Diana Y. Barhyte

Donor hepatitis C virus status does not adversely affect short-term outcomes in HCV+ recipients in renal transplantation.

BACKGROUND Recipient hepatitis C virus (HCV) seropositivity has been associated with inferior outcomes in renal transplantation (RTx). We sought to determine whether donor HCV+ status influenced the incidence of rejection, liver dysfunction, and graft survival in HCV+ recipients. METHODS We reviewed 44 HCV+ recipients (R+) receiving RTx from HCV+ (D+) and HCV- (D-) donors between February 1991 and September 1996. All patients were followed to the end of the study period (mean=36 months, range=12-60 months). We compared the R+ group with a demographically matched cohort of 44 HCV- recipients (R-). RESULTS Of the 44 R+, 25 (57%) had a total of 48 rejection episodes. Among the 44 R-, 32 (73%) had 58 rejection episodes (P>0.1). Within the R+ group, 28 were D+/R+; of these 14 (50%) had 27 rejection episodes, whereas among the 16 D-/R+, 11 (68%) had 21 rejection episodes (P>0.3). Graft and patient survival was similar in both the groups (86.4% and 91%, respectively). Liver dysfunction was slightly increased in the R+ group (4/44 vs. 0/44, P>0.1), with one death due to liver failure in this group. CONCLUSION Donor HCV+ status had no influence on outcomes in HCV+ recipients after kidney transplantation in the short term. The incidence of rejection, graft loss, and mortality was comparable between the D+/R+ and D-/R+ groups. Furthermore, rejection, graft loss, and death were identical in R+ and R-groups throughout the 5-year study period. We therefore conclude that HCV+ recipients can safely receive kidney transplants without concern about donor HCV status or fear of adverse events from their own HCV+ status.

Successful long-term kidney-pancreas transplants regardless of C-peptide status or race.

Background. We have previously shown that our patient population of 60% minority races has end-stage renal disease primarily as a result of diabetes mellitus and hypertension. It therefore was logical to explore the restoration of normal insulin production and renal function by simultaneous pancreas-kidney (SPK) transplantation, without regard to race. This study represents new analyses integrating race with C-peptide status and reports the outcome of 136 SPK transplantations performed over the last 10 years. Results. Of the 49 African-Americans with diabetes mellitus and end-stage renal disease, 60% were type I and 40% were type II, based on C-peptide levels. In comparison, only 16% of Caucasians were type II. The average age at onset of diabetes mellitus was 15.7 years for type I compared with 20.7 years for type II (P >0.05). The actuarial 10-year survival rates for the 136 SPKs were 91.79% (patient), 85.07% (pancreas), and 83.58% (kidney). The type I and type II survival rates were similar in the two diabetic groups. Conclusions. The data strongly suggest that pretransplant C-peptide status does not influence the outcome of SPK transplantation in patients with renal failure from diabetes mellitus. SPK transplants should be offered to all suitable diabetic patients with renal failure regardless of C-peptide status or race.

A rapid organ recovery program for non-heart-beating donors.

We report a successful method for rapid organ recovery from the non-heart-beating donor, which can open a new resource of organs for transplantation. The RORP is not controversial, is simple in design and execution, and results in kidneys that are viable for transplantation. Special personnel and equipment are needed but are easily incorporated in the overall budget of an OPO or donor hospital. Clearly more research is needed to rebuild ischemically damaged cells ex vivo and to develop new agents/methods to minimize the reperfusion response. When these processes are better understood and managed, the full potential of the NHBD as a donor resource will be fully achieved. We agree with others that the donor shortage could be entirely relieved by routine organ recovery from NHBD trauma victims.

Long-term graft survival after transplantation with kidneys from uncontrolled nonheartbeating donors

BACKGROUND Notwithstanding the widely acknowledged organ-donor shortage coupled with the expanded waiting list for organs, many transplant programs have been reluctant to use kidneys from nonheartbeating donors. Some reasons expressed by those programs include a higher rate of delayed graft function, additional dialysis requirements, more medication usage, and inferior graft survival rates. To refute the common misperceptions, we reviewed our 4-year experience with 31 nonheartbeating donor kidneys recovered from uncontrolled donors (Maashticht classification) at our institution. METHODS After cardiac arrest and declaration of death, all donors underwent intravascular and intraperitoneal cooling. Immediately after bilateral en bloc nephrectomy, kidneys were placed on the Waters MOX pulsatile preservation machine. Preservation parameters were monitored hourly, using pharmacologic agents (Stelazine, dexamethasone, Humulin R) as indicated by those parameters. RESULTS The nonheartbeating donors ranged in age from 15 to 53 years, 83% were males, and 60% of deaths were caused by trauma. For the 21 recovered and transplanted at our center, delayed graft function occurred with 16 kidneys; there was no primary nonfunction. There was no obvious correlation between functional status and donor age. It was noted that the immediate-function kidneys had shorter warm ischemia and total preservation times compared with the delayed graft function group. Nineteen of the 21 grafts continue to function. All patients are surviving. CONCLUSIONS This series suggests that to obtain excellent results with nonheartbeating donor kidneys certain principles should be followed: use machine preservation to resuscitate and evaluate viability, choose immunologically low-risk recipients, avoid immediate exposure to immunophilin antagonists, and perform biopsy frequently for allograft dysfunction to exclude low-grade rejection.

