Development and validation of the dialysis dementia risk score: A retrospective, population-based, nested case-control study.

BACKGROUND: Dementia is prevalent and underdiagnosed in the dialysis population. We aimed to develop and validate a simple dialysis dementia scoring system to facilitate identification of individuals who are at high risk for dementia. METHODS: We applied a retrospective, nested case-control study design using a national dialysis cohort derived from the National Health Insurance Research Database in Taiwan. Patients aged between 40 and 80 years were included and 2940 patients with incident dementia were matched to 29,248 non-dementia controls. All subjects were randomly divided into the derivation and validation sets with a ratio of 4:1. Conditional logistic regression models were used to identify factors contributing to the risk score. The cutoff value of the risk score was determined by Youden's J statistic and the graphic method. RESULTS: The dialysis dementia risk score (DDRS) finally included age and 10 comorbidities as risk predictors. The C-statistic of the model was 0.71 (95% confidence interval [CI] 0.70-0.72). Calibration revealed a strong linear relationship between predicted and observed dementia risk (R2  = 0.99). At a cutoff value of 50 points, the high-risk patients had an approximately three-fold increased risk of having dementia compared to those with low risk (odds ratio [OR] 3.03, 95% CI 2.78-3.31). The DDRS performance, including discrimination (C-statistic 0.71, 95% CI 0.69-0.73) and calibration (p value of Hosmer-Lemeshow test for goodness of fit = 0.18), was acceptable during validation. The OR value (2.82, 95% CI 2.37-3.35) was similar to those in the derivation set. CONCLUSION: The DDRS system has the potential to serve as an easily accessible screening tool to determine the high-risk groups who deserve subsequent neurological evaluation in daily clinical practice.

Healthcare utilization and expenditure among individuals with end-stage kidney disease in Taiwan.

BACKGROUND/PURPOSE: The prevalence of end-stage kidney disease (ESKD) in Taiwan has been increasing in recent decades. ESKD care and medical expenditures constitute an important part of the entire healthcare system. METHODS: This study analyzed data collected from the National Health Insurance (NHI) Research Database from 2010 to 2018. RESULTS: The annual medical cost increased by approximately 4% both in the entire Taiwanese population and in its ESKD population. The total medical expenditure in the ESKD population from 2010 to 2018 increased from 48.03 to 65.65 billion reimbursement points, with dialysis treatments costing higher than non-dialysis treatments. ESKD outpatient and inpatient costs accounted for 10.4%-11.1% and 4.8%-5.6% of the entire NHI expenditure, respectively. The leading cause of inpatient costs was circulatory diseases, accounting for 29.3% of the total ESKD inpatient costs in 2018. Furthermore, percutaneous coronary intervention had the highest cost followed by simple percutaneous transluminal angioplasty. In 2018, the hemodialysis population had the highest average monthly cost of 73 thousand points per person, while the kidney transplant population had the lowest average monthly cost of 39 thousand points per person. CONCLUSION: Medical expenditure, including both inpatient and outpatient costs, of the ESKD population continued to grow from 2010 to 2018. The non-dialysis cost in the ESKD population was mainly for cardiovascular disease management and vascular access care, for which prevention will always be challenging.

Nephrotoxins and acute kidney injury - The consensus of the Taiwan acute kidney injury Task Force.

The Taiwan Acute Kidney Injury (AKI) Task Force conducted a review of data and developed a consensus regarding nephrotoxins and AKI. This consensus covers: (1) contrast-associated AKI; (2) drug-induced nephrotoxicity; (3) prevention of drug-associated AKI; (4) follow up after AKI; (5) re-initiation of medication after AKI. Strategies for the avoidance of contrast media related AKI, including peri-procedural hydration, sodium bicarbonate solutions, oral N-acetylcysteine, and iso-osmolar/low-osmolar non-ionic iodinated contrast media have been recommended, given the respective evidence levels. Regarding anticoagulants, both warfarin and new oral anticoagulants have potential nephrotoxicity, and dosage should be reduced if renal pathology exam proves renal injury. Recommended strategies to prevent drug related AKI have included assessment of 5R/(6R) reactions - risk, recognition, response, renal support, rehabilitation and (research), use of AKI alert system and computerized decision support. In terms of antibiotics-associated AKI, avoiding concomitant administration of vancomycin and piperacillin-tazobactam, monitoring vancomycin trough level, switching from vancomycin to teicoplanin in high-risk patients, and replacing conventional amphotericin B with lipid-based amphotericin B have been shown to reduce drug related AKI. With respect to non-steroidal anti-inflammatory drug associated AKI, it is recommended to use these drugs cautiously in the elderly and in patients receiving renin-angiotensin-aldosterone system inhibitors/diuretics triple combinations.

