Active DNA damage eviction by HLTF stimulates nucleotide excision repair.

Nucleotide excision repair (NER) counteracts the onset of cancer and aging by removing helix-distorting DNA lesions via a "cut-and-patch"-type reaction. The regulatory mechanisms that drive NER through its successive damage recognition, verification, incision, and gap restoration reaction steps remain elusive. Here, we show that the RAD5-related translocase HLTF facilitates repair through active eviction of incised damaged DNA together with associated repair proteins. Our data show a dual-incision-dependent recruitment of HLTF to the NER incision complex, which is mediated by HLTF's HIRAN domain that binds 3'-OH single-stranded DNA ends. HLTF's translocase motor subsequently promotes the dissociation of the stably damage-bound incision complex together with the incised oligonucleotide, allowing for an efficient PCNA loading and initiation of repair synthesis. Our findings uncover HLTF as an important NER factor that actively evicts DNA damage, thereby providing additional quality control by coordinating the transition between the excision and DNA synthesis steps to safeguard genome integrity.

A disease-associated XPA allele interferes with TFIIH binding and primarily affects transcription-coupled nucleotide excision repair.

XPA is a central scaffold protein that coordinates the assembly of repair complexes in the global genome (GG-NER) and transcription-coupled nucleotide excision repair (TC-NER) subpathways. Inactivating mutations in XPA cause xeroderma pigmentosum (XP), which is characterized by extreme UV sensitivity and a highly elevated skin cancer risk. Here, we describe two Dutch siblings in their late forties carrying a homozygous H244R substitution in the C-terminus of XPA. They present with mild cutaneous manifestations of XP without skin cancer but suffer from marked neurological features, including cerebellar ataxia. We show that the mutant XPA protein has a severely weakened interaction with the transcription factor IIH (TFIIH) complex leading to an impaired association of the mutant XPA and the downstream endonuclease ERCC1-XPF with NER complexes. Despite these defects, the patient-derived fibroblasts and reconstituted knockout cells carrying the XPA-H244R substitution show intermediate UV sensitivity and considerable levels of residual GG-NER (~50%), in line with the intrinsic properties and activities of the purified protein. By contrast, XPA-H244R cells are exquisitely sensitive to transcription-blocking DNA damage, show no detectable recovery of transcription after UV irradiation, and display a severe deficiency in TC-NER-associated unscheduled DNA synthesis. Our characterization of a new case of XPA deficiency that interferes with TFIIH binding and primarily affects the transcription-coupled subpathway of nucleotide excision repair, provides an explanation of the dominant neurological features in these patients, and reveals a specific role for the C-terminus of XPA in TC-NER.

Two interaction surfaces between XPA and RPA organize the preincision complex in nucleotide excision repair.

The xeroderma pigmentosum protein A (XPA) and replication protein A (RPA) proteins fulfill essential roles in the assembly of the preincision complex in the nucleotide excision repair (NER) pathway. We have previously characterized the two interaction sites, one between the XPA N-terminal (XPA-N) disordered domain and the RPA32 C-terminal domain (RPA32C), and the other with the XPA DNA binding domain (DBD) and the RPA70AB DBDs. Here, we show that XPA mutations that inhibit the physical interaction in either site reduce NER activity in biochemical and cellular systems. Combining mutations in the two sites leads to an additive inhibition of NER, implying that they fulfill distinct roles. Our data suggest a model in which the interaction between XPA-N and RPA32C is important for the initial association of XPA with NER complexes, while the interaction between XPA DBD and RPA70AB is needed for structural organization of the complex to license the dual incision reaction. Integrative structural models of complexes of XPA and RPA bound to single-stranded/double-stranded DNA (ss/dsDNA) junction substrates that mimic the NER bubble reveal key features of the architecture of XPA and RPA in the preincision complex. Most critical among these is that the shape of the NER bubble is far from colinear as depicted in current models, but rather the two strands of unwound DNA must assume a U-shape with the two ss/dsDNA junctions localized in close proximity. Our data suggest that the interaction between XPA and RPA70 is key for the organization of the NER preincision complex.

