Chung Hee Baek

Does stage III chronic kidney disease always progress to end-stage renal disease? A ten-year follow-up study

Abstract Objective. Clinically, it may be appropriate to subdivide patients with stage 3 chronic kidney disease (CKD) into two subgroups, as they show different risks for kidney outcomes. This study evaluated the proportion of patients with stage 3 CKD who progressed to stage 4 or 5 CKD over 10 years and independent predictors of progression of renal dysfunction. It sought to validate whether stage 3 CKD patients should be subdivided. Material and methods. This retrospective cohort study enrolled 347 stage 3 CKD patients between January 1997 and December 1999, who were followed up through June 2010. The baseline clinical characteristics and outcomes were compared in patients with stage 3A [45 <estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2] and stage 3B (30 < eGFR <45 ml/min/1.73 m2) CKD. Results.Of the 347 patients, 196 (58.2%) were in stage 3A. The only difference in baseline characteristics between stages 3A and 3B patients was the degree of albuminuria. During follow-up, 167 patients (48.1%) did not progress, 60 (17.3%) progressed to stage 4 and 120 (34.6%) progressed to stage 5, with 91 (26.2%) starting dialysis. Multivariate Cox regression analysis showed that macroalbuminuria [(hazard ratio (HR) 3.06, 95% confidence interval (CI) 1.48–2.89, p < 0.001], microalbuminuria (HR 1.99 95% CI 1.04–3.85, p = 0.038), microscopic haematuria (HR 2.07 95% CI 1.48–2.89, p < 0.001) and stage 3B CKD (HR 2.99 95% CI 2.19–4.10, p < 0.001) were independent predictors of progression of renal dysfunction. Stage 3B patients had higher risks of adverse renal and cardiovascular outcomes than stage 3A patients. Conclusions.About half of the patients with stage 3 CKD progressed to stage 4 or 5, as assessed by eGFR, over 10 years. Degree of albuminuria, stage 3 subgroup and microscopic haematuria were important risk factors for progression of stage 3 CKD. It would be appropriate to divide the present stage 3 CKD into two subgroups.

Infectious risks and optimal strength of maintenance immunosuppressants in rituximab-treated kidney transplantation.

Background: Rituximab, an anti-CD20 antibody, effectively depletes B lymphocytes. It is not clear whether the use of conventional doses of mycophenolate mofetil (MMF), methylprednisolone and tacrolimus as maintenance immunosuppression in rituximab-treated kidney transplantation is associated with increased risk. Methods: We retrospectively evaluated 67 patients who underwent HLA-sensitized or ABO-incompatible living donor kidney transplantation after one dose of rituximab (200 or 500 mg) (group 1). Eighty-seven kidney transplant recipients who did not require rituximab served as a control (group 2). Results: Cytomegalovirus infection (16.4 vs. 5.7%, p = 0.031) and pneumonia (9.0 vs. 1.1%, p = 0.043) occurred more often in group 1, and 2 patients of group 1 died of infection. The doses of methylprednisolone and tacrolimus levels of the two groups were not different. MMF dose was reduced when serious infection occurred. The doses of MMF (in grams/day) at the following times postoperatively were lower in group 1 than in group 2: 1 month: 1.26 ± 0.42 vs. 1.40 ± 0.39, p = 0.033; 3 months: 1.14 ± 0.51 vs. 1.36 ± 0.39, p = 0.011; 6 months: 1.07 ± 0.50 vs. 1.30 ± 0.42, p = 0.012; 1 year: 0.88 ± 0.52 vs. 1.19 ± 0.44, p = 0.009; 2 years: 0.69 ± 0.55 vs. 1.25 ± 0.49, p = 0.059, but the reduction of MMF doses did not increase the incidence of acute rejection in group 1 (4.5% in group 1 vs. 9.2% in group 2, p = 0.351). If patients who died with functioning graft were excluded, graft survival was 98.5% in group 1 and 100% in group 2. Conclusions: Serious infectious complications were increased in rituximab-treated kidney transplant recipients and it might be adequate to reduce the MMF dose from the early postoperative period.