Diuretics prevent thiazolidinedione-induced cardiac hypertrophy without compromising insulin-sensitizing effects in mice.

Much concern has arisen regarding critical adverse effects of thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, on cardiac tissue. Although TZD-induced cardiac hypertrophy (CH) has been attributed to an increase in plasma volume or a change in cardiac nutrient preference, causative roles have not been established. To test the hypothesis that volume expansion directly mediates rosiglitazone-induced CH, mice were fed a high-fat diet with rosiglitazone, and cardiac and metabolic consequences were examined. Rosiglitazone treatment induced volume expansion and CH in wild-type and PPARγ heterozygous knockout (Pparg(+/-)) mice, but not in mice defective for ligand binding (Pparg(P465L/+)). Cotreatment with the diuretic furosemide in wild-type mice attenuated rosiglitazone-induced CH, hypertrophic gene reprogramming, cardiomyocyte apoptosis, hypertrophy-related signal activation, and left ventricular dysfunction. Similar changes were observed in mice treated with pioglitazone. The diuretics spironolactone and trichlormethiazide, but not amiloride, attenuated rosiglitazone effects on volume expansion and CH. Interestingly, expression of glucose and lipid metabolism genes in the heart was altered by rosiglitazone, but these changes were not attenuated by furosemide cotreatment. Importantly, rosiglitazone-mediated whole-body metabolic improvements were not affected by furosemide cotreatment. We conclude that releasing plasma volume reduces adverse effects of TZD-induced volume expansion and cardiac events without compromising TZD actions in metabolic switch in the heart and whole-body insulin sensitivity.

The role of echocardiographic study in patients with chronic kidney disease.

Despite the recent enormous advances in medicine, high mortality and morbidity rates among the chronic kidney disease (CKD) patients remain an important but unresolved issue. Cardiovascular disease is a major cause of mortality and morbidity in patients with CKD. Abnormal left ventricular geometry and functions are common in this patient group and have been proven to be correlated with a high cardiovascular mortality/morbidity and all-cause mortality. For this reason, echocardiographic study plays an important role in evaluating cardiac structure and functions as well as in stratifying prognostic risk. We here summarize the reported findings on the usefulness of echocardiographic methodologies and identify their roles in diagnostic and prognostic clinical approaches.

Rapid identification of bacteria and Candida pathogens in peritoneal dialysis effluent from patients with peritoneal dialysis-related peritonitis by use of multilocus PCR coupled with electrospray ionization mass spectrometry.

PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was compared with culture for pathogen detection in peritoneal dialysis (PD)-related peritonitis. Of 21 samples of PD effluent, PCR/ESI-MS identified microorganisms in 18 (86%) samples, including Mycobacterium tuberculosis in 1 culture-negative sample. Of 15 double-positive samples, PCR/ESI-MS and culture reached levels of agreement of 100% (15/15) and 87.5% (7/8) at the genus and species levels, respectively. PCR/ESI-MS can be used for rapid pathogen detection in PD-related peritonitis.

Risk of stroke in long-term dialysis patients compared with the general population.

