Urinary microRNA in Diabetic Kidney Disease: A Literature Review.

Diabetic kidney disease is the most common primary disease of end-stage kidney disease globally; however, a sensitive and accurate biomarker to predict this disease remains awaited. microRNAs are endogenous single-stranded noncoding RNAs that have intervened in different post-transcriptional regulations of various cellular biological functions. Previous literatures have reported its potential role in the pathophysiology of diabetic kidney disease, including regulation of Transforming Growth Factor-ß1-mediated fibrosis, extracellular matrix and cell adhesion proteins, cellular hypertrophy, growth factor, cytokine production, and redox system activation. Urinary microRNAs have emerged as a novel, non-invasive liquid biopsy for disease diagnosis. In this review, we describe the available experimental and clinical evidence of urinary microRNA in the context of diabetic kidney disease and discuss the future application of microRNA in routine practice.

Associations of Three-Dimensional Anthropometric Body Surface Scanning Measurements and Coronary Artery Disease.

Background and Objectives: The relationship between three-dimensional (3D) scanning-derived body surface measurements and biomarkers in patients with coronary artery disease (CAD) were assessed. Methods and Methods: The recruitment of 98 patients with CAD confirmed by cardiac catheterization and 98 non-CAD patients were performed between March 2016 and December 2017. A health questionnaire on basic information, life style variables, and past medical and family history was completed. 3D body surface measurements and biomarkers were obtained. Differences between the two groups were assessed and multivariable analysis performed. Results: It was found that chest width (odds ratio [OR] 0.761, 95% confidence interval [CI] = 0.586-0.987, p = 0.0399), right arm length (OR 0.743, 95% CI = 0.632-0.875, p = 0.0004), waist circumference (OR 1.119, 95% CI = 1.035-1.21, p = 0.0048), leptin (OR 1.443, 95% CI = 1.184-1.76, p = 0.0003), adiponectin (OR 0.978, 95% CI = 0.963-0.994, p = 0.006), and interleukin 6 (OR 1.181, 95% CI = 1.021-1.366, p = 0.0254) were significantly associated with CAD. The combination of biomarker scores and body measurement scores had the greatest area under the curve and best association with CAD (area under the curve of 0.8049 and 95% CI = 0.7440-0.8657). Conclusions: Our study suggests that 3D derived body surface measurements in combination with leptin, adiponectin, and interleukin 6 levels may direct us to those at risk of CAD, allowing a non-invasive approach to identifying high-risk patients.

Hospitalization in patients with dialysis in Taiwan: A nationwide population-based observational study.

BACKGROUND: The hospitalization rate is higher in patients with end-stage kidney disease (ESKD) than in the general population. However, the national estimates in Taiwan remain unclear. Therefore, we investigated the hospitalization rates of ESKD patients in a disease-specific manner from 2010 to 2018 in Taiwan. METHODS: This population-based study was conducted using data from the National Health Insurance Research Database. We analyzed the hospitalization rates of patients with ESKD, defined as continuous dialysis for at least three successive months. The first diagnosis at discharge for each hospitalization was defined as the main diagnosis of hospitalization. The hospitalization rate in a certain year was calculated as the number of hospitalizations divided by the number of patients undergoing chronic dialysis in the respective year. RESULTS: Hospitalization occurred in half of all prevalent ESKD patients, with an increasing trend over time. The hospitalization rate increased from 964.1 per 1000 person-years in 2010 to 1037.9 per 1000 person-years in 2018. ESKD patients who were male, aged over 75 years, and receiving hemodialysis had higher hospitalization rates. Infection-related hospitalization was the main cause of hospitalization, followed by cardiovascular disease. The 30-day re-admission rate was 19%, and the in-hospital mortality rate was 9%. CONCLUSION: Hospitalization rates continued to increase from 2010 to 2018. The high hospitalization rates for infection-related diseases and hemodialysis patients call for further strategies to be developed that reduce the hospitalization burden.

Thermal Perception Abnormalities Can Predict Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.

