Diego Bogetti

Impact of non-compliance on outcome after pediatric kidney transplantation: An analysis in racial subgroups

Abstract:  Renal transplantation is the therapy of choice for children with end‐stage renal disease. Despite excellent patient survival, long‐term graft survival is poor, especially in the African‐American (AA) population. This article addresses non‐compliance as a major cause of late‐term graft loss in the pediatric population. Between July 1995 and September 2002, a total of 50 pediatric kidney transplants were performed at our institution. We have analyzed data for 44 of these kidney transplants. Twelve recipients were AA, 14 Caucasian (C) and 18 Hispanic (H). The remaining six patients of different racial origin were not included in this analysis. The mean age of the recipients was 10.9 yr (range 1.7–17.8). Thirty‐one were cadaveric and 13 were living donor transplants. We analyzed creatinine level and graft and patient survival at 1, 3 and 5 yr post‐transplant. Compliance was evaluated based on trends in cyclosporine levels, attendance to clinic visits, individual interviews and unexplained late graft dysfunction. One‐ and 3‐yr patient survival rates were 100% for all racial groups, except the 3‐yr patient survival rate for C, which was 86%. One and 3‐yr graft survival rates for AA, C and H were 92 and 67%, 86 and 79% and 100 and 100%, respectively. However, at 5 yr, we found that AA recipients had a significantly higher rate of graft loss when compared to both H and C recipients (42 vs. 95 vs. 71%, respectively). Non‐compliance was the main factor, accounting for 71% of cases of late graft loss. In conclusion, non‐compliance is a problem of great importance in the pediatric transplant population, particularly in AA recipients, where it plays a major role in late‐term graft loss.

Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury

Abstract:  Background:  Interventions that minimize hepatic ischemia/reperfusion injury (IRI) can expand the donor organ pool. Thymoglobulin (TG) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients. This controlled randomized trial was designated to assess the ability of TG to protect against IRI in liver transplant recipients.

Simultaneous pancreas-kidney transplant from living related donor: A single-center experience

Background. Simultaneous pancreas and kidney transplantation (SPK) from cadaveric donors has become a widely accepted therapeutic option for insulin-dependent uremic patients. In 1996 the first SPK from a live donor was performed. This procedure offers the advantage of a better immunologic match, reduced cold ischemia injury, and decreased waiting time. As such, it is an attractive alternative treatment for diabetic patients with end-stage nephropathy with an available living donor. Methods. We performed six SPKs from living-related donors. There were four men and two women among the recipients; median age was 34 (range, 29–39) years. All donors were recipients’ siblings with excellent HLA matching. Donors underwent standardized metabolic workup, anti-insulin and anti-islet antibody assays, and computed tomography of the abdomen. Both donors and recipients were treated with octreotide for 5 days perioperatively. After transplantation, the patients were maintained on tacrolimus-based immunosuppression, with the exception of one recipient of SPK from an identical twin, who received cyclosporine monotherapy. Results. All the donors are doing well and have normal renal function and blood glucose levels. One-year patient, renal, and pancreatic graft survival rates were 100%, 100%, and 83%, respectively. Acute kidney rejection was documented in two patients, and both recovered completely after OKT3 therapy. No rejection of pancreatic graft has been documented. Except for one patient who lost the graft because of hemorrhagic pancreatitis, all recipients maintained serum glucose levels at less than 130 mg/dL without insulin therapy. No major surgical complications such as graft thrombosis, intra-abdominal infection, or abscess were reported. Conclusions. Living donor SPK can represent a successful alternative to cadaveric donor SPK. The procedure can be performed safely in the donor and with low morbidity in the recipient.

Standard chronic immunosuppression after kidney transplantation for systemic lupus erythematosus eliminates recurrence of disease

Abstract:  Background:  There is only limited experience in patients with systemic lupus erythematosus (SLE) with drugs that have developed for immunosuppression after organ transplantation, namely calcineurin inhibitors (CI). The aim of this study is to determine the effect of these drugs on disease activity after kidney transplant in patients affected by SLE.

Auto-islet transplantation after pancreatectomy

Chronic pancreatitis (CP) is an inflammatory disease that causes progressive and irreversible structural changes to the pancreas, resulting in permanent impairment of both endocrine and exocrine functions. In advanced cases of CP, pain can be relieved only with pancreatic resection. However, even partial resection of the pancreas in this setting may cause diabetes. Furthermore, postsurgical diabetes (PSD) always occurs after total or near-total pancreatectomy, which is commonly performed for CP. Auto transplantation of pancreatic islets into the portal vein after pancreatic resection can prevent PSD. The results of this strategy, which are already encouraging, are likely to improve in the near future because of significant progress in the isolation and preservation of pancreatic islets. This review discusses the current status and future prospects for auto-islet transplantation after pancreatic resection for CP.

Successful Simultaneous Pancreas Kidney Transplantation from Living‐Related Donor Against Positive Cross‐Match

A positive pretransplant flow cytometry cross‐match (FC‐XM) allows precise identification of high‐risk recipients vulnerable to hyperacute or accelerated rejection after transplantation. Living donor kidney transplant recipient candidates with positive cross‐match have been successfully treated with a combination of plasmapheresis (therapeutic plasma exchange, TPEX) and intravenous immunoglobulin (IVIG), achieving conversion to negative cross‐match and successful transplant. We report the first successful case of simultaneous pancreas kidney transplant (SPKT) from a living donor (LD) performed against an initially positive FC‐XM, converted to negative using a protocol based on TPEX and IVIG in combination with antiCD20 monoclonal antibody. This strategy of overcoming the cross‐match barriers in living donation may offer a chance of successful transplantation to highly sensitized candidates for SPKT, for whom cadaveric transplant is difficult to achieve.

