Chong-Myung Kang

Preemptive Living-Donor Renal Transplantation: Outcome and Clinical Advantages

INTRODUCTION Kidney transplant recipients have a higher quality of life and consume fewer health care resources compared with patients on dialysis. However, optimal timing of transplantation has been controversial. Recent studies have clearly demonstrated that preemptive renal transplantation is associated with better graft survival, lower complications, and better cost-effective outcomes. We evaluated differential effects on long-term outcomes according to dialysis type/duration versus no dialysis. MATERIALS AND METHODS We retrospectively analyzed 499 cases of first living-donor kidney transplantations performed in our center from January 1990 to January 2007. We compared 3 groups according to graft survival, acute and chronic rejection, postoperative complication, and delayed graft function rates. The mean duration of follow-up was 119.1 +/- 47.2 months. RESULTS Among 499 cases, 81 cases were preemptive renal transplantations with 418 cases hemodialysis [HD], 343 cases, peritoneal dialysis [PD] 75 cases) performed after dialysis. The 1-, 5-, and 10-year graft survival rates were 98.8%, 89.5%, 79.4% among the preemptive renal transplantation group and 92.4%, 78.2%, and 69.2% and 85.3%, 74.5%, and 68.2% (P = .03) in the dialysis groups (HD, PD), respectively. The differential effect of pretransplantation HD or PD was not significant. However, the graft survival rates in the HD group were not significantly higher than the PD group (P = .61). The duration of dialysis was not associated with graft survival. CONCLUSION We suggest that preemptive renal transplantation should be the first choice of treatment for patients with end-stage renal disease.

A 6-Month, Multicenter, Single-Arm Pilot Study to Evaluate the Efficacy and Safety of Generic Tacrolimus (TacroBell) After Primary Renal Transplantation

OBJECTIVE Tacrolimus has been shown to be an important immunosuppressive agent in organ and bone marrow transplantation. Previously, we reported that there were no statistically significant differences between the pharmacokinetic parameters of the oral formulation of generic tacrolimus (TacroBell) and the conventional formulation (Prograf). This study was designed to evaluate the efficacy and safety of oral capsules of TacroBell in de novo renal transplantation. METHODS Ninety-six renal transplant recipients from 9 transplantation centers in South Korea were enrolled between November 2005 and July 2007. De novo renal recipients ranged from 19-65 years old. Ninety-four patients who underwent renal transplantation were administered study drug at least one time in the intent-to-treat (ITT) analysis. This phase 4 clinical trial was a 26-week, open-label, noncomparative, multicenter study. RESULTS An acute rejection episode developed in 10/94 recipients (10.6%, 95% confidence interval, 4.4%-16.9%). There were no patient deaths during the study. The 6-month graft survival rate was 96.8%. CONCLUSION Based on this study, treatment with TacroBell is considered to be efficient and safe after primary renal transplantation.

Clinical Outcomes of Multicenter Domino Kidney Paired Donation

Domino kidney paired donation (KPD) is a method by which an altruistic living nondirected donor (LND) is allocated to a pool of incompatible donor–recipient pairs (DRP) and a series of KPDs is initiated. To evaluate the feasibility and clinical outcomes of multicenter domino KPD, we retrospectively analyzed a cohort of DRPs who underwent domino KPD between February 2001 and July 2007 at one of 16 transplant centers. One hundred seventy‐nine kidney transplants were performed, with 70 domino chains initiated by altruistic LND. There were 45 two‐pair chains, 15 three‐pair chains, 7 four‐pair chains, 2 five‐pair chains and 1 six‐pair chain. A majority of donors were spouses (47.5%) or altruistic LNDs (39.1%). DRPs with a blood type O recipient or an AB donor comprised 45.9% of transplanted DRPs. HLA mismatch improved in transplanted donors compared to intended donors in pairs enrolled to improve HLA mismatch (3.4 ± 0.7 vs. 4.8 ± 1.0, p < 0.001). One‐year and 5‐year graft survival rates were 98.3% and 87.7%, respectively, with a median follow‐up of 46 months. One‐year and 5‐year patient survival rates were 97.2% and 90.8%, respectively. In conclusion, multicenter domino KPD could multiply the benefits of donation from LNDs, with patients and graft survival rates comparable to those seen with conventional KPD.