Self-Charging Power System Empowered by Bismuth Halide Perovskite-Based Hybrid Nanogenerator and Lithium-ion Battery.

Halide perovskite, renowned for its multifunctional properties, shows considerable promise for realizing self-charging power systems. In this study, a lead-free methylammonium bismuth iodide (MA3Bi2I9) perovskite is used to create a self-charging power unit (SPU). This involves constructing a hybrid piezoelectric-triboelectric nanogenerator (Hybrid-TENG) and utilizing MA3Bi2I9 for energy storage as an anode in a lithium-ion battery (LIB). Initially, MA3Bi2I9 nanorods are synthesized and composited with a polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene polymer. The dielectric and mechanical properties of composite films having perovskite loading content are investigated. The optimized Hybrid-TENG exhibits superior performance, generating a voltage of 537 V, current density of 13.2 µA cm- 2, and maximum power density of 3.04 mW cm-2, which can be attributed to the high piezoelectric coefficient of MA3Bi2I9 nanorods (≈20.6 pm V-1). A MA3Bi2I9 thin film, serving as an electrode in LIB, demonstrates a high specific capacity of 2378.9 mAh cm-3 (578.8 mAh g-1) with a capacity retention of ≈87.5% over 100 cycles, underscoring its stable performance. Furthermore, a Hybrid-TENG is employed to charge the MA3Bi2I9-based LIB, thus realizing an SPU for driving portable electronics. This study highlights the promising potential of perovskites for developing efficient nanogenerators and LIBs, paving the way for sustainable energy solutions in small-scale electronics.

Non-contrast low-dose CT can be used for volumetry of ADPKD.

BACKGROUND: Kidney volume provides important information for the diagnosis and prognosis of autosomal dominant polycystic kidney disease (ADPKD), as well as for the evaluation of the effects of drugs such as tolvaptan. Non-contrast computed tomography (CT) is commonly used for volumetry, and this study examined the correspondence and correlation of kidney volume measured by standard-dose or low-dose CT. METHODS: Axial standard-dose and low-dose CT images with 1-mm slices were obtained from 24 ADPKD patients. The kidney was segmented in the Synapse 3D software and the kidney volume was calculated using stereology. The kidney volume was compared between the two sets of images using R2, Bland-Altman plots, coefficient of variation, and intra-class correlation coefficients (ICCs). RESULTS: The mean age of the 24 patients was 48.4 ± 10.9 years, and 45.8% were men (n = 11). The mean total kidney volume on standard-dose CT was 1501 ± 838.2 mL. The R2 of volume between standard-dose and low-dose CT was 0.995. In the Bland-Altman plot, except for one case with a large kidney volume, the two measurements were consistent, and the coefficient of variation and ICC were also good (0.02, 0.998). The CT radiation dose (dose-length product) was 229 ± 68 mGy·cm for standard-dose CT and 50 ± 19 mGy·cm for low-dose CT. A comparable volume was obtained with 20% of the radiation dose of standard-dose CT. CONCLUSIONS: Standard-dose and low-dose CT showed comparable kidney volume in ADPKD. Therefore, low-dose CT can substitute for ADPKD volumetry while minimizing radiation exposure.

Effect of low-density lipoprotein level and mortality in older incident statin-naïve hemodialysis patients.

