allopurinol and Primary-Graft-Dysfunction

To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.. A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31. All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1 (RR = 0.02, 95%CI: 0.01-0.03,. Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.

Topics: Adenosine; Allopurinol; Disaccharides; Electrolytes; Glucose; Glutamates; Glutathione; Graft Survival; Histidine; Humans; Insulin; Liver Transplantation; Mannitol; Odds Ratio; Organ Preservation; Organ Preservation Solutions; Potassium Chloride; Primary Graft Dysfunction; Procaine; Raffinose; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome

Adenine phosphoribosyl transferase (APRT) deficiency is a rare genetic form of kidney stones and/or kidney failure characterized by intratubular precipitation of 2,8 dihydroxyadenine crystals. Early diagnosis and prompt management can completely reverse the kidney injury.. 44 year old Indian male, renal transplant recipient got admitted with acute graft dysfunction. Graft biopsy showed light brown refractile intratubular crystals with surrounding giant cell reaction, consistent with APRT deficiency. Patient improved after receiving allopurinol and hydration.. APRT forms a reversible cause of crystalline nephropathy. High index of suspicion is required for the correct diagnosis as timely diagnosis has therapeutic implications.

Topics: Adenine; Adenine Phosphoribosyltransferase; Adult; Allopurinol; Antimetabolites; Biopsy; Crystallization; Humans; Hydrotherapy; Kidney Transplantation; Male; Metabolism, Inborn Errors; Primary Graft Dysfunction; Urolithiasis

No consensus exists on the optimal heart preservative solution (HPS) for cardiac allograft preservation. The significance of varying degrees of acute ischemic necrosis (AIN) in early transplant biopsy specimens is unknown. We investigated the effects of HPS on early cardiac histopathology by developing a novel grading system of AIN.. A retrospective review of our institutional database of orthotopic heart transplants (OHT) identified hearts preserved with University of Wisconsin (UW) or Celsior solutions. AIN severity was graded on early post-transplant biopsy specimens. Primary stratification was by HPS. Multivariable models examined mortality, AIN grade, primary graft dysfunction (PGD), and right heart failure (RHF).. From 1996 to 2010, 42 of 174 adult OHTs were preserved with UW and 132 with Celsior, from which 431 biopsy specimens were reviewed. UW and Celsior had similar 30-day (p = 0.79) and 1-year mortality (p = 0.92). Celsior was associated with significantly more AIN on the first (p = 0.02) and second (p = 0.04) specimens and persisted on multivariable analysis for the first (odds ratio, 2.93; 95% confidence interval, 1.26-6.83; p = 0.01) and second biopsy specimen (2.08; 0.99-4.34; p = 0.05). When stratified by AIN score, 30-day and 1-year mortality were similar (p > 0.05). Adjusted analysis showed increasing AIN score on the first biopsy was strongly associated with an increased incidence of PGD (1.59; 1.02-2.47; p = 0.04) and RHF (2.45; 1.14-5.27; p = 0.02).. Our grading system provides a simple, reproducible method for determining AIN. UW is associated with less AIN than Celsior solution. Early biopsy ischemia is associated with PGD and RHF. AIN may have prognostic significance and its routine evaluation should be considered.

Topics: Adenosine; Adult; Allopurinol; Biopsy; Disaccharides; Electrolytes; Female; Glutamates; Glutathione; Graft Rejection; Heart Failure; Heart Transplantation; Histidine; Humans; Incidence; Insulin; Male; Mannitol; Middle Aged; Multivariate Analysis; Myocardial Reperfusion Injury; Myocardium; Necrosis; Organ Preservation; Organ Preservation Solutions; Primary Graft Dysfunction; Raffinose; Retrospective Studies; Survival Rate; Transplantation, Homologous

