Proteins Secreted by Lung Cancer Cells Induce the Onset of Proteinuria via Focal Adhesion Kinase Signaling in Mice.

Paraneoplastic nephrotic syndrome (PNS) is a complication seen in cancer patients. Ultrastructural examination shows the accumulation of proteins and the presence of foot process (FP) effacement in the glomeruli of PNS patients. Previously, we reported that orthotopic xenografts of Lewis lung carcinoma 1 in C57BL/6 mice caused them to develop lung cancer with albuminuria. This implies that these mice can be used as a model of human disease and suggests that Lewis lung carcinoma 1 cell-secreted proteins (LCSePs) contain nephrotoxic molecules and cause inflammation in renal cells. As podocyte effacement was present in glomeruli in this model, such podocyte injury may be attributable to either soluble LCSeP or LCSeP deposits triggering pathological progression. LCSePs in conditioned media was concentrated for nephrotoxicity testing. Integrin-focal adhesion kinase (FAK) signaling and inflammatory responses were evaluated in podocytes either exposed to soluble LCSePs or seeded onto substrates with immobilized LCSePs. FAK phosphorylation and interleukin-6 expression were higher in podocytes attached to LCSePs substrates than in those exposed to soluble LCSePs. Notably, LCSeP-based haptotaxis gave rise to altered signaling in podocytes. When podocytes were stimulated by immobilized LCSePs, FAK accumulated at focal adhesions, synaptopodin dissociated from F-actin, and disrupting the interactions between synaptopodin and α-actinin was observed. When FAK was inhibited by PF-573228 in immobilized LCSePs, the association between synaptopodin and α-actinin was observed in the podocytes. The association of synaptopodin and α-actinin with F-actin allowed FP stretching, establishing a functional glomerular filtration barrier. Therefore, in this mouse model of lung cancer, FAK signaling prompts podocyte FP effacement and proteinuria, indicative of PNS.

High risk of renal outcome of metabolic syndrome independent of diabetes in patients with CKD stage 1-4: The ICKD database.

AIMS: To investigate whether metabolic syndrome (MetS) could predict renal outcome in patients with established chronic kidney disease (CKD). MATERIALS AND METHODS: We enroled 2500 patients with CKD stage 1-4 from the Integrated CKD care programme, Kaohsiung for delaying Dialysis (ICKD) prospective observational study. 66.9% and 49.2% patients had MetS and diabetes (DM), respectively. We accessed three clinical outcomes, including all-cause mortality, RRT, and 50% decline in estimated glomerular filtration rate events. RESULTS: The MetS score was positively associated with proteinuria, inflammation, and nutrition markers. In fully adjusted Cox regression, the hazard ratio (HR) (95% confidence interval) of MetS for composite renal outcome (renal replacement therapy, and 50% decline of renal function) in the DM and non-DM subgroups was 1.56 (1.15-2.12) and 1.31 (1.02-1.70), respectively, while that for all-cause mortality was 1.00 (0.71-1.40) and 1.27 (0.92-1.74). Blood pressure is the most important component of MetS for renal outcomes. In the 2 by 2 matrix, compared with the non-DM/non-MetS group, the DM/MetS group (HR: 1.62 (1.31-2.02)) and the non-DM/MetS group (HR: 1.33 (1.05-1.69)) had higher risks for composite renal outcome, whereas the DM/MetS group had higher risk for all-cause mortality (HR: 1.43 (1.09-1.88)). CONCLUSIONS: MetS could predict renal outcome in patients with CKD stage 1-4 independent of DM.

Incidence and survival variations of upper tract urothelial cancer in Taiwan (2001-2010).

OBJECTIVES: To assess temporal patterns and regional differences in the incidence rate, and factors associated with survival of urinary tract urothelial carcinoma. METHODS: The medical records of 8830 patients with new diagnoses of urinary tract urothelial carcinoma in the years 2001-2010 were retrieved from Taiwan National databases. Temporal trends, regional disparity and related survival factors were evaluated using the Cochran-Armitage trend test, local Moran's I statistic and log-rank test, respectively. RESULTS: The annual urinary tract urothelial carcinoma incidence rates (standardized by age) were steady at approximately 3.14-3.41 per 100 000 person-years. Notably, women had a significantly higher annual urinary tract urothelial carcinoma incidence than men in most of the years studied (range of female-to-male annual standardized rate ratio: 2.08-3.25), and diabetes prevalence in urinary tract urothelial carcinoma increased significantly from 12.3% to 23.4% per year over the 10 years. High urinary tract urothelial carcinoma incidence cluster areas other than the latest endemic area of "blackfoot disease" were newly identified by local Moran's I statistic (P < 0.05). Furthermore, older age, male sex, end-stage kidney disease and more advanced tumor grade were associated with lower 5-year overall survival probabilities in the 2001-2015 cohort. CONCLUSIONS: The incidence and survival of urinary tract urothelial carcinoma over the decade 2001-2010 were different according to population and regional features. Various urinary tract urothelial carcinoma screening, prevention, treatment and care plans should be developed depending on age, sex, comorbidity and area of residence.

