Short-Term Outcomes of ABO-Incompatible Living Donor Kidney Transplantation With Uniform Protocol: Significance of Baseline Anti-ABO Titer.

Antibody-mediated rejection (AMR) is one of the major causes of poor outcomes in ABO-incompatible kidney transplantation (ABOi KT). Studies investigating AMR risk factors found that anti-ABO titer is a major issue. However, the significance of antibody titer has been debated. This retrospective study analyzed AMR risk factors in 59 patients who underwent ABOi KT between August 2010 and January 2015. We also analyzed AMR risk factors in recipients with high anti-ABO baseline titers (≥1:64 on dithiothreitol at 37°C phase or ≥1:256 on antihuman globulin phase). The 2-year patient survival rate was 95.8%, and the 2-year graft survival rate was 94.9%. Nine patients (15.3%) experienced clinical (6 of 59 [10.2%]) or subclinical (3 of 59 [5.1%]) AMR. One patient experienced graft loss from hyperacute rejection. AMR risk factor analysis revealed that baseline antibody titer was associated with incidence of AMR. In patients with high baseline titers, low doses of rituximab (200-mg single-dose), an antibody against CD20, was predictive for AMR. Six patients who received pretransplant intravenous immunoglobulin did not experience AMR even when they had high baseline antibody titers. Our results indicate that a high baseline antibody titer affected the incidence of AMR. ABOi KT candidates with high baseline titers need to undergo an intensified preconditioning protocol, including high-dose rituximab (375 mg/m(2)) and intravenous immunoglobulin.

Comparison of cadaveric kidney transplantation from in-center and external center donors.

INTRODUCTION: Renal transplantation is the best treatment modality for end-stage renal disease. We investigated the effects of donor source on renal allograft and patient survival in deceased donor transplants. METHODS: We analyzed retrospectively 190 cadaver kidney transplants performed in our center from January 2000 to December 2009. Of these, 136 kidneys were harvested in our transplantation center and 54 were from external donors. Primary outcome of graft survival was assessed with the Kaplan-Meier method and the significance of possible variables was determined with the Cox proportional hazard model. RESULTS: There was no difference between groups in the age of donor and recipient, recipient body mass index, duration of dialysis, or panel reactive antibody >30%. Twenty recipients lost their grafts (14 from external donors and 6 from internal donors). Graft survival at 1, 3, and 5 years was 99.2%, 97.3%, and 95.5% for in-center donors and 98.1%, 88.9%, and 86.2% for external donor transplants (P = .01). There was no difference in patient survival rates between the groups. Acute rejection episodes (hazard ratio [HR], 13.2; P < .001) and external hospital donor (HR, 9.3; P = .008) were independent factors associated with failure. Higher age of recipient was associated with increased patient death rate (HR, 1.2; P = .02). CONCLUSION: Graft survival of cadaveric transplants from in-center donors was better than that of transplants from external center donors. Acute rejection episodes and location of harvest were significant factors for graft survival. Further study is needed to evaluate the effects of center-level factors on allograft outcomes.

Presence of vesicoureteral reflux in the graft kidney does not adversely affect long-term graft outcome in kidney transplant recipients.

INTRODUCTION: We studied the incidence of vesicoureteral reflux (VUR) in the graft kidney and its effect on the occurrence of urinary tract infection (UTI) and long-term graft function. METHODS: We performed a retrospective analysis of 64 adult kidney transplant recipients based upon voiding cystourethrography at 12 months post-transplantation. Patients underwent analysis of survival, incidence of UTIs beyond 1 year, and graft function. RESULTS: Thirty-seven male and 27 female patients in the study populations showed a mean age 42 years. VUR in the transplanted kidney at 12 months post-transplant occurred among 78.1% (50/64) of subjects: grade I (n = 6), grade II (n = 30), or grade III (n = 14) reflux. Patients followed for a median 61 months (range 44-74s) showed 11 cases of UTIs in 9 subjects. There were no significant differences in clinical characteristics or incidence of, UTIs according to the presence or severity of VUR (P = .81) or the Serum creatinine and estimated glomerular filtration rate values at 12, 36, 48, or 60 months post-transplantation. CONCLUSIONS: VUR present in 78.1% of patients after kidney transplantation affected neither graft functions or graft survival. The incidence of UTI did not differ according to the presence of VUR.

