Seung Seok Han

Lean Mass Index: A Better Predictor of Mortality than Body Mass Index in Elderly Asians

OBJECTIVES: To evaluate the correlation between body mass index (BMI), body composition, and all‐cause mortality in an elderly Asian population.

Sulfatide-Reactive Natural Killer T Cells Abrogate Ischemia-Reperfusion Injury

There is a significant immune response to ischemia-reperfusion injury (IRI), but the role of immunomodulatory natural killer T (NKT) cell subtypes is not well understood. Here, we compared the severity of IRI in mice deficient in type I/II NKT cells (CD1d(-/-)) or type I NKT cells (Jα18(-/-)). The absence of NKT cells, especially type II NKT cells, accentuated the severity of renal injury, whereas repletion of NKT cells attenuated injury. Adoptively transferred NKT cells trafficked into the tubulointerstitium, which is the primary area of injury. Sulfatide-induced activation of type II NKT cells protected kidneys from IRI, but inhibition of NKT cell recruitment enhanced injury. In co-culture experiments, sulfatide-induced activation of NKT cells from either mice or humans attenuated apoptosis of renal tubular cells after transient hypoxia via hypoxia-inducible factor (HIF)-1α and IL-10 pathways. Renal tissue of patients with acute tubular necrosis (ATN) frequently contained NKT cells, and the number of these cells tended to negatively correlate with ATN severity. In summary, sulfatide-reactive type II NKT cells are renoprotective in IRI, suggesting that pharmacologic modulation of NKT cells may protect against ischemic injury.

Additional role of urine output criterion in defining acute kidney injury

BACKGROUND Diagnosis of acute kidney injury (AKI) has been a major concern due to its association with increased morbidity and mortality. However, the clinical implication of the urine output criterion (UOCr) in diagnosing AKI has not been fully established. METHODS We assessed the incidence of AKI among 1625 critically ill patients and analysed the overall survival rates based on the serum creatinine criterion (CrCr) and UOCr, both of which have been defined by the AKI Network (AKIN). RESULTS Within 7 days of admission, the risk rate of AKI was 57.0% and the rate determined by UOCr alone was 25.7%. AKI determined by the UOCr alone increased hazard ratios (HRs) for mortality; 1.81 (Stage 1), 2.96 (Stage 2) and 4.17 (Stage 3) compared to non-AKI. However, the difference in mortality between Stages 2 and 3 using the CrCr alone was not significant (P = 0.881). In patients with Stages 2 and 3 by the CrCr, the UOCr further separated the survival rates (P = 0.001 among the four UOCr stages). The diuretic dose did not alter the discriminative function of the UOCr for survival rates. However, 42.1% of non-AKI cases, as determined by the UOCr, were identified as AKI cases by the CrCr. CONCLUSION Although some AKI cases were not identified by the UOCr alone, the UOCr has an additional role in AKI staging, regardless of diuretic use.

Impact of recurrent disease and chronic allograft nephropathy on the long-term allograft outcome in patients with IgA nephropathy.

Although recurrent IgA nephropathy (IgAN) may lead to graft dysfunction after transplantation, donation from living related donor (LRD), with whom the risk of recurrence may be higher, is not a contraindication. Herein, we evaluated the natural history of allograft in recipients with IgAN and the risk factors influencing long‐term allograft outcome. Recurrence rate and graft survival were assessed retrospectively in 221 IgAN patients, including transplants from 139 LRDs (62.9%). Ten‐year cumulative rate for recurrent IgAN was 30.8%. The operation at younger age and donation from LRD were significant for the recurrence by multivariate analysis. Ten‐year graft survival was affected by recurrent IgAN (61.0% in recurrent IgAN group vs. 85.1% in nonrecurrent, P < 0.01). However, transplants from LRDs did not show poor graft survival when compared with those from other types of donors. In transplants from LRDs, the incidence of chronic allograft nephropathy (CAN) was lower than those in grafts from deceased donors (10.8% vs. 19.5%, P < 0.05). When CAN was considered in addition to recurrence, the variance of graft survival was affected significantly by the development of CAN than by the recurrence. These results suggest that the detection and adequate management of CAN could improve graft outcome in transplant recipients with IgAN.

