The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis).

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications.

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond.

The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.

Simultaneous pancreas-kidney transplantation: is the failure of the grafts also simultaneous?

INTRODUCTION: It is well known that after a simultaneous pancreas and kidney transplantation (SPKT) there is a higher incidence of pancreatic graft loss in the acute period, due to technical problems. However, there is little information about the survival of pancreatic and kidney grafts 1 year after transplantation. AIMS: To analyze the causes of long-term graft loss of SPKT in our hospital and to determine if this loss occurs simultaneously or is isolated. PATIENTS AND METHODS: We analyzed the data of 63 SPKTs performed between February 1983 and October 2005, including the cases with normal renal and pancreatic function after 1 year of transplantation, and with a loss of one or two organs during the follow-up period (8 +/- 4 years). We defined simultaneous SPKT failure as failure that occurs at the same time or when the period between pancreatic and renal graft failure is shorter than 9 months. RESULTS: In 28 patients (44%), there was a simultaneous graft failure, whereas in 35 (56%) the loss of function occurred in only one organ or in both, but separately. Death was responsible for 75% (21/28) of simultaneous graft losses, representing 25% (9/35) of isolated graft failures. Cardiovascular disease was the leading cause of death. In 14 of 35 isolated graft failures, there was loss of renal and pancreatic function (11/14 kidney failed first) with a 2.9 +/- 2.3 years of interval. In 12 cases there was only loss of pancreatic function, whereas in nine cases the affected organ was the kidney. Graft chronic nephropathy and chronic rejection in the pancreas were the main causes of graft failure. CONCLUSIONS: The main cause of simultaneous SPKT failure is patient death; however, among isolated or separated SPKT failures, the kidney failed first, more frequently.

[Parathyroid carcinoma associated to secondary hyperparathyroidism in hemodialyzed patients. Two cases reports]. / Carcinoma de paratiroides asociado a hiperparatiroidismo secundario en pacientes en hemodiálisis.

Parathyroid carcinoma (PC) is an infrequent disease with a subtle initial presentation and a variable course, necessitating a high index of suspicion to make the correct diagnosis. In chronic failure patients on haemodialysis it becomes even more difficult to suspect this entity since the high prevalence of secondary hyperparathyroidism(SHP). Two patients with PC out of a series of 160 patients with moderate-to-severe SHP submitted for parathyroidectomy are reported. Their clinical features are compared with those of the twenty-two cases previously reported in the literature with a discussion of this pathology. Patients with PC showed higher blood levels of iPTH, total calcium, phosphate and total alkaline phosphatase than the SHP population. The final diagnosis of PC was made after histological study revealing capsular or blood vessel invasion.

K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance.

PURPOSE: Previous studies have demonstrated the presence of K-ras mutations in the plasma of patients with pancreatic carcinoma. However, the diagnostic utility and the prognostic significance of this finding have never been addressed. PATIENTS AND METHODS: Forty-four consecutive patients with histologically confirmed primary pancreatic ductal adenocarcinoma were included. A control group of 37 patients with chronic pancreatitis, 10 patients with other tumors of the pancreatic area, nine patients with acute pancreatitis, and four healthy volunteers was also included. Plasma DNA was isolated and K-ras codon-12 mutations were analyzed by means of restriction fragment length polymorphism-polymerase chain reaction and single-strand conformation polymorphism techniques. Patients were followed up to establish their clinical outcome. RESULTS: The mutant-type K-ras gene was found in plasma DNA samples of 12 (27%) of 44 patients with pancreatic ductal adenocarcinoma; this finding was related to the tumor stage (P = .05), mainly in the presence of distant metastases (P = .02). In addition, K-ras mutations were detected in the plasma DNA of two (5%) of 37 patients with chronic pancreatitis. In the subset of patients with pancreatic masses, the sensitivity and specificity of plasma K-ras analysis for pancreatic adenocarcinoma were 27% and 100%, respectively. Finally, pancreatic carcinoma patients with the mutant-type K-ras gene in plasma DNA exhibited a shorter survival time than patients with the wild-type gene (P<.005), and plasma K-ras mutations were identified as the only independent prognostic factor (odds ratio, 1.51; 95% confidence interval, 1.02 to 2.23). CONCLUSION: Plasma K-ras analysis is a highly specific, low-sensitivity approach that has diagnostic and prognostic clinical implications in patients with pancreatic carcinoma.