BACKGROUND: This study aimed to analyze low-density lipoprotein cholesterol (LDL-C) levels and their relationship with mortality in order to identify the appropriate lipid profile for older Korean hemodialysis patients. METHODS: We enrolled a total of 2,732 incident hemodialysis patients aged > 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology from 2010 Jan to 2017 Dec, which included 17 academic hospitals in South Korea. Of these patients, 1,709 were statin-naïve, and 1,014 were analyzed after excluding those with missing LDL-C level data. We used multivariate Cox regression analysis to select risk factors from 20 clinical variables among the LDL-C groups. RESULTS: The mean age of the entire patient population was 78 years, with no significant differences in age between quartiles Q1 to Q4. However, the proportion of males decreased as the quartiles progressed towards Q4 (p < 0.001). The multivariate Cox regression analysis, which included all participants, showed that low LDL-C levels were associated with all-cause mortality. In the final model, compared to Q1, the hazard ratios (95% confidence interval) were 0.77 (0.620-0.972; p = 0.027), 0.85 (0.676-1.069; p = 0.166), and 0.65 (0.519-0.824; p < 0.001) for Q2, Q3, and Q4, respectively, after adjusting for covariates, such as conventional and age-specific risk factors. The final model demonstrated that all-cause mortality increased as LDL-C levels decreased, as confirmed by a restrictive cubic spline plot. CONCLUSIONS: In older hemodialysis patients who had not previously received dyslipidemia treatment, elevated LDL-C levels were not associated with increased all-cause mortality. Intriguingly, lower LDL-C levels appear to be associated with an unfavorable effect on all-cause mortality among high-risk hemodialysis patients.

Investigation of Ordering on Oxygen-Deficient LiNi0.5 Mn1.5 O4-δ Thin Films for Boosting Electrochemical Performance in All-Solid-State Thin-Film Batteries.

All-solid-state thin-film batteries (ASSTFBs) are promising next-generation battery systems, but critical challenges such as low-energy-density remain. The low-energy-density might persist with low-voltage cathode material; hence, high-voltage cathode material development is required. While LiNi0.5 Mn1.5 O4 (LNM) has been considered a promising high-voltage cathode material. This study investigates the electrochemical properties of LNM thin films based on the correlation between the ordering of cations (Ni and Mn) and oxygen vacancies (VO ). The authors find that the cations' order changes from a disordered structure to an ordered structure with an increased oxygen flow rate during deposition. The optimized LNM fabricated using a 60:40 ratio of Ar to O2 exhibits the highest rate capability (321.4 mAh cm-3 @ 20 C) and most prolonged cycle performance for 500 cycles. The role of VO within the LNM structure and the lower activation energy of ordered LNM compared to disordered LNM through first-principles density functional theory calculations is elucidated. The superior electrochemical performance (276.9 mAh cm-3 @ 0.5 C) and high cyclic performance (at 93.9%, 500 cycles) are corroborated by demonstrating flexible ASSTFB cells using LiPON solid-state electrolyte and thin-film Li anode. This work paves the way for future research on the fabrication of high-performance flexible ASSTFBs.

Association between physical activity and risk of renal function decline and mortality in community-dwelling older adults: a nationwide population-based cohort study.

BACKGROUND: Physical activity (PA) is an important risk factor associated with health outcomes. However, the relationship between PA and kidney function decline in older adults remains unclear. We examined the influence of PA on kidney function decline and mortality in community-dwelling older adults. METHODS: Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 who had available health checkup data from 2009 to 2010 were included. The cohort was followed annually through December 2015 for anthropometric, sociodemographic, and medical information including outcomes and biennially for laboratory information from the health checkup. We divided these patients into three groups according to self-reported PA (Inactive group: no leisure-time PA, Active group: vigorous activity for at least 80 min/week or a sum of moderate-intensity activity and walking for at least 300 min/week, Low-active group: level of PA between the definitions of the other two groups). Associations between the intensity of PA and death, cardiovascular death, and ≥ 50% eGFR decline were investigated. RESULTS: Among 102,353 subjects, 32,984 (32.23%), 54,267 (53.02%), and 15,102 (14.75%) were classified into the inactive, low-active, and active groups, respectively. The active group was younger, contained a higher proportion of men, and had higher frequencies of hypertension, diabetes mellitus, drinking, and smoking than the other groups. The active group had significantly lower incidence rates of mortality, cardiovascular mortality, and kidney function decline than the other groups (all p < 0.001). The active group also showed lower all-cause (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.70-0.82) and cardiovascular mortality (HR, 0.64; 95% CI, 0.53-0.78) and protection against ≥ 50% eGFR decline (HR, 0.81; 95% CI, 0.68-0.97) compared with the inactive group in the fully adjusted Cox proportional hazards regression model. CONCLUSIONS: High PA was an independent modifiable lifestyle factor for reducing mortality and protecting against declines in kidney function in older adults.

