Urine creatinine concentration influences the prognostic value of proteinuria for MACE prediction from the findings of the KNOW-CKD study.

Proteinuria is typically quantified according to the spot urine protein-creatinine ratio (UPCR) and an association with cardiovascular events has not been thoroughly investigated in chronic kidney disease (CKD) patients. We investigated whether the severity of proteinuria assessed by spot UPCR is associated with an increased risk for cardiovascular outcomes in the CKD population, and whether the relationship is influenced by urine creatinine concentration. We analyzed 1746 patients enrolled as part of The KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable Cox proportional hazard analysis was performed to evaluate models with proteinuria as a predictor of renal events and extended major adverse cardiovascular events (eMACEs). Risk for renal events was significantly associated with proteinuria across all eGFR and UPCR categories. By contrast, risk for eMACEs increased significantly with UPCR in patients with eGFR ≥ 60 mL/min/1.73 m2 (hazard ratio [HR] 2.109; 95% confidence interval [CI] 1.375-3.235; P = 0.001), but not in patients with eGFR < 60 mL/min/1.73 m2 (HR 1.086; 95% CI 0.910-1.296; P = 0.358). However, in those with the lower eGFR, risk for eMACEs increased significantly with UPCR in participants with urine creatinine concentration ≥ 95 mg/dL (HR 1.503; 95% CI 1.047-2.159; P = 0.027). In non-dialysis CKD patients, the prognostic value of UPCR for eMACEs is weakened in patients with reduced eGFR levels, for whom it has prognostic significance only in patients with high urine creatinine concentration.

Low-dose aspirin was associated with an increased risk of cardiovascular events in patients with chronic kidney disease patients and low bodyweight: results from KNOW-CKD study.

The benefits and risks of aspirin therapy for patients with chronic kidney disease (CKD) who have a high burden of cardiovascular events (CVE) are controversial. To examine the effects of low-dose aspirin on major clinical outcomes in patients with CKD. As a prospective observational cohort study, using propensity score matching, 531 aspirin recipients and non-recipients were paired for analysis from 2070 patients and fulfilled the inclusion criteria among 2238 patients with CKD. The primary outcome was the first occurrence of major CVE. The secondary outcomes were kidney events defined as a > 50% reduction of estimated glomerular filtration rate from baseline, doubling of serum creatinine, or onset of kidney failure with replacement therapy, the all-cause mortality, and bleeding event. The incidence of CVE was significantly greater in low-dose aspirin users than in non-users (HR 1.798; P = 0.011). A significant association between aspirin use and an increased risk of CVE was observed only in the lowest quartile of body weight (HR 4.014; P = 0.019) (Q1 < 60.0 kg). Secondary outcomes were not significantly different between aspirin users and non-users. It needs to be individualized of prescribing low-dose aspirin for the prevention of cardiovascular events in patients with chronic kidney disease, particularly patients with low bodyweight (< 60 kg).

Reduction of Secreted Frizzled-Related Protein 5 Drives Vascular Calcification through Wnt3a-Mediated Rho/ROCK/JNK Signaling in Chronic Kidney Disease.

Vascular calcification (VC) is commonly associated with bone loss in patients with chronic kidney disease (CKD). The Wingless-related integration site (Wnt) regulates osteoblast activation through canonical signaling pathways, but the common pathophysiology of these pathways during VC and bone loss has not been identified. A rat model of adenine-induced CKD with VC was used in this study. The rats were fed 0.75% adenine (2.5% protein, 0.92% phosphate) with or without intraperitoneal injection of calcitriol (0.08 µg/kg/day) for 4 weeks. Angiotensin II (3 µM)-induced VC was achieved in high phosphate medium (3 mM) through its effect on vascular smooth muscle cells (VSMCs). In an mRNA profiler polymerase chain reaction assay of the Wnt signaling pathway, secreted frizzled-related protein 5 (sFRP5) levels were significantly decreased in the CKD rat model compared with the control group. The repression of sFRP5 on VSMC trans-differentiation was mediated through Rho/Rho-associated coiled coil containing protein kinase (ROCK) and c-Jun N-terminal kinase (JNK) pathways activated by Wnt3a. In a proof of concept study conducted with patients with CKD, serum sFRP5 concentrations were significantly lower in subjects with VC than in those without VC. Our findings suggest that repression of sFRP5 is associated with VC in the CKD environment via activation of the noncanonical Wnt pathway, and thus that sFRP5 might be a novel therapeutic target for VC in CKD.