BACKGROUND: Previous studies have illustrated clinical associations between diabetic peripheral neuropathy (DPN) and diabetic kidney disease (DKD). Quantitative sensory testing (QST) can accurately detect thermal perception abnormalities and aid in the early diagnosis of asymptomatic small-fiber DPN in patients with type 2 diabetes. The aim of this study was to determine the predictive value of thermal perception abnormalities by QST to detect DKD. METHODS: We prospectively enrolled 432 patients with type 2 diabetes (50.2% male, mean age 57.2 years, and average duration of diabetes 9.9 years) at our hospital between 2016 and 2017. Demographic and clinical data of the patients were recorded and analyzed. Diagnosis and staging of DKD were determined by urinary albumin excretion rate and estimated glomerular filtration rate. The presence of thermal perception abnormalities was determined by QST. Multiple logistic regression and receiver operating characteristic (ROC) analyses were performed to investigate the relationships between thermal perception abnormalities and DKD in these patients. RESULTS: In multiple regression analysis, abnormal cold perception in the lower limbs was associated with an increased risk of advanced DKD. Area under the ROC curve analysis revealed that four-limb cold perception abnormalities had the best discriminatory power (0.741 ± 0.053) to predict advanced DKD. CONCLUSIONS: Our results demonstrate the value of using thermal perception abnormalities to identify patients with type 2 diabetes also at risk of DKD.

Early retinal microvascular abnormalities in patients with chronic kidney disease.

OBJECTIVE: To evaluate early retinal microvascular abnormalities in patients with chronic kidney disease (CKD) via optical coherence tomography angiography. METHODS: A cross-sectional study. Two hundred patients with CKD stage ≧3 were enrolled in the CKD group, and 50 age-matched healthy subjects were enrolled in the control group. Main outcome measures were the differences in parafoveal vessel densities in the superficial vascular plexus (SVP) and deep vascular plexus (DVP) between the CKD and control groups. RESULTS: The mean ages were 62.7 ± 10.1 in the CKD group and 61.9 ± 9.7 (P = 0.622) in the control group. The CKD group had reduced parafoveal vessel densities in SVP (46.7 ± 4.3 vs 49.7 ± 2.9, P < 0.001) and DVP (50.1 ± 4.1 vs 52. 6 ± 2.9, P < 0.001) when compared to those of the control group. In multiple linear regression models, age, diabetes, estimated glomerular filtration rate, and use of anti-hypertensive drugs were factors associated with vessel density in SVP, whereas age, diabetes, and smoking were factors associated with vessel density in DVP. CONCLUSION: Patients with CKD had reduced vessel densities in parafoveal SVP and DVP, as compared to that of control subjects. Microvasculature in the different retinal layers may be affected by different systemic factors.

Higher risk of malignant neoplasms in young adults with end-stage renal disease receiving haemodialysis: A nationwide population-based study.

AIM: Previous investigations have shown that end-stage renal disease (ESRD) is associated with an increased risk of malignancies. The aim of this study was to explore the association between ESRD in patients undergoing maintenance haemodialysis (HD) and the incidence of malignancies according to age. METHODS: We analysed a nationwide cohort retrieved from Taiwan's National Health Insurance Research Database to study the incidence of malignancies in patients who were and were not receiving HD. One million beneficiaries were randomly selected and followed from 2005 to 2013. Of these 1 000 000 patients, 3055 developed ESRD and commenced maintenance HD during this period. For each HD patient, four age-, gender- and diabetes-matched controls were selected from the database (n = 12 220). We further stratified the patients according to age. The study endpoint was the occurrence of malignancy. RESULTS: The incidence rates of malignancy were 6.8% and 4.9% in the HD and control groups, respectively. Competing risk regression analysis indicated that age, HD, male gender and diabetes were associated with an increased risk of malignancy. When further stratified according to age, the odds ratios of developing cancer were 5.8, 1.9, 1.9 and 1.5 among the HD patients aged <40 years, 40-49 years, 50-59 years and 60-69 years, respectively. CONCLUSION: The patients with ESRD who received HD had a significantly higher cumulative risk of malignancy, especially those with a young age. Therefore, specialized cancer screening protocols for young HD patients might help to prolong their lifespan.