Consistency of the estimated target weights and ECW/TBW using BIA after hemodialysis in patients between standing and lying-down positions.

BACKGROUND: As hemodialysis is administered with the patient lying down, the distribution of body fluid is stable in the lying position, which is why this position is recommended for bioimpedance analysis (BIA). Although the InBody S10 is widely used for hemodialysis patients in the lying position, clinicians must make the measurements in person. In contrast, patients can use the InBody 770 to obtain measurements by themselves in the standing position, which may be more convenient. Therefore, this study compared the measurements of hemodialysis patients' estimated target weight and ECW/TBW obtained lying down using the S10 to those obtained in the standing position using the 770. METHODS: This study was conducted among maintenance hemodialysis patients at Chuncheon Sacred Heart Hospital in October 2020. Measurements from 56 patients before and after hemodialysis were obtained using the 2 machines. Each (S10 or 770) estimated target weight, both pre- and post-hemodialysis, was considered ideal when the ECW/TBW ratio was 0.380. R2 was calculated and the Bland-Altman test was performed. RESULTS: The patients' median age was 64 years old, and 51% were men. The actual ultrafiltration was 2 kg, and the mean TBW change measured using the InBody devices was 1.5 L (R2 = 0.718) for the S10 and 1.7 L (R2 = 0.616) for the 770. The estimated target weight at pre- and post-hemodialysis showed a remarkably high correlation with the patients' actual pre- and post-hemodialysis weight (R2 > 0.095). The correlation between these measurements (lying vs. standing) before and after hemodialysis was also very close (R2 = 1.0000). In addition, ECW/TBW had a good correlation (R2 ≥ 0.970) The Bland-Altman test of dry weight and ECW/TBW yielded similar results. CONCLUSIONS: This study showed that patients' estimated target weights in the lying position using the InBody S10 device and in the standing position using the InBody 770 device were consistent in both pre- and post-hemodialysis states.

High cortisol levels are associated with oxidative stress and mortality in maintenance hemodialysis patients.

BACKGROUND: Chronic stimulation of the mineralocorticoid receptor has been suggested as one of the potential causes of cardiovascular events and death in patients with end-stage renal disease. This observational cohort study was performed to demonstrate that serum cortisol might be a predictive marker for patient mortality and to evaluate its association with oxidized low-density lipoprotein (oxLDL) in hemodialysis (HD) patients. METHODS: Patients receiving HD three times a week were screened for enrollment at two institutions. Baseline cortisol levels were measured before each HD session, and the patients were divided into two groups according to the median value of serum cortisol before analysis. The baseline characteristics and laboratory values of the high and low cortisol groups were compared. Serum cortisol, adrenocorticotropic hormone, renin, aldosterone, and oxLDL were measured in 52 patients to evaluate the effect of oxidative stress on serum cortisol levels. RESULTS: A total of 133 HD patients were enrolled in this cohort study. Compared to the patients with low serum cortisol levels, the patients with high serum cortisol levels (baseline cortisol ≥ 10 µg/dL) showed higher rates of cardiovascular disease (59.7% vs. 39.4%, P=0.019) and left ventricular systolic dysfunction (LVSD) (25.9% vs. 8.0%, P=0.016). The patients in the high cortisol group demonstrated higher all-cause mortality than those in the low cortisol group. The serum cortisol level was an independent risk factor for patient mortality (hazard ratio 1.234, 95% confidence interval 1.022-1.49, P=0.029). Among the 52 patients with oxLDL measurements, oxLDL was an independent risk factor for elevated serum cortisol levels (Exp(B) 1.114, P=0.013) and LVSD (Exp(B) 12.308, P=0.045). However, plasma aldosterone levels did not affect serum cortisol levels. CONCLUSIONS: Serum cortisol is a useful predictive marker for all-cause death among patients receiving HD. OxLDL is an independent marker for elevated serum cortisol among HD patients.

