Jung Nam An

Urinary N-acetyl-β-D glucosaminidase as a surrogate marker for renal function in autosomal dominant polycystic kidney disease: 1 year prospective cohort study

BackgroundRenal failure is one of the most serious complications associated with autosomal dominant polycystic kidney disease (ADPKD). To date, early markers have failed to predict renal function deterioration at the early stages. This 1-year prospective study evaluated N-acetyl-β-D-glucosaminidase (NAG) as a new surrogate marker for renal function in ADPKD.MethodsA total of 270 patients were enrolled in the study, and we measured urinary NAG, β2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) prospectively for 1 year to compare their predictive values for renal function.ResultsBaseline urinary NAG/Cr was negatively correlated with estimated glomerular filtration rate (GFR) (r2 = 0.153, P < 0.001) and positively correlated with total kidney volume (TKV) (r2 = 0.113, P < 0.001). Among other biomarkers, urinary NAG/Cr better discriminated patients with decreased renal function from those with conserved renal function, showing the largest area under the curve (AUC 0.794). Immunohistochemical study revealed strong staining along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. However, both single and repeated measurements of urinary NAG/Cr failed to predict renal function decline in 1 year.ConclusionsUrinary NAG/Cr may be a useful surrogate marker for renal function in ADPKD patients.

Effect of Dialysis Initiation Timing on Clinical Outcomes: A Propensity-Matched Analysis of a Prospective Cohort Study in Korea

Background Controversy persists regarding the appropriate initiation timing of renal replacement therapy for patients with end-stage renal disease. We evaluated the effect of dialysis initiation timing on clinical outcomes. Initiation times were classified according to glomerular filtration rate (GFR). Methods We enrolled a total of 1691 adult patients who started dialysis between August 2008 and March 2013 in a multi-center, prospective cohort study at the Clinical Research Center for End Stage Renal Disease in the Republic of Korea. The patients were classified into the early-start group or the late-start group according to the mean estimated GFR value, which was 7.37 ml/min/1.73 m2. The primary outcome was patient survival, and the secondary outcomes were hospitalization, cardiovascular events, vascular access complications, change of dialysis modality, and peritonitis. The two groups were compared before and after matching with propensity scores. Results Before propensity score matching, the early-start group had a poor survival rate (P<0.001). Hospitalization, cardiovascular events, vascular access complications, changes in dialysis modality, and peritonitis were not different between the groups. A total of 854 patients (427 in each group) were selected by propensity score matching. After matching, neither patient survival nor any of the other outcomes differed between groups. Conclusions There was no clinical benefit after adjustment by propensity scores comparing early versus late initiation of dialysis.

Circulating TNF receptors are significant prognostic biomarkers for idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (iMN) is a common cause of nephrotic syndrome in adults. A biomarker to accurately indicate the severity of iMN and predict long-term prognosis is insufficient. Here, we evaluated the clinical significance of circulating tumor necrosis factor receptors (cTNFRs) as prognostic biomarkers of iMN with nephrotic syndrome. A total of 113 patients with biopsy-proven iMN and 43 healthy volunteers were enrolled in this study. Ninety patients with iMN had nephrotic range proteinuria. Levels of cTNFRs were measured by using serum samples collected at the time of initial diagnosis. Levels of cTNFRs were higher in the patients with nephrotic syndrome than in those with subnephrotic range proteinuria or in the healthy volunteers (P for trend <0.001). Estimated glomerular filtration rate and proteinuria tended to worsen as the cTNFRs levels increased. Having a cTNFR1 level within the highest tertile was a significant risk factor for renal progression after adjustment, in comparison with the other tertiles (hazard ratio [HR], 3.39; 95% confidence interval [95% CI], 1.48–7.78; P = 0.004). The cTNFR2 level within the highest tertile also significantly increased the risk of renal progression (HR, 3.29; 95% CI, 1.43–7.54; P = 0.005). Renal tubular TNFRs expression was associated with cTNFRs level. However, the cTNFRs levels were not associated with autoantibody against phospholipase A2 receptor reactivity/levels or treatment response. This study demonstrated that cTNFRs levels at the time of initial diagnosis could predict renal progression in patients with iMN.