Quality of life and mortality from a nephrologist's view: a prospective observational study

BackgroundAlthough health-related quality of life (HRQOL) is a potential independent predictor of mortality, nephrologists have shown little interest in HRQOL with respect to mortality in chronic kidney disease (CKD). The aim of this article is to evaluate the impact of HRQOL on mortality in the elderly, who are likely to develop or already have CKD.MethodsAmong 1,000 randomly sampled participants aged more than 65 years (sourced from the Korean Longitudinal Study on Health and Ageing), 944 subjects were evaluated for HRQOL. HRQOL was assessed using a 36-item Short-Form health survey (SF36). A cumulative survival rate was calculated according to tertiles of SF36 scores and classified by the presence of CKD (estimated GFR <60 ml/min/1.73 m2).ResultsAmong 944 subjects, 46.6% had CKD. CKD patients had lower total and physical component scores compared with subjects without CKD. The 3-year cumulative survival rate was 90.0% (non-CKD vs. CKD: 92.6% vs. 87.4%, P = 0.005 by log rank test). After adjusting for multiple variables, a reduced SF36 score (physical and mental components) was a strong predictor of all-cause mortality. Physical components were consistently able to predict mortality after CKD classification, but mental components were statistically significant only in the CKD group.ConclusionIn addition to traditional risk factors of mortality, nephrologists should be aware of HRQOL as a predictor of mortality and should make efforts to improve HRQOL in CKD patients.

Outcome of renal allograft in patients with Henoch-Schönlein nephritis: single-center experience and systematic review.

Background. Henoch-Schönlein nephritis (HSN) is a rare condition resulting in end-stage renal disease. Therefore, graft outcomes and recurrence rates after transplantation are not well studied. Also, the effect of donor type on graft outcome has not been evaluated thoroughly. Methods. The graft outcome and recurrence rate in 20 kidney recipients with HSN were compared with age-, sex-, and donor source-matched controls (control A, primary immunoglobulin A nephropathy; control B, other causes; 40 recipients per group). To assess the effect of donor type, we pooled our data with two previous cohort studies where donor type had been described in detail. Results. Overall graft survival rates were 87.7% at 10 years. The overall recurrence rate of HSN was 15.4% over 10 years. Graft survival and recurrence rates in the HSN group were similar to those of control A and control B. The pooled data showed a 29.4% incidence rate for recurrent HSN. Living related donor transplantation showed a trend of higher recurrence compared with recipients with nonrelated grafts, although it was marginally significant (P=0.059). However, the graft survival rate in related-donor recipients was not inferior to that in the unrelated-donor recipients. Conclusions. Long-term graft survival and recurrence rates in kidney recipients with HSN were comparable to those of recipients with primary immunoglobulin A nephropathy. The type of donor did not significantly affect long-term graft survival.

HIP1R interacts with a member of Bcl-2 family, BCL2L10, and induces BAK-dependent cell death.

The Bcl-2 family members are evolutionally conserved and crucial regulators of apoptosis. BCL2L10 (human Diva or BCL-B) is a member of the Bcl-2 family that has contradictory functions in apoptosis. In the present study, we identified the Huntington-interacting protein 1-related (HIP1R) protein following a search for Diva-interacting proteins using the yeast two-hybrid system. HIP1R is a multi-domain protein that regulates the clathrin-mediated endocytic machinery and actin assembly in cells. Interaction of endogenous proteins of BCL2L10 and HIP1R in 293T cells was determined by immunoprecipitation, and their direct association was confirmed by the Far-Western analysis. The deletion of both the AP180-homology (ANTH) and F-actin-binding the talin-HIP1/R/Sla2p actin-tethering C-terminal homology (THATCH) domains of HIP1R greatly compromised its binding ability to BCL2L10. Ectopic expression of HIP1R resulted in moderate cell death of 293T cells in conjunction with the dissipation of mitochondrial membrane potential and caspase 9 activation. A member of proapoptotic Bcl-2 family, BAK, was required for HIP1R to induce cell death, while BAX was dispensable. In addition, BCL2L10 was associated with endogenous caspase 9, and their binding was augmented by HIP1R overexpression. Thus, this study provided the previously unknown function of HIP1R involved in the intrinsic cell death pathway and further explored possible mechanisms by which HIP1R induces cell death.