Living related small bowel transplantation in children: 3‐dimensional computed tomography donor evaluation

Abstract:  The evaluation of the small bowel vascular anatomy of living small bowel donors (LSBD) is usually performed with conventional angiography (CA). Recently, angio computed tomography (CT) has become a valid study of the vascular anatomy for kidney and liver living donors. We studied the applicability of angio CT with 3‐D reconstruction (3‐D‐ACT) in the evaluation of LSBD. Potential LSBDs for pediatric transplant underwent both CA and 3‐D‐ACT to evaluate the anatomy of the distal branches of the superior mesenteric artery and vein. Angio‐CT was performed with General Electric Lightspeed Scanner. The 3‐D reconstruction was performed on the TeraRecon workstation. Adverse reactions, contrast dosage, test duration, invasiveness, hospital‐stay, patient discomforts and accuracy were evaluated. Four potential donors (four female; mean age: 30.5 yr; mean BMI: 28.4) underwent both tests. Adverse reactions correlated to contrast agent used (90 mL CA, 150 mL 3‐D‐ACT) were not reported. CA required a hospitalization of 6 h as opposed to immediate discharge after the 3‐D‐ACT. The CA required the placement of transfemoral catheter and therefore greater patient discomfort than with 3‐D‐ACT. The 3‐D‐ACT arterial images were rated as equivalent to CA, however, 3‐D‐ACT venous images were rated better than the CA in all cases. CT‐angiography with 3‐D reconstruction is an acceptable method for vascular evaluation. When compared with routine angiography, it is less invasive, better tolerated and faster, but does require a significantly greater volume of venous contrast. 3‐D‐ACT also offers a better evaluation of the venous phase, and thus may become the test of choice to evaluate the vascular anatomies of LSBD candidates.

Hepatic venous outflow reconstruction in adult living donor liver transplants without portal hypertension.

Abstract:  Graft congestion is one of the causes of poor graft function in segmental liver transplantation. Three factors are implicated in segmental graft congestion: graft size, hepatic venous outflow and portal inflow. The graft size must be matched to the body weight, which is conventionally done by using graft to body weight ratio. Hepatic blood outflow must be optimized by hepatic vein reconstruction, which can be complicated. High portal blood flow has been shown to be detrimental to small‐for‐size grafts. These factors are strictly connected to each other. They can all contribute to graft congestion and poor function, while one factor can compensate for the others and decrease congestion. Ideally, all the accessory veins should be reconstructed, if possible, to maximize the outflow. In the absence of portal hypertension and with an adequate sized graft, complex venous reconstruction may not be necessary. We present a case report of an adult living donor liver transplant with the favorable conditions of normal portal pressure and a large sized graft, but complicated by the presence of several accessory hepatic veins. A simple hepatic vein anastomosis was sufficient for adequate outflow and prompt graft function.

Squamous cell carcinoma in a chronically rejected renal allograft

The malignant degeneration of a chronically rejected kidney allograft has been rarely reported. Almost invariably such malignancies originated in the transitional epithelium. We herein present the first occurrence of squamous cell carcinoma (SCC), originating from occult donor cells, in a chronically rejected renal allograft. Nearly 20 years after chronic rejection and loss of function of a cadaver renal graft, our patient developed increasing abdominal discomfort, decrease in appetite and weight loss. A CT‐scan of the abdomen showed an abnormally enlarged and irregularly contoured mass at the level of the rejected allograft. Given the clinical and radiologic picture suggestive of either an infectious or intraparenchymal hemorrhagic process, a transplant nephrectomy was performed. At surgery, it was immediately evident that a malignant degenerative process had affected the graft. The histological features of the specimen were diagnostic for a well‐differentiated SCC. The donor origin of the tumor was established through a DNA microchimerism assay performed on the operative specimens. The patient did well after resection of the malignancy, although he died 5 months later owing to a myocardial infarction. In summary, even several years following the transplant, the possibility of a malignancy of donor origin developing within a failed allograft should always be considered as part of the differential diagnosis in unusual post‐transplant settings.

Liver transplantation for propylthiouracil-induced acute hepatic failure

We present the case of a 17-year-old female with a history of hyperthyroidism who developed fulminant hepatitis after being treated with propylthiouracil (PTU). Acute hepatitis developed shortly after PTU had been started, and the liver injury did not heal after PTU was stopped. The patient underwent a successful emergency liver transplant and has since returned to her normal activities. In most of the cases when PTU is stopped, the liver fully recovers. Nevertheless, in about 30% of the patients, the damage can progress to liver necrosis and complete hepatic failure. In these patients, emergency liver transplantation represents the only therapeutic option and is the best path toward a full recovery. Thioamide-type drugs like propylthiouracil were introduced in the 1940s, and have become the drug of choice for treatment of hyperthyroidism. Despite the broad use of PTU, very few episodes of acute liver toxicity have been reported, and in the majority of the cases the injury was resolved with discontinuation of the drug. Those patients whose liver function did not improve after PTU discontinuation have had a fatal outcome. The lack of improvement of the clinical condition of such patients and of the liver biochemistries after PTU discontinuation should be regarded as a grave prognosis and should prompt the emergency listing of the patient for a liver transplant.