Establishment of an outreach, grouping healthcare system to achieve microelimination of HCV for uremic patients in haemodialysis centres (ERASE-C).

OBJECTIVE: HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme. DESIGN: The ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up). RESULTS: At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively. CONCLUSION: Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population. CLINICALTRIALSGOV IDENTIFIER: NCT03803410 and NCT03891550.

Evolutionary seroepidemiology of viral hepatitis and the gap in hepatitis C care cascades among uraemic patients receiving haemodialysis in Taiwan-the Formosa-Like Group.

Uraemic patients undergoing haemodialysis are at high risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We aimed to evaluate the evolutionary seroprevalence of viral hepatitis and the gap in HCV care cascades in this special population by a large-scale surveillance study in Taiwan. Uraemic patients on maintenance haemodialysis from 22 sites (FORMOSA-LIKE group) in 2012 (n = 1,680) and 2019 (n = 2,326) were recruited for this study. The distributions and sequential changes of viral hepatitis markers were analysed. The prevalence of anti-HCV antibody and hepatitis B surface antigen (HBsAg) seropositivity was 13.6% (316/2326) and 11.5% (267/2326), respectively, in 2019 compared with 17.3% (290/1680, P = .002) and 13.6% (229/1680, P = .046), respectively, in 2012. The HCV-viremic rate among anti-HCV-seropositive patients was significantly lower in 2019 than in 2012 (56.3% [178/316] vs. 73.8% [214/290], P < .001). The HCV treatment rate increased from 2.3% (5/217) in 2012 to 21.7% (49/226) in 2019 (P < .001). In the sequential analysis of the 490 patients who participated in both screens, 17 of the 55 HCV-viremic patients became HCV RNA seronegative, including 13 by antivirals and four spontaneously. By contrast, one anti-HCV-seropositive but nonviremic patient became viremic, and six anti-HCV-seronegative patients became anti-HCV-seropositive in 2019. The annual incidence of new HCV was 0.2%/year. Seven HBsAg-seropositive patients experienced HBsAg loss (1.25%/year). Two patients had new anti-HBc seropositivity (new HBV exposure: 0.57%/year). The seroprevalence of viral hepatitis decreased in an 8-year follow-up but remained prevalent, and the treatment of HCV infection was underutilized in uraemic patients. Additional efforts are needed to enhance the HCV treatment uptake of uraemic patients. Clinical Trial IDs: NCT03803410, NCT01766895.

Comorbidities in patients with chronic hepatitis C and hepatitis B on hemodialysis.

BACKGROUND AND AIM: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis. METHODS: A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision. RESULTS: Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P < 0.001) and NBNC groups (2.9 ± 1.5, P = 0.004), mainly due to the higher prevalence of ischemic heart disease, respiratory disorders, and mental/behavioral disorders. The HBV and NBNC groups exhibited comparable burdens of comorbidities. CONCLUSIONS: Hemodialysis patients had a high prevalence of multiple comorbidities. Hemodialysis patients with HCV exhibited a higher burden of comorbidities, especially ischemic heart diseases, respiratory disorders, and mental/behavioral disorders, than HBV and NBNC patients did.

Predominant global glomerulosclerosis in patients of upper urinary tract urothelial carcinoma with pre-existing renal function impairment is a predictor of poor renal outcomes.