BAFF and APRIL expression as an autoimmune signature of membranous nephropathy.

BACKGROUND: Based on the fact that B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have a regulatory role in B cell biology, excessive levels of these cytokines can promote autoimmune pathogenesis. However, the expression and implication remain unresolved in cases of membranous nephropathy (MN). RESULTS: The plasma BAFF levels of the primary MN patients were higher than those of healthy controls but lower than those of secondary MN patients, whereas the APRIL levels were similar between the MN patients and healthy controls. The BAFF levels were higher in relapse cases, whereas the APRIL levels were higher in the patients who did not experience remission compared with the counterpart patients. The ectopic expression of BAFF and APRIL was observed in the glomeruli or circulating B cells of MN patients, and this high expression trend was similar to that of lupus patients. CONCLUSIONS: Expression profile of BAFF and APRIL in MN is similar to that of other autoimmune disease, which affects the kidney outcomes. METHODS: Plasma BAFF and APRIL levels were measured upon kidney biopsy in patients with primary (n = 89) and secondary MN (n = 13), and the results were compared with the levels in healthy controls (n = 111). The kidney outcomes (e.g., remission and relapse) were traced for the median of 3 years. Aberrant expression of the cytokines was evaluated in the kidney and circulating B cells using immunohistochemistry and flow cytometry analyses, respectively.

The association of kidney function with repetitive breath-hold diving activities of female divers from Korea, Haenyeo.

BACKGROUND: Voluntary apnea during breath-hold diving (BHD) induces cardiovascular changes including bradycardia, reduced cardiac output, and arterial hypertension. Although the impacts of repetitive BHD on cardiovascular health have been studied previously, the long-term risk for kidney dysfunction has never been investigated. METHODS: A cross-sectional propensity score-matched study was performed to evaluate the influence of repetitive long-lasting BHD on kidney function. Using matching propensity scores (PS), 715 breath-hold female divers (Haenyeo) and non-divers were selected for analysis from 1,938 female divers and 3,415 non-divers, respectively. The prevalence of chronic kidney disease (CKD) defined as an estimated glomerular filtration rate (eGFR) calculated to be less than 60 ml/min/1.73 m2 was investigated in both diver and non-diver groups. RESULTS: The prevalence of CKD was significantly higher in breath-hold divers compared with non-divers after PS matching (12.6% vs. 8.0%, P = 0.004). In multivariate analysis, BHD activity was significantly associated with the risk of CKD in an unmatched cohort (OR, 1.976; 95% CI, 1.465-2.664). In the PS-matched cohort, BHD remained the independent risk factor for CKD even after adjusting for multiple covariates (OR 1.967; 95% CI, 1.341-2.886). CONCLUSION: Shallow but repetitive intermittent apnea by BHD, sustained for a long period of time, may potentially cause a deterioration in kidney function, as a long-term consequence.

The Impact of Renin-Angiotensin System Blockade on Renal Outcomes and Mortality in Pre-Dialysis Patients with Advanced Chronic Kidney Disease.

Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071-1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123-1.500; P < 0.001). The risk of composite outcomes was higher in RAS blockade users in IPTW (HR, 1.154; 95% CI, 1.016-1.310; P = 0.027), but was marginal significance in PS matched analysis (HR, 1.243; 95% CI, 0.996-1.550; P = 0.054). The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.

Validation of the Korean coefficient for the modification of diet in renal disease study equation.

BACKGROUND/AIMS: Race and ethnicity are important determinants when estimatingglomerular filtration rate (GFR). The Korean coefficients for the isotope dilution mass spectrometry (IDMS) Modification of Diet in Renal Disease (MDRD) Study equations were developed in 2010. However, the coefficients have not been validated. The aim of this study was to validate the performance of the Korean coefficients for the IDMS MDRD Study equations. METHODS: Equation development and validation were performed in separate groups (development group, n = 147 from 2008 to 2009; validation group, n = 125 from 2010 to 2012). We compared the performance of the original IDMS MDRD equations and modified equations with Korean coefficients. Performance was assessed by comparing correlation coefficients, bias, and accuracy between estimated GFR and measured GFR, with systemic inulin clearance using a single injection method. RESULTS: The Korean coefficients for the IDMS MDRD equations developed previously showed good performance in the validation group. The new Korean coefficients for the four- and six-variable IDMS MDRD equations using both the development and validation cohorts were 1.02046 and 0.97300, respectively. No significant difference was detected for the new Korean coefficients, in terms of estimating GFR, between the original and modified IDMS MDRD Study equations. CONCLUSIONS: The modified equations with Korean coefficients for the IDMS MDRD Study equations were not superior to the original equations for estimating GFR. Therefore, we recommend using the original IDMS MDRD Study equation without ethnic adjustment in the Korean population.