The Effect of Donor-Recipient Relationship on Long-Term Outcomes of Living Related Donor Renal Transplantation

BACKGROUND Presensitization to human leukocyte antigen (HLA) tends to decrease renal graft survival. During the pregnancy, fetal blood is frequently exposed to the maternal circulation possibly inducing maternal immunization to paternal HLA inherited by the fetus. In this way, pregnancy may occasionally present a hazard to renal graft survival. In this study, we compared retrospectively graft survivals according to living related donor-recipient pairs. MATERIALS AND METHODS From July 1979 to January 2011, 374 patients underwent living related renal transplantation sharing at least one HLA haplotype with their donor. We compared acute rejection and complication rates as well as long-term graft survival according to the donor-recipient paring: child-to-mother, child-to-father, mother-to-child, father-to-child, and one haplotype-matched siblings. All patients received immunosuppressive therapy, consisting of a calcineurin inhibitor, mycophenolate mofetil, or azathioprine and prednisolone. RESULTS Twenty-one cases (5.6%) were child-to-father paring; 28 (7.5%), child-to-mother; 179 (47.9%), one-haplotype-matched siblings; 46 (12.3%), father-to-child; and 100 (26.7%), mother-to-child paring. Child-to-father pairing displayed the best graft survival; child-to-mother (hazard ratio [HR] = 1.709, P = .662) and one-haplotype-matched siblings (HR = 6.589, P = .062) showed no significant difference. Father-to-child pares experienced poorer outcomes than child-to-father pairs (HR = 11.579, P = .017) and mother-to-child, the poorest graft survival (HR 17.188, P = .005). CONCLUSION Pregnancy continues to be a significant source of presensitization in the course of gestation and after parturition. Graft failure can result from an anamnestic reaction subsequent to intrauterine exposure of the mother to HLA of a fetus due to sensitization.

Mizoribine Versus Mycophenolate Mofetil in Combination Therapy With Tacrolimus for De Novo Kidney Transplantation: Evaluation of Efficacy and Safety

The present study compared the efficacy and safety of mizoribine (MZR) with mycophenolate mofetil (MMF) in kidney transplantation. This multicenter, randomized clinical trial. Employed doses of study drug tailored to the immunosuppressive need. The primary efficacy outcome was the incidence of biopsy-proven acute rejection episodes (BPAR). The safety of the study drug was assessed using the incidences of adverse events, drug discontinuations, and abnormal laboratory results. The 7 (6.4%) BPARs above grade II were observed in the MZR group noninferior to the 2 (1.8%) in the MMF group (95% confidence interval, -0.007-0.097 > noninferiority limit [-0.2]). BPAR was significantly decreased in the MZR group after the dose change (17/41 [41.4%] vs 8/69 [11.6%]; P < .0001) and the incidence of BPAR was similar between the MZR and MMF groups after the dose change (P = .592). The uric acid level was significantly elevated in the MZR group (P = .002). In conclusion, the efficacy and safety of MZR were similar and statistically noninferior to MMF in combination therapy with tacrolimus.

Association between a change in donor kidney function and long-term allograft outcomes in kidney transplant recipients.

Reserve capacity of donated kidney may be an important determinant of allograft survival in kidney transplantation (KT). Here, we investigate change in estimated glomerular filtration rate of donor kidney (ΔeGFR(Donor)) over 30 days after KT as a predictor of the allograft function. A total of 222 recipients were divided into two groups according to ΔeGFR(Donor) as follows: Group I (n = 110), ΔeGFR(Donor)  ≥ -25%; Group II (n = 112), ΔeGFR(Donor)  < -25%. Three years after KT, Group I had a higher eGFR(Recipient) than Group II (55 ± 21 vs. 47 ± 22 mL/min/1.73 m2, P < 0.05). However, no differences in eGFR(Recipient) were detected between the two groups after 10 years. Linear regression analysis showed that ΔeGFR(Donor) was significantly associated with the eGFR(Recipient) at 3 years post-transplantation, but not at 10 years post-transplantation. In Kaplan-Meier analysis, Group I had a greater dialysis-free survival rate than Group II at the 10-year follow-up (84% vs. 76%, P < 0.05). However, no difference in overall survival rate between groups was detected. In the multivariate-adjusted Cox proportional-hazard model, ΔeGFR(Donor) was independently associated with future allograft loss (hazard ratio 0.973; 95% confidence interval 0.949-0.999). These results suggest that larger recovery of donor kidney function after KT donation is associated with better short/intermediate-term allograft outcomes. Follow-up assessment of donor kidney function may be useful to monitor KT recipients at risk for allograft loss.