BACKGROUND: Patients undergoing maintenance dialysis are at increased risk of stroke. STUDY DESIGN: We performed a nationwide retrospective cohort study to determine the risks for ischemic stroke and hemorrhagic stroke among incident hemodialysis (HD) and peritoneal dialysis (PD) patients in comparison to a reference group in Taiwan. SETTING & PARTICIPANTS: Data for 74,192 HD patients, 5,974 PD patients, and 669,773 nondialysis individuals who were older than 18 years and had no history of stroke or cancer were retrieved from the National Health Insurance Research Database for 1998-2009. PREDICTORS: Patient demographics, comorbid conditions. OUTCOME: First hospitalization for stroke, defined as a diagnosis at discharge (either primary or 1 of 4 secondary diagnoses) of ischemic or hemorrhagic stroke using International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS: HD and PD patients had higher incidences of hospitalized ischemic stroke (102.6 and 100.1/10,000 person-years) and hemorrhagic stroke (74.7 and 59.4/10,000 person-years) in comparison to the age- and sex-matched reference cohort (42.4 and 13.0/10,000 person-years, respectively). In addition to HD and PD therapy, older age, male sex, diabetes, and hypertension were found to be independent risk factors for both ischemic and hemorrhagic strokes. Using the HD group as the comparison group, we found that PD patients had a lower risk of hemorrhagic stroke (HR, 0.75; 95% CI, 0.58-0.96), and there was no significant difference in risks of ischemic stroke between PD and HD patients after adjusting for all potential confounders and competing risk of death, and matched by propensity scores. LIMITATIONS: This was a retrospective study, and some important variables were not available. CONCLUSIONS: Patients undergoing dialysis are at elevated risk of stroke. Patients undergoing PD appear to be less likely to develop hemorrhagic stroke than those undergoing HD. Comprehensive control of hypertension and diabetes is necessary when delivering dialysis treatment.

Estimation of physical functional disabilities and long-term care needs for patients under maintenance hemodialysis.

BACKGROUND AND OBJECTIVES: Physical functional disabilities in hemodialysis (HD) patients may increase their mortality and long-term care needs. The aim of this study was to estimate the changes of proportion for different physical functional disabilities along time after beginning HD and the lifelong care needs. METHODS: We used a population-based cohort consisting of 84,657 incident HD patients in Taiwan between 1998 and 2009 to estimate the survival function and extrapolate to lifetime through a semiparametric method. The Barthel Index (BI) was used to measure the functional disability levels cross-sectionally in 1334 HD patients recruited from 9 HD centers. A BI score <50 was considered as severe disability. Lifetime care needs were obtained by extrapolating the age-stratified survival functions to lifetime and then multiplying them with proportions of different kinds of functional disabilities over time. RESULTS: On average, HD patients had at least 6.4, 2.0, and 1.3 years without disability, with moderate disability, and severe disability, respectively. The most common care needs were stair-climbing and bathing, which were 3.0 and 1.7 years, respectively. HD patients were expected to have about 3 years living with disabilities for those beginning HD at an age above 35 years; however, the older the patient, the higher the proportion of functional disabilities and care needs. CONCLUSIONS: HD patients are in need of long-term care and require early intervention and resource planning. The method developed in this study can also be applied to other chronic illnesses with various functional disabilities.

Cystatin C as a predictor for outcomes in patients with negligible renal function.

BACKGROUND: High serum cystatin C (CysC) has been associated with clinical risks independently of the glomerular filtration rate (GFR). This study aims to investigate the predictive power of CysC in patients with a negligible GFR. METHODS: Patients on chronic hemodialysis or peritoneal dialysis were enrolled for measurement of CysC levels and were followed up for one year. A daily urine amount <100 ml was considered negligible residual renal function (RRF). RESULTS: CysC results were available in 183 dialysis patients. Of these, 131 patients had a negligible RRF. The multivariate Cox proportional hazards model showed that CysC was an independent predictor of fatal and nonfatal cardiovascular and infection events in all dialysis patients and in dialysis patients with a negligible RRF. CONCLUSION: CysC maintained its predictive power for adverse outcomes in patients with no meaningful GFR, indicating that the prognostic value of CysC is independent of the GFR.

Ambient temperature and the occurrence of intradialytic hypotension in patients receiving hemodialysis.