Serum Bilirubin Affects Graft Outcomes through UDP-Glucuronosyltransferase Sequence Variation in Kidney Transplantation

Background Oxidative stress is a major mediator of adverse outcome after kidney transplantation. Bilirubin is produced by heme oxygenase-1 (HO-1), catalyzed by UDP-glucuronosyltransferase (UGT1A1), and has potential as an antioxidant. In this study, we investigated the effects of HO-1 and UGT1A1 sequence variations on kidney allograft outcomes. Methods Clinical data were collected from 429 Korean recipients who underwent kidney transplantation from 1990–2008. Genotyping for UGT1A1*28 and HO-1 (A−413T) was performed. Acute rejection and graft survival were monitored as end-points. Results Serum levels of total bilirubin were significantly increased after transplantation (0.41±0.19 mg/dL to 0.80±0.33 mg/dL, P<0.001). Post-transplant 1-year bilirubin level was higher in 6/7 or 7/7 carriers compared with 6/6 homozygotes in terms of the UGT1A1*28 polymorphism (6/6 vs. 6/7 vs. 7/7: 0.71±0.27 vs. 1.06±0.36 vs. 1.10±0.45 mg/dL, P<0.001). According to an additive model of genotype analysis, the 7-allele genotype had a protective effect on the development of acute rejection compared with the 6-allele (odds ratio 0.43, 95% CI 0.25–0.73, P for trend = 0.006). Multivariate Cox regression analysis revealed that individuals carrying the 7-allele had a decreased risk of graft loss, by a factor of 0.36 (95% CI 0.15–0.85, P = 0.019). The HO-1 (A−413T) polymorphism had no effect on serum bilirubin levels or graft outcomes. Conclusions The UGT1A1*28 polymorphism is associated with changes in serum bilirubin and with graft outcome after kidney transplantation.

The reciprocal interaction between LV remodelling and allograft outcomes in kidney transplant recipients

Objective This study aimed to investigate the incidence and related clinical factors of LV hypertrophy (LVH) regression after kidney transplantation and its effect on graft outcome. Methods Among the 3373 kidney transplant recipients who were enrolled in a multicentre cohort from 1997 to 2012, a total of 767 patients who underwent echocardiography before and after transplantation were included in this study followed for a median of 7.5 years. Results LVH regression steadily increased from 7.4% at 1 year to 35.4% at 5 years over the 5-year post-transplantation period. The probability of LVH regression decreased in the patients who received a kidney transplant due to end-stage renal disease of unknown aetiology (p=0.041) or who underwent pretransplant haemodialysis (p=0.020). The probability of LVH regression also decreased as the pretransplant LV mass index (p<0.001) and post-transplant systolic blood pressure increased (p=0.005). Conversely, LVH regression was significantly associated with the highest tertile of the pretransplant haemoglobin level (p=0.029). Furthermore, in the 5th year after transplantation, persistent LVH was independently associated with allograft failure (HR 1.95; 95% CI 1.14 to 3.33; p=0.015) and the LV mass index reliably predicted graft outcome. Conclusions LVH consistently regressed after kidney transplantation in most patients. Persistent LVH, low haemoglobin levels and elevated blood pressure were associated with an increased risk of allograft failure in kidney transplant recipients.