The Rate of Decline of Glomerular Filtration Rate Is a Predictor of Long-term Graft Outcome After Kidney Transplantation

BACKGROUND To improve the long-term outcome of kidney transplantation (KT), it is important to identify and take active steps to reduce the number or severity of novel risk factors. We investigated whether changes in estimated glomerular filtration rate over the first year after KT (ΔeGFR12-3) was associated with long-term renal allograft function and survival. METHODS Four hundred twenty-eight allograft recipients transplanted between 1990 and 2001 underwent ΔeGFR12-3 calculation using the equation: ΔeGFR12-3 = ([eGFR at 12 months post-KT - eGFR at 3 months post-KT]/[eGFR at 3 months post-KT]) × 100%. Recipients were divided into 3 groups according to their ΔeGFR12-3: group I (n = 150), ΔeGFR12-3 ≥ 10%; group II (n = 151), 10 > ΔeGFR12-3 ≥ -10%; and group III (n = 127), ΔeGFR12-3 < -10%. Multiple linear regression analysis was used to adjust for confounding variables that may affect long-term renal allograft function, and Kaplan-Meier analysis, to compare allograft survival. RESULTS At a mean follow-up of 120 ± 58 months, we observed 112 renal allograft losses. The ΔeGFR over 10 years post-KT (ΔeGFR120-3) was significantly associated with the serum uric acid levels at 3 months post-transplantation and ΔeGFR12-3. Group III showed poor renal allograft survival; group I, 194 ± 8 months; group II, 197 ± 7 month and; group III, 163 ± 4 months; (log-rank test, P < .05). A Cox proportional hazard model revealed ΔeGFR12-3 to be independently associated with future renal allograft loss (hazard ratio, 0.981; 95% confidence interval, 0.974-0.992). CONCLUSION Our results suggested that ΔeGFR12-3 may be an independent predictor of kidney allograft survival. Routine application of eGFR is strongly recommended to identify patients at risk for chronic allograft dysfunction.

The utilization and advantages of an exchange donor program in living donor renal transplantation: a single-center experience.

INTRODUCTION The availability of donors is a major limiting factor in living donor renal transplantation. Approximately one third of patients with end-stage renal disease have willing potential living donors who are blood type or cross-match incompatible. The living donor kidney exchange has become an efficient solution for recipients in this situation. We analyzed the outcome and advantages of an exchange donor program compared with ABO-incompatible transplantation and desensitized protocol transplantation for highly sensitized patients. MATERIALS AND METHODS We retrospectively reviewed the medical records of 152 exchange donor cases from 1991 to 2010. We analyzed the risk factors, outcomes, matching factors, complication rates, and acute rejection rates of this program compared with other alternative strategies. RESULTS In our center, 22% of total living donor kidney transplantations were performed through an exchange program and an expanded donor pool. The graft survival, complication, and acute rejection rates were not significantly different compared with the alternatives. The severe complication rates were lower than with the alternatives and the immunosuppressant protocol and preoperative preparation were simpler. Blood type O recipients who registered in the exchange program showed no significant differences from the living related groups (P = .45), which were similar to the proportions for other ABO types. Upon multivariate analysis, an acute rejection episode and use of mycophenolate mofetil (MMF) were significant factors associated with graft survival (P = .015 and P = .007; odds ratio [OR] 5.968 and 7.324; 95% confidence interval [CI] .003-.533 and .098-.690). CONCLUSION Although exchange donor programs are not the sole solution, they show several advantages, such as the prescription of standard immunosuppression, simple preoperative preparation, low cost, and modest rates of severe complications compared with ABO-incompatible transplantation or desensitized protocols.

The Role of the Altruistic Unbalanced Chain in Exchange Living Donor Renal Transplantation: Single-Center Experience

BACKGROUND The exchange donor program in renal transplantation is an efficient solution for recipients with a blood type or crossmatch-incompatible donor. However, this program has some difficulties to define unacceptable human leukocyte antigen matches, deteriorating clinical potential recipient condition, and withdrawal of donor consent. We analyzed the outcomes of exchange donor renal transplantation through the altruistic unbalanced chain. METHODS Among 152 cases of exchange donor renal transplantation from 1991 to 2010 in our hospital, we performed 58 procedures through altruistic unbalanced chains. We compared their outcomes with the direct and balanced chain group. We analyzed retrospectively whether this program expanded the donor pool, seeking better immunologic, size, and age matching. RESULTS The graft survival and acute rejection rates did not differ significantly in the two groups. Of 152 cases, 58 (38.2%) renal transplantations were performed through an unbalanced chain. Seventeen waiting list recipients were transplanted through an altruistic unbalanced chain. In blood type O recipients (n = 32), the causes of registration in the exchange program were ABO incompatibility (93.3%), and positive crossmatch (6.7%). Nine altruistic blood type O donors and 9 (28.1%) type O recipients underwent transplantations through this chain. CONCLUSIONS We suggest the altruistic unbalanced chain may expand the donor pool with advantages for difficult-to-match pairs. The disadvantages of type O recipients may be overcome through the use of an unbalanced chain. The altruistic unbalanced exchange transplantation program can help easy-to-match subjects, shortening the waiting periods.