Vitamin D deficiency in northern Taiwan: a community-based cohort study.

BACKGROUND: Vitamin D deficiency has become an important public health problem, however few studies have been conducted in subtropical countries, and the predictors of vitamin D deficiency in people with healthy renal function are unclear. The objective of this study was to evaluate the prevalence and factors associated with vitamin D deficiency in northern Taiwan. METHODS: The cross-sectional study was performed between August 2013 and August 2017, and included 3954 participants without chronic kidney disease (CKD) aged ≥30 years in northern Taiwan. Serum 25-hydroxyvitamin D [25(OH)-D] levels, biochemistry, sociodemographic variables (age, sex, education, occupation) and lifestyle habits (tea, coffee consumption and physical activities) were recorded. Associations between vitamin D status and these variables were examined using a regression model. The definition of deficiency was defined as a serum 25(OH)-D level < 20 ng/mL (50 nmol/L). RESULTS: The mean 25(OH)-D concentration was 28.9 ng/mL, and 22.4% of the study population had vitamin D deficiency. There was a significantly higher vitamin D deficiency ratio in the women compared to the men (22.9% vs 9.9%, p < 0.001). Vitamin D deficiency was most prevalent (38.4%) in those aged 30-39 years. Those with a graduate degree had the highest rate of vitamin D deficiency (31.5%). The predictors of vitamin D deficiency included female sex, young age, high education level, living in an urban area and physical inactivity. Tea consumption was negatively associated with vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency is prevalent in subtropical areas such as northern Taiwan in healthy individuals without CKD.

The association between chronic musculoskeletal pain and clinical outcome in chronic kidney disease patients: a prospective cohort study.

BACKGROUND AND OBJECTIVES: Chronic musculoskeletal (MS) pain is common in chronic kidney disease (CKD) patients. The association of chronic MS pain and CKD progression has not yet been established. METHOD: We conducted a prospective cohort study to evaluate the association of chronic MS pain and CKD progression of pre-dialysis CKD patients. RESULT: A total of 53.2% of pre-dialysis CKD patients had chronic MS pain. Patients classified as progression and non-progression had a similar prevalence of chronic MS pain at baseline, and similar baseline use of NSAIDs and Chinese herbal medicines. Univariate Cox analysis indicated that chronic MS pain and baseline NSAID or Chinese herbal medicine use were not significantly associated with progression of CKD. But multivariate Cox regression found chronic MS pain was independently significantly associated with all-cause mortality (HR, 2.912, 95% CI, 1.004-8.444; p = .049). However, serum levels of hs-CRP were similar between those chronic MS pain patients and without chronic MS pain patients (4.96 ± 9.4 vs. 4.25 ± 13.3 mg/L, p = .535). CONCLUSION: The CKD patients with chronic MS pain was independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.

Protein-bound uremic toxins induce tissue remodeling by targeting the EGF receptor.

Indoxyl sulfate and p-cresol sulfate have been suggested to induce kidney tissue remodeling. This study aimed to clarify the molecular mechanisms underlying this tissue remodeling using cultured human proximal renal tubular cells and half-nephrectomized mice treated with indoxyl sulfate or p-cresol sulfate as study models. Molecular docking results suggested that indoxyl sulfate and p-cresol sulfate dock on a putative interdomain pocket of the extracellular EGF receptor. In vitro spectrophotometric analysis revealed that the presence of a synthetic EGF receptor peptide significantly decreased the spectrophotometric absorption of indoxyl sulfate and p-cresol sulfate. In cultured cells, indoxyl sulfate and p-cresol sulfate activated the EGF receptor and downstream signaling by enhancing receptor dimerization, and increased expression of matrix metalloproteinases 2 and 9 in an EGF receptor-dependent manner. Treatment of mice with indoxyl sulfate or p-cresol sulfate significantly activated the renal EGF receptor and increased the tubulointerstitial expression of matrix metalloproteinases 2 and 9. In conclusion, indoxyl sulfate and p-cresol sulfate may induce kidney tissue remodeling through direct binding and activation of the renal EGF receptor.

