Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Once a rarely used subset of medical treatments, protein therapeutics have increased dramatically in number and frequency of use since the introduction of the first recombinant protein therapeutic--human insulin--25 years ago. Protein therapeutics already have a significant role in almost every field of medicine, but this role is still only in its infancy. This article overviews some of the key characteristics of protein therapeutics, summarizes the more than 130 protein therapeutics used currently and suggests a new classification of these proteins according to their pharmacological action.

Protein therapeutics: a summary and pharmacological classification

Background Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens. Methods We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft–Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival. Results The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than i...

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Reduced exposure to calcineurin inhibitors in renal transplantation.

Skin cancers are the most common tumors in patients who have received organ transplants. This review discusses the epidemiology, pathogenesis, and management of squamous-cell and basal-cell carcinomas, cancers of the anogenital region, Kaposi's sarcoma, melanoma, neuroendocrine skin carcinoma, and cutaneous manifestations of lymphoma in transplant recipients.

Skin cancers after organ transplantation.

Suppression of allograft rejection is central to successful organ transplantation; thus, immunosuppressive agents are crucial for successful allograft function. Immunosuppressive drugs are used for induction (intense immunosuppression in the initial days after transplantation), maintenance, and reversal of established rejection. This review considers the use of immunosuppressive drugs in organ transplantation, focusing on renal transplantation.

https://www.nejm.org/doi/pdf/10.1056/NEJMra033540

Immunosuppressive Drugs for Kidney Transplantation

The influence of donor age on the short- and long-term outcome of cadaveric kidney transplantation was analyzed at our institution. During a 6-year period, 34 and 806 patients underwent kidney transplantation from cadaver donors over or less than age 60, respectively. Graft and patient survivals were compared throughout follow-up and herewith reported. In addition, main medical and surgical complications among recipients of elderly cadaver donors are detailed.

Renal transplantation from cadaver donors over 60 years old.

INTRODUCTION The objective of this study was to evaluate the results and surgical complications of total pancreas transplantation with enteric exocrine drainage since the beginning of our experience with this type of transplantation. PATIENTS AND METHODS From November 1999 to December 2002, 62 total pancreas transplantations were performed, consisting of 51 combined kidney-pancreas transplantations, 10 after renal transplantation and 1 pancreas-liver transplantation. Kidneys and pancreases were washed and stored in either Belzer solution or Celsior solution. Transplantation was performed via a midline transperitoneal incision with venous anastomosis at the root of the inferior vena cava (54 cases) or, more recently, in the superior mesenteric vein (8 cases). The arterial anastomosis was then performed in the right common iliac artery. Exocrine drainage was performed by side-to-side anastomosis between the donor duodenum and the recipient jejunum. The kidney was transplanted onto the left external iliac vessels and was extraperitonealised. RESULTS The mean age of the recipients and donors was 41 +/- 9 years and 33 +/- 11 years, respectively. The mean cold ischaemia time was 14 +/- 5 hours. Four pancreases were lost due to venous thrombosis, 1 due to severe pancreatitis with haemodynamic collapse and venous thrombosis and another due to total necrosis of the duodenum. Seventeen patients (27%) were reoperated, including 10 during the first postoperative month and 7 during the first year. No cases of fistula of the gastrointestinal anastomosis were observed. All patients with a functional graft no longer required exogenous insulin. The actuarial patient and graft three-year survival was 96% and 86% respectively. CONCLUSION Despite their high frequency, surgical complications did not have any harmful effects on either control of diabetes or graft and patient survival.

Results and surgical complications of pancreas transplantation with enteric exocrine drainage

Pancreatic static cold storage (SCS) is the gold-standard method for pancreas preservation. Our main objective was to evaluate feasibility of hypothermic perfusion (HP) of nonhuman primates' pancreases for potential organ transplantation. Seven baboon pancreases were tested. Animals were included in a study approved by the French Research Ministry of Health. Two groups were compared: the control group (n = 2) was preserved using conventional SCS for 24-h and the perfusion group (n = 5) used HP for 24-h, with three different perfusion pressures (PP): 15 (n = 3), 20 (n = 1), and 25 mm Hg (n = 1). In the control group, focal congestion of islets was observed after 6-h. At 24-h, ischemic necrosis and multifocal congestion also occurred. In the HP group, at 15 mm Hg PP, multifocal congestion of islets was present at 24-h. At 20 mm Hg PP, no ischemic necrosis was found after 6-h. At 12-h and 24-h, focal congestion of islets was seen. At 25 mm Hg PP, focal congestion of islets appeared after 12-h. Immunostaining for insulin, glucagon, and somatostatin was normal and similar in controls and perfused pancreas transplants even after 24-h. Apoptosis index represented by cleaved caspase 3 activity, was less than 1% in perfusion and control groups, even after 24-h. HP of nonhuman primate pancreas is feasible and not deleterious as far as 24-h compared to SCS. SCS for more than 12-h was harmful for the transplants. Systolic perfusion pressure between 15-20 mm Hg did not cause any pathological injury of the tested organs.