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.

Development of a disease specific quality of life (QoL) questionnaire module to supplement the EORTC core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. EORTC Study Group on Quality of Life.

There is overwhelming consensus that quality of life assessment is urgently required in pancreatic cancer, yet little research has been conducted. We report on the development of a disease specific questionnaire module to supplement the EORTC core cancer module, the QLQ-C30 in patients with pancreatic cancer, using EORTC quality of life study group guidelines for module development. Relevant QoL issues were generated from literature searches and interviews with health professionals and patients with pancreatic cancer. Issues were constructed into items and provisionally translated. The provisional module was pretested in patients in 8 European centres. The resulting module the QLQ-PAN26 includes 26 items related to disease symptoms, treatment side-effects and emotional issues specific to pancreatic cancer. This should ensure that the module will be sensitive to assess the small but important disease and treatment related QoL changes in pancreatic cancer. The use of the QLQ-C30 and QLQ-PAN26 will provide a comprehensive system of QoL assessment in international trials of pancreatic cancer.

The impact of arterialization on prostanoid generation after liver transplantation in the rat.

Arterial reconstruction is not applied in most studies of hepatic transplantation. Differences in some parameters related to the microcirculatory status, depending on whether the graft has been subjected to both arterial and venous or only venous reconstruction have been demonstrated. We have evaluated whether arterialization has an effect on the production of inflammatory event-related mediators such as eicosanoids and oxygen free radicals. For this purpose, we have measured tissue eicosanoid levels, lipid peroxidation, and superoxide dismutase activity in livers subjected to arterial and venous or only venous reconstruction. No changes were observed in lipid peroxidation or superoxide dismutase activity when single and double revascularization were compared. Prostacyclin and thromboxane metabolites showed increased levels after 24-hr preservation when only venous reconstruction was carried out. In contrast, these metabolites remained unaltered when double revascularization was performed. This result suggests that eicosanoid metabolism is altered only when venous reconstruction was employed, and this fact can help explain microcirculatory changes reported in this experimental model of liver transplantation.

Experimental and clinical experience with urine amylase monitoring for early diagnosis of rejection in pancreas transplantation.

Pancreas allograft rejection in dogs with pancreaticocystostomy can be predicted in advance of hyperglycemia by monitoring the urinary amylase (UA) concentration (U/L): In initial experiments, UA values declined to less than 1000 1.3 +/- 0.2 days before hyperglycemia in nonimmunosuppressed dogs, 3.3 +/- 1.0 days in dogs treated with cyclosporine (CsA), and 9.3 +/- 0.7 days in dogs treated with CsA, azathioprine (Aza), and prednisone (triple therapy). Autotransplanted control dogs maintained high urine amylase concentrations indefinitely (mean 125,544 +/- 36,931). In a subsequent experiment, in 19 dogs with bladder-drained pancreas allografts on CsA only for prophylactic immunosuppression, a five-day course of antirejection treatment with Aza (5.0 mg/kg) and antilymphocyte globulin ALG (1 mg/kg) was started in group A (n = 10) when a raise in serum glucose was detected, and in group B (n = 9) when a drop of UA below 1000 was observed. The functional allograft survival rate was 9.2 +/- 0.5 days in group A (treatment started after hyperglycemia) and 29.0 +/- 5.7 days in group B (treatment started after drop in UA) (P = .002). The UA dropped in all dogs before hyperglycemia, at a mean of 2.7 days in group A and 20.8 days in group B. Clinically, 8 patients received a whole cadaver pancreas transplant with urinary drainage of the exocrine secretions. All were followed with UA monitoring. Three recipients lost the grafts for technical reasons. Three recipients lost the grafts for technical reasons. One had a primary non-function and UA was below 1000 U/24 hr; two developed abscesses and the grafts were removed while functioning with high UA values. Five grafts are currently functioning; 3 recipients had no rejection episodes and their UA values ranged from 30,000 to 100,000 U/24 hr during their entire postoperative course. The other two had rejection episodes. In both cases UA decreased to baseline levels 1 and 4 days in advance of the hyperglycemia. After antirejection treatment UA rose again to high values and plasma glucose levels declined. Both patients are currently insulin-independent, with UA values ranging from 10,000 to 200,000 U/24 hr. Both experimentally and clinically UA is an early predictor of pancreas allograft rejection. The institution of early treatment of rejection episodes in dogs, based on UA, significantly improved allograft survival. Urine amylase monitoring in pancreas transplant recipients could lead to an early treatment of rejection and improve graft survival.