Structural basis of the fanconi anemia-associated mutations within the FANCA and FANCG complex.

Monoubiquitination of the Fanconi anemia complementation group D2 (FANCD2) protein by the FA core ubiquitin ligase complex is the central event in the FA pathway. FANCA and FANCG play major roles in the nuclear localization of the FA core complex. Mutations of these two genes are the most frequently observed genetic alterations in FA patients, and most point mutations in FANCA are clustered in the C-terminal domain (CTD). To understand the basis of the FA-associated FANCA mutations, we determined the cryo-electron microscopy (EM) structures of Xenopus laevis FANCA alone at 3.35 Å and 3.46 Å resolution and two distinct FANCA-FANCG complexes at 4.59 and 4.84 Å resolution, respectively. The FANCA CTD adopts an arc-shaped solenoid structure that forms a pseudo-symmetric dimer through its outer surface. FA- and cancer-associated point mutations are widely distributed over the CTD. The two different complex structures capture independent interactions of FANCG with either FANCA C-terminal HEAT repeats, or the N-terminal region. We show that mutations that disturb either of these two interactions prevent the nuclear localization of FANCA, thereby leading to an FA pathway defect. The structure provides insights into the function of FANCA CTD, and provides a framework for understanding FA- and cancer-associated mutations.

MiR223-3p promotes synthetic lethality in BRCA1-deficient cancers.

Defects in DNA repair give rise to genomic instability, leading to neoplasia. Cancer cells defective in one DNA repair pathway can become reliant on remaining repair pathways for survival and proliferation. This attribute of cancer cells can be exploited therapeutically, by inhibiting the remaining repair pathway, a process termed synthetic lethality. This process underlies the mechanism of the Poly-ADP ribose polymerase-1 (PARP1) inhibitors in clinical use, which target BRCA1 deficient cancers, which is indispensable for homologous recombination (HR) DNA repair. HR is the major repair pathway for stressed replication forks, but when BRCA1 is deficient, stressed forks are repaired by back-up pathways such as alternative nonhomologous end-joining (aNHEJ). Unlike HR, aNHEJ is nonconservative, and can mediate chromosomal translocations. In this study we have found that miR223-3p decreases expression of PARP1, CtIP, and Pso4, each of which are aNHEJ components. In most cells, high levels of microRNA (miR) 223-3p repress aNHEJ, decreasing the risk of chromosomal translocations. Deletion of the miR223 locus in mice increases PARP1 levels in hematopoietic cells and enhances their risk of unprovoked chromosomal translocations. We also discovered that cancer cells deficient in BRCA1 or its obligate partner BRCA1-Associated Protein-1 (BAP1) routinely repress miR223-3p to permit repair of stressed replication forks via aNHEJ. Reconstituting the expression of miR223-3p in BRCA1- and BAP1-deficient cancer cells results in reduced repair of stressed replication forks and synthetic lethality. Thus, miR223-3p is a negative regulator of the aNHEJ DNA repair and represents a therapeutic pathway for BRCA1- or BAP1-deficient cancers.

Stepwise achievement of high convection volume in post-dilution hemodiafiltration: A prospective observational study.

High-volume online hemodiafiltration (HDF) has been reported to reduce the patient's mortality. However, achieving a high convection volume is challenging. In this prospective study, we investigated the feasibility of achieving high-volume HDF with ≥21 L substitution volume via modification of blood flow rate (BFR), needle size, and dialysis membrane. In 30 patients undergoing hemodialysis, we followed a stepwise protocol and gradually increased the BFR (280→300→330 ml/min; steps 1, 2, and 3) and needle size (16→15 G; step 4). After changing dialyzer surface area (1.8 m2 →2.5 m2 ), the BFR and needle size were similarly increased stepwise (steps 5, 6, 7, and 8). The mean substitution volume was 18.7 ± 2.2 L at step 1 and it significantly increased to 25.1 ± 2.6 L by step 8. A substitution volume of 21 L was achieved by 13.3% of patients in step 1 and by 96.7% after step 8. The substitution volume was higher for the dialyzer with a large surface area and for the larger needle (15 G). Between steps 1 and 8, the Kt/V and ß2 microglobulin reduction ratios also improved significantly. High-volume HDF is feasible through a stepwise increase in the BFR, needle size, and surface area of the dialysis membrane.