Anti-Phospholipase A2 Receptor Antibody as Prognostic Indicator in Idiopathic Membranous Nephropathy.

BACKGROUND: Anti-phospholipase A2 receptor antibody (PLA2R-Ab) is useful in diagnosing idiopathic membranous nephropathy (IMN). We investigated the clinical relevance of PLA2R-Ab enzyme-linked immunosorbent assay (ELISA) in patients with IMN. METHODS: We measured PLA2R-Ab with an ELISA kit from the serum of 160 patients with IMN (n = 93), secondary MN (n = 14) and other glomerulonephritis (n = 41) as well as healthy controls (n = 12) at the time of renal biopsy and investigated the correlation of titers of PLA2R-Ab with clinical parameters. RESULTS: PLA2R-Ab was positive in 41 of 93 patients (44.1%) with IMN. No samples from the patients with secondary MN and other glomerulonephritis or healthy controls were positive with the ELISA test. The PLA2R-Ab-positive patients showed severe disease activity and a low remission rate. The PLA2R-Ab titer positively correlated with proteinuria and was negatively associated with renal function and serum albumin. The patients with a high titer of PLA2R-Ab had significantly decreased remission rates. The cumulative probabilities of remission was significantly lower in patients with PLA2R-Ab (p = 0.01) and even so in patients with a high titer of PLA2R-Ab (p = 0.04). When we compared the ELISA titers with Western blot (WB) data of 43 patients who had been enrolled in our previous study, 18 and 30 patients were positive on ELISA (41.9%) and WB (69.8%), respectively. WB and ELISA had a concordance rate of 72.1% and were positively correlated (r = 0.590, p < 0.001). CONCLUSION: The presence, as well as a high titer, of PLA2R-Ab on ELISA was associated with poor prognosis of IMN. Assessment of PLA2R-Ab with ELISA is an easy and reliable tool for the diagnosis and guidance of therapeutic plans.

Recovery of Corneal Endothelial Cells from Periphery after Injury.

BACKGROUND: Wound healing of the endothelium occurs through cell enlargement and migration. However, the peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium in endothelial injury. AIM: To investigate the recovery process of corneal endothelial cells (CECs) from corneal endothelial injury. METHODS: Three patients with unilateral chemical eye injuries, and 15 rabbit eyes with corneal endothelial chemical injuries were studied. Slit lamp examination, specular microscopy, and ultrasound pachymetry were performed immediately after chemical injury and 1, 3, 6, and 9 months later. The anterior chambers of eyes from New Zealand white rabbits were injected with 0.1 mL of 0.05 N NaOH for 10 min (NaOH group). Corneal edema was evaluated at day 1, 7, and 14. Vital staining was performed using alizarin red and trypan blue. RESULTS: Specular microscopy did not reveal any corneal endothelial cells immediately after injury. Corneal edema subsided from the periphery to the center, CEC density increased, and central corneal thickness decreased over time. In the animal study, corneal edema was greater in the NaOH group compared to the control at both day 1 and day 7. At day 1, no CECs were detected at the center and periphery of the corneas in the NaOH group. Two weeks after injury, small, hexagonal CECs were detected in peripheral cornea, while CECs in mid-periphery were large and non-hexagonal. CONCLUSIONS: CECs migrated from the periphery to the center of the cornea after endothelial injury. The peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium.

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.

Non-linear association of serum 25-hydroxyvitamin D with urinary albumin excretion rate in normoalbuminuric subjects.