Association between human leucocyte antigen subtypes and risk of end stage renal disease in Taiwanese: a retrospective study.

BACKGROUND: End stage renal disease (ESRD) is prevalent in Taiwan. Human leukocyte antigens (HLA) have been found to be associated with the pathogenesis of autoimmune diseases, allergies and inflammatory bowel diseases, and there are emerging evidences of correlations between HLA genotypes and renal diseases such as diabetic nephropathy, IgA nephropathy, and glomerulonephritis. The aim of this study is to investigate detailed HLA subtypes in a case-control study of Taiwanese individuals. METHODS: The polymorphisms of HLA class I and II antigens in ESRD patients and a healthy control group were retrospectively analyzed. The information of 141 ESRD patients was obtained from the medical record of the Keelung branch of Chang Gung Memorial Hospital and was compared to the HLA type of a control group comprized of 190 healthy unrelated Taiwanese from one of our previous studies. In order to standardize the HLA designation of prior low-resolution typings with the more advanced DNA based typings, all HLA-A, -B and -DR were analyzed using a low resolution serologic equivalent. RESULTS: The current work suggests that HLA-DR3 (odds ratio = 1.91, 95 % CI = 1.098-3.324, P = 0.024, Pc = 0.312) and HLA-DR11 (odds ratio = 2.06, 95 % CI = 1.133-3.761, P = 0.021, Pc = 0.273) may represent susceptibility risk factors for the development of ESRD in Taiwanese individuals. On the other hand, HLA-DR8 (odds ratio = 0.47, 95 % CI = 0.236-0.920, p = 0.027. Pc = 0.351) may be a protective factor. HLA-A and -B antigens did not show any contribution of progression to ESRD. However, we note that the significance of all these findings is lost when the results are corrected for multiple comparisons according to Bonferroni. Further investigation with a larger group of patients and control is needed to resolve this issue. CONCLUSIONS: HLA typing might be a useful clinical method for screening patients with high risk of progression to ESRD.

Correlation and presentation of thyroid functional status with thyroid autoantibodies in long-term follow-up of autoimmune thyroiditis: A study of 116 cases.

BACKGROUND/PURPOSE: The most common diagnostic finding of autoimmune thyroid disease (AITD) is the presence of antithyroid antibodies. While autoimmune thyroiditis (AT) is a common AITD, aspiration cytology is one of the important diagnostic tools of AT. METHODS: We evaluated 116 AT patients with ultrasound-guided aspiration cytology and then analyzed the correlation between thyroid hormone status and thyroid autoantibodies. This was a retrospective analysis with prospective collection of data with a mean follow-up period of 68.8 ± 37.8 months. The patients were classified as either euthyroid, hypothyroid, or hyperthyroid (HT). Of the 116 patients, 22 were hypothyroid, 37 were euthyroid, and 57 were HT. RESULTS: During the follow-up period, 95.5% of the hypothyroid group remained hypothyroid and only one patient improved to euthyroid. In the euthyroid group, 16.2% progressed to hypothyroid and 83.8% remained euthyroid. In the HT group, 8.7% progressed to hypothyroid, 70.2% progressed to euthyroid, and 21.1% remained HT. Most patients with a high titer of thyroglobulin antibody (TgAb) will progress to hypothyroid, and patients with a high titer of thyroid stimulating hormone (TSH) receptor antibody (TRAb) will remain HT. Strong correlations between thyroid functional status and positive number of thyroid autoantibodies were seen in this study. Patients with all the three antibodies positive had a high prevalence of hyperthyroidism. CONCLUSION: In our study, most patients were HT; this may be because of the early diagnosis and treatment of AT in our clinic. Although antithyroperoxidase antibody (TPOAb) is a hallmark antibody of HT, it cannot predict the initial presentation and clinical outcome.

Oral adsorbent AST-120 potentiates the effect of erythropoietin-stimulating agents on Stage 5 chronic kidney disease patients: a randomized crossover study.

