Background α-Klotho is reported to have protective effects against kidney injury, and its renal expression is decreased in many experimental models of kidney disease. However, circulating α-klotho ...levels in human chronic kidney disease (CKD) and the relationship to progression are unknown. Study Design Post hoc analysis of a prospective cohort study. Setting & Participants 243 of 301 participants from a CKD cohort at our institution between January 2006 and December 2011 were eligible for the study. Predictor Baseline α-klotho levels. Outcomes Primary outcome was the composite of doubling of baseline serum creatinine concentration, end-stage renal disease, or death. End-stage renal disease was defined as onset of treatment by renal replacement therapy. Measurements Serum α-klotho and fibroblast growth factor 23 (FGF-23) were measured using enzyme-linked immunosorbent assay. Results Lower serum α-klotho levels were associated with more severe CKD stage in the cross-sectional analysis of the baseline data ( P for trend < 0.001). In the adjusted multivariable linear regression model, log(α-klotho) was associated independently with estimated glomerular filtration rate (β = 0.154; P = 0.001). Cox regression analysis showed that baseline α-klotho level independently predicted the composite outcome after adjustment for age, diabetes, blood pressure, estimated glomerular filtration rate, proteinuria, parathyroid hormone level, and FGF-23 level (HR per 10-pg/mL increase, 0.96; 95% CI, 0.94-0.98; P < 0.001). When patients were categorized into 2 groups according to baseline median α-klotho value, 43 (35.2%) patients with α-klotho levels ≤396.3 pg/mL reached the primary composite outcome compared with 19 (15.7%) with α-klotho levels >396.3 pg/mL (HR, 2.03; 95% CI, 1.07-3.85; P = 0.03). Limitations Uncontrolled dietary phosphorus intake and use of frozen samples. Conclusions This observational study showed that low circulating α-klotho levels were associated with adverse kidney disease outcome, suggesting that α-klotho is a novel biomarker for CKD progression. More data from larger prospective longitudinal studies are required to validate our findings.
The purpose of the present study was to evaluate the incidence rate (IR) of suicide in elderly patients with hip fracture on the basis of a nationwide cohort and to analyze the change in the hazard ...ratio for suicide after hip fracture over time in comparison with a control group.
Patients with hip fracture and their matched controls were selected from the National Health Insurance Service-Senior cohort (NHIS-Senior) of the Republic of Korea. The NHIS-Senior consists of 558,147 people selected by a 10% simple random-sampling method from a total of 5.5 million subjects ≥60 years of age in 2002. Risk-set matching (1:2) on the propensity score was performed with use of a nearest neighbor matching algorithm with a maximum caliper of 0.1 for the hazard components. The IR of suicide and 95% confidence interval (CI) were calculated on the basis of a generalized linear model with a Poisson distribution. The effect size was presented as a hazard ratio (HR) with use of the Cox proportional-hazard model with a robust variance estimator that accounts for clustering within matched pairs.
A total of 11,477 patients with hip fracture and 22,954 matched controls were included. The mean duration of follow-up was 4.59 years, generating 158,139 person-years. During follow-up, a total of 170 suicides were identified. Comparisons at up to 180 days and 365 days showed that patients with hip fracture were at higher risk for suicide than matched controls (p = 0.009 and 0.004, respectively; stratified log-rank test). During the first 180 days of follow-up, 14 suicides were identified in patients with hip fracture during 11,152 person-years (IR, 266.1 per 100,000 person-years; 95% CI, 157.6 to 449.4). Patients with hip fracture were 2.97 times more likely to kill themselves than their matched controls during the same period (HR = 2.97; 95% CI, 1.32 to 6.69).