Ex situ hypothermic perfusion of nonhuman primate pancreas: A feasibility study.

Objectifs: Une analyse economique des consequences cliniques de la strategie immunosuppressive comportant du mycophenolate mofetil chez les nouveaux transplantes renaux a ete entreprise, en considerant le point de vue de l'Assurance-Maladie. Methodes: L'analyse est fondee sur les resultats de 3 etudes cliniques controlees, randomisees, en double insu comparant mycophenolate mofetil au placebo ou a l'azathioprine et porte sur 1003 des 1493 patients inclus dans les essais. La consommation des soins medicaux associees a chaque evenement a ete determinee par interrogation de 7 experts francais dans le domaine de la transplantation renale representant six services hospitaliers. Les couts medicaux directs cumules sur une periode de six mois apres la transplantation pour les strategies etudiees ont ete compares. Resultats: Ces etudes ont mis en evidence une difference sur l'incidence du rejet aigu et des echecs de traitement quelle qu'en soit la raison. S'agissant d'evenements generant des consommations de ressources, l'objectif de l'analyse economique est d'evaluer l'importance des couts evites par la strategie comportant du mycophenolate mofetil par rapport aux strategies actuelles. Les couts associes a la prise en charge des infections opportunistes ont egalement ete consideres. Les trois essais ont montre que l'introduction de mycophenolate mofetil dans le protocole d'immunosuppression generait une economie comprise entre 19 et 38 p. 100 par rapport aux strategies actuelles pendant les 6 mois suivant la greffe, en raison d'une reduction importante de l'incidence des rejets aigues, des nephrectomies et des jours de dialyse consecutive a la perte de greffon. L'analyse de sensibilite effectuee sur les facteurs de couts les plus importants, a savoir le prix d'une journee d'hospitalisation et la duree de la periode d'hospitalisation pour greffe ont confirme la robustesse des resultats. Conclusion: L'utilisation du mycophenolate mofetil dans le traitement immunosuppresseur apres transplantation renale permet une reduction des couts directs pendant les six mois suivant la greffe.

Economic contribution of mofetil mycofenolate as preventive immunosuppressive treatment after renal transplantation from cadaver

Antiblast globulins (GAB) were prepared by immunization of rabbits with activated T lymphocytes (AT) derived from a rejected kidney allograft. AT consisted of a CD4+ (CD3+, CD2+ TCR alpha+ beta+) clone cytotoxic for HLA DR8-positive targets. The immunizing cells were adapted to industrial growth conditions by repetitive stimulations with an EBV-transformed line from the kidney donor and recombinant IL-2. In the pilot study, GAB (1.0-1.5 mg/kg/day) was given in 12-hr infusions, in association with prednisone (Pred) 1 mg/kg/day and azathioprine (Aza) 2 mg/kg/day, as prophylactic treatment of rejection in 12 kidney-transplanted patients during the first 2 weeks postgrafting. GAB dosage was further adapted according to the level of circulating E-rosette-forming T cells (ERFT). Cyclosporine A (8 mg/kg/day) was given at day 14 as a monotherapy after Pred and Aza were progressively tapered. No patient died, but one kidney was lost from surgical complication. No rejection occurred under GAB treatment; 41% of patients had at least one episode in the first 3 months and 16% from 3 to 9 months. GAB side effects were minor (skin rash: 2, low grade fever: 4) except for one acute serum sickness. Platelet and white blood cell counts were unchanged, but there was a significant decrease in hemoglobin during the 2 weeks of GAB infusions. Few infectious episodes occurred (3 bacterial, 2 viral). GAB monitoring showed a dramatic drop in T11+, T3+, T4+, and T8+ circulating T cells (less than 10% of normal values between days 3 and 14), whereas EFRT cells had a delayed and somewhat lower decrease (less than 10% after day 6 only). Consequently, mean GAB doses had to be raised to 1.3 mg/kg/day at day 4 and 1.6 at days 8 and 14. This pilot study suggests that this new bioreagent should be of major interest in the prophylaxis and treatment of rejection in allograft recipients. A controlled study is in progress.

Polyclonal rabbit gamma globulins against a human cytotoxic CD4 T cell clone. II: Use in prevention of rejection in kidney transplantation: a pilot study

Diego Cantarovich

Papers

Renal transplantation from cadaver donors over 60 years old.

Results and surgical complications of pancreas transplantation with enteric exocrine drainage

Ex situ hypothermic perfusion of nonhuman primate pancreas: A feasibility study.

Economic contribution of mofetil mycofenolate as preventive immunosuppressive treatment after renal transplantation from cadaver

Polyclonal rabbit gamma globulins against a human cytotoxic CD4 T cell clone. II: Use in prevention of rejection in kidney transplantation: a pilot study