Small Increases in Plasma Sodium Are Associated with Higher Risk of Mortality in a Healthy Population

Elevated blood pressure (BP) is the most common cause of cardiovascular disease. Salt intake has a strong influence on BP, and plasma sodium (pNa) is increased with progressive increases in salt intake. However, the associations with pNa and BP had been reported inconsistently. We evaluated the association between pNa and BP, and estimated the risks of all-cause-mortality according to pNa levels. On the basis of data collected from health checkups during 1995-2009, 97,009 adult subjects were included. Positive correlations between pNa and systolic BP, diastolic BP, and pulse pressure (PP) were noted in participants with pNa ≥138 mM/L (P<0.001). In participants aged ≥50 yr, SBP, DBP, and PP were positively associated with pNa. In participants with metabolic syndrome components, the differences in SBP and DBP according to pNa were greater (P<0.001). A cumulative incidence of mortality was increased with increasing pNa in women aged ≥50 yr during the median 4.2-yr-follow-up (P<0.001). In women, unadjusted risks for mortality were increased according to sodium levels. After adjustment, pNa ≥145 mM/L was related to mortality. The positive correlation between pNa and BP is stronger in older subjects, women, and subjects with metabolic syndrome components. The incidence and adjusted risks of mortality increase with increasing pNa in women aged ≥50 yr.

Circulating Tumor Necrosis Factor α Receptors Predict the Outcomes of Human IgA Nephropathy: A Prospective Cohort Study

The circulating tumor necrosis factor receptors (TNFRs) could predict the long-term renal outcome in diabetes, but the role of circulating TNFRs in other chronic kidney disease has not been reported. Here, we investigated the correlation between circulating TNFRs and renal histologic findings on kidney biopsy in IgA nephropathy (IgAN) and assessed the notion that the circulating TNFRs could predict the clinical outcome. 347 consecutive biopsy-proven IgAN patients between 2006 and 2012 were prospectively enrolled. Concentrations of circulating TNFRs were measured using serum samples stored at the time of biopsy. The primary clinical endpoint was the decline of estimated glomerular filtration rate (eGFR; ≥ 30% decline compared to baseline). Mean eGFR decreased and proteinuria worsened proportionally as circulating TNFR1 and TNFR2 increased (P < 0.001). Tubulointerstitial lesions such as interstitial fibrosis and tubular atrophy were significantly more severe as concentrations of circulating TNFRs increased, regardless of eGFR levels. The risks of reaching the primary endpoint were significantly higher in the highest quartile of TNFRs compared with other quartiles by the Cox proportional hazards model (TNFR1; hazard ratio 7.48, P < 0.001, TNFR2; hazard ratio 2.51, P = 0.021). In stratified analysis according to initial renal function classified by the eGFR levels of 60 mL/min/1.73 m2, TNFR1 and TNFR2 were significant predictors of renal progression in both subgroups. In conclusion, circulating TNFRs reflect the histology and clinical severity of IgAN. Moreover, elevated concentrations of circulating TNFRs at baseline are early biomarkers for subsequent renal progression in IgAN patients.

Not Early Referral but Planned Dialysis Improves Quality of Life and Depression in Newly Diagnosed End Stage Renal Disease Patients: A Prospective Cohort Study in Korea

Background Health-related quality of life (HRQOL) has recently become an important issue. It reportedly affects morbidity and mortality in patients with end-stage renal disease (ESRD). In this study, we investigated whether early referral and planned dialysis improve the HRQOL and depression of patients with ESRD. Methods We prospectively enrolled newly diagnosed patients with ESRD, from 31 hospitals in Korea, who completed questionnaires at 3 months after dialysis. We also got follow-up survey at 1 year after dialysis. To measure HRQOL and depression, Kidney Disease Quality of Life Short Form 36 (KDQOL-36) and Beck’s Depression Inventory (BDI) were utilized. Results A total of 643 patients were analyzed. Referral type did not affect either KDQOL-36 or BDI scores. However, the planned dialysis group showed significantly better scores in 4 of 5 KDQOL-36 domains than did the unplanned group at 3 months after dialysis and partly, the effect was sustained for 1 year after dialysis. The benefit of planned dialysis was significant after adjusting for age, sex, type of dialysis, marital status, educational attainment, occupation, modified Charlson comorbidity index, albumin, and hemoglobin levels. BDI scores were also lower which indicate less depressive mood in planned dialysis group than those in unplanned group both at 3 months and 1 year after dialysis. Conclusions Not early referral but planned dialysis improved both the short- and long-term HRQOL and depression of patients with ESRD. Nephrologists should try to help patients to initiate dialysis in a planned manner.

