Indian data from South India and Gujarat show a lower patient and graft survival as compared to the Western literature (limited experience could be a factor).
ATG has additional effects of preventing the L flooding of the donor kidney if given Intraop, endothelial protection and effects on rolling and adhesion of lymphocytes. Cochrane review also showed similar results, in which there was a reduction in AR only. A RCT (2006)on 278 (high imm. risk) DDKT had a lower incidence of acute rejection but similar incidences of graft loss, DGF and death with ATG induction compared to basiliximab. ATG group also had higher risk of infection.
OPTN data published in 2007 showed that Campath had higher incidence of AR at 6 months and 1 yr postTx but similar graft loss. Rapid and profound depletion of Lymphocyte counts and slow repopulation results in near tolerance specially marked with Campath. Significant proportion of patients in INTAC were DDKT in all the three groups.
NDT study is a metanalysis of 34 studies from1988 through2007.
Even though there are conditions like acute arterial thrombosis, acute CNI toxicity, accelerated or AR, post renal cause etc, the mc cause of DGF is ischemic ATN.
CCB (DHPs)-RCT multicentric on isradipinefialed to show results.
When a diagnosis of DGF is made, it is taken for granted that all the other issues are investigated and resolved like hypovolemia, acute pyelonephritis, vascular causes etc. Recovery usually starts at 7-10 days post Tx but can be delayed by weeks.
Recipient issues in Surgery DDKT are generally conducted at a short notice. Immediate pretransplant dialysis should be avoided to minimize DGF. If HD is necessary, UF should be minimal. Some differences in surgical techniques (Carrel aortic patch, IVC extensions, dual kidney transplantation).
Induction Immunosuppression. ATG is traditionally used in patients at high risk for acute rejection. ATG also theoretically benefits recovery from DGF due to delayed start of CNIs.
Induction Immunosuppression.Anti CD52 antibody (Alemtuzumab): Off label use. “prope” (almost) tolerance enabling lowering the CNI dose or early steroid withdrawal. The INTAC study showed lesser AR compared to IL2Ra in low risk(n=335) and similar results to ATG in high-risk (n=139) patients at the end of 3 yrs in an early steroid withdrawal protocol (but ECD, DCD, prolonged CIT and cross match positive were excluded). Hanaway et al. N Engl J Med 2011;364:1909-19.
High Risk factors for acute rejection (KDIGO): Number of HLA mismatches. Younger recipient age. Older donor age. Blacks. PRA>0% Presence of DSA. ABO incompatibility. Cold ischemia time >24 hoursIn these settings the KDIGO guidelines favor the use of lymphocyte depleting agents rather than an IL2Ra
Other immunosuppresive protocols in DDKT Steroid withdrawal protocols has been found to be successful in DDKT even in those with ECD.Data from Cornell Medical center, NY Transplantation 2012;94
Data from Cornell Medical center, NY Transplantation 2012;94
Data from the OPTN/UNOS showed that rATG based induction perform better than IL2Ra and Alemtuzumab induction in a Tac/MMF/Early CSWD regimen. This could be due to the favorable effects of rATG induction in high-immune risk patients. Sureshkumar et al. Transplantation2012;93: 799–805
Delayed Graft Function Defined as: “failure of the kidney allograft to function immediately post transplant with the need of more than dialysis session within one week.”Incidence of DGF is variable: Living Donors Tx--------------3% Standard Criteria DDKT-----21% Expanded criteria DDKT----29% USRDS Data
It can be compounded by acute rejection and CAN. DGF translates to a 40% reduction in long term graft survival. Patients with both DGF and acute rejection had a 5-year survival rate of 34%. Transplantation 1997; 63: 968–974. Patients with DGF had a 49% pooled incidence of acute rejection compared to 35% incidence in non-DGF patients. Nephrol Dial Transplant 2009; 24: 1039–1047.
Causes of ischemia in thedeceased donor kidneys.1. Preharvest donor state 4. Transplantation of recipient Prolonged second warm2. Organ procurement ischemia time surgery Trauma to renal vessels Hypovolemia/hypotension3. Organ transport and storage 5. Postoperative period Cyclosporine/tacrolimus Acute heart failure (MI) Hemodialysis
Strategies to prevent DGF Ischemic preconditioning. Vasodilatory agents (endothelin receptor antagonists, CCB and adenosine A1 receptor antagonists. Anti-inflammatory agents. Induction immunosuppression (suppression of leucocyte-rich vascular congestion & endothelial injury).
Post-transplant dialytic therapy Best is to avoid dialysis. Minimal anticoagulation. Avoidance of hemodynamic instability. Peritoneal dialysis is best avoided in the 1st week due to risks of peritonitis and spillage over the wound site. PD can be safely started in extraperitoneal transplants with small volumes and gradually increased.