Up-Regulation of SIRT1 Reduces Endoplasmic Reticulum Stress and Renal Fibrosis.

Background: Endoplasmic reticulum (ER) stress is emerging as an important factor in the development of organ fibrosis. Therefore, modulation of ER stress may serve as one of the possible therapeutic approaches to renal fibrosis. SIRT1, a class III histone deacetylase, has been found to exert beneficial effects in kidney diseases. However, it is largely unknown whether and how SIRT1 suppresses the ER stress. We postulated that upregulation of SIRT1 would suppress the ER stress through induction of heme oxygenase-1 (HO-1) and thioredoxin. Methods: HK-2 tubular cells, experimental mouse models of tunicamycin (TM)-induced ER stress and unilateral ureteral obstruction (UUO) were used. Expression of ER stress-induced protein was measured by Western blot analysis and immunohistochemical staining. ER stress was induced by chemical ER stress inducers [TM [,]thapsigargin (TG)] and non-chemical inducers such as angiotensin II, aldosterone, high glucose and albumin. Results: SIRT1 activator (SRT1720) induced SIRT1 expression in a time- and dose-dependent manner in HK-2 cells. SRT1720 suppressed the TM- or TG-induced ER stress, as shown by inhibition of TM- or TG-induced upregulation of glucose-related protein 78 (GRP78), phosphor-specific eukaryotic translation initiation factor-2α and C/EBP homologous protein through HO-1 and thioredoxin, which were abolished by pretreatment with SIRT1 inhibitor (sirtinol). SRT1720 also suppressed the ER stress induced by angiotensin II, aldosterone, high glucose and albumin. In animal studies, treatment with SRT1720 reduced the tubular expression of GRP78 and increased the expression of HO-1 and thioredoxin. SRT1720 also reduced the UUO-induced renal fibrosis. Conclusion: SIRT1 may serve as a promising therapeutic target by reducing ER stress and fibrosis.

The clinical outcomes of second kidney transplantation in IgA nephropathy: a multicenter retrospective study.

BACKGROUND Recurrent IgA nephropathy (IgAN) after kidney transplantation (KT) has been reported to range between 12 and 65%. However, few data are available on second transplantation in recurrent IgAN. Therefore, this study aimed to build bottom-line data for the possibility of second transplantation in patients who lost first transplanted kidney due to recurrent IgAN. METHODS Patients who received KT twice due to recurrent IgAN at four large academic hospitals in Korea between March 1985 and December 2013 were reviewed. They were followed up until October 2014. All patients were identified as having recurrent IgAN in the first graft biopsies. The clinical outcomes of the second KT in these patients were compared with the first KT and with all cases of second KT (n = 169) performed at one center in the same period. RESULTS 28 patients were enrolled in this study. First grafts failed after 106.64 ± 48.72 months (mean ± SD). Following the second transplantation, recurrent IgAN was identified in only 2 patients during the follow-up of 61.61 ± 47.23 months. In 1 patient, the second graft was lost due to chronic rejection without mesangial IgA deposit. The second KT showed comparable graft survival compared with the first KT and the overall second KT (p = 0.308 by log-rank test). At the final follow-up, the serum creatinine level was 1.16 ± 0.33 mg/dL in the second graft except in 1 patient. CONCLUSIONS Second KT in recurrent IgAN showed reasonably good long-term results. Therefore, clinicians might be able to suggest second transplantation as an option for patients who lost the first graft due to recurrent IgAN.