BACKGROUND: Vitamin D deficiencies and increases in urinary albumin excretion (UAE) are both important and potentially related health problems; however, the nature of their relationship has not been established in normoalbuminuric subjects. METHODS: We obtained data from 14,594 normoalbuminuric Korean adults who underwent voluntary health screenings. We used a generalized additive model to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and urinary-albumin creatinine ratio (UACR) levels. We conducted multivariate logistic regression for high-normal UAE (UACR, 10-29 mg/g), according to various categories of vitamin D status. RESULTS: The generalized additive model confirmed a non-linear relationship between serum 25(OH)D and UACR levels, and the threshold concentration of 25(OH)D was 8.0 ng/mL after multivariate adjustment. Comparing subjects who fell into the lowest category of serum 25(OH)D levels with subjects who were in the reference range (the highest category), we observed that the multivariate adjusted odds ratio (OR) for high-normal UAE was significantly increased, regardless of the criteria used to categorize vitamin D levels: OR of the 1st quartile over the 4th quartile, 1.20 (95% CI, 1.04-1.39); OR of the 1.0-4.9th percentile over the 50-100th percentile, 1.56 (95% CI, 1.25-1.93); and OR of vitamin D deficiency group over vitamin D sufficiency group, 1.28 (95% CI, 1.08-1.52). CONCLUSIONS: We demonstrated that there was an inverse relationship between serum 25(OH)D less than 8.0 ng/mL and UACR in normoalbuminuric subjects, suggesting that severe vitamin D deficiency could cause an increase in UAE in subjects with normoalbuminuria.

Non-linear relationship between serum 25-hydroxyvitamin D and hemoglobin in Korean females: the Korean National Health and Nutrition Examination Survey 2010-2011.

BACKGROUND: Anemia and vitamin D deficiency are both important health issues; however, the nature of the association between vitamin D and either hemoglobin or anemia remains unresolved in the general population. METHODS: Data on 11,206 adults were obtained from the fifth Korean National Health and Nutritional Examination Survey. A generalized additive model was used to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and hemoglobin levels. A multivariate logistic regression for anemia was conducted according to 25(OH)D quintiles. All analyses were stratified according to sex and menstrual status. RESULTS: The generalized additive model confirmed a threshold 25(OH)D level of 26.4 ng/mL (male, 27.4 ng/mL; premenopausal females, 11.8 ng/mL; postmenopausal females, 13.4 ng/mL). The threshold level affected the pattern of association between 25(OH)D and anemia risk: the odds ratio of the 1(st) quintile but not the 2(nd), 3(rd), and 4(th) quintiles were significantly different from the 5(th) quintile in both premenopausal and postmenopausal females, however there was no obvious trend in males. CONCLUSIONS: This population-based study demonstrated a non-linear relationship with a threshold effect between serum 25(OH)D and hemoglobin levels in females. Further interventional studies are warranted to determine whether the appropriate level of hemoglobin can be achieved by the correction of vitamin D deficiency.

Autoantibodies against phospholipase A2 receptor in Korean patients with membranous nephropathy.

The data were presented in abstract form at the 45(th) meeting of the American Society of Nephrology, October 30-November 04 2012, San Diego, CA, USA. Circulating autoantibodies against M-type phospholipase A2 receptor (PLA2R) are important pathogenic antibodies of idiopathic membranous nephropathy (MN) in adults. However, previous studies on the clinical impact of anti-PLA2R antibodies demonstrated several limitations, including insufficient numbers of study subjects and different time points and methods for anti-PLA2R antibody measurement. To verify the clinical significance of anti-PLA2R antibodies in Korean patients with MN, we measured autoantibodies in serum samples obtained at the time of biopsy from a total of 100 patients with idiopathic MN who had not yet received immunosuppressive treatment. We detected anti-PLA2R antibody in 69 patients, and we observed that autoantibody reactivity reflected the severity of disease activity. Proteinuria and hypoalbuminemia were more severe in patients with anti-PLA2R than in those without the autoantibodies (2.95 g/g vs. 6.85 g/g, P = 0.003; 3.1 g/dL vs. 2.5 g/dL, P = 0.004, respectively). Additionally, the clinical severities worsened proportionally as the levels of anti-PLA2R antibodies increased (P = 0.015 and P for trend <0.001 for proteinuria and hypoalbuminemia, respectively). However, neither the levels nor the presence or absence of anti-PLA2R antibody showed a significant correlation with clinical outcomes, such as remission rate and time to remission. In conclusion, we observed that anti-PLA2R antibodies are highly prevalent in Korean patients with idiopathic MN and that they reflect the clinical disease activity before the administration of immunosuppressive treatment. However, the levels of anti-PLA2R antibody at the time of kidney biopsy may not predict the clinical outcomes in current clinical practice.

Altered expression of adrenocorticotropic hormone in the epileptic gerbil hippocampus following spontaneous seizure.