BACKGROUND: Incidence of renal dysfunction and risks of progression to end-stage renal disease (ESRD) were reported higher in upper urinary tract urothelial carcinoma (UTUC) than in renal cell carcinoma (RCC) patients after unilateral nephrectomy. METHODS: Totally 193 renal cancer patients, including 132 UTUC and 61 RCC, were studied to clarify whether the pathological changes of the kidney remnant removed from nephrectomy and the clinical factors might predict the risk of ESRD. Renal tubulointerstitial (TI) score and global glomerulosclerosis (GGS) rate were examined by one pathologist and two nephrologists independently under same histopathological criteria. RESULTS: The glomerular filtration rates at the time of surgery were lower in UTUC than RCC groups (p < 0.001). Average GGS score and average TI rate were higher in UTUC than in RCC groups (p < 0.001; p < 0.001). Competitive risk factor analysis revealed that abnormal GGS rate not related to age, predominant in UTUC with pre-existing renal function impairment, was a histopathological predictor of poor renal outcomes (creatinine doubling or ESRD) within 5 years in UTUC patients. CONCLUSION: Pre-existing renal function and pathological change of kidney remnant in both UTUC and RCC have the value for prediction of renal outcomes.

Decreased incidence of gout in diabetic patients using pioglitazone.

Objective: The incidence and prevalence of gout are increasing, but the management is poor. Considering the increased prevalence of gout in the diabetic population, this study evaluated the effects of pioglitazone, an insulin resistance inhibitor, on the incidence of gout in the diabetic population. Methods: We used data from the National Health Insurance program in Taiwan. The pioglitazone cohort contained 30 100 patients and each patient was age and sex matched with three non-pioglitazone users who were randomly selected from the diabetic population. Cox proportional hazards regression analysis was conducted to estimate the effects of pioglitazone on the incidence of gout in the diabetic population. Results: The incidence of gout was significantly lower in pioglitazone users than in non-pioglitazone users [adjusted hazard ratio (aHR) 0.81 (95% CI 0.78, 0.85)]. The HR for the incidence of gout was lower in both male [aHR 0.80 (95% CI 0.75, 0.85)] and female [aHR 0.83 (95% CI 0.78, 0.88)] pioglitazone users than in non-pioglitazone users. An analysis of three age groups (<40, 40-59 and ⩾60 years) revealed that the HRs of both the 40-59 years [aHR 0.78 (95% CI 0.73, 0.83)] and the ⩾60 years [aHR 0.85 (95% CI 0.80, 0.91)] age groups were significantly lower among pioglitazone users than non-pioglitazone users. Conclusion: Compared with the non-pioglitazone users, the incidence of gout in the diabetic population using pioglitazone was less.

Decreased incidence of diabetes in patients with gout using benzbromarone.

Objective: Insulin resistance is inversely correlated with the clearance rate of uric acid, which may indicate that improvement in the clearance rate of uric acid could reduce insulin resistance. Considering the increased prevalence of diabetes mellitus (DM) in the gout population, this study evaluated the effects of benzbromarone, a uricosuric agent, on the incidence of DM in the gout population. Methods: We used data from the Taiwan National Health Insurance program. The benzbromarone user cohort included 8678 patients; each patient was age- and sex-matched with one benzbromarone non-user who was randomly selected from the gout population. The Cox proportional hazard regression analysis was conducted to estimate the effects of benzbromarone on the incidence of DM in the gout population. Results: The incidence of DM was significantly lower in benzbromarone users than in benzbromarone non-users [adjusted hazard ratio (HR) = 0.86; 95% CI: 0.79, 0.94]. The HR for the incidence of DM was lower in male benzbromarone users (adjusted HR = 0.77; 95% CI: 0.69, 0.86) than in benzbromarone non-users. An analysis of three age groups (<40, 40-59 and ⩾60 years) indicated that the HRs of the age groups of 40-59 years (adjusted HR = 0.86; 95% CI: 0.76, 0.98) and ⩾60 years (adjusted HR = 0.82; 95% CI: 0.71, 0.94) were significantly lower among benzbromarone users than among benzbromarone non-users. Conclusion: In the gout population, the incidence of DM was lower in benzbromarone users than in benzbromarone non-users.

Dialysis Increases the Risk of Bladder Recurrence in Patients with Upper Tract Urothelial Cancer: A Population-Based Study.