Efficacy and Safety of Febuxostat in Kidney Transplant Patients

OBJECTIVES Febuxostat, a nonpurine xanthine oxidase, is known to be effective and safe, even in patients with chronic kidney disease. However, there are insufficient data about the efficacy and safety of febuxostat in kidney transplant patients. MATERIALS AND METHODS We reviewed medical records of all kidney transplant patients who were prescribed febuxostat between August 2012 and May 2015 at Asan Medical Center in Seoul, Korea. The efficacy and safety results of febuxostat in transplant patients were evaluated. To compare the efficacy of febuxostat, results of kidney transplant patients who were prescribed benzbromarone or allopurinol for more than 1 year during the same period were also reviewed. RESULTS Thirty-one patients were included in this study. The initial serum uric acid level of 481.83 ± 143.36 μmol/L decreased to 302.18 ± 150.50 μmol/L after 1 month of febuxostat use. Only 1 patient had altered sense of taste after taking febuxostat, but this symptom quickly improved and he continued treatment. No other adverse events were reported. In addition, at 12 months, mean serum uric acid levels were 280.77 ± 78.52 μmol/L in the febuxostat, 332.52 ± 72.57 μmol/L in the benzbromarone, and 363.45 ± 60.08 μmol/L in the allopurinol group. However, we found no apparent effect on estimated glomerular filtration rate (P = .344). The mean doses of febuxostat, benzbromarone, and allopurinol were 52.31 ± 5.33 mg/day, 42.19 ± 1.69 mg/day, and 146.67 ± 16.52 mg/day. CONCLUSIONS Febuxostat reduced serum uric acid levels effectively in kidney transplant patients without severe adverse events.

Differential Characteristics of Kidney Transplant Recipients According to 1-Year Chronic Kidney Disease Stage 3a and Stage 3b Graft Function

The outcomes of transplantation have improved, but more than 50% of kidney transplantation (KT) recipients are still reported to have renal function of chronic kidney disease (CKD) stage 3 at 1 year after KT. We reviewed all 1235 patients who received a KT in our institution between 2008 and 2012. Among these recipients, 77 and 289 cases were included in the estimated glomerular filtration rate (eGFR) at 1 year after KT 30-44 (CKD stage 3b) group and eGFR 45-59 (CKD stage 3a) group, respectively. Longer duration of dialysis (odds ratio [OR] = 1.007, 95% confidence interval [CI], 1.000-1.014, P = 0.047), older donors (OR = 1.064, 95% CI, 1.031-1.098, P < 0.001), delayed graft function (OR = 3.601, 95% CI, 1.031-1.098, P < 0.001), BK virus infection (OR = 2.567, 95% CI, 1.242-5.305, P = 0.011), and pneumonia (OR = 4.451, 95% CI, 1.388-14.279, P = 0.012) were contributing factors to eGFR 30-44 mL/min. Especially, ureteral stricture occurred more frequently in eGFR 30-44 group of deceased donor KT. However, acute rejection was not a significant risk factor of lower eGFR. Graft survival was better in the eGFR 45-59 group. However, this difference was smaller in deceased donor KT. Infections and urologic complications are also important contributing factors of lower graft function in CKD stage 3. In addition, dividing CKD stage 3 into subgroups might be more useful in living donor kidney transplantation.

Risk Factors for Hypertension After Living Donor Kidney Transplantation in Korea: A Multivariate Analysis

BACKGROUND Post-transplantation hypertension is very common and is associated with cardiovascular complications and poor graft survival in kidney transplant recipients. This study aimed to identify risk factors for hypertension after living donor kidney transplantation. METHODS We retrospectively analyzed patients who underwent renal transplantation between January 2009 and April 2012. Hypertension was defined as the use of antihypertensive medications at 12 months post-transplantation. Student t test and chi-squared test were performed for univariate analysis. Logistic regression analysis was performed for multivariate analysis. RESULTS Five-hundred thirty-nine patients were enrolled in the analyses. The rate of antihypertensive medication use was 67% at 12 months. In multivariate analysis, male gender (odds ratio [OR], 2.68; 95% confidence interval [CI], 1.55-4.61), pretransplantation hypertension (OR, 4.65; 95% CI, 2.14-10.11), donor hypertension (OR, 3.23; 95% CI, 1.05-9.96), high body mass index (BMI; OR, 1.21; 95% CI, 1.12-1.29), and use of cyclosporine (OR, 2.05; 95% CI, 1.28-3.27) were associated with post-transplantation hypertension. CONCLUSION These data show that male recipient, hypertension before transplantation, donor hypertension, high BMI, and cyclosporine use were independent factors associated with hypertension. It would be useful to predict and prevention the hypertension after kidney transplantation.