Background: Intradialytic hypotension (IDH) is a common hemodialysis complication causing adverse outcomes. Despite the well-documented associations of ambient temperatures with fluid removal and pre-dialysis blood pressure (BP), the relationship between ambient temperature and IDH has not been adequately studied. Methods: We conducted a cohort study at a tertiary hospital in southern Taiwan between 1 January 2016 and 31 October 2021. The 24-h pre-hemodialysis mean ambient temperature was determined using hourly readings from the weather station closest to each patient's residence. IDH was defined using Fall40 [systolic BP (SBP) drop of ≥40 mmHg] or Nadir90/100 (SBP <100 if pre-dialysis SBP was ≥160, or SBP <90 mmHg). Multivariate logistic regression with generalizing estimating equations and mediation analysis were utilized. Results: The study examined 110 400 hemodialysis sessions from 182 patients, finding an IDH prevalence of 11.8% and 10.4% as per the Fall40 and Nadir90/100 criteria, respectively. It revealed a reverse J-shaped relationship between ambient temperature and IDH, with a turning point around 27°C. For temperatures under 27°C, a 4°C drop significantly increased the odds ratio of IDH to 1.292 [95% confidence interval (CI) 1.228 to 1.358] and 1.207 (95% CI 1.149 to 1.268) under the Fall40 and Nadir90/100 definitions, respectively. Lower ambient temperatures correlated with higher ultrafiltration, accounting for about 23% of the increased IDH risk. Stratified seasonal analysis indicated that this relationship was consistent in spring, autumn and winter. Conclusion: Lower ambient temperature is significantly associated with an increased risk of IDH below the threshold of 27°C, irrespective of the IDH definition. This study provides further insight into environmental risk factors for IDH in patients undergoing hemodialysis.

Nonprotein calorie supplement improves adherence to low-protein diet and exerts beneficial responses on renal function in chronic kidney disease.

OBJECTIVE: Malnutrition is common in patients with chronic kidney disease (CKD) who are on low-protein diets and is a powerful predictor of morbidity and mortality in CKD. Studies have shown that patients on low-protein diets often have difficulty meeting nutritional energy requirements. Our study evaluated the effects of a nonprotein calorie (NPC) supplement on renal function and nutritional status in patients on a low-protein diet. DESIGN: This was a prospective, randomized, open-label, controlled clinical trial. SUBJECTS: A total of 109 patients with CKD (men, 67%; mean age, 54.5 ± 13 years) with stage 3 to 4 disease were randomly assigned to the intervention group (n = 55) or the control group (n = 54). INTERVENTION: All participants received individualized dietary counseling aimed at achieving a daily protein intake of 0.6 to 0.8 g and a daily energy intake of 30 to 35 kcal/kg. The intervention group consumed a 200-kcal NPC supplement daily. The control group received dietary counseling only. MAIN OUTCOME MEASURE: The estimated glomerular filtration rate (eGFR) was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Urine protein excretion, dietary protein and energy intake, and serum levels of creatinine, urea nitrogen, cholesterol, triglycerides, and albumin were assessed at baseline, at 12 weeks, and at 24 weeks. RESULTS: Dietary protein intake and urine protein excretion levels decreased significantly in the intervention group and were significantly lower than those of the control group. In addition, serum levels of creatinine and urea nitrogen decreased significantly, and eGFR increased significantly in the intervention group compared with baseline assessments. No significant differences were observed in the control group. CONCLUSIONS: The NPC supplement improved patient adherence to the low-protein diet and reduced urine protein excretion in patients with CKD.

Progression of stages 3b-5 chronic kidney disease--preliminary results of Taiwan national pre-ESRD disease management program in Southern Taiwan.

BACKGROUND/PURPOSE: The outcomes and their predictors, and rates of estimated glomerular filtration rate (eGFR) changes among Taiwanese, an ethnic Chinese population, with chronic kidney disease (CKD) stages 3b-5, enrolled in a nationwide pre-end-stage renal disease (pre-ESRD) management program that have not been previously reported. METHODS: This study focused on a cohort of patients enrolled in the Taiwan's pre-ESRD disease management program from Southern Taiwan, including 4061 CKD 3b-5 patients who received more than 12 weeks of follow-up from 2007 to 2010. The decline rates of eGFR, outcomes, and the predictors of initiating dialysis were analyzed. RESULTS: The study participants consisted of patients who were 70.1 ± 12.3 years old, of whom 56.4% were male, 46.3% were diabetic, and 72.1% were hypertensive. The mean annual eGFR changes were 0.47 ± 0.42 mL/min/1.73 m(2)/year, -1.27 ± 0.32 mL/min/1.73 m(2)/year, and -2.69 ± 0.39 mL/min/1.73 m(2)/year for stages 3b, 4, and 5, respectively; however, more rapid declines were noted in diabetic patients. The Kaplan-Meier analyses revealed that the probabilities of patients remaining alive and free of dialysis treatment for CKD stage 3b, 4, and 5 without or with diabetes were 89.46% versus 84.65%, 79.88% versus 55.68%, and 34.42% versus 9.64%, respectively, during 42 months of follow-up. Male gender, diabetes, lower baseline eGFR, higher systolic blood pressure, lower hematocrit, and albumin levels were the significant risk factors for initiating dialysis. CONCLUSION: Even though we cannot conclude with certainty that the Taiwan pre-ESRD disease management program is beneficial in slowing the progression of CKD stages 3b-5, our preliminary results seem to suggest this trend. Furthermore, the program may be improved by integrating it with other programs, such as those on diabetes and hypertension, thus making it a more patient-centered, multidisciplinary program.