Hormonal differences between female kidney transplant recipients and healthy women with the same gynecologic conditions.

BACKGROUND: End-stage renal disease is associated with severe abnormalities in reproductive function. However, the abnormalities are reversed by successful kidney transplantation. The aim of the present study was to compare hormonal levels between recipients with successful kidney transplantations and healthy women with the same gynecologic conditions. METHODS: The study group consisted of 31 women of reproductive age with end-stage renal disease who underwent successful kidney transplantation. The ratio of the control group, composed of healthy woman, to the study group was 3:1 matched for age and symptoms. RESULTS: Abnormal bleeding (n = 14) and infertility were the most common gynecologic conditions in kidney transplant recipients. The levels of estrogen (E2) and follicle-stimulating hormone (FSH) in the study group were higher than in the control group, but the levels of progesterone (P4) and luteinizing hormone (LH) were lower in the study group than in the control group. There were no significant differences in prolactin and thyroid-stimulating hormone between the two groups. The incidence of infertility in patients who receive steroid was higher than those with no steroid use (P = .007). CONCLUSIONS: Compared with healthy age- and symptom-matched women, female kidney transplant recipients have increased levels of E2 and FSH and decreased levels of P4 and LH. These differences in hormone profiles may predispose kidney transplant recipients to increased risk of gynecologic pathologies.

Rabbit antithymocyte globulin compared with basiliximab in kidney transplantation: a single-center study.

BACKGROUND: Induction therapy is used to reduce the incidence of acute rejection and to prevent or treat delayed graft function. We compared basiliximab with rabbit antithymocyte globulin (ATG) as induction therapies for kidney transplant recipients. METHODS: We retrospectively analyzed the clinical data from 514 patients who received ATG or basiliximab. The patients in the ATG group (n = 152) received ATG (1.5 mg/kg/d) for 5-7 days and those in the basiliximab group (n = 362) were given 2 doses of basiliximab (20 mg) on posttransplantation days 0 and 4. All patients received standard triple immunosuppressive therapy with calcineurin inhibitors, mycophenolate mofetil, and steroids. RESULTS: There were statistically significant differences in the incidences of delayed graft function, 1-year acute rejection rate, death-censored graft survival, and patient survival between the 2 groups, even though the ATG group had more kidney transplants from deceased donors, higher levels of panel reactive antibodies, and more retransplantations. The incidences of cytomegalovirus (CMV) infection and parvovirus infection in the ATG group were higher than those in the basiliximab group. However, there was no statistically significant difference in the incidence of CMV disease between the 2 groups. CONCLUSIONS: ATG is safe and efficacious for use in kidney transplant recipients. Our results suggest that ATG should be considered for induction therapy in high-risk patients, such as those who have a kidney allograft from a deceased donor, high levels of panel reactive antibodies, and are undergoing retransplantation.

Urinary angiotensinogen levels reflect the severity of renal histopathology in patients with chronic kidney disease.

BACKGROUND/AIMS: Recent studies have suggested that urinary angiotensinogen (AGT) reflects the activity of the intrarenal renin angiotensin system (RAS), which is involved in tissue injury in patients with chronic kidney disease. In this study, we investigated whether urinary AGT directly reflected the severity of histopathology in such patients. METHODS: AGT was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) on urine and plasma samples obtained from 58 patients on the day of renal biopsy. We measured the urinary transforming growth factor (TGF)-beta1, a representative cytokine of fibrogenic property, and analyzed the correlation among urinary TGF-beta1, urinary AGT, and the severity of renal injury. Mesangial proliferation, glomerulosclerosis, tubular atrophy and interstitial fibrosis were scored for the biopsied tissues. RESULTS: Urinary AGT levels correlated positively with proteinuria, urinary TGF-beta1 levels and diastolic blood pressure, but negatively with the estimated glomerular filtration rate (GFR). Urinary AGT concentrations were increased in patients with severe glomerulosclerosis, tubular atrophy and interstitial fibrosis. CONCLUSION: Urinary AGT levels correlated with the deterioration of renal function in patients with chronic kidney disease and reflected the histological severity of renal injury.