Serum uric acid is associated with coronary artery calcification in early chronic kidney disease: a cross-sectional study.

BACKGROUND: Although uric acid (UA) is regarded as a risk factor for cardiovascular disease, whether UA is an independent risk factor contributing to coronary artery calcification in chronic kidney disease (CKD) is not well known. We evaluated whether UA level is associated with coronary artery calcium (CAC) score in a predialysis CKD cohort. METHODS: A total of 1,350 subjects who underwent coronary computed tomography as part of the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease were analysed. We conducted a logistic regression analysis to evaluate the association between UA and the presence of CAC. RESULTS: CAC was detected in 705 (52.2 %) patients, and the level of UA was significantly higher in CAC > 0 patients. UA showed a positive relationship with CAC > 0 in age- and sex-adjusted logistic regression analysis (Odds ratio (OR) 1.11, 95 % confidence interval (CI) 1.04-1.19, P = 0.003). However, UA showed no association with CAC > 0 in multivariate analysis. Further analysis showed that UA showed a positive association with CAC > 0 only in estimated glomerual filtration rate (eGFR) > 60 ml/min/1.73 m2 (OR 1.23, 95 % CI 1.02-1.49, P = 0.036) but not in eGFR 30-59 ml/min/1.73 m2 (OR 0.92, 95 % CI 0.78-1.08, P = 0.309) or < 30 ml/min/1.73 m2 (OR 0.92, 95 % CI 0.79-1.08, P = 0.426). CONCLUSIONS: UA level was significantly associated with CAC in early CKD, but not in advanced CKD.

Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B.

DNA repair is critical for maintaining genomic integrity. Finding DNA lesions initiates the entire repair process. In human nucleotide excision repair (NER), XPC-RAD23B recognizes DNA lesions and recruits downstream factors. Although previous studies revealed the molecular features of damage identification by the yeast orthologs Rad4-Rad23, the dynamic mechanisms by which human XPC-RAD23B recognizes DNA defects have remained elusive. Here, we directly visualized the motion of XPC-RAD23B on undamaged and lesion-containing DNA using high-throughput single-molecule imaging. We observed three types of one-dimensional motion of XPC-RAD23B along DNA: diffusive, immobile and constrained. We found that consecutive AT-tracks led to increase in proteins with constrained motion. The diffusion coefficient dramatically increased according to ionic strength, suggesting that XPC-RAD23B diffuses along DNA via hopping, allowing XPC-RAD23B to bypass protein obstacles during the search for DNA damage. We also examined how XPC-RAD23B identifies cyclobutane pyrimidine dimers (CPDs) during diffusion. XPC-RAD23B makes futile attempts to bind to CPDs, consistent with low CPD recognition efficiency. Moreover, XPC-RAD23B binds CPDs in biphasic states, stable for lesion recognition and transient for lesion interrogation. Taken together, our results provide new insight into how XPC-RAD23B searches for DNA lesions in billions of base pairs in human genome.

Identification and Study of Biomarkers from Novichok-Inhibited Butyrylcholinesterase in Human Plasma.

To identify biomarkers of ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A234)- or methyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A232)-inhibited butyrylcholinesterase (BChE), we investigated nonapeptide adducts containing the active site serine, which plays a key role in enzyme activity, using LC-MS/HRMS. Biomarkers were acquired as expected, and they exhibited a significant amount of fragment ions from the inhibiting agent itself, in contrast to the MS2 spectra of conventional nerve agents. These biomarkers had a higher abundance of [M+2H]2+ ions than [M+H]+ ions, making doubly charged ions more suitable for trace analysis.

Foods contributing to nutrients intake and assessment of nutritional status in pre-dialysis patients: a cross-sectional study.