We investigated the temporal alterations of adrenocorticotropic hormone (ACTH) immunoreactivity in the hippocampus after seizure onset. Expression of ACTH was observed within interneurons in the pre-seizure group of seizure sensitive gerbils, whereas its immunoreactivities were rarely detected in seizure resistant gerbil. Three hr after the seizure, ACTH immunoreactivity was significantly increased in interneurons within all hippocampal regions. On the basis of their localization and morphology through immunofluorescence staining, these cells were identified as GABAA α1-containing interneurons. At the 12 hr postictal period, ACTH expression in these regions was down-regulated, in a similar manner to the pre-seizure group of gerbils. These findings support the increase in ACTH synthesis that contributes to a reduction of corticotrophin-releasing factor via the negative feedback system which in turn provides an opportunity to enhance the excitability of GABAergic interneurons. Therefore, ACTH may play an important role in the reduction of excitotoxicity in all hippocampal regions.

Cdk1 protein-mediated phosphorylation of receptor-associated protein 80 (RAP80) serine 677 modulates DNA damage-induced G2/M checkpoint and cell survival.

Post-translational phosphorylation plays critical roles in the assembly of signaling and repair proteins in the DNA damage response pathway. RAP80, a component of the BRCA1-A complex, is crucial in cell cycle checkpoint activation and DNA damage repair. However, its molecular mechanism is unclear. In this study, we identified Cdk1 as a new RAP80-binding protein and demonstrated that the Cdk1-cyclin B(1) complex phosphorylates RAP80 at Ser-677 using an in vitro kinase assay and a phosphopeptide-specific antibody against phospho-Ser-677 of RAP80. RAP80 Ser-677 phosphorylation occurred in the M phase of the cell cycle when Cdk1 was in an active state. In addition, ionizing radiation (IR) induced RAP80 phosphorylation at Ser-677. Mutation of Ser-677 to alanine sensitized cells to IR and functioned in G(2)/M checkpoint control. These results suggest that post-translational phosphorylation of RAP80 by the Cdk1-cyclin B(1) complex is important for RAP80 functional sensitivity to IR and G(2)/M checkpoint control.

Alterations in hyperpolarization-activated cyclic nucleotidegated cation channel (HCN) expression in the hippocampus following pilocarpine-induced status epilepticus.

To understand the effects of HCN as potential mediators in the pathogenesis of epilepsy that evoke long-term impaired excitability; the present study was designed to elucidate whether the alterations of HCN expression induced by status epilepticus (SE) is responsible for epileptogenesis. Although HCN1 immunoreactivity was observed in the hippocampus, its immunoreactivities were enhanced at 12 hrs following SE. Although, HCN1 immunoreactivities were reduced in all the hippocampi at 2 weeks, a re-increase in the expression at 2-3 months following SE was observed. In contrast to HCN1, HCN 4 expressions were un-changed, although HCN2 immunoreactive neurons exhibited some changes following SE. Taken together, our findings suggest that altered expressions of HCN1 following SE may be mainly involved in the imbalances of neurotransmissions to hippocampal circuits; thus, it is proposed that HCN1 may play an important role in the epileptogenic period as a compensatory response.

Soluble epoxide hydrolase activity determines the severity of ischemia-reperfusion injury in kidney.

Soluble epoxide hydrolase (sEH) in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs), which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI) in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA). The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME) and its metabolite dihydroxyoctadec-12-enoic acid (DHOME). Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury.

The association of moderate renal dysfunction with impaired preference-based health-related quality of life: third Korean national health and nutritional examination survey.

BACKGROUND: Only a few large-scale studies have investigated the association between health-related quality of life (HRQOL) and renal function. Moreover, the HRQOL of patients with moderate renal dysfunction is frequently underestimated by healthcare providers. This study assessed the impact of renal function on preference-based HRQOL in Korean adult population. METHODS: We analyzed data for 5,555 adults from the 3(rd) Korean National Health and Nutritional Examination Survey 2005. The EuroQol-5D (EQ-5D) utility score was used to evaluate HRQOL. The study subjects were stratified into three groups based on their estimated glomerular filtration rates (eGFRs): ≥ 90.0, 60.0-89.9 and 30.0-59.9 mL/min/1.73 m(2). Individuals with advanced renal dysfunction were excluded from the analysis. RESULTS: The proportions of participants who reported problems in each of the five EQ-5D dimensions increased significantly with decreasing eGFR. However, a significant decrease in the EQ-5D utility score was observed among participants with an eGFR of 30.0-59.9 mL/min/1.73 m(2). Participants with an eGFR of 30.0-59.9 mL/min/1.73 m(2) had an almost 1.5-fold higher risk of impaired health utility (the lowest quartile of EQ-5D utility score) compared with those participants with eGFRs ≥ 90.0 mL/min/1.73 m(2), after adjustment for age, gender, health-related behaviors, socioeconomic and psychological variables, and other comorbidities. Among the five dimensions of the EQ-5D, an eGFR of 30.0-59.9 mL/min/1.73 m(2) was an independent determinant of self-reported problems in the mobility and pain/discomfort dimensions. CONCLUSIONS: Although age affects the association between renal dysfunction and the EQ-5D, moderate renal dysfunction seems to be an important determinant of impaired health utility in a general population and may affect the mobility and pain/discomfort dimensions of health utility.