A fully validated HPLC method for the simultaneous determination of acitretin and etretinate in plasma and its application to a pharmacokinetic study in healthy Korean subjects.

OBJECTIVE: Acitretin is used for the treatment of psoriasis. The purpose of this study was to validate an HPLC method for the determination of acitretin and etretinate and to investigate the pharmacokinetic characteristics of acitretin in healthy Korean subjects. MATERIALS AND METHODS: Plasma samples or calibrators were mixed with acetonitrile and retinyl acetate (internal standard). Butanol: acetonitrile (1:1 v/v) and K2HPO4 were added later. After vortexing, 30 microl of the supernatant was injected directly into the analytical column of an HPLC system. The samples were separated by C18 reversed phase HPLC and UV detection was performed at 350 nm. Various assay performances were evaluated. RESULTS: The linearity of acitretin and etretinate was adequate up to 500 ng/ml (R2 = 0.9937 for acitretin and R2 = 0.9923 for etretinate). The accuracy was 89.5 - 113.5% and the precision was satisfactory (within-run CV, 4.4 - 15.8%; between-run CV, 3.3 - 17.4%). The LLOQ was 2 ng/ml and the stability and specificity were satisfactory. However, after storage at room temperature for 24 h under light exposure, the concentrations of acitretin and etretinate decreased by 26.0 - 66.5%. Extraction recovery was 75.1 - 91.5%. Nine healthy Korean subjects were evaluated to study the pharmacokinetics of acitretin. A single oral dose of 30 mg acitretin (Neotigason, Roche Pharmaceuticals) was given to all volunteers. The mean +/- SD pharmacokinetics of acitretin in Koreans were as follows: Cmax 148.7 +/- 93.0 ng/ml, tmax 3.2 +/- 1.3 h, t1/2 81.2 +/- 26.5 h, and AUClast 2641.9 +/- 1274.8 ng h/ml. CONCLUSION: A simple HPLC method for the simultaneous determination of acitretin and etretinate was validated, and the pharmacokinetic characteristics of acitretin in the Korean population were investigated.

Effect of panel-reactive antibody positivity on graft rejection before or after kidney transplantation.

INTRODUCTION: Because it is well known that kidney transplant recipients with preformed lymphocytotoxic antibodies against HLA antigens have increased graft rejection rates, a serological crossmatch is routinely performed before kidney transplantation. But, the presence of these antibodies is not routinely monitored after transplantation. We investigated the panel-reactive antibody (PRA) response to know whether variations before or after kidney transplantation were associated with graft rejection. METHODS: We prospectively analyzed sera from 350 renal allograft recipients from September 1998 to March 2003. Pretransplantation and posttransplantation sera at 3 or 5 weeks postoperatively were tested in PRA. Recipients were stratified into 3 groups according to their PRA levels group I, PRA = 0; group II, PRA = less than 50%, and group III, PRA = more than 50%. RESULTS: The total graft rejection rate among 350 recipients was 9.4% (n = 33). Twenty-four pretransplantation PRA-positive recipients had a graft rejection rate of 20.8% (n = 5), compared with an 8.6% (n = 28) rate among 326 pretransplantation PRA-negative recipients. Six of 24 posttransplantation PRA-positive recipients (25%) experienced a graft rejection versus 27 (8.3%) of 326 posttransplantation PRA-negative subjects. Among the pretransplantation PRA stratae, the rejection rate in group III was 25% (1 of 4) versus 20% (4 of 20) in group II and 8.6% (28 of 326) in group I (P < .05). According to the postransplantation PRA level, 37.5% (3 of 8) in group III versus 18.8% (3 of 16) in group II and 8.3% (27 of 326) in group I (P < .05) had a graft rejection. CONCLUSION: Our study suggests that the PRA response pretransplantation and in the early posttransplantation period correlates with the kidney allograft rejection rate.

Prognostic factors affecting graft and patient survival in cadaveric and living kidney transplantation.