BACKGROUND: For chronic kidney disease (CKD) patients, management of nutritional status is critical for delaying progression to end-stage renal disease. The purpose of this study is to provide the basis for personalized nutritional intervention in pre-dialysis patients by comparing the foods contributing to nutrients intake, nutritional status and potential dietary inflammation of CKD patients according to the diabetes mellitus (DM) comorbidity and CKD stage. METHODS: Two hundred fifty-six outpatients referred to the Department of Nephrology at SNUH from Feb 2016 to Jan 2017 were included. Subjects on dialysis and those who had undergone kidney transplantation were excluded. Bioelectrical impedance analysis (BIA), subjective global assessment (SGA), dietary intake, and biochemical parameters were collected. Subjects were classified into 4 groups according to DM comorbidity (DM or Non-DM) and CKD stage (Early or Late) by kidney function. Two-way analysis of variance and multinomial logistic regression analysis were performed for statistical analysis. RESULTS: Total number of malnourished patients was 31 (12.1%), and all of them were moderately malnourished according to SGA. The body mass index (BMI) of the DM-CKD group was significantly higher than the Non-DM-CKD group. The contribution of whole grains and legumes to protein intake in the DM-CKD group was greater than that in the Non-DM-CKD group. The DM- Early-CKD group consumed more whole grains and legumes compared with the Non-DM-Early-CKD group. The subjects in the lowest tertile for protein intake had lower phase angle, SGA score and serum albumin levels than those in the highest tertile. The potential for diet-induced inflammation did not differ among the groups. CONCLUSIONS: Significant differences in intakes of whole grains and legumes between CKD patients with or without DM were observed. Since contribution of whole grains and legumes to phosphorus and potassium intake were significant, advice regarding whole grains and legumes may be needed in DM-CKD patients if phosphorus and potassium intake levels should be controlled. The nutritional status determined by BIA, SGA and serum albumin was found to be different depending on the protein intake. Understanding the characteristics of food sources can provide a basis for individualized nutritional intervention for CKD patients depending on the presence of diabetes.

Maternal, neonatal, and child health systems under rapid urbanization: a qualitative study in a suburban district in Vietnam.

BACKGROUND: Vietnam has been successful in increasing access to maternal, neonatal, and child health (MNCH) services during last decades; however, little is known about whether the primary MNCH service utilization has been properly utilized under the recent rapid urbanization. We aimed to examine current MNCH service utilization patterns at a district level. METHODS: The study was conducted qualitatively in a rural district named Quoc Oai. Women who gave a birth within a year and medical staff at various levels participated through 43 individual in-depth interviews and 3 focus group interviews. RESULTS: Primary MNCH services were underutilized due to a failure to meet increased quality needs. Most of the mothers preferred private clinics for antenatal care and the district hospital for delivery due to the better service quality of these facilities compared to that of the commune health stations (CHSs). Mothers had few sociocultural barriers to acquiring service information or utilizing services based on their improved standard of living. A financial burden for some services, including caesarian section, still existed for uninsured mothers, while their insured counterparts had relatively few difficulties. CONCLUSIONS: For the improved macro-efficiency of MNCH systems, the government needs to rearrange human resources and/or merge some CHSs to achieve economies of scale and align with service volume distribution across the different levels.

Dietary Assessment of Korean Non-dialysis Chronic Kidney Disease Patients with or without Diabetes.

