Bum-Soon Choi

Comparison of Clinical Outcomes by Different Renal Replacement Therapy in Patients with End-Stage Renal Disease Secondary to Lupus Nephritis

Background/Aims Many studies have compared patients with systemic lupus erythematosus (SLE) on renal replacement therapy (RRT) with non-lupus patients. However, few data are available on the long-term outcome of patients with end-stage renal disease (ESRD) secondary to SLE who are managed by different types of RRTs. Methods We conducted a retrospective multicenter study on 59 patients with ESRD who underwent maintenance RRT between 1990 and 2007 for SLE. Of these patients, 28 underwent hemodialysis (HD), 14 underwent peritoneal dialysis (PD), and 17 patients received kidney transplantation (KT). We analyzed the clinical outcomes in these patients to determine the best treatment modality. Results The mean follow-up period was 5 ± 3 years in the HD group, 5 ± 3 years in the PD group, and 10 ± 5 years in the KT group (p = 0.005). Disease flare-up was more common in the HD group than in the KT group (p = 0.012). Infection was more common in the PD and HD groups than in the KT group (HD vs. KT, p = 0.027; PD vs. KT, p = 0.033). Cardiovascular complications were more common in the HD group than in the other groups (p = 0.049). Orthopedic complications were more common in the PD group than in the other groups (p = 0.028). Bleeding was more common in the HD group than in the other groups (p = 0.026). Patient survival was greater in the KT group than in the HD group (p = 0.029). Technique survival was lower in the PD group than in the HD group (p = 0.019). Conclusions Among patients with ESRD secondary to SLE, KT had better patient survival and lower complication rates than HD and lower complication rates than PD. The prognosis between the HD and PD groups was similar. We conclude that if KT is not a viable treatment option, any alternative treatment should take into account the patients general condition and preference.

Aldosterone-induced TGF-β1 Expression is Regulated by Mitogen-Activated Protein Kinases and Activator Protein-1 in Mesangial Cells

Aldosterone has been shown to stimulate renal TGF-β1 expression. However, the mechanisms for aldosterone-induced TGF-β1 expression have not been clearly determined in mesangial cells. We examined the role of extracellular-signal regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1) in the aldosterone-induced TGF-β1 expression in rat mesangial cells. TGF-β1 protein in the conditioned medium released from rat mesangial cells was measured by sandwich ELISA, TGF-β1 mRNA expression was analyzed by Northern blotting, AP-1 DNA binding activity was measured by EMSA and the ERK1/2, JNK activity was analyzed by western blotting. Aldosterone significantly stimulated TGF-β1 protein production and TGF-β1 mRNA expression in mesangial cells in a dose-dependent manner. Aldosterone significantly increased AP-1 DNA binding activity in mesangial cells. Pre-treatment of cells with AP-1 inhibitor, curcumin, blocked aldosterone-induced AP-1 DNA binding activity as well as aldosterone-induced TGF-β1 production. Aldosterone increased phosphorylation of ERK1/2 and JNK in mesangial cells. Pre-treatment of cells with ERK1/2 inhibitor, PD98059, or JNK inhibitor, SP600125 significantly inhibited aldosterone-induced ERK1/2 and JNK activity and subsequently TGF-β1 production, respectively. We conclude that aldosterone-induced TGF-β1 expression in mesangial cells is regulated by the ERK1/2, JNK and AP-1 intracellular signaling pathways.

Effectiveness of Rituximab and Intravenous Immunoglobulin Therapy in Renal Transplant Recipients with Chronic Active Antibody-Mediated Rejection

BACKGROUND Chronic active antibody-mediated rejection (CAMR) is an important cause of chronic kidney allograft dysfunction, but there has been no effective treatment protocol established for it. METHODS Six renal transplant recipients who showed progressive deterioration in graft function and CAMR as diagnosed by biopsy were enrolled. We administered a single dose of rituximab (375 mg/m(2)), followed by intravenous immunoglobulin (IVIg, 0.4 g/kg) for 4 days. The efficacy of this protocol was assessed on the basis of the improvement in allograft function, the amount of proteinuria, and the change in donor-specific antibodies (DSAs). We categorized the patients into 2 groups, responders and nonresponders, according to their response to the treatment. RESULTS All of the patients showed progressive deterioration of graft function before the diagnosis of CAMR. Luminex solid-phase assays showed that 3 patients had DSAs. After the treatment, allograft function improved or stabilized in 3 patients in the responder group, but still showed a deteriorating pattern in the nonresponder group. In the responder group, the amount of proteinuria also decreased after the treatment, but it increased in the nonresponder group. On diagnosis of CAMR, the nonresponders showed a longer posttransplantation period, a higher degree of transplant glomerulopathy, more severely deteriorated allograft function, and higher proteinuria compared with the responders. CONCLUSIONS The combination of rituximab and IVIg was effective in early-stage CAMR, but the effect was limited in the advanced stage.