Dialysis Modality and Mortality in the Elderly: A Meta-Analysis

BACKGROUND AND OBJECTIVES Identifying the appropriate choice between hemodialysis (HD) and peritoneal dialysis (PD) is an unresolved issue in elderly patients with ESRD, who are at high risk for death but have a low chance of receiving kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data on 13,065 incident dialysis Korean patients (age≥65 years) receiving HD (n=10,675) or PD (n=2390) were obtained from the Korean Health Insurance dataset. Multiple statistical approaches, including the multivariate Cox model, were used to compare mortality between Korean patients receiving PD and those receiving HD. Subsequently, meta-analysis of previous comparison studies (published since the year 2000; population-based studies) and the Korean dataset was performed. RESULTS During a mean duration of 1.8±1.3 years (maximum of 5 years), the Korean PD group had a higher mortality rate than the Korean HD group (hazard ratio [HR], 1.20 [95% confidence interval (95% CI), 1.13 to 1.28]; P<0.001 by multivariate Cox model). The discrepancy between the two modalities was greater in the presence of certain conditions, such as diabetes mellitus or longer dialysis duration. In the meta-analysis, 15 studies involving >631,421 elderly patients were reviewed. Compared with HD, the pooled HR with PD was 1.10 (95% CI, 1.01 to 1.20). When the meta-analysis was stratified by confounding factors, the survival benefit from HD was particularly strong in subgroups that had diabetes mellitus, had long dialysis duration (>1 year), or contained cohorts starting dialysis in the 1990s. CONCLUSIONS A meta-analysis that included results in Korean patients suggests a higher risk for death in elderly patients receiving PD than in those receiving HD.

Association between body fat and vitamin D status in Korean adults.

The relationship between body fat mass and vitamin D appears to vary by ethnicity, but our understanding of this predisposition in Asians is limited due to the scarcity of prior investigations. Data on 1,697 Korean adults were obtained from the second and third years (2008-2009) of the fourth Korean National Health and Nutritional Examination Survey. Body fat mass was measured using dual-energy X-ray absorptiometry. Both linear regression analysis for serum 25-hydroxyvitamin D [25(OH)D] and logistic analysis for vitamin D deficiency [25(OH)D <20 ng/mL] were performed to determine significant predictors among BMI, waist circumference (WC), and body fat percentage (BF), after adjustment of multiple covariates. To explore a possible non-linear relationship between them, the fractional polynomials method was used. All analyses were conducted following stratification by sex. In linear regression analysis, BMI and WC were not associated with 25(OH)D. However, BF was inversely related to 25(OH)D, irrespective of the fat location (both appendicular and truncal fat) in both sexes. In logistic regression analysis, the highest quartile group of BF had a greater OR for vitamin D deficiency than the lower quartile groups, irrespective of the fat location and sex. However, the quartiles of BMI and WC were not associated with vitamin D deficiency. The linear relationships between BF and 25(OH)D (or vitamin D deficiency) were confirmed despite use of the fractional polynomials method. Body fat mass is inversely associated with serum 25(OH)D in Korean adults. Monitoring of vitamin D deficiency in Korean adults with high fat mass is needed.

Metabolic Acidosis and Long-Term Clinical Outcomes in Kidney Transplant Recipients

Metabolic acidosis (MA), indicated by low serum total CO2 (TCO2) concentration, is a risk factor for mortality and progressive renal dysfunction in CKD. However, the long-term effects of MA on kidney transplant recipients (KTRs) are unclear. We conducted a multicenter retrospective cohort study of 2318 adult KTRs, from January 1, 1997 to March 31, 2015, to evaluate the prevalence of MA and the relationships between TCO2 concentration and clinical outcomes. The prevalence of low TCO2 concentration (<22 mmol/L) began to increase in KTRs with eGFR<60 ml/min per 1.73 m2 and ranged from approximately 30% to 70% in KTRs with eGFR<30 ml/min per 1.73 m2 Multivariable Cox proportional hazards models revealed that low TCO2 concentration 3 months after transplant associated with increased risk of graft loss (hazard ratio [HR], 1.74%; 95% confidence interval [95% CI], 1.26 to 2.42) and death-censored graft failure (DCGF) (HR, 1.66; 95% CI, 1.14 to 2.42). Cox regression models using time-varying TCO2 concentration additionally demonstrated significant associations between low TCO2 concentration and graft loss (HR, 3.48; 95% CI, 2.47 to 4.90), mortality (HR, 3.16; 95% CI, 1.77 to 5.62), and DCGF (HR, 3.17; 95% CI, 2.12 to 4.73). Marginal structural Cox models adjusted for time-varying eGFR further verified significant hazards of low TCO2 concentration for graft loss, mortality, and DCGF. In conclusion, MA was frequent in KTRs despite relatively preserved renal function and may be a significant risk factor for graft failure and patient mortality, even after adjusting for eGFR.