A. Kahl

Perioperative factors influencing patient outcome after liver transplantation

Abstract We have previously shown that the development of multiple organ dysfunction syndrome (MODS) after liver transplantation significantly reduced patient survival. Therefore, the question arises of which are the most prominent perioperative donor and recipient factors leading to MODS after transplantation. In total, 634 patients with 700 liver transplants were analyzed. Donor factors included age, increase in transaminases, sex mismatch, requirement for catecholamines, intensive care time, histology, and macroscopic graft appearence. Recipient factors included Child classification, preoperative gastrointestinal (GI) bleeding, mechanical ventilation, hemodialysis, and requirement for catecholamines. MODS was defined by more than two severe organ dysfunctions. The cumulative 2 to 9‐year patient survival was 90.9 % in patients developing less than 3 severe organ dysfunctions following transplantation. Survival decreased to 60.3 % in patients with MODS. Neither any of the donor factors nor the duration of cold ischemia (CIT) was associated with an increase in MODS or decrease in survival. On the other hand, duration of warm ischemia, amount of blood loss, requirement for red packed blood cells, and reoperation had an influence on the development of MODS (40%‐56%) and decreased patient survival to 58%‐69%. Preoperative therapy with catecholamines, GI bleeding, mechanical ventilation, and hemodialysis were associated with the development of MODS in 54 %‐88 %. Patient survival following MODS decreased to 50%‐74%. Initial graft function had a slight influence on the development of MODS, but no influence on the long‐term patient survival. In conclusion, patient survival was significantly influenced by the development of postoperative MODS. The most prominent factors in this were recipient and intraoperative ones. No major influence was observed for donor factors, CIT, and initial graft function. Prevention of MODS will further improve the outcome after liver transplantation.

Die kombinierte Leber- und Nierentransplantation: Indikationen und Langzeitverlauf

Abstract.Introduction: In patients suffering from chronic liver and kidney disease combined liver-kidney transplantation is the only therapeutic option. However, in these patients, it is mandatory to distinguish between chronic and acute renal failure prior to transplantation, because acute renal failure may recover after successful liver transplantation. In this study we investigated the indications and results of this combined procedure. Patients and Methods: We report on 27 patients who underwent liver and kidney transplantation. The underlying diseases were viral hepatitis (n = 12), polycystic liver and kidney disease (n = 9), primary hyperoxaluria (n = 4), and cryptogenic cirrhosis (n = 2) with end-stage renal disease due to glomerulonephritis, diabetic nephropathy or renal failure caused by nephrotoxicity of immunosuppressive therapy after liver transplantation. Nine patients had lymphocytotoxic antibodies and 5/27 patients had a positive crossmatch pretransplant. Results: One patient died due to bleeding complications, two patients lost the kidney graft due to initial non-function or technical problems. The incidence of acute and steroid-resistant rejections was 60 % and 20 % in patients with a positive cross-match compared to 32 % and 14 % in negative cross-match transplants. Only two patients experienced a rejection episode of the kidney (3.7 %). No hyperacute rejection of the kidney graft occurred. Long-term patient and graft survival was not impaired in the presence of a positive cross-match. The 1- and 5-year survival rates of patients who underwent combined transplantation was 97 % and 93 % versus 91 % and 83 % in patients with liver transplantation alone. Conclusion: Combined liver-kidney transplantation is a safe treatment for endstage liver and kidney disease even in the face of a positive cross-match.Zusammenfassung.Einleitung: Bei Patienten mit einer terminalen Leber- und Nierenerkrankung ist die kombinierte Transplantation dieser Organe die einzig mögliche Therapie. Hierbei ist eine Differenzierung zwischen chronischer und akuter Niereninsuffizienz wichtig, denn akute Nierenversagen sind nach erfolgreicher Lebertransplantation häufig reversibel. In dieser Studie untersuchten wir die Indikationen und Ergebnisse dieses Verfahrens. Patienten und Methoden: Wir berichten retrospektiv über 27 kombinierte Leber- und Nierentransplantationen. Die zugrundeliegenden Erkrankungen waren Virushepatitiden (n = 12), polycystische Leber- und Nierenerkrankungen (n = 9), primäre Hyperoxalurie (n = 4) und kryptogene Lebercirrhose (n = 2) mit terminaler Niereninsuffizienz bei Glomerulonephritis, diabetischer Nephropathie oder chronischer Cyclosporintoxizität nach Lebertransplantation und Transplantatinsuffizienz. Neun Patienten hatten vor Transplantation positive lymphocytotoxische Antikörper und 5 Patienten wurden bei einem positiven Crossmatch transplantiert. Ergebnisse: Ein Patient verstarb an rezidivierenden intraabdominellen Blutungen, 2 Patienten verloren das Nierentransplantat früh-postoperativ aufgrund einer initialen Nichtfunktion und technischer Probleme. Keiner der Patienten mit einem positiven Crossmatch oder lymphocytotoxischen Antikörpern entwickelte eine hyperakute Abstoßung des Nierentransplantats. Die Incidenz akuter und steroidresistenter Abstoßungen des Lebertransplantats war 60 % und 20 % bei Patienten mit einem positiven und 32 % und 14 % bei Patienten mit einem negativen Crossmatch. Nur 2 Patienten hatten eine akute Rejektion des Nierentransplantats (3,7 %). Das Langzeitpatienten- und Transplantatüberleben war bei Patienten mit einem positiven Crossmatch nicht beeinträchtigt. Das aktuelle 1- und 5-Jahresüberleben der kombiniert transplantierten Patienten betrug 97 % und 93 % verglichen mit 91 % und 83 % bei nur lebertransplantierten Patienten. Schlussfolgerungen: Die kombinierte Leber- und Nierentransplantation ist ein sicheres Verfahren in der Therapie terminaler Leber- und Niereninsuffizienzen. Ein positives Crossmatch ist keine Kontraindikation für das kombinierte Vorgehen.

Clinical use of the euglycemic hyperinsulinemic clamp for diagnosis of tacrolimus-induced insulin resistance after combined pancreas–kidney transplantation

INSULIN resistance and hyperinsulinism after pancreas transplantation are well known consequences due to immunosuppressive therapy and systemic insulin delivery. Impaired glycemic control may develop. The differentiation from pancreas rejection may be difficult; pancreas biopsy is still a diagnostic tool not widely used. Glucose tolerance tests provide information on the secretory function of the b cell. Fasting insulin levels are often variable and interpretation can be difficult. To assess insulin resistance in recipients of a pancreas–kidney transplant we employ the euglycemic hyperinsulinemic clamp (EHC) as developed by De Fronzo in 1979. The following case report illustrates the use of EHC to investigate the impact of immunosuppressant drugs in a patient with progressively deteriorating glycemic control within the first 6 months after transplantation.