Kiil Park

Exchange donor program in kidney transplantation.

The donor organ shortage has been one of the major barriers to kidney transplantation in Korea, even though there has been a small but steady flow of cadaveric kidney donations for the last decade. To expand the donor pool in kidney transplantation, we have developed the exchange donor program at our institution and in Korea. The donor exchange program was first started for end-stage renal disease patients who had willing but incompatible related donors due to positive lymphocyte cross-match. The kidney transplantations were performed using exchanged kidneys between two families with successful results. Since this success, we have expanded the donor pool by accepting close relatives, spouses, friends of recipients, and willing voluntary donors as candidates for exchange donors with careful donor screening procedures. It helps relieve stress on donor supply. Particularly in those countries where brain death has not been socially or legally accepted, living donors including related, unrelated, and exchange donors should be considered as potential donors for kidney transplantation to relieve the pressure on donor organ shortage.

Ratio of donor kidney weight to recipient bodyweight as an index of graft function

Reduced renal mass or mismatching kidney size are risk factors for chronic allograft nephropathy. We assessed the effect of mismatching donor kidney weight and recipient bodyweight on renal graft function in 82 live donor kidney transplant recipients who did not have acute rejection. We calculated the donor kidney weight to recipient bodyweight ratio, and established the relation between this ratio and renal indices with a mixed model regression. We showed that recipients with a high ratio had better graft function.

Mycophenolic Acid Inhibits Platelet-Derived Growth Factor-Induced Reactive Oxygen Species and Mitogen-Activated Protein Kinase Activation in Rat Vascular Smooth Muscle Cells

Vascular smooth muscle cell (VSMC) proliferation is the major pathologic feature associated with chronic allograft nephropathy, and mycophenolic acid (MPA) inhibits VSMC proliferation. Since the role of inosine monophosphate dehydrogenase (IMPDH)‐dependent de novo guanosine synthesis is limited in VSMCs, we examined the effects of MPA on platelet‐derived growth factor (PDGF)‐induced cellular ROS and mitogen‐actived protein kinases (MAPK) activation in VSMCs. Primary cultured rat VSMCs were stimulated with PDGF‐BB in the presence or absence of MPA. Cell proliferation was assessed by [3H]‐thymidine incorporation, ROS by flow cytometry and MAPK activation by Western blot analysis. PDGF increased cell proliferation, cellular ROS and extracellular‐regulated protein kinase (ERK) 1/2 and p38 MAPK activation by 3.4‐, 1.6‐, 3.3‐ and 3.9‐fold, respectively. MPA at above 1 μM inhibited PDGF‐induced cellular ROS and ERK 1/2 and p38 MAPK activation, as well as proliferation. Structurally different anti‐oxidants and inhibitor of ERK or p38 MAPK blocked PDGF‐induced proliferation. Anti‐oxidants also inhibited ERK 1/2 and p38 MAPK activation. Exogenous guanosine partially recovered the inhibitory effect of MPA on VSMC proliferation. These results suggest that MPA may inhibit PDGF‐induced VSMC proliferation partially through inhibiting cellular ROS, and subsequent ERK 1/2 and p38 MAPK activation in addition to inhibiting IMPDH.

Live donor renal allograft in end-stage renal failure patients from immunoglobulin A nephropathy.

Background. The purpose of this study was to attempt to resolve two important issues, i.e. to determine (1) whether the course of recurrent immunoglobulin A nephropathy (IgAN) is benign, and (2) whether it is advisable to use a related donor. Methods. We evaluated the long-term outcome, in terms of recurrence and graft survival, after live related or unrelated donor renal transplantation, and assessed the validity of the use of related donors in 90 grafts in 89 IgAN patients. Results. Ten-year graft survival for IgAN patients was 66%, compared with 84% for 107 reference recipients who had other kinds of glomerulonephritis (GN), and with 69% in 90 other recipients who had non-GN renal failure (P =0.27). In 43 grafts, 54 event graft biopsies were performed, documenting the presence of mesangial IgA deposits in 19 of those grafts. In eight grafts, lesions were accompanied by chronic rejection (CR). Ten-year cumulative recurrence was 44%. Ten grafts were lost: by CR (n=3) or acute rejection (n=1) in 24 recurrence-free recipients, by CR (n=2) or recurrence (n=2) in 19 recurrent patients, and by patient death (n=2) in 46 patients devoid of graft biopsy. We found no difference in 10-year graft survival between the recurrent and recurrence-free patients (63% vs. 74%, P =0.98), or the proportion of related donors (68% vs. 83%, P =0.25). The presence or matching of HLA B12, B35, or DR4 did not affect the recurrence. Conclusions. Recurrence increased to 44% with longer follow-up, but this did not limit the graft outcome. Recurrence was not affected by the kind of live donor. We conclude that live related or unrelated kidneys should be offered to IgAN patients.

RETROPERITONEAL ENDOSCOPIC LIVE DONOR NEPHRECTOMY: REPORT OF 3 CASES

In a variation of laparoscopic surgery we performed retroperitoneal surgery using endoscopy and a special retractor in 3 cases of live donor nephrectomy. The procedure using retroperitoneal endoscopy offers several advantages compared to conventional live donor nephrectomy. With the development of retractors to obtain operating space and the further development of surgical techniques retroperitoneal endoscopic live donor nephrectomy can be established as an alternative surgical method for harvesting donated kidneys.

Evidence that the ratio of donor kidney weight to recipient body weight, donor age, and episodes of acute rejection correlate independently with live-donor graft function.