Hepatic ischemia/reperfusion (I/R) injury significantly influences short-term and long-term outcomes after liver transplantation (LTx). The critical step initiating the injury is known to include sinusoidal endothelial cell (SEC) alteration during the cold preservation period. As carbon monoxide (CO) has potent cytoprotective functions on vascular endothelial cells, this study examined if CO treatment of excised liver grafts during cold storage could protect SECs and ameliorate hepatic I/R injury. Rat liver grafts were preserved in University of Wisconsin (UW) solution containing 5% CO (CO-UW solution) for 18 to 24 hours and were transplanted into syngeneic Lewis rats. After 18 hours of cold preservation, SEC damage was evident with propidium iodide (PI) nuclear staining on SECs, and the frequency of PI(+) SECs was significantly lower in grafts stored in CO-UW solution versus those stored in control UW solution. SEC protection with CO was associated with decreased intercellular cell adhesion molecule translocation and less matrix metalloproteinase release during cold preservation. After LTx with 18 hours of cold preservation, serum alanine aminotransferase levels and hepatic necrosis were significantly less in the CO-UW group than in the control UW group. With 24 hours of cold storage, 35% (7/20) survived with control UW solution, whereas the survival with CO-UW solution improved to 80% (8/10). These beneficial effects of CO-UW solution were associated with a significant reduction of neutrophil extravasation, down-regulation of hepatic messenger RNA for tumor necrosis factor alpha and intercellular cell adhesion molecule 1, and less hepatic extracellular signal-regulated kinase activation. Liver grafts from Kupffer cell-depleted donors or pseudogerm-free donors showed less SEC death during cold preservation, and CO-UW solution further reduced SEC death. In conclusion, CO delivery to excised liver grafts during cold preservation efficiently ameliorates SEC damage and hepatic I/R injury.

Topics: Adenosine; Allopurinol; Animals; Carbon Monoxide; Cryopreservation; Cryoprotective Agents; Endothelial Cells; Glutathione; Graft Survival; Hepatitis; Insulin; Kupffer Cells; Liver Transplantation; Male; MAP Kinase Signaling System; Matrix Metalloproteinases; Neutrophils; Organ Preservation; Organ Preservation Solutions; Primary Graft Dysfunction; Raffinose; Rats; Rats, Inbred Lew; Reperfusion Injury

University of Wisconsin solution (UWS) is the gold standard for graft preservation. Celsior solution (CS) is a new solution not as yet widely used in liver grafts. The aim of this study was to compare the liver function of transplanted grafts stored in these 2 preservation solutions. The primary endpoints were the rates of primary nonfunction (PNF) and primary dysfunction (PDF). We performed a prospective and pseudorandomized study that included 196 patients (representing 104 and 92 livers preserved in UWS and CS, respectively) at La Fe University Hospital (Valencia, Spain) between March 2003 and May 2005. PNF and PDF rates, liver function laboratory parameters, postoperative bleeding, vascular and biliary complications, and patient and graft survival at 3 years were compared for the 2 groups. The 2 groups were similar in terms of donor variables, recipient variables, and surgical techniques. The PNF rates were 2.2% and 1.9% in the CS and UWS groups, respectively (P = not significant), and the PDF rates were 15.2% and 15.5% in the CS and UWS groups, respectively (P = not significant). There were no significant differences in the laboratory parameters for the 2 groups, except for alanine aminotransferase levels in month 3, which were lower in the CS group (P = 0.01). No significant differences were observed in terms of complications. Three-year patient and graft survival rates were as follows for years 1, 2, and 3: 83%, 80%, and 76% (patient) and 80%, 77%, and 73% (graft) for the UWS group and 83%, 77%, and 70% (patient) and 81%, 73%, and 67% (graft) for the CS group (P = not significant). In conclusion, this study shows that CS is as effective as UWS in liver preservation.

Topics: Adenosine; Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Biliary Tract Diseases; Disaccharides; Electrolytes; Female; Glutamates; Glutathione; Graft Survival; Histidine; Humans; Insulin; Liver; Liver Function Tests; Liver Transplantation; Male; Mannitol; Middle Aged; Organ Preservation; Organ Preservation Solutions; Pilot Projects; Postoperative Hemorrhage; Primary Graft Dysfunction; Prospective Studies; Raffinose; Time Factors; Transplantation, Homologous; Vascular Diseases; Young Adult