BACKGROUND: Indoxyl sulfate (IS) suppresses erythropoietin (EPO) activity and exerts renal damage. The oral adsorbent AST-120 reduces IS load and has antioxidant and renoprotective properties; however, its roles in the treatment of anemia remain unclear in chronic kidney disease (CKD) patients. METHODS: Fifty-one Stage 5 predialysis CKD patients with hemoglobin <10 g/dL were randomly assigned to receive two period treatments with AST-120 plus once-monthly administration of continuous EPO receptor activator (CERA, A) and CERA alone (B), with a 4-week washout period in between. Mean changes of serum creatinine, estimated glomerular filtration rate (eGFR) and hemoglobin levels from the baseline were compared between two treatments. RESULTS: The baseline and postintervention mean creatinine levels were 5.48 and 5.36 mg/dL in the Treatment A, and 5.14 mg/dL and 5.61 g/dL in the Treatment B group, respectively (treatment effect P = 0.025, period effect P = 0.467, carryover effect P = 0.384). The baseline and postintervention mean hemoglobin levels were 9.27 and 10.47 g/dL in the Treatment A, and 9.63 g/dL and 9.54 g/dL in the Treatment B group, respectively (treatment effect P = 0.039, period effect P = 0.001, carryover effect P = 0.060). Use of AST-120 significantly reduced IS and p-cresyl sulfate (PCS) levels. Hierarchical regression showed that eGFR was an independent predictor for hemoglobin after adjustment of serum free IS and PCS levels (B = 0.049, P = 0.005). CONCLUSIONS: Use of adjuvant AST-120 may improve renal function and hemoglobin levels than use of CERA alone in late-stage CKD patients. The change of eGFR might play an intermediate role between serum IS/PCS and improve hemoglobin levels. The finding offered insight into novel therapeutic strategies of anemia for late-stage CKD patients.

Factors associated with chronic musculoskeletal pain in patients with chronic kidney disease.

BACKGROUND: Chronic musculoskeletal (MS) pain is common in patients with chronic kidney disease (CKD) undergoing haemodialysis. However, epidemiological data for chronic MS pain and factors associated with chronic MS pain in patients with early- or late-stage CKD who are not undergoing dialysis are limited. METHOD: A cross-sectional study to evaluate the prevalence of chronic MS pain and factors associated with chronic MS pain in patients with early- and late-stage CKD who were not undergoing dialysis, was conducted. In addition, the distribution of pain severity among patients with different stages of CKD was evaluated. RESULTS: Of the 456 CKD patients studied, 53.3% (n = 243/456) had chronic MS pain. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, as well as with the calcium × phosphate product levels. In CKD patients with hyperuricemia, chronic MS pain showed a negative, independent significant association with diabetes mellitus as a co-morbidity (odds ratio: 0.413, p = 0.020). However, in the CKD patients without hyperuricemia as a co-morbidity, chronic MS pain showed an independent significant association with the calcium × phosphate product levels (odds ratio: 1.093, p = 0.027). Furthermore, stage-5 CKD patients seemed to experience more severe chronic MS pain than patients with other stages of CKD. CONCLUSION: Chronic MS pain is common in CKD patients. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, and with the calcium × phosphate product levels in early- and late-stage CKD patients who were not on dialysis.

Prescription of psychotropic drugs in patients with chronic renal failure on hemodialysis.