Hip fracture in elderly patients increased suicide risk within a year. A new approach to psychiatric evaluation and management is needed in elderly patients with hip fracture.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Background. The impact of dialysis modality on the rates and types of infectious complications has not been well studied. The aim of the present investigation was to evaluate the rates of hepatitis C ...virus (HCV) and hepatitis B virus (HBV) infections in peritoneal dialysis (PD) and haemodialysis (HD) patients in the Asia-Pacific region. Methods. The study included the most recent period-prevalent data recorded in the national or regional dialysis registries of the 10 Asia-Pacific countries/areas (Australia, New Zealand, Japan, China, Taiwan, Korea, Thailand, Hong Kong, Malaysia and India), where such data were available. Longitudinal data were also available for all incident Australian and New Zealand patients commencing dialysis between 1 April 1995 and 31 December 2005. Rates of HCV and HBV infections were compared by chi-square, Poisson regression and Kaplan–Meier survival analyses, as appropriate. Results. Data were obtained on 201 590 patients (HD 173 788; PD 27 802). HCV seroprevalences ranged between 0.7% and 18.1% across different countries and were generally higher in HD versus PD populations (7.9% ± 5.5% versus 3.0% ± 2.0%, P = 0.01). Seroconversion rates on dialysis were also significantly higher in HD patients (incidence rate ratio PD versus HD 0.33, 95% CI 0.13–0.75). HCV infection was highly predictive of mortality in Japan (relative risk 1.37, 95% CI 1.15–1.62, P = 0.003) and in Australia and New Zealand (adjusted hazards ratio 1.29, 95% CI 1.05–1.58). HBV infection data were limited, but less clearly influenced by dialysis modality. Conclusions. Dialysis modality selection significantly influences the risk of HCV infection experienced by end-stage renal failure patients in the Asia-Pacific region. No such association could be identified for HBV infection.
Background Despite the theoretical benefits of biocompatible physiological-pH bicarbonate/lactate-buffered (B/L) peritoneal dialysis solution, there is only limited evidence supporting a superior ...clinical outcome associated with its use. Study Design Observational study. Settings & Participants 2,163 patients starting peritoneal dialysis therapy between July 2003 and December 2006 from 54 centers in Korea were enrolled. Predictors B/L solution and icodextrin use. Outcomes All-cause mortality and technique failure. Measurements Patient outcomes were compared between patients prescribed B/L and conventional solutions by using propensity score and intention-to-treat analyses. Results 542 patients initiated peritoneal dialysis therapy with B/L solution, and 1,621, with conventional solution. Fifteen patients prescribed B/L solution switched to conventional solution, and 386 of those initially using conventional solution switched to B/L solution during follow-up. Propensity score matching yielded 542 matched pairs of patients. In the matched cohort, there were no significant differences in age, diabetes, cardiovascular comorbidity, socioeconomic status, icodextrin use, or center experience between the 2 groups. All-cause deaths occurred in 52 (9.6%) patients in the B/L-solution group compared with 102 (18.9%) in the conventional-solution group (hazard ratio HR, 0.70; 95% confidence interval CI, 0.50 to 0.98; P = 0.04). In addition, icodextrin use was significantly associated with a reduced risk of death (HR, 0.40; 95% CI, 0.28 to 0.58; P < 0.001). Thirty-three (6.1%) and 48 (8.9%) technique failures occurred in the B/L- and conventional-solution groups, respectively (HR, 0.91; 95% CI, 0.58 to 1.43; P = 0.7). The survival benefit of B/L solution persisted in the unmatched cohort (HR, 0.69; 95% CI, 0.52 to 0.93; P = 0.02). Limitations Retrospective analysis, lack of laboratory data, and unknown indications for use of B/L solution. Conclusion Use of a biocompatible B/L peritoneal dialysis solution with physiological pH is associated with improved survival compared with conventional solution. Large randomized clinical trials are warranted to confirm this finding.
Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown.
We conducted a retrospective observational study ...in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR.
During a median follow-up duration of 65 (12-154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of <0.3 g/g compared to 6 (2.7%) patients with TA-P of 0.3-0.99 g/g (hazard ratio, 2.82; P = 0.35). Risk of reaching a 50% decline in eGFR markedly increased in patients with TA-P of 1.0-2.99 g/g (P = 0.002) and those with TA-P≥3.0 g/g (P<0.001). ESRD did not occur in patients with TA-P<1.0 g/g compared to 26 (20.0%) and 8 (57.1%) patients with TA-P of 1.0-2.99 and ≥3.0 g/g, respectively. Kidney function of these two groups deteriorated faster than those with TA-P<1.0 g/g (P<0.001). However, patients with TA-P of 0.3-0.99 g/g had a greater decline of eGFR than patients with TA-P<0.3 g/g (-0.41±1.68 vs. -0.73±2.82 ml/min/1.73 m2/year, P = 0.03).