Deletion of NADPH oxidase 2 attenuates cisplatin-induced acute kidney injury through reducing ROS-induced proximal tubular cell injury and inflammation.

Backgrounds: Cisplatin is a commonly used chemotherapeutic agent in cancer treatment. However, its high nephrotoxicity limits its therapeutic application and efficacy. Cisplatin induces nephrotoxicity mainly through oxidative stress and inflammation. Reactive oxygen species (ROS) in the kidneys mainly arise from nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 2 (NOX2), which is highly upregulated during ischemia-reperfusion injury and diabetes mellitus. However, its role in cisplatin-induced acute kidney injury (AKI) remains unknown. Methods: A 8-10-week-old NOX2 gene-knockout and wild-type mice were injected with 25 mg/kg cisplatin intraperitoneally for experiments. Results: We investigated the role of NOX2 in cisplatin-induced AKI and found that NOX2-mediated ROS production is a key inflammatory mediator of proximal tubular cell injury in cisplatin-induced AKI. NOX2 gene-knockout alleviated cisplatin-induced renal function decline, tubular injury score, kidney injury molecule-1(Kim-1) expression, and interleukin (IL)-6 and IL-1α levels with a reduction of ROS production. Moreover, in cisplatin-induced AKI, intercellular adhesion molecule 1 (ICAM-1) and the chemoattractant CXC ligand 1 (CXCL1) were highly expressed in association with neutrophil infiltration, which were all attenuated by deletion of NOX2. Conclusion: These data indicate that NOX2 aggravates cisplatin nephrotoxicity by promoting ROS-mediated tissue injury and neutrophil infiltration. Thus, appropriate targeting of NOX2/ROS pathway may minimize the risk of cisplatin-induced kidney injury in patients receiving cancer therapy.

Effect of dialysis modalities on risk of hospitalization for gastrointestinal bleeding.

Dialysis patients are at risk of both thromboembolic and bleeding events, while thromboembolism prevention and treatment may confer a risk of major bleeding. Gastrointestinal (GI) bleeding is a great concern which can result in high subsequent mortality rates. Our object was to clarify whether hemodialysis (HD) and peritoneal dialysis (PD) confer different incidence of GI bleeding, and further assist individualized decision-making on dialysis modalities. We conducted a population-based retrospective cohort study which included all incident dialysis patients above 18 years old derived from the National Health Insurance database from 1998 to 2013 in Taiwan. 6296 matched pairs of HD and PD patients were identified. A propensity score matching method was used to minimize the selection bias. The adjusted hazard ratio for GI bleeding was 1.13 times higher in the HD group than in the PD group, and data from the unmatched cohort and the stratified analysis led to similar results. Among subgroup analysis, we found that the use of anticoagulants will induce a much higher incidence of GI bleeding in HD patients as compared to in PD patients. We concluded that PD is associated with a lower GI bleeding risk than HD, and is especially preferred when anticoagulation is needed.

YAP nuclear translocation induced by HIF-1α prevents DNA damage under hypoxic conditions.

Maladaptive repair of acute kidney injury (AKI) is associated with a high risk of developing chronic kidney disease deemed irremediable even in present days. When AKI arises from ischemia-reperfusion injury, hypoxia usually plays a major role. Although both hypoxia-inducible factor-1α (HIF-1α) and yes-associated protein (YAP) have been proven to promote renal cell survival under hypoxia, there is a lack of research that studies the crosstalk of the two and its effect on kidney repair. In studying the crosstalk, CoCl2 was used to create a mimetic hypoxic environment. Immunoprecipitation and proximity ligation assays were performed to verify protein interactions. The results show that HIF-1α interacts with YAP and promotes nuclear translocation of YAP at a high cell density under hypoxic conditions, suggesting HIF-1α serves as a direct carrier that enables YAP nuclear translocation. This is the first study to identify HIF-1α as a crucial pathway for YAP nuclear translocation under hypoxic conditions. Once translocated into a nucleus, YAP protects cells from DNA damage and apoptosis under hypoxic conditions. Since it is unlikely for YAP to translocate into a nucleus without HIF-1α, any treatment that fosters the crosstalk between the two holds the potential to improve cell recovery from hypoxic insults.