OBJECTIVE: Patients on hemodialysis commonly have comorbid depression and require treatment with psychotropic drugs. This study aimed to investigate the prevalence of the use of psychotropic drugs among patients on hemodialysis and to elucidate the factors associated with use of each class of psychotropic medication. METHODS: This cross-sectional study enrolled 195 hemodialysis patients with a mean age of 58.5 years. Patients were assessed using the Mini International Neuropsychiatric Interview, Hospital Anxiety and Depression Scale, Chalder Fatigue Scale and Short-form Health-related Quality of Life. We analyzed the frequency of psychiatric outpatient department visits within six months prior to interview and psychotropic drugs use within one month prior to interview, including antidepressants, antipsychotics, mood stabilizers, benzodiazepines (BZDs) and hypnotics. RESULTS: Of the 195 patients, 47 (24.1%) fulfilled the DSM-IV criteria for major depressive disorder (MDD). Only 6.4% of patients diagnosed with MDD visited the psychiatry outpatient department within six months prior to interview. Of the total patients, the proportions with use of antidepressants, antipsychotics, mood stabilizers, BZDs and hypnotics were 5.6%, 1.0%, 3.1%, 42.6% and 20.0%, respectively. Having MDD was an independent factor associated with taking antidepressants (adjusted OR = 3.98, p = 0.036) and taking hypnotics (adjusted OR = 2.75, p = 0.011). CONCLUSIONS: Depression is generally undetected or not well-managed among hemodialysis patients in the clinical setting. Only a small proportion of depressed patients received antidepressant treatment. BZDs and/or hypnotics might be exorbitantly prescribed. Clinicians should pay more attention to patients' emotional distress and provide appropriate treatment.

Chronic kidney disease stage is a modulator on the association between high-sensitivity C-reactive protein and coronary vasospastic angina.

The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1-3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD.

Long-term impacts of endocrine-disrupting chemicals exposure on kidney function: A community-based cohort study.

This study explores the extended renal effects of endocrine-disrupting chemicals (EDCs) exposure, a linkage already established with adverse health outcomes, notably chronic kidney disease. To delve deeper, the Chang Gung Community Research Center conducted a longitudinal study with 887 participants. Among them, 120 individuals were scrutinized based on EDC scores, analyzing 17 urinary EDCs and renal function. Findings revealed elevated mono-(2-ethylhexyl) phthalate (MEHP) and bisphenol A levels in higher EDC exposure cases. MEHP notably correlated with increased urinary albumin-to-creatinine ratio (UACR), predicting a > 15% decline in estimated glomerular filtration rate. Higher MEHP levels also hinted at declining renal function. UACR escalation linked significantly with specific EDCs: MEHP, methylparaben, nonylphenol, and 4-tert-octylphenol. This research underscores enduring renal hazards tied to environmental EDC exposure, particularly MEHP, emphasizing the urgent call for robust preventive public health strategies.

Endocrine-Disrupting Chemicals Exposure and Neurocognitive Function in the General Population: A Community-Based Study.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. METHODS: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire. RESULTS: These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (ß ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively. CONCLUSION: Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.

Re-evaluating the predictive roles of metabolic complications and clinical outcome according to eGFR levels--a four-years prospective cohort study in Taiwan.

BACKGROUND: Metabolic complications are associated with clinical outcomes in patients with chronic kidney disease (CKD). These outcomes differ among patients according to the different stages of disease. The prevalence and association of type and number of metabolic complications with renal progression and death in patients having different eGFR levels has high clinical value, but this fact has been rarely evaluated in prospective studies. METHODS: We prospectively followed a cohort of 1157 CKD patients from 2006 to death or until 2010, and evaluated the prevalence of CKD-related complications and their association with renal progression (defined as a decline in eGFR by > 50% from baseline, or end-stage renal disease requiring dialysis) and death in patients with eGFRs above and below 45 mL/min/1.73 m(2) using Cox-proportional hazard models. RESULTS: The estimated rate (per 100 patient-years) of renal progression and death were 11.9 and 4.9, respectively. The eGFR thresholds determined by ROC analysis with a sensitivity of 90% for any metabolic complication were 60.8 mL/min/1.73 m(2) and 74.3 mL/min/1.73 m(2) using the MDRD and CKD Epidemiology Collaboration equations, respectively. CKD-related complications associated with renal progression in patients having eGFR < 45 mL/min/1.73 m(2) were hyperphosphatemia, anemia, microinflammation and hypoalbuminemia. Those CKD-related complications associated with death were hypoalbuminemia and hyperuricemia. Hypoalbuminemia predicted renal progression, and, hypoalbuminemia and microinflammation predicted death in patients with eGFR ≥ 45 mL/min/1.73 m(2). The number of complications (≥ 3) independently predicted both endpoints in patients with eGFR < 45 mL/min/1.73 m(2). CONCLUSIONS: Hypoalbuminemia was a unique and strong predictor of renal progression and all-cause mortality in CKD patients, independent of their demographic characteristics, traditional risk factors, renal function severity, the presence of cardiovascular disease and other metabolic abnormalities. Most other metabolic complications and the number of complications (≥ 3) were associated with the clinical outcomes of patients with eGFR < 45 mL/min/1.73 m(2) rather than in those with higher eGFRs. The findings from the present study offer a novel insight into the association between metabolic complications and patient outcomes and may help to refine risk stratification according to disease stage.