Is laparoscopic donor nephrectomy here to stay

BACKGROUND Open live donor nephrectomy is safe and provides kidneys of excellent quality. The complexity of the laparoscopic donor technique has raised considerable concerns. METHOD Twenty-six laparoscopic live donor nephrectomies were done from October 1997 to October 1998. RESULTS All kidneys had immediate function. All recipients except 1 had serum creatinines less than 2.0 mg at 2 months posttransplantation. Three complications (wound infection, neuroma, reoperation) occurred. There was no mortality. CONCLUSIONS Proper surgical training and patient selection can result in a safe donor operation that provides kidneys of excellent quality.

Ablating the ischemia-reperfusion injury in non-heart-beating donor kidneys.

BACKGROUND The objective of this study was to determine if allopurinol (AL) and/or trifluoperazine (TFP) added to the Belzer machine preservation solution (MPS) improves the function of non-heart-beating donor (NHBD) canine kidneys. METHODS Anesthetized canines underwent bilateral dissection of the renal vessels, obtaining baseline flow. After removing one kidney (heart-beating donor [HBD]), the dog was exsanguinated. After remaining in situ for 120 min (30-min warm ischemia time, 90-min cold ischemia time), the second kidney was removed (NHBD), flushed, biopsied, and weighed. The kidneys were machine-perfused separately for 20 hr, and pressure, flow, and resistance were measured serially. The kidneys were randomly assigned to a perfusate group (G): G1=MPS, G2=MPS+TFP, G3=MPS+AL, and G4=MPS+TFP+AL. Kidneys were implanted separately into a single recipient dog. Flow, resistance, and urine output were measured serially for 4 hr. Blood and urine samples and kidney biopsies were then obtained. All measurements were standardized to 100 g of kidney weight. RESULTS HBD kidneys functioned better than NHBD kidneys in all groups, as expected. Although perfusate G1 was the most effective solution for HBD kidneys, the TFP additive (perfusate G2) more effectively reversed the vasospastic effects of ischemia/reperfusion for NHBD than the MPS solution (G1) with or without other additives. In HBD kidneys, the addition of AL resulted in the best creatinine clearance; however, AL was less effective than MPS alone in NHBD kidneys. TFP+AL together were completely ineffective in preserving renal function, regardless of whether the kidneys were from HBD or NHBD. CONCLUSIONS MPS+TFP more effectively protected renal function against reperfusion injury in the NHBD than MPS alone, AL, or AL+TFP. AL exerts a salutary effect on creatinine clearance in HBD but not in the NHBD. The TFP and AL combination should not be used together with the MPS in machine preservation of kidneys.

Daclizumab induction/tacrolimus sparing: a randomized prospective trial in renal transplantation

Abstract: Tacrolimus inhibits lymphocyte responses by blocking calcium‐dependent signalling pathways important in IL‐2 generation. Daclizumab, a humanized monoclonal antibody, binds with high affinity to the Tac subunit of the IL‐2 receptor complex. We reasoned therefore that the absence of IL‐2R should permit lower doses of tacrolimus and thereby less toxicity. Twenty‐eight patients were randomized and followed for 6 months: Group 1, high dose (HD) tacrolimus (trough 12–17 ng/mL; n = 13); Group 2, low dose (LD) tacrolimus (trough 5–10 ng/mL; n = 15). All patients received daclizumab induction (2 mg/kg) on days 0 and 14, mycophenolate mofetil (2 g/d except for one patient who received 1 g) and rapid prednisone taper. Serious infections were minimal in both groups. Hospitalizations, for various reasons, were HD (n = 12) and LD (n = 6). All patients and grafts survived for the 6‐month study period. There was one rejection episode in a non‐compliant patient at 101 d. LD tacrolimus appears equally effective as HD tacrolimus in preventing rejection episodes and may be associated with fewer adverse events.