Background. We demonstrated that higher donor kidney weight-to-recipient body weight (KW/BW) ratio showed better graft function in acute rejection-free renal recipients. Methods. We investigated the impacts of KW/BW ratios on the graft function including acute rejection and donor’s age in 259 live-donor renal recipients. Renal parameters were measured yearly. Correlations between the variables and each parameter were assessed by mixed regression and analysis of variance. Results. Renal function showed a positive correlation with the KW/BW ratio, but an inverse correlation with the rejection episodes and donor’s age. The regression slope for serum creatinine or creatinine clearance by these covariants was consistent each year. On comparing the lower KW/BW ratios (<3.0) with higher ratios (≥4.5), the higher was associated with better graft function. Increased donor’s age was associated with worse graft function. Conclusions. KW/BW ratio, donor’s age, and the number of acute rejections are independent covariants for graft function.

Exchange living-donor kidney transplantation: merits and limitations.

Background. The shortage of donor organs is one of the major barriers to transplantation worldwide. After the success of the direct exchange donor (swap) program in Korea since 1991, we have developed a swap-around program. However, reports on the long-term outcomes of exchange donor programs are scarce. Methods. From September 1995 to September 2006, we performed 1193 cases of renal transplantation, including 398 cases from living-unrelated donors. The living-unrelated donors included 129 exchange donors and 269 nonexchange donors. We compared the outcomes of the exchange program with that of the nonexchange program, and examined the merits and limitations of the exchange program. Results. The reasons for the exchange program were ABO incompatibility (n=84, 65.1%), human leukocyte antigen mismatching beyond our criteria (n=39, 30.2%), or positive lymphocyte crossmatch (n=6, 4.7%). The overall 10-year graft survival (86.3%) of exchange transplantation was comparable with that of nonexchange (82.3%) or one- haplotype matched living-related (81.2%) transplantation (P=0.2994). In multivariate analysis, exchange versus nonexchange donors did not affect graft survival. The proportion of blood-type O donors was much lower in the exchange group (29.5%) than in the nonexchange group (42.4%; P=0.026). Blood-type O kidneys were preferentially allocated to blood-type O recipients (78.9%) in the exchange group as compared with the nonexchange group (54.4%; P=0.007). Conclusion. We achieved excellent outcomes by using a donor exchange program as an option to reduce the donor organ shortage. However, the exchange donor program has no added benefit for blood-type O recipients.

Clear benefit of mycophenolate mofetil-based triple therapy in reducing the incidence of acute rejection after living donor renal transplantations.

BACKGROUND According to a pooled analysis of three randomized clinical studies concerning the prevention of acute rejection in cadaveric renal transplantation, mycophenolate mofetil (MMF) proved superior to azathioprine or placebo in conjunction with cyclosporine (CsA) and steroids. MMF-treated patients showed reduced incidence and severity of acute rejection, similar graft survival, and better graft function over 12 months. However, the multicenter trials did not include the Asian recipients of living donor kidneys. METHODS To assess the efficacy of MMF as the third component of a triple therapy in addition to CsA-Neoral and steroids in living donor renal transplantation recipients in Asians, a total of 100 recipients were randomized to receive CsA-Neoral and steroids (control group, n=50), or MMF-based triple therapy (1.0 g of MMF twice daily from postoperative day 2, MMF group, n=50). The dosing plan for Neoral and steroids was essentially same between groups. During 12 months of follow-up, we compared the incidence of acute rejection, adverse events such as infections, and 12-month actual graft and patient survival. RESULTS The graft and patient survival at 1 year was excellent in both groups: 96/98% in the control group and 98/100% in the MMF group, respectively. MMF significantly reduced the proportion of patients with at least one episode of acute rejection (34% in the control group vs. 14% in the MMF group), cumulative incidence of acute rejection episodes (46% vs. 16%), and requirement of antilymphocyte antibody (21.7% vs. 12.5%). In the MMF group, viral infection such as herpes zoster or chicken pox was more prevalent than in the control group. CONCLUSIONS Like cadaveric renal transplantation, this open clinical trial showed MMF to be effective in reducing the incidence and severity of acute rejection if used in conjunction with Neoral and steroids after living donor renal transplantation in Asian ethnicity.

Segmental glomerulosclerosis in IgA nephropathy after renal transplantation: relationship with proteinuria and therapeutic response to enalapril

Abstract: Introduction: Although graft dysfunction has been increasingly reported in post‐transplant IgA nephropathy (Tx‐IgAN), intragraft morphological changes have been largely overlooked. We evaluated glomerular changes in Tx‐IgAN to identify the histological features pertaining to significant proteinuria and therapeutic response to enalapril.

Long-Term Results of Kidney Transplantation Between HLA-Identical Siblings

Abstract Long-term data on HLA-identical renal transplants are scarce, and the advantages of using cyclosporine (CsA) over azathioprine (AZA) have yet to be elucidated. In 68 recipients from HLA-identical donors (37 under AZA-steroids and 31 under CsA-steroids), we estimated the graft and patient survival to posttransplant 120 months, and compared the results between patients on different protocols. Episodes of rejection, causes of graft loss or patient death, and long-term complications were also compared retrospectively. The 10-year patient/graft survivals were comparable: 82.7/67.6% for the AZA and 78.4/63.5% for the CsA patients. The incidence of acute rejection during the first year after transplant was also comparable. We lost 25 grafts. The major causes of graft loss were patient death (7/13 in AZA and 5/12 in CsA patients) and chronic rejection (3/13 in AZA and 3/12 in CsA patients). Four grafts were lost due to poor compliance. We lost 12 patients due mostly to cerebrovascular disease and infections. There was no difference in the prevalence of complications between patients. In conclusion, the long-term outcome was excellent in this subgroup of transplant patients. We could not find any advantages of using CsA over AZA in these patients after a long-term follow-up. To achieve better results, continued attention should be paid to the prevention of poor compliance and complications.