Retinal Neurodegeneration and Visual Acuity Decline in Patients with Chronic Kidney Disease.

INTRODUCTION: Chronic kidney disease (CKD) has been associated with accelerated retinal neurodegeneration. The purpose of this study is to evaluate the association between retinal neurodegeneration and the best-corrected visual acuity (BCVA) decline in patients with CKD. METHODS: Post hoc analysis of two prospective studies. Patients with CKD stage ≥ 3 were enrolled. Macular thickness, peripapillary retinal nerve fiber layer (pRNFL) thickness, and macular ganglion cell complex (GCC) thickness were measured by optical coherence tomography. Eyes were classified into three groups: Group 1, no GCC defect; Group 2, GCC defect confined to parafoveal area; and Group 3, GCC defects extending beyond the parafoveal area. Each group was matched for age, sex, axial length, lens status, and cataract grading. RESULTS: A total of 120 eyes (40 eyes in each group) from 120 patients (age 63.0 ± 10.3 years) were included. The logMAR BCVA was 0.076 ± 0.101, 0.100 ± 0.127, and 0.196 ± 0.191 in Group 1, 2, and 3, respectively. Group 3, but not Group 2, had a significantly worse BCVA than Group 1. In simple linear regression, parafoveal inner retinal thickness, pRNFL thickness, presence of pRNFL defect, GCC thickness, GCC global loss volume, GCC focal loss volume, and GCC defect extending beyond parafoveal area were associated with BCVA. Central subfield retinal thickness (CRT), parafoveal full retinal thickness, and parafoveal outer retinal thickness were not associated with BCVA. In backward stepwise linear regression, age and GCC defects extending beyond the parafoveal area were factors associated with BCVA. Moreover, GCC defect extending beyond parafoveal area was connected with worse BCVA in both phakic and pseudophakic subgroups. CONCLUSIONS: GCC defect extending beyond parafoveal area could be an independent biomarker associated with decreased BCVA in patients with CKD. However, macular thinning measured by CRT or parafoveal full retinal thickness might have low discriminative power in determining BCVA.

Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients--a prospective cohort study.

BACKGROUND: The mortality rate of elderly hemodialysis (HD) patients is high. Serum p-cresyl sulfate (PCS) and indoxyl sulfate (IS) are associated with cardiovascular (CV) disease and mortality in renal patients. The association between such biomarkers and mortality in elderly HD patients has a high clinical value but remains unclear. METHODS: This prospective cohort study investigated the association of serum IS and PCS with all-cause and CV mortality in elderly HD patients. Multivariate Cox regression analysis was used to estimate the risk of all-cause and CV mortality in this prospective cohort. RESULTS: Of 112 patients, 45 deaths (18 CV deaths) were identified after a mean follow-up of 33.2 months. The cumulative and CV survival of patients with lower free PCS was significantly better than high free PCS patients. In multivariate Cox regression analysis, serum free PCS was associated with all-cause and CV mortality after various adjustments, including age, gender and diabetes status (Model 1), albumin (Model 2), Ca × P product and intact parathyroid hormone (Model 3), hemoglobin and high-sensitivity C-reactive protein (Model 4) and hierarchically selected covariates (age, diabetes status and albumin, Model 5). CONCLUSION: Serum free PCS levels may help in predicting risk of all-cause and CV mortality in elderly HD patients beyond traditional and uremia related risk factors.