Nitric oxide and arachidonate metabolism in ischemia-reperfusion associated with pancreas transplantation.

The role of eicosanoid metabolism and its relationship with nitric oxide production in the ischemia-reperfusion associated with pancreas transplantation in the rat is explored in this study. Twenty-six male Sprague-Dawley rats were randomized into 3 groups, as follows: group 1, control animals not surgically manipulated; group 2, pancreas transplantation, after 12 hr of organ preservation in University of Wisconsin solution; group 3, same as group 2 but with administration of NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) (10 mg/kg) before organ revascularization. The results show posttransplantation increases in edema and in 6-keto-prostaglandin F1 alpha (x1.9), thromboxane B2 (x4), and prostaglandin E2 (x5) levels in pancreatic tissue. Nitric oxide synthase inhibition reversed the increases in edema and eicosanoid production, which suggests that eicosanoid generation in the recipient rat would be mediated, in part, through a nitric oxide-dependent mechanism.

Tissular prostanoid release, phospholipase A2 activity, and lipid peroxidation in pancreas transplantation.

Free radical species have been implicated as important agents in ischemia-reperfusion injury associated to transplantation procedures. This study was carried out to investigate the possible relationship between phospholipase A2 activity (PLA2), lipoperoxidation, and the changes in arachidonic acid metabolism during ischemia reperfusion injury in pancreas transplantation, as well as the effect of a free radical scavenger such as superoxide dismutase on these changes. For this purpose male Lewis rat groups (n = 7) were classified as follows: group I--control; group II--syngenic pancreas transplantation after 15 min preservation in Collins solution at 4 degrees C; group III--syngenic pancreas transplantation after 18 hr preservation in the same conditions; group IV--same as III but with administration of SOD (i.v.) immediately before revascularization in the recipient rat. The results indicate that significant increases in PLA2 activity and lipoperoxide levels occur concomitantly with an increase of thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) in pancreatic tissue after pancreas transplantation. The counteracting effect of a free radical scavenger such as SOD supports the role of oxygen free radicals (OFR) mediating activation of PLA2 and subsequent formation of eicosanoids in pancreas transplantation.

Immunocytochemical study of pancreatic islet revascularization in islet isograft. Effect of hyperglycemia of the recipient and of in vitro culture of islets.

We studied the revascularization process of isogeneic islets grafted into the kidney subcapsular space of streptozotocin-induced diabetic and nondiabetic rats by a double-labeling, indirect immunofluorescence technique using a rabbit antiserum to human factor VIII-related antigen (which identifies endothelial cells) and a guinea pig anti-insulin antiserum (which labels pancreatic beta cells). Freshly isolated islets contained a network of capillary endothelial cells, whereas 1-week-cultured islets at 37 degrees C have completely lost their intra-islet endothelial cells. Overnight cultured islets contained only occasional endothelial cells. When these islets were grafted under the kidney capsule of nondiabetic rats, they rapidly acquired a new endothelial cell lining as demonstrated by the positivity of staining for factor VIII-related antigen at day 5 after implantation. On the other hand, 1-week-cultured islets failed to become fully revascularized until day 7 after transplantation. Streptozotocin-induced diabetic rats grafted with 1000 islets normalized their blood glucose values (< 11 mM/L) 2-4 weeks after implantation, whereas transplantation of 2500-3000 islets resulted in normoglycemia after 4.7 +/- 2 days (mean +/- SD). Nevertheless, hyperglycemia of the recipient did not adversely affect the process of revascularization of islet isografts which initiated at day 3 and was almost completed by day 5 after implantation.

Recurrence of immunological markers for type 1 (insulin-dependent) diabetes mellitus in immunosuppressed patients after pancreas transplantation.