A postoperative 1-Year eGFR of More Than 45 ml/min May be the Cutoff Level for a Favorable Long-Term Prognosis in Renal Transplant Patients.

BACKGROUND One-year renal function after kidney transplantation (KT) classified by the Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) staging has been reported to be associated with graft survival. However, the outcomes of KT are improving. Therefore, the distribution and prognostic value of 1-year estimated glomerular filtration rate (eGFR) in recently performed transplants were re-evaluated in this study. MATERIAL AND METHODS We reviewed all patients who received KT between 2008 and 2011 at our institution, and followed them until June 2015. The distribution of 1-year eGFR, graft survival according to CKD staging, the cutoff level for a favorable prognosis, and the occurrence of rejection and infection were analyzed. RESULTS A total of 758 patients were included in this study. Unlike previous studies, most patients (56.2%) were in the CKD stage 2 (eGFR 60-89) rather than stage 3 (eGFR 30-59). In addition, the CKD stage 3a (eGFR 45-59) group showed better graft survival than the CKD stage 3b (eGFR 30-44) group. However, CKD stage 2 and CKD stage 3a groups did not show significant differences in graft survival. Patients with postoperative 1-year eGFR ≥45 ml/min showed a more favorable outcome compared with those with postoperative 1-year eGFR <45 ml/min. One-year eGFR<45 ml/min, acute cellular rejection, antibody-mediated rejection, and CMV infection after 1 year were adjusted risk factors for graft failure. CONCLUSIONS A 1-year eGFR ≥45 ml/min may be the appropriate cutoff level for predicting favorable outcomes in KT. In addition, KDIGO CKD staging may no longer be useful in recently performed KT.

A case series of asymptomatic hemodialysis catheter-related right atrial thrombi that are incidentally detected prior to kidney transplantation

A hemodialysis (HD) catheter-related right atrial thrombus (RAT) is rarely encountered prior to kidney transplantation (KT) but necessitates a decision about whether to anticoagulate and/or delay the surgery. There is controversy surrounding the clinical implications of a RAT in this situation. It is sometimes considered fatal but other opinions consider it to be benign, especially when incidentally detected. We reviewed the clinical characteristics, management, and outcomes of a patient series with HD catheter-related RAT detected prior to KT and speculated on its clinical significance. Among 3677 cases of KT performed on 3607 patients between January 1997 and September 2015 in our single tertiary center, 11 cases of HD catheter-related RAT detected on transthoracic echocardiography (TTE) prior to KT were included for analysis. The average maximal diameter of the RAT was 23.2 ± 16.3 (SD in mm) and 9 (81.8%) of these 11 patients had no symptoms associated with the RAT. Four patients (36.3%) had their catheters replaced, 5 patients (45.5%) had their catheters removed, and the catheters were maintained in the remaining 2 patients (18.2%). Six patients (54.5%) were anticoagulated with either heparin or warfarin. However all 11 patients had a successful KT suggesting that a HD catheter-related RAT incidentally detected prior to this surgery may not be as serious as previously considered and should not be a reason for delaying the transplantation.

Clinical significance of isoagglutinin titer with the current desensitization protocol in ABO-incompatible kidney transplantation: Isoagglutinin titer in ABO incompatible KT

ABO‐incompatible (ABOi) kidney transplantation (KT) has become a routine procedure with graft survival rates comparable to those of ABO‐compatible KT. However, the clinical significance of the isoagglutinin titre in ABOi KT remains uncertain. Therefore, in this study, we analysed the clinical outcomes of ABOi KT according to the baseline and post‐operative isoagglutinin titre.