In this study, patients with TA-P<1.0 g/g show favorable outcomes. However, given the faster eGFR decline in patients with TA-P of 0.3-0.99 g/g than in patients with TA-P<0.3 g/g, the ultimate optimal goal of proteinuria reduction can be lowered in the management of IgAN.
Background. The prevalence of glomerular diseases differs according to geographic area, race, age and indications for a renal biopsy. This study was conducted to evaluate the distribution and ...changing patterns of renal diseases during the past 20 years in a large patient population in Korea. Methods. Patients aged 16 years or older who underwent a renal biopsy at Severance Hospital in the Yonsei University Health System from 1987 to 2006 were enrolled. All medical records were reviewed retrospectively. Results. In total, 1818 patients (M:F = 1.02:1) were reviewed. Glomerulonephritis (GN) comprised 85.9% of the total biopsied cases. The most common primary GN was IgA nephropathy (IgAN) (28.3%), which was followed by minimal change disease (MCD) (15.5%), membranous nephropathy (MN) (12.3%), focal segmental glomerulosclerosis (FSGS) (5.6%) and membranoproliferative GN (MPGN) (4.0%). The most common secondary GN was lupus nephritis (8.7%). The most common idiopathic nephrotic syndrome was MCD (38.5%), which was followed by MN and IgAN. Among 128 (7.4%) patients who were HBsAg-positive, MN (30.5%) and MPGN (21.1%) were the most common GN. When the incidence rates between 1987–91 and 2002–06 were compared, IgAN increased from 25.6 to 34.5%, while MCD (from 23.2 to 7.0%) and MPGN (from 6.7 to 1.7%) decreased significantly (P < 0.01). Conclusions. IgAN was the most common primary GN, and MCD was the most common cause of nephrotic syndrome. In the 5-year quartile comparison, the relative frequency of IgAN increased, while the relative frequency of MCD and MPGN decreased significantly during the past 20 years.
Protein-energy wasting (PEW) is prevalent among patients on dialysis and has emerged as an important risk factor for morbidity and mortality in these patients. Numerous factors, including ...inflammation, inadequate dialysis, insufficient nutrient intake, loss of protein during dialysis, chronic acidosis, hypercatabolic illness and comorbid conditions, are involved in the development of PEW. The causes and clinical features of PEW in patients on peritoneal dialysis and hemodialysis are comparable; assessment of the factors that lead to PEW in patients receiving peritoneal dialysis is important to ensure that PEW is managed correctly in these patients. For the past 20 years, much progress has been made in the prevention and treatment of PEW. However, the results of most nutritional intervention studies are inconclusive. In addition, the multifactorial and complicated pathogenesis of PEW makes it difficult to assess and treat. This Review summarizes the nutritional issues regarding the causes, assessment and treatment of PEW, with a focus on patients receiving peritoneal dialysis. In addition, an in-depth overview of the results of nutritional intervention studies is provided.
A model/sensor hybrid approach is implemented to conduct failure prognostics of an automotive electronic control unit (ECU). A 3-D finite-element model simulating a complex ECU is built, and its ...predictability is calibrated and verified by an optical displacement measurement technique called moiré interferometry. On the sensor front, a silicon-based piezoresistive stress sensor is embedded into the ECU to provide in situ stress measurements during operations. A stress metric is defined using the stress values of 12 cells in each sensor, and it is converted to in situ loading histories using the calibrated finite-element model. The modeling and verification steps that lead to the predictive finite-element model are described. The proposed hybrid approach is implemented using the data obtained from a molded ECU subjected to thermal cycling conditions, and the forces at an interface between an aluminum wire bond and metal pad are investigated.
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