. Methods. Of 158 patients who underwent SKPT, 7 were identified with posttransplant complications that required surgical salvage of the pancreas allograft. The surgical salvage technique consisted of the following: pancreatoduodenectomy with conversion from whole-pancreas transplant with bladder or enteric diversion to segmental graft with duct injection (three cases) and conversion from whole-pancreas transplant with duct injection (four cases). Results. Five of seven pancreas allografts are still functioning, with a mean follow-up of 28 months (range, 6–42 months). Conclusion. The described surgical treatment may be useful for surgical salvage of the pancreatic allograft, without major impairment of endocrine function.

Kidney-pancreas transplantation is associated with near-normal sexual function in uremic type 1 diabetic patients.

Background. Sexual function is altered in patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD), thus affecting quality of life. The present study aimed to analyze sexual function in patients with T1D and ESRD (T1D+ESRD) who received a simultaneous kidney-pancreas (KP) or kidney-alone (KD) transplantation. Methods. Ten KP, 10 KD, 9 T1D+ESRD patients and 11 healthy control subjects were evaluated according to the following parameters: (1) medical/sexual history and physical examination; (2) International Index of Erectile Function; (3) Becks inventory for depression; (4) assessment of hormonal profile; (5) quantitative sensory testing of both hand and penile sensory thresholds; and (6) hemodynamic penile assessment. Results. Controls and KP patients showed a higher rate of self-reported satisfactory erectile function as compared with KD and T1D+ESRD patients. Circulating androgens level resulted lower in both groups of transplanted patients and in patients with T1D+ESRD compared with healthy controls, albeit a relatively better profile was observed in KP. Both transplanted and T1D+ESRD patients showed peripheral hyposensitivity; however, healthy controls and KP showed better penile hemodynamic parameters compared with KD and T1D+ESRD. Conclusions. Our study demonstrates that sexual function, circulating sex steroids milieu, penile sensitivity, and hemodynamics are near-normalized for the most part in KP transplantation. Further studies are needed to assess the beneficial role and the overall impact of KP transplantation on sexual function in a long-term setting and a larger cohort of patients.