A threshold value of estimated glomerular filtration rate that predicts changes in serum 25-hydroxyvitamin D levels: 4th Korean National Health and Nutritional Examination Survey 2008.

BACKGROUND: Vitamin D deficiency is known as an important risk factor for mortality in patients with chronic kidney disease (CKD). Nevertheless, the association of renal function itself with vitamin D status or serum 25-hydroxyvitamin D (25OHD) level has not been investigated thoroughly. METHODS: We examined the association between the estimated glomerular filtration rate (eGFR) and serum 25OHD levels using data from the 4th Korean National Health and Nutritional Examination Survey 2008. Generalized additive models (GAMs) were used to examine the relationship between eGFR and serum 25OHD levels and to estimate a threshold value of eGFR that predicts changes in serum 25OHD levels. RESULTS: The mean serum 25OHD level was 20.4 ± 9.1 ng/mL, and the overall prevalence of vitamin D deficiency was 29.9% in this population. The prevalence of vitamin D deficiency began to increase at eGFR levels <45 mL/min/1.73 m(2). After adjustment, the logistic regression of dichotomized eGFR levels with a cut-point of 45 mL/min/1.73 m(2) yielded an increased odds ratio for vitamin D deficiency. Additionally, the continuous relationship between eGFR and 25OHD levels was explored using GAMs adjusted for various confounding factors. In this analysis, the difference from the mean serum 25OHD started to increase below an eGFR threshold of 55.4 mL/min/1.73 m(2), which suggests that renal function is directly related to the serum 25OHD levels in patients with CKD Stages 3-5. CONCLUSION: Although moderate renal dysfunction (eGFR < 45 mL/min/1.73 m(2)) is an important predictor of vitamin D deficiency, serum 25OHD levels start to decrease below an eGFR level of ~60 mL/min/1.73 m(2) independent of other risk factors. These results suggest that more careful attention to 25OHD levels may be needed when patients reach Stage 3 CKD.

Incidence of post-transplant glomerulonephritis and its impact on graft outcome.

BACKGROUND: Herein, the significance of post-transplant glomerulonephritis (PTGN) has been revisited to investigate whether PTGN induces allograft failure. The aim of this study was to identify the incidence of PTGN and its association with allograft failure, as well as to analyze the risk factors for PTGN. METHODS: Among the 996 Korean patients who underwent kidney transplantation in a multicenter cohort from 1995 to 2010, 764 patients were enrolled in this study. RESULTS: The incidence rate of PTGN was 9.7% and 17.0% at 5 and 10 years of follow-up, respectively. PTGN was diagnosed in 17.8% of the recipients with results of biopsy tests or clinical diagnosis identifying glomerular diseases as the underlying cause, compared with 0.0%, 4.4%, 4.9%, 5.5%, and 5.7% of the recipients with renal vascular diseases, renal interstitial diseases/pyelonephritis/uropathy, diabetic renal disease, hereditary renal diseases, and diseases with unknown etiologies, respectively. Allograft survival was significantly decreased in patients with PTGN. PTGN was associated with a fourfold increase in graft failure with a hazard ratio of 7.11 for both acute rejection and PTGN. Results of the risk factor analysis for PTGN revealed that the underlying glomerular renal diseases and treatment methods using drugs such as tacrolimus and basiliximab significantly increased PTGN development, after adjusting for other risk factors. CONCLUSION: We conclude that PTGN is strongly associated with poor kidney allograft survival. Therefore, optimal management of recurrent or de novo GN should be the critical focus of post-transplant care.