Elderly Peritoneal Dialysis Compared with Elderly Hemodialysis Patients and Younger Peritoneal Dialysis Patients: Competing Risk Analysis of a Korean Prospective Cohort Study

The outcomes of peritoneal dialysis (PD) in elderly patients have not been thoroughly investigated. We aimed to investigate the clinical outcomes and risk factors associated with PD in elderly patients. We conducted a prospective observational nationwide adult end-stage renal disease (ESRD) cohort study in Korea from August 2008 to March 2013. Among incident patients (n = 830), patient and technical survival rate, quality of life, and Beck’s Depression Inventory (BDI) scores of elderly PD patients (≥65 years, n = 95) were compared with those of PD patients aged ≤49 years (n = 205) and 50~64 years (n = 192); and elderly hemodialysis (HD) patients (n = 315). The patient death and technical failure were analyzed by cumulative incidence function. Competing risk regressions were used to assess the risk factors for survival. The patient survival rate of elderly PD patients was inferior to that of younger PD patients (P<0.001). However, the technical survival rate was similar (P = 0.097). Compared with elderly HD patients, the patient survival rate did not differ according to dialysis modality (P = 0.987). Elderly PD patients showed significant improvement in the BDI scores, as compared with the PD patients aged ≤49 years (P = 0.003). Low albumin, diabetes and low residual renal function were significant risk factors for the PD patient survival; and peritonitis was a significant risk factor for technical survival. Furthermore, low albumin and hospitalization were significant risk factors of patient survival among the elderly. The overall outcomes were similar between elderly PD and HD patients. PD showed the benefit in BDI and quality of life in the elderly. Additionally, the technical survival rate of elderly PD patients was similar to that of younger PD patients. Taken together, PD may be a comparable modality for elderly ESRD patients.

Urinary Periostin Excretion Predicts Renal Outcome in IgA Nephropathy

Background: Periostin is a matricellular protein and plays a vital role in tissue regeneration, fibrosis and wound healing. However, data about its significance in nephrology are limited. We investigated the correlation between urinary periostin excretion and its clinical significance including renal histologic findings and prognosis in IgA nephropathy (IgAN). Methods: Of 399 patients from a glomerulonephritis cohort recruited between January 2009 and December 2014, 314 were enrolled. Serum and urine periostin (uPOSTN) were measured using enzyme-linked immunosorbent assay. We divided the patients into 3 groups by uPOSTN/creatinine (uPOSTN/Cr): group 1 (undetectable), group 2 (lower than the median) and group 3 (higher than the median). Results: The uPOSTN level was correlated with pathologic classifications and both initial and final IDMS-MDRD estimated glomerular filtration rates (eGFRs; p < 0.001). Histologically, group 3 patients were correlated with severe interstitial fibrosis/tubular atrophy (p = 0.004), interstitial inflammation (p = 0.007), hyaline arteriolosclerosis (p = 0.001) and glomerular sclerosis (p < 0.001). A higher initial uPOSTN/Cr level was associated with a greater decline in eGFR during follow-up (p = 0.043 when initial eGFR ≥60; p = 0.025 when eGFR <60 ml/min/1.73 m2), and the renal outcomes with end-stage renal disease (ESRD; p = 0.003), ESRD and/or eGFR decrease of >30% (p = 0.033) and ESRD and/or eGFR decrease of >50% (p = 0.046) occurred significantly more in group 3. In multivariate analysis, uPOSTN group 3 (hazards ratio 2.839, 95% CI 1.013-7.957; p = 0.047) was independently associated with ESRD in IgAN patients. Conclusion: uPOSTN/Cr value at initial diagnosis correlated with renal fibrosis and predicted the renal outcomes in patients with IgAN. It could be a promising urinary biomarker for renal fibrosis.