The Long-Term Outcomes of Transplantation of Kidneys With Multiple Renal Arteries

Kidneys with multiple renal arteries are increasingly procured for transplantation. To compare the outcomes of kidney transplantation using allografts with multiple arteries, we studied long-term graft function and survival according to their number of arterial anastomoses during an 18-year period from July 1, 1990, through December 31, 2008, in which only the recipients external iliac artery or internal iliac artery was used for anastomosis (n = 1186). The recipients were divided into four groups: group I, single renal artery with single anastomosis (n = 890, 75.0%); group Il, multiple renal arteries, single anastomosis (n = 26, 2.2%); group Ill, multiple renal arteries, multiple anastomoses (n = 236, 19.9%); and group IV, polar artery ligation (n = 34, 2.9%). We compared the following variables patient and graft survivals; mean creatinine levels at 1 and 6 months, as well as 1-, 3-, and 5-years posttransplant; the number of acute rejection episodes, and the rates of vascular and urologic complications. The creatinine values and incidences of acute rejection episodes did not differ significantly (P = 0.399 and P = 0.990, respectively). There were no significant differences among the four groups in graft survival (P = 0.951), patient survival (P = 0.751), incidence of vascular (P = 0.999) or urologic complications (P = 0.371). The four groups were subdivided according to the recipient arterial anastomosis to the main graft renal artery. The subdivided groups showed no significant differences in graft or patient survival, or complications rates. The results indicated that multiplicity of renal arteries in kidney transplantation did not adversely affect allograft or patient survival compared with single renal artery transplantation. Moreover, the type of the arterial anastomosis (main renal artery end-to-end anastomosed to internal iliac artery or end-to-side anastomosed to external iliac artery appeared to not affect graft or patient survival or the incidence of vascular or urologic complications.

Combined use of rituximab and plasmapheresis pre‐transplant increases post‐transplant infections in renal transplant recipients with basiliximab induction therapy

We investigated the effect of combined use of rituximab (RTX) and plasmapheresis (PP) pre‐transplant on post‐transplant infection.

Long-Term Outcomes of Kidney Transplantation From Expanded Criteria Deceased Donors at a Single Center: Comparison With Standard Criteria Deceased Donors

Our objective was to compare the clinical outcomes of adult kidney transplants from expanded criteria deceased donors (ECD) with those from concurrent standard criteria deceased donors (SCD). Between January 2000 and December 2011, we transplanted 195 deceased donor renal transplants into adult recipients, including 31 grafts (15.9%) from ECDs and 164 grafts (84.1%) from SCDs. ECDs were classified using the United Network for Organ Sharing (UNOS) definitions. Donor and recipient risk factors were analyzed separately and their correlation with recipient graft function and survival was evaluated (minimum 6-month follow-up). ECDs were older (56.8 ± 6.3 years), showed an increased incidence of hypertension, diabetes, and cerebrovascular brain death, and had a higher preretrieval serum creatinine level than SCDs. ECD kidney recipients had a shorter waiting time (P = .019) but other baseline characteristics (age, gender, body mass index [BMI], cause of end-stage renal disease, type of renal replacement therapy, incidence of diabetes and hypertension, number of HLA antigen mismatches, positivity for panel-reactive antigen, and cold ischemic time) were not significantly different from those of SCD kidney recipients. Mean glomerular filtration rate (GFR) at 1 month, 6 months, 1 year, and 3 years after transplantation was significantly lower in recipients of ECD transplants than recipients of SCD transplants, but the GFR level at 5 and 10 years was not significantly different between ECD and SCD recipient groups (P = .134 and .702, respectively). Incidence of acute rejection episodes and surgical complications did not differ significantly between the 2 recipient groups, but the incidence of delayed graft function (DGF) and infectious complications was higher in ECD kidney recipients than SCD kidney recipients (P = .007 and P = .008, respectively). Actual patient and graft survival rates were similar between the 2 recipient groups with a mean follow-up of 43 months. There were no significant differences in graft survival (P = .111) or patient survival (P = .562) between the 2 groups. Although intermediate-term renal function followed longitudinally was better in SCD kidney recipients, graft and patient survival of ECD kidney recipients were comparable with those of SCD kidney recipients. In conclusion, use of renal grafts from ECDs is a feasible approach to address the critical organ shortage.

Long-term risk of hypertension and chronic kidney disease in living kidney donors.

OBJECTIVE The aim of this study was to assess the long-term risks of chronic kidney disease and arterial hypertension in living kidney donors. METHODS Donors who were followed for more than 1 year after nephrectomy were included. We assessed each donors blood pressure, urine protein, and estimated glomerular filtration rate (eGFR). RESULTS The follow-up rate was 11% (154 out of 1,356 donors), only 19% of whom were followed by nephrologists. Blood pressure had increased from 113/75 to 116/77 mm Hg (P < .01), urinary protein excretion after donation did not increase, and renal function was well preserved after donor nephrectomy. However, 33 patients (21.4%) showed a decreased eGFR of <60 mL/min/1.73 m(2), and 3 donors developed end-stage renal disease that required renal replacement therapy. CONCLUSIONS The follow-up rate of living donors after donation was low, and we observed an increased risk of developing chronic kidney disease after donation.