Numerous studies have reported various prognostic factors that affect graft and patient survival in living and cadaveric donor kidney transplantation (KT). The purpose of this study was to evaluate the clinical outcomes and prognostic factors affecting graft and patient survivals in living and cadaveric donor KT. Between February 1995 and December 2001, 421 patients who had undergone cadaveric donor KT (group I: 216 cases, 51.3%) or living donor KT (group II: 205 cases, 48.7%), were retrospectively analyzed. Five-year overall graft survival rates in living was significantly better than that in cadaveric donor KT, respectively (P = .0234). There was no difference in patient survival rates between the two groups. Such factors as absence of rejection, female donor, female recipient, adult KT according to recipient age (>14 years), and donor serum creatinine level just before transplantation (< 2.5 mg/dL) were significantly associated with good graft survival among cadaveric donor KT, whereas two factors-absence of rejection and adult KT according to recipient age (>14 years)-influenced graft survival in living donor KT. In multivariate analysis, the only significant prognostic factor related to graft survival was the presence of rejection. In conclusion, we suggest that the presence of rejection is the only factor that impairs graft survival in both cadaveric and living donor KT, while other factors affected graft survival differently in the two groups.

Randomized trial of tacrolimus versus cyclosporine in steroid withdrawal in living donor renal transplant recipients.

The introduction of new immunosuppressants has prompted trials of steroid withdrawal. However, several groups have reported a higher incidence of rejection. We conducted a randomized two-arm, parallel-group, open-label, prospective study to compare steroid withdrawal (at 6 months posttransplant) from the regimens of tacrolimus + mycophenolate mofetil (MMF) (FK group) versus cyclosporine + MMF (CSA group). The entry criteria were recipients of first living donor transplants with no diabetes mellitus (DM), congestive heart failure, chronic liver disease, or acute rejection within 6 months posttransplant. The primary endpoint was a biopsy-proven acute rejection episode or treatment failure within 1 year posttransplant. While 87 recipients were assigned to FK (n = 43) and CSA groups (n = 44) before transplantation, 76 recipients (FK 39, CSA 37) could be tapered off steroids at 6 months posttransplant, since 11 were excluded due to acute rejection within 6 months posttransplant (FK two, CSA three) or protocol violations (FK two, CSA four). After steroid withdrawal, the incidence of acute rejection episodes was 0% in the FK group and 13.5% in the CSA group (P < .05). Other results at 12 months posttransplantation were comparable: the incidences of DM 7.8% versus 0% (FK group vs CSA group), hypercholesterolemia 41.0% versus 59.5%, hypertensives 48.7% versus 59.6% as well as the levels of plasma creatinine 1.21 +/- 0.24 versus 1.31 +/- 0.50 mg/dL (P > .05 in every variable). These data suggest that steroid withdrawal is successful in first living donor renal transplant recipients. Tacrolimus may be significantly more effective than cyclosporine to prevent acute rejection after steroid withdrawal.

Polymerase chain reaction for the diagnosis of human polyomavirus-associated nephropathy in renal transplant recipients.

Human polyomavirus type BK may be related to interstitial nephropathy or renal-allograft dysfunction. Patients with nephropathy due to infection with human polyomavirus may be identified early using the polymerase chain reaction(PCR). We attempted to evaluate whether the positive response in the PCR test of BK virus DNA in the plasma of renal transplant recipients affects the function of the renal allograft. Seventy-seven patients were prospectively analyzed according to the operative sex, age, sources of allograft, serum creatinine levels during PCR test for BK virus, postoperative type of immunosuppressant, and presence of graft rejection. Two groups were distinguished according to the PCR result for BK virus: group 1 (n = 12) positive PCR reaction and group 2 (n = 65) negative reaction. The mean follow-up was 32.6 weeks. The incidence of positive PCR tests for BK virus replication after renal transplantation was 15.6%. Decoy cells in the urine were detected in 20.7%. The incidence of BK virus nephropathy was 1.3%. The mean serum creatinine levels of group 1 and 2 at the time of the PCR tests were 1.34 and 1.22, respectively. The rejection rates in group 1 and 2 were 8% and 4.5%, respectively (P > .05). We consider that a PCR assay to detect BK virus in renal recipients blood may be useful to identify patients at risk for nephropathy. It may serve as a noninvasive indicator of BK virus replication, although this study is limited by the short follow-up and small numbers.