NLRP3 inflammasome activation, metabolic danger signals, and protein binding partners.

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an oligomeric complex that assembles in response to exogenous signals of pathogen infection and endogenous danger signals of non-microbial origin. When NLRP3 inflammasome assembly activates caspase-1, it promotes the maturation and release of the inflammatory cytokines interleukin-1B and IL-18. Aberrant activation of the NLRP3 inflammasome has been implicated in various diseases, including chronic inflammatory, metabolic, and cardiovascular diseases. The NLRP3 inflammasome can be activated through several principal mechanisms, including K+ efflux, lysosomal damage, and the production of mitochondrial reactive oxygen species. Interestingly, metabolic danger signals activate the NLRP3 inflammasome to induce metabolic diseases. NLRP3 contains three crucial domains: an N-terminal pyrin domain, a central nucleotide-binding domain, and a C-terminal leucine-rich repeat domain. Protein-protein interactions act as a 'pedal or brake' to control the activation of the NLRP3 inflammasome. In this review, we present the mechanisms underlying NLRP3 inflammasome activation after induction by metabolic danger signals or via protein-protein interactions with NLRP3 that likely occur in metabolic diseases. Understanding these mechanisms will enable the development of specific inhibitors to treat NLRP3-related metabolic diseases.

Recovery of severe dialysis disequilibrium syndrome with uncal herniation following therapy with mannitol, hyperventilation and hypertonic saline.

Dialysis disequilibrium syndrome (DDS) is a rare complication of dialysis, especially with the general application of preventive strategies. Severe DDS with brain herniation is believed to be fatal. We present a patient presenting with bilateral uncal herniation after receiving two dialysis sessions with low-efficiency settings. Serial brain magnetic resonance imaging studies showed the temporal evolution of DDS-induced cerebral edema. With aggressive treatment of hypertonic saline and mannitol, the patient made a remarkable recovery. This case highlights that we should be cautious about this severe complication of dialysis even with preventive strategies, and recovery is possible with prompt recognition and treatment.

Effects of helping relationships on health-promoting lifestyles among patients with chronic kidney disease: A randomized controlled trial.

BACKGROUND: Healthy behaviors can slow the progression of chronic kidney disease. Professional healthcare providers deliver education, physical exercise programs, motivation consultations, and stage-tailored strategies for improving health behaviors, but their effectiveness reported mixed. The helping relationships of significant others based on the transtheoretical model have been shown to be beneficial in facilitating and practicing health-promoting behaviors. However, few studies have examined the effects of helping relationships on health-promoting behaviors among patients with chronic kidney disease. OBJECTIVES: The aim of this study was to examine the effects of the intervention strategies of significant others in their helping relationships with patients to advance stages of exercise and diet behaviors, and to improve health-promoting lifestyles. DESIGN: A randomized controlled study. SETTINGS: Two outpatient nephrology clinics in southern Taiwan. PARTICIPANTS: Sixty participants in each of the two groups. METHODS: Patients were randomly assigned to either the intervention group (n = 60) whose significant others received strategies for helping relationships for 12 months, or the control group (n = 60). The Stage of Change of Exercise and Diet Behaviors, and Health Promoting Lifestyle Profile-II Chinese version were assessed at baseline and 3, 6, 9, and 12 months after receiving the helping relationship interventions tailored to stage of change from significant others. RESULTS: Generalized estimating equation analyzes revealed that the intervention group, when compared to the control group, had significantly advanced stages of change in exercise and diet, and improvement in health-promoting lifestyle over time. Adult children and spouses were the most common significant others to help patients practice healthy behaviors, compared to previous studies where professional healthcare providers were the significant others. CONCLUSIONS: Individualized plans for healthy behaviors should take into consideration patients' readiness for adopting stage-tailored strategies of helping relationships of significant others to adhere to the health-promoting lifestyle. To promote a healthier lifestyle, significant others, such as spouses and adult children, should be included in treatment programs.