Delayed graft function in living-donor renal transplantation: 10-year experience.

BACKGROUND Delayed graft function (DGF), a dialysis requirement within a week after transplantation, can occur in deceased-donor renal transplantation. DGF is rare, in living-donor renal transplantation (LDRT) and its incidence and risk factors have not been established. METHODS We investigated the incidence and clinical characteristics of DGF in LDRT over 10 years. We compared HLA mismatches, panel reactive antibody status, frequency of nonrelated donors, donor age, sex match, recipient-donor body weight ratio, total ischemia time, and transplanted kidney weight between DGF and non-DGF patients. RESULTS The incidence of DGF in LDRT was 1.6%, which differed from earlier reports. HLA mismatch, female recipient frequency, and nonrelated donors were higher among the DGF group, but no risk factor for DGF was significant after multivariate logistic regression analysis. Biopsy findings showed 2 cases to be associated with rejection, 1 with acute pyelonephritis and 1 with acute tubular necrosis. The cases with rejection resulted in graft failure within 3 years after transplantation, but the other cases were followed with favorable graft function. CONCLUSIONS The incidence of DGF among LDRT was lower than that reported earlier studies, and the factors previously reported to cause DGF were not associated with DGF herein. Because DGF with rejection responses has a poor prognosis, strenuous strategies, including biopsy, should be performed in cases of DGF after LDRT.

Safety and Efficacy of a Quinolone-Based Regimen for Treatment of Tuberculosis in Renal Transplant Recipients

BACKGROUND Rifampin (RFP) is a first-line antituberculosis drug, but it increases the risk of acute rejection (AR) in transplant recipients. This study evaluated whether quinolone (QNL) can replace RFP in renal transplant recipients with tuberculosis. METHODS One hundred nine patients with active tuberculosis were included. Patients consisted of RFP (n = 91) and QNL (n = 18) groups based on the initial treatment regimen. Patients with RFP-associated adverse effects were subdivided into RFP-maintenance (RFP-M; n = 18) and QNL-conversion (QNL-C; n = 8) groups. Clinical outcomes were compared between groups. RESULTS The incidence of AR was higher in the RFP group than in the QNL group (24.2% vs 5.6%). The QNL group showed significantly higher 10-year graft survival rates than the RFP group (88.1% vs 66.5%; P = .022). The QNL-C group showed significantly higher 10-year graft survival rates than the RFP-M group (87.5% vs 27.8%; P = .011). The rate of complete functional recovery after AR was higher in the QNL-C group than in the RFP-M group (50% vs 22.2%). CONCLUSIONS A QNL-based regimen may be safe and effective for treatment of tuberculosis and may lower the risk of graft failure in renal transplant recipients.

The role of kidney biopsy to determine donation from prospective kidney donors with asymptomatic urinary abnormalities.

BACKGROUND There are no definite guidelines about donation among prospective donors with asymptomatic urinary abnormalities. We evaluated the pathology of prospective kidney donors with asymptomatic urinary abnormalities and assessed the clinical outcomes of their organs. METHODS We reviewed the medical records of 15 prospective kidney donors who underwent kidney biopsy. We evaluated the role of kidney biopsy in terms of graft function, protocol biopsy, and follow-up biopsy. We further assessed the clinical outcomes of donors and recipients. RESULTS Thin basement membrane nephropathy (TBMN) is the most common cause of the persistent microscopic hematuria (n = 7; 50%), followed by nonspecific findings (n = 4; 29%), IgA nephropathy (n = 2; 14%), and focal segmental glomerulosclerosis (n = 1; 7%). Of the 14 candidate donors with persistent microscopic hematuria, 9 were accepted as kidney donors: 5 with TBMN, 3 with mild mesangiopathy, and 1 with nonspecific interstitial changes. The function of the 9 grafts was relatively stable (mean serum creatinine level 2.38 mg/dL) over a mean follow-up of 57 months. Graft failure that developed in 2 grafts was not associated with biopsy findings: acute rejection and patient death with a functioning graft. Interestingly, basement membrane thickness in 2 allografts from donors with TBMN appeared normal by electron microscopy follow-up biopsy; the allografts did not show hematuria. Moreover, the clinical outcomes of donors were favorable (mean serum creatinine 0.94 ± 0.32 mg/dL) during the mean follow-up period of 34.7 ± 42.5 months. We did not observe new-onset hypertension or proteinuria in donors. CONCLUSIONS Kidney biopsy in prospective kidney donors with urinary abnormalities is a safe and effective diagnostic procedure to stratify candidates. Therefore, kidney biopsy should be actively performed to improve the prognosis of both donors and recipients.