BACKGROUND: Dietary intervention at the early stage of chronic kidney disease (CKD) is important for preventing progression to the end-stage renal disease (ESRD). However, few studies have investigated dietary intake of CKD patients in non-dialysis stage. Therefore, we investigated the dietary intake of Korean non-dialysis CKD patients and aimed to establish baseline data for the development of dietary education and intervention strategies for CKD patients. METHODS: Three hundred fifty CKD patients who visited Seoul National University Hospital outpatient clinic from February 2016 to January 2017 were recruited for this cross-sectional study. Subjects on dialysis and those who had undergone kidney transplantation were excluded. Dietary intake, demographic information, and biochemical characteristics of 256 subjects who completed three-day dietary records were analyzed. Subjects were divided into four groups based on diabetes mellitus (DM) (DM-CKD and Non-DM-CKD groups) and kidney function (Early-CKD and Late-CKD groups). RESULTS: Total energy intake was lower in the Late-CKD group compared with the Early-CKD group. In men, carbohydrate intake was higher and protein and fat intakes tended to be lower in the Late-CKD group compared with the Early-CKD group. In women, carbohydrate intake tended to be lower in the DM-CKD group than the Non-DM-CKD group. Protein intake tended to be higher in the DM-CKD groups. Phosphorus and sodium intakes were higher in the DM-CKD groups compared with the Non-DM-CKD groups in women, and tended to be higher in the DM-CKD groups in men. CONCLUSION: DM and kidney function affected energy and nutrient intakes. Subjects in the Late-CKD group consumed less energy than those in the Early-CKD group. Non-DM subjects seemed to restrict protein intake starting from the Early-CKD stage than subjects with DM. Subjects in this study had low energy and high sodium intakes compared with recommended levels. Protein intake was lower in advanced CKD patients, but their intake level was still higher than the recommendation. Dietary intervention strategies for non-dialysis CKD patients need to be customized depending on the presence of DM and kidney function.

Urinary Angiotensinogen in addition to Imaging Classification in the Prediction of Renal Outcome in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Intrarenal renin-angiotensin system (RAS) is known to play the major role in the development of hypertension and renal progression in autosomal dominant polycystic kidney disease (ADPKD). Urinary angiotensinogen to creatinine ratio (AGT/Cr) was suggested as a novel biomarker to reflect intrarenal RAS activity. This study was performed to evaluate urinary AGT/Cr as a predictive biomarker for renal function decline in addition to imaging classification in a prospective ADPKD cohort. METHODS: From 2011 to 2016, a total of 364 ADPKD patients were enrolled in the prospective cohort called the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Among them, a total of 207 subjects in chronic kidney disease stage 1-4 with baseline urinary AGT and total kidney volume and subsequent renal function follow-up data over more than 1 year were included in the analysis. Patients were defined as slow progressors (SP) if they are classified as 1A or 1B by imaging classification whereas rapid progressors (RP) if they are classified as 1C-1E. Patients were divided according to AGT/Cr quartiles and annual estimated glomerular filtration rate (eGFR) slope was compared among highest quartile (hAGT group) and the rest of quartiles (lAGT group). Patients were divided into 4 groups to evaluate the predictive value of urinary AGT/Cr in addition to imaging classification: SP/lAGT, SP/hAGT, RP/lAGT, and RP/hAGT. The Cox regression model was used to evaluate the hazard ratio (HR) between groups. RESULTS: The mean age was 45.9 years and 88.9% had hypertension. Baseline eGFR was 79.0 ± 28.4 mL/min/1.73 m² and median height-adjusted total kidney volume was 788.2 (471.2; 1,205.2) mL/m. The patients in the hAGT group showed lower eGFR (72.4 ± 24.8 vs. 81.1 ± 29.2 mL/min/1.73 m², P = 0.039), lower plasma hemoglobin (13.0 ± 1.4 vs. 13.7 ± 1.6 g/dL, P = 0.007), higher urinary protein to creatinine ratio (0.14 [0.09, 0.38] vs. 0.07 [0.04, 0.12] g/g, P = 0.007) compared to the lAGT group. The hAGT group was an independent risk factor for faster eGFR decline after adjusting for gender, RP, baseline eGFR, and other known risk factors. During median follow-up duration of 4.6 years, a total of 29 renal events (14.0%) occurred. The SP/hAGT group showed significantly higher risk of developing renal outcome compared to SP/lAGT group (HR, 13.4; 95% confidence interval, 1.282-139.324; P = 0.03). CONCLUSION: Urinary AGT/Cr can be a useful predictive marker in the patients with relatively small ADPKD. Various biomarkers should be considered to define RP when implementing novel treatment in the patients with ADPKD.