Transforming growth factor-{beta}1 induces Smad3-dependent {beta}1 integrin gene expression in epithelial-to-mesenchymal transition during chronic tubulointerstitial fibrosis.

Transforming growth factor-ß1 (TGF-ß1)-induced epithelial-to-mesenchymal transition (EMT) contributes to the pathophysiological development of kidney fibrosis. Although it was reported that TGF-ß1 enhances ß(1) integrin levels in NMuMG cells, the detailed molecular mechanisms underlying TGF-ß1-induced ß(1) integrin gene expression and the role of ß(1) integrin during EMT in the renal system are still unclear. In this study, we examined the role of ß(1) integrin in TGF-ß1-induced EMT both in vitro and in vivo. TGF-ß1-induced augmentation of ß(1) integrin expression was required for EMT in several epithelial cell lines, and knockdown of Smad3 inhibited TGF-ß1-induced augmentation of ß(1) integrin. TGF-ß1 triggered ß(1) integrin gene promoter activity as assessed by luciferase activity assay. Both knockdown of Smad3 and mutation of the Smad-binding element to block binding to the ß(1) integrin promoter markedly reduced TGF-ß1-induced ß(1) integrin promoter activity. Chromatin immunoprecipitation assay showed that TGF-ß1 enhanced Smad3 binding to the ß(1) integrin promoter. Furthermore, induction of unilateral ureteral obstruction triggered increases of ß(1) integrin in both renal epithelial and interstitial cells. In human kidney with chronic tubulointerstitial fibrosis, we also found a concomitant increase of ß(1) integrin and α-smooth muscle actin in tubule epithelia. Blockade of ß(1) integrin signaling dampened the progression of fibrosis. Taken together, ß(1) integrin mediates EMT and subsequent tubulointerstitutial fibrosis, suggesting that inhibition of ß(1) integrin is a possible therapeutic target for prevention of renal fibrosis.

Handgrip strength is an independent predictor of renal outcomes in patients with chronic kidney diseases.

BACKGROUND: In dialysis patients, protein-energy wasting (PEW) is associated with high mortality, and some indicators of PEW, such as serum albumin value, subjective global assessment (SGA) score and handgrip strength (HGS), may predict mortality. However, whether PEW is associated with poor renal outcomes and whether the indicators of PEW can predict renal outcomes in patients with non-dialysis-dependent chronic kidney disease (CKD-ND) is still unclear. METHODS: We enrolled 128 clinically stable patients with CKD-ND and followed up for 33.8 ± 9.2 months. Baseline characteristics, echocardiographic information, laboratory data, HGS, SGA scores, anthropometric parameters, bioimpedance analyses and other indicators of PEW were examined in relation to the risk of reaching renal composite end points of pre-dialysis mortality or dialysis-dependent end-stage renal disease. RESULTS: Twenty-six patients reached composite renal end points. Multivariate Cox regression analyses showed that HGS was an independent predictor of renal outcome in patients with CKD-ND of Stages 1-5 [CKD(1-5), hazard ratio (HR) = 0.90, P = 0.004] or advanced CKD-ND of Stages 3b [defined as estimated glomerular filtration rate (eGFR) of 30-44 mL/min/1.73 m(2)] to 5 (CKD(3b-5), HR = 0.91, P = 0.031), but not serum albumin, SGA score or other indicators of PEW. When the cutoffs were set at 24.65 kg in men with CKD(1-5), 20.15 kg in men with CKD(3b-5) and 10.15 kg in women with CKD(1-5) or CKD(3b-5), which were deduced from receiver-operating characteristics analyses, patients with lower HGS had significantly poor renal outcomes in Kaplan-Meier survival analyses in all subgroups and higher HR for reaching renal end points in multivariate Cox regression analyses in all subgroups except for women with CKD(3b-5), whose HR had marginal significance (HR = 3.78, P = 0.068) after adjusting for age and eGFR. CONCLUSIONS: This is the first study demonstrating that HGS is an independent predictor of composite renal outcomes in CKD-ND patients. HGS can be incorporated to clinical practice for assessing nutrition status and renal prognosis in patients with CKD-ND.