BACKGROUND: Type 1 (insulin dependent) diabetes mellitus (IDDM) is an autoimmune disease in which autoantibodies against islet cells develop concomitantly with or even preceding diagnosis. Because the recurrence of diabetes can be the cause of graft failure in patients with pancreas transplantation, we studied the possible recurrence of IDDM immunomarkers after transplantation. METHODS: The following determinations were performed every 1-2 years after transplantation in 50 immunosuppressed IDDM patients with simultaneous kidney and pancreas transplantation (bladder drainage of exocrine secretion): islet cell antibodies (ICA) by direct immunofluorescence, antibodies against glutamic acid decarboxylase (GADab) by radiobinding assay, and the oral glucose tolerance test. The mean follow-up was 4.1+/-6.3 (range 1 to 9 years). RESULTS: GADab were detected in 11 patients after transplantation, 10 of whom had been positive beforehand. ICA reappearance after transplantation was detected in seven patients (14%). The presence of ICA was related to GADab positivity (P=0.001) and HLA DR3 patients (P=0.04), but not with pancreatitis and rejection episodes, immunosuppression induction therapy, or donor HLA haplotype. During follow-up, an abnormal oral glucose tolerance test was more frequent in ICA-positive patients (P=0.02), with no differences in metabolic control or insulin secretion. CONCLUSION: We conclude that GADab persist and ICA reappear despite immunosuppressive therapy in patients with functioning pancreas transplants. The relevance and the risk that this implies for IDDM development should be determined.

Effect of a platelet-activating factor antagonist and desferrioxamine administration on eicosanoid production in rat pancreas transplantation.

Eicosanoid metabolism and its relationship with platelet-activating factor and oxygen free radical production in rat pancreas transplantation has been studied herein. Male Sprague-Dawley rats were classified in 4 experimental groups (n = 8 each) as follows: group 1, control; group 2, pancreas transplantation, after 12 hr of organ preservation in University of Wisconsin solution; group 3, same as group 2 with desferrioxamine administration before revascularization of the organ in the recipient rat; and group 4, same as group 3 with administration of a platelet-activating factor antagonist (BN-52021). The results show post-transplantation increases in eicosanoid production in pancreatic tissue. The fact that desferrioxamine and BN-52021 administration could reverse increases in thromboxane B2, leukotriene B4, and 12-hydroxyeicosatetraenoic acid but only BN-52021 affected 6-keto-PGF1 alpha levels suggests the existence of a close relationship between platelet-activating factor and oxygen free radical in eicosanoid production in pancreas transplantation and it points to a differential role of metabolites produced by circulatory cells and endothelial cells.

Laparoscopic pancreatic surgery in patients with neuroendocrine tumours: indications and limits.

Laparoscopic pancreatic procedures are still at an evaluation stage with regard to their indications and techniques. Between January 1998 and December 2000, 13 patients with endocrine pancreatic tumours - 11 insulinomas and 2 non-functioning tumours-underwent laparoscopic surgery, laparoscopic ultrasonography being used in all the patients. Enucleation was performed in five patients. The operative time was 2-3 hours. Distal pancreatectomy was performed in six patients with insulinomas, and spleen preservation with intact splenic vessels was feasible in five. Splenectomy was necessary in one patient for technical reasons. Laparoscopic distal pancreatectomy with splenic vessel preservation was performed in two patients with a large (6 and 8 cm) non-functioning tumour. The mean operative time for all the patients undergoing distal pancreatectomy was 4 hours, ranging from 3 to 5 hours. A pancreatic fistula occurred in three patients after tumour enucleation and in two patients after distal pancreatectomy; the mean hospital stay for all patients was 5 days. Enucleation guided by laparoscopic ultrasonography thus allows safe tumour dissection and excision, laparoscopic distal pancreatectomy also being feasible and safe. Splenic salvage with splenic vessel preservation is technically possible. The laparoscopic approach allows a shorter hospital stay and an earlier return to normal activities.

Prevention by whole pancreas transplantation of glomerular basement membrane thickening in alloxan diabetes.

