Byung-Ha Chung

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.

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.

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.

ABO incompatible living donor kidney transplantation in Korea: highly uniform protocols and good medium-term outcome

The organ shortage is as serious in Korea as in other parts of the world. As about one‐third of the potential living donors are ABO incompatible (ABOi), transplantation across the blood group barrier can help overcome this shortage. One hundred and twenty‐five ABOi kidney transplantations (KTs) were performed between 2007 and 2010 in Korea. We collected the perioperative and follow‐up data for 118 of these patients until September 2011. The preconditioning and immunosuppressive protocols were almost identical across the different transplant centers, with rituximab but no splenectomy; pre‐transplant plasmapheresis (PP) with target anti‐A/B titer 8 or 16 on transplant day, on‐demand, rather than routine, post‐transplant PP, and tacrolimus‐based immunosuppressants. The number of patients and participating centers showed a rapid increase over time, and in 2010, ABOi KT (n = 79) comprised 10% of all the living donor KTs in Korea. The mean follow‐up period was 21 months (range, 1–56 months). Sixteen (14%) patients developed acute rejection, and three of these had antibody‐mediated rejection (AMR). Two‐yr patient and graft survival were 99.2% and 97.5%, respectively. No graft was lost due to AMR. ABOi KT is rapidly expanding in Korea with excellent medium‐term outcome and will help mitigate the organ shortage.

Optimization of adipose tissue-derived mesenchymal stem cells by rapamycin in a murine model of acute graft-versus-host disease

IntroductionMesenchymal stem cells (MSCs) can protect bone marrow transplantation (BMT) recipients from the lethal acute graft-versus-host disease (aGVHD) development. However, the mechanisms underlying the anti-inflammatory properties of MSCs in aGVHD remain to be elucidated. The immunoregulatory properties of MSCs are mediated by their production of anti-inflammatory molecules, including IL-10 and TGF-β. On the other hand, MSCs can also produce proinflammatory cytokines during their normal growth, such as IL-1β and IL-6. These opposite actions may limit their therapeutic application in aGVHD. Therefore, optimization of the functional properties of MSCs can increase their benefits.MethodsThe expressions of mRNA and protein were analyzed by real-time PCR and western blotting, respectively. Expression of MSC markers was assessed by flow cytometry. An animal model of aGVHD was established by transplanting C57BL/6 donor bone marrow cells and spleen cells into lethally irradiated BALB/c recipient mice. The recipient mice were divided into the control group and the therapy [adipose tissue-derived human MSCs (Ad-hMSCs) or rapamycin-treated Ad-hMSCs] groups. The survival, body weight and clinical score of aGVHD in transplanted mice were monitored.ResultsRapamycin pre-treatment of Ad-hMSCs increased mRNA synthesis of IL-10, indoleamine 2,3-dioxygenase, and TGF-β compared with untreated Ad-hMSCs. Rapamycin-treated Ad-hMSCs suppressed clonal expansion of interleukin-17-producing CD4+ T (Th17) cells more effectively than untreated cells. mRNA expression of autophagy markers such as ATG5, LC3A and LC3B was significantly increased in the rapamycin-treated Ad-hMSCs compared with untreated Ad-hMSCs. Transmission electron microscopy revealed that Ad-hMSCs exposure to rapamycin resulted in the appearance of autophagic vacuoles. Interestingly, in vitro migration efficiency of rapamycin-treated Ad-hMSCs toward the CD4+ T cells was increased significantly compared with the untreated cells. And, these effects were associated with autophagy induction capacity of rapamycin. In vivo, the inhibiting properties of MSCs on the clinical severities of aGVHD were greater in the mice receiving rapamycin-treated Ad-hMSCs compared with untreated Ad-hMSCs. The beneficial effects of rapamycin treatment in Ad-hMSCs shown in vivo were associated with a reduction of Th17 cells and an increase in regulatory T cells.ConclusionsRapamycin can optimize the immunomodulatory potential of Ad-hMSCs, suggesting a promising strategy of MSC use in aGVHD treatment.

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.

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.

Experience of Anti-Viral Therapy in Hepatitis B-Associated Membranous Nephropathy, Including Lamivudine-Resistant Strains

Background/Aims Chronic hepatitis B infection is a common cause of secondary membranous nephropathy (MN) in endemic areas. Lamivudine treatment improves renal outcome in patients with hepatitis B virus-associated MN (HBV-MN), but prolonged use leads to the emergence of lamivudine-resistant variants. We describe our experience treating lamivudine-resistant and other strains of HBV-MN with new antiviral drugs. Methods Of the 89 patients biopsied and diagnosed with MN from 1996 to 2011, 10 positive for hepatitis B surface antigen were recruited for this study. We investigated the clinical courses, therapeutic responses, and prognoses of patients with HBV-MN. Results The incidence of HBV-MN among the original 89 patients was 11.2%. Of these patients, four were treated with supportive care and six with antiviral drugs. One of the four patients treated with supportive care had a spontaneous remission. Four of the six patients treated with antiviral drugs were given lamivudine, and the other two were given entecavir. Two of the four patients treated with lamivudine achieved complete remission with seroconversion (i.e., development of anti-hepatitis B e antigen antibodies), whereas the other two had lamivudine-resistant strains, which were detected at 22 and 23 months after lamivudine treatment, respectively. We added adefovir to the treatment regimen for one of these patients, and for the other patient we substituted clevudine for lamivudine. Both of these patients experienced complete remission, as did the two patients initially treated with entecavir, neither of whom showed resistance to the drug. Conclusions New nucleoside analogues, such as entecavir, adefovir, and clevudine, can be effective for treatment of HBV-MN, including lamivudine-resistant strains.

Clinical Usefulness of 3-Dimensional Computerized Tomographic Renal Angiography to Detect Transplant Renal Artery Stenosis

OBJECTIVE The aim of this study was to evaluate whether 3-dimensional computerized tomographic angiography (3D-CTA) is useful to detect transplant renal artery stenosis (TRAS). METHODS Fourteen patients with clinically suspected TRAS underwent color Doppler ultrasonography (CDU) and 3D-CTA before renal angiography. We compared 3D-CTA and CDU for accuracy based on the results of renal angiography. The safety of 3D-CTA was investigated by measuring the estimated glomerular filtration rate (eGFR) before and after the 3D-CTA examination. RESULTS The 10 men and 4 women who participated in this study showed a mean eGFR of 75 mL/min/1.73 m(2) (range 60-94). Of these, 9 patients were diagnosed with TRAS. 3D-CTA detected stenoses in all 9 patients, but CDU failed to detect it in 3, including, 2 with end-to-side arterial anastomoses, which may be more challenging to detect compared with end-to-end anastomoses. The stenotic area in 3D-CTA was similar to that detected by renal angiography (70 ± 12 vs 68 ± 11). The eGFR did not differ significantly before versus after the 3D-CTA examination; 72 ± 13 vs 69 ± 14 mL/min/1.73 m(2). CONCLUSIONS 3D-CTA was an effective safe method to detect renal artery stenosis among transplant recipients with an eGFR >60 mL/min/1.73 m(2).

Mechanical thromboprophylaxis is sufficient to prevent the lower extremity deep vein thrombosis after kidney transplantation

Purpose Deep vein thrombosis (DVT) is a severe and common complication that occurs after the major operation. Despite the commonality of DVT there is limited data on the incidence of DVT after kidney transplantation (KT). Furthermore, most studies have been retrospective in design and were conducted in western countries. The aim of this study was to evaluate the incidence of lower extremity DVT with mechanical thromboprophylaxis within 1 month of KT in Korea. Methods A total of 187 consecutive patients who underwent KT were included in this study. Patients used a graduated elastic stocking (n = 93) or an intermittent pneumatic compression device (n = 94) to prevent DVT. The frequency of DVT during the first month after KT was evaluated using serial color duplex ultrasound on postoperative days 7 ± 2, 14 ± 2, and 28 ± 3. All patients were tested for eight thrombophilic factors before KT. Results DVT occurred in four patients (2.1%) during the first month after KT. All DVT developed in the graduated elastic stocking group. Interestingly, none of the patients had the factor V Leiden mutation or the prothrombin gene 20210A mutation. Conclusion The incidence of DVT in this study was relatively lower than that of western populations. We did not encounter a factor V Leiden mutation or a prothrombin gene 20210A mutation in our study population. These findings suggest that inherited thrombophilic risk factors may be partially responsible for the difference in DVT incidence rates between different nationalities and/or ethnicities.