Serial thickness measurements of the glomerular basement membrane were performed over a 24-month period in four groups of inbred male Lewis rats. Group I consisted of normal animals age-matched to the remaining experimental groups. In groups II, III, and IV, diabetes was induced by intravenous alloxan (42 to 44 mg/kg). Group II was subsequently untreated. One week after induction of diabetes, groups III and IV received vascularized isografts of the pancreas and duodenum or duct-ligated pancreas alone, respectively. Animals in all groups were killed monthly and X 11,000 electron photomicrographs prepared of the kidney. The thickness of the glomerular basement membrane was measured by a quantitative morphometric technique. Untreated diabetic animals developed significant thickening of the basement membrane when compared to normal animals and the differences remained significant throughout life. Animals undergoing pancreas transplantation were completely protected from the diabetic changes in the basement membrane and showed no increase in basement membrane thickness when compared to normal animals. Pancreaticoduodenal and duct-ligated isografts offered equal protection against changes in the basement membrane. All groups showed age-related thickening of the basement membrane; this change was accelerated in the untreated diabetic group and normalized in the transplanted rats.

Effect of fusidic acid on pancreatic islet allograft rejection.

We examined in fully mismatched rats, the survival of pancreatic islet allografts in recipients treated with either fusidic acid (FA), an antistaphyllococcal antibiotic that has been shown to possess an immunosuppressive effect in vitro and in vivo, or cyclosporin-A (CsA). Islets were isolated by collagenase digestion, separated from acinar tissue by handpicking under a dissecting microscope and transplanted into the liver by portal vein injection of streptozotocin(STZ)-induced diabetic rats. The results indicated that while a temporary immunosuppression with CsA achieved an indefinite islet allograft survival, FA administered to recipients daily was not able to prevent islet allograft rejection across a major histocompatibility barrier. We conclude that despite the fact that fusidic acid has been claimed to act as an-immunosuppressant drug in vitro with effects similar to those of CsA, unlike CsA, FA given either orally or by s.c. injection was not effective to prolong islet allograft survival in vivo.

Cyclosporine does not inhibit the process of revascularization of pancreatic islet transplantation.

The immunosuppressive drug cyclosporin-A (CsA) has been widely used to prevent pancreatic islet allograft rejection. Because it has been suggested that CsA may inhibit the process of revascularization of transplanted islets, the purpose of the study was to analyze by a double indirect immunofluorescence technique the revascularization process of isolated islets grafted in the liver and in the renal subcapsular space of rats treated with immunosuppressive doses of CsA. Lewis rats were grafted with either Lewis (isografts) or Wistar (allografts) pancreatic islets obtained by collagenase digestion. Rats were killed at different days after implantation and the liver and kidney bearing the grafted islets were snap frozen and immunohistochemically stained with a double immunofluorescence technique using a rabbit antifactor-VIII antiserum (which labels endothelial cells) and a guinea pig antiinsulin antibody. Islets implanted into nonimmunosuppressed hosts completed revascularization by days 3-7 after transplantation, as shown by the detection of endothelial cells within and surrounding the islets. The identical staining pattern of revascularization was observed in nonrejecting allografts as well as in isografts treated with CsA. We conclude that CsA did not inhibit the process of revascularization of rat islets after free transplantation. This finding is relevant for human islet transplantation, where CsA is currently employed to prevent kidney and islet allograft rejection.

Prostanoids and cyclosporin-mediated nephrotoxicity in rats: a critical appraisal.

The involvement of arachidonic acid metabolism in cyclosporin (CsA) nephrotoxicity depending on CsA vehicle has been explored in this study. For this purpose creatinine clearance, urinary excretion and renal levels of eicosanoids were measured in the following rat experimental groups: group I, control; group II, CsA was administered in olive oil by gavage at 15 mg/kg/d for 7 d; group III, same as group II but 30 mg/kg/d; group IV, CsA was administered in fish oil by gavage at 15 mg/kg/d for 7 d; group V, same as group IV but 30 mg/kg/d; group VI, CsA was administered in olive oil at 15 mg/kg/d with prednisolone (1 mg/kg/d). The results indicate that (1) CsA nephrotoxicity and prostanoid alterations seem to be greatly improved when fish results indicate that (1) CsA nephrotoxicity and prostanoid alterations seem to be greatly improved when fish oil substitutes olive oil as a vehicle for CsA administration and (2) a correlation was found between eicosanoids measured and renal function, except in group II in which creatinine clearance remains unmodified but eicosanoids were altered, thus suggesting that other factors play a role in mediating nephrotoxicity due to cyclosporin.