BACKGROUND: The relation of dialysis to tumor recurrence in patients with upper tract urothelial cancer (UTUC) is unknown; however, a limited number of small-scale studies suggest that patients with renal diseases prior to UTUC are more likely to exhibit bladder recurrence. We performed a population-based analysis to determine the effect of dialysis on bladder recurrence for patients with UTUC. METHODS: This retrospective cohort study included patients diagnosed with UTUC (2002-2007) from the Taiwan National Cancer Registry and divided them into two groups-dialysis and non-dialysis groups. These patients were followed up until bladder recurrence, death, or the end of 2010. Competing risk analyses adjusting covariates and death were applied to determine the relation of dialysis and bladder recurrence. RESULTS: Of the 5141 eligible patients, 548 (10.7%) were undergoing dialysis. The cumulative bladder recurrence was significantly higher in the dialysis group than in the non-dialysis group (29% vs. 21%, modified log-rank p < 0.001). In the multivariable analysis, the dialysis group exhibited a 64% increased bladder recurrence risk (cause-specific hazard ratio 1.64, 95% confidence interval 1.34-2.01, p < 0.001), which was confirmed using stratification and propensity score weighting methods. The other prognostic factors for bladder recurrence were sex, diabetes, cardiac disorder, Charlson Comorbidity Index, and tumor grade. CONCLUSIONS: Despite unknown reasons, approximately one-tenth of patients with UTUC have experienced dialysis treatment. Patients undergoing dialysis have a higher risk of bladder recurrence. Various treatment and screening strategies should be developed for dialysis and non-dialysis patients.

The application of blood flow sound contrastive learning to predict arteriovenous graft stenosis of patients with hemodialysis.

End-stage kidney disease (ESKD) presents a significant public health challenge, with hemodialysis (HD) remaining one of the most prevalent kidney replacement therapies. Ensuring the longevity and functionality of arteriovenous accesses is challenging for HD patients. Blood flow sound, which contains valuable information, has often been neglected in the past. However, machine learning offers a new approach, leveraging data non-invasively and learning autonomously to match the experience of healthcare professionas. This study aimed to devise a model for detecting arteriovenous grafts (AVGs) stenosis. A smartphone stethoscope was used to record the sound of AVG blood flow at the arterial and venous sides, with each recording lasting one minute. The sound recordings were transformed into mel spectrograms, and a 14-layer convolutional neural network (CNN) was employed to detect stenosis. The CNN comprised six convolution blocks with 3x3 kernel mapping, batch normalization, and rectified linear unit activation function. We applied contrastive learning to train the pre-training audio neural networks model with unlabeled data through self-supervised learning, followed by fine-tuning. In total, 27,406 dialysis session blood flow sounds were documented, including 180 stenosis blood flow sounds. Our proposed framework demonstrated a significant improvement (p<0.05) over training from scratch and a popular pre-trained audio neural networks (PANNs) model, achieving an accuracy of 0.9279, precision of 0.8462, and recall of 0.8077, compared to previous values of 0.8649, 0.7391, and 0.6538. This study illustrates how contrastive learning with unlabeled blood flow sound data can enhance convolutional neural networks for detecting AVG stenosis in HD patients.

The Association between Iron Deficiency and Renal Outcomes Is Modified by Sex and Anemia in Patients with Chronic Kidney Disease Stage 1-4.

Iron deficiency is prevalent in women and patients with chronic kidney disease (CKD). Iron deficiency is not only related to anemia but contributes to adverse consequences for the kidney as well. Whether iron status is associated with renal outcomes after considering sex and anemia in patients with CKD stage 1-4 is unclear. Thus, we investigated the association of iron or iron saturation with renal outcomes in a CKD cohort. During a follow-up of 8.2 years, 781 (31.2%) patients met the composite renal outcome of renal replacement therapy and a 50% decline in renal function. In linear regression, iron was associated with sex, hemoglobin (Hb), and nutritional markers. In a fully adjusted Cox regression model, the male patients with normal iron had a significantly decreased risk of renal outcomes (hazard ratio (HR) 0.718; 95% confidence interval (CI) 0.579 to 0.889), but the female patients did not exhibit this association. The non-anemic patients (Hb ≥ 11 g/dL) had a decreased risk of renal outcomes (HR 0.715; 95% CI 0.568 to 0.898), but the anemic patients did not. In the sensitivity analysis, transferrin saturation (TSAT) showed similar results. When comparing iron and TSAT, both indicators showed similar prognostic values. In conclusion, iron deficiency, indicated by either iron or iron saturation, was associated with poor renal outcomes in the male or non-anemic patients with CKD stage 1-4.

Non-insulin-based insulin resistance indices for predicting all-cause mortality and renal outcomes in patients with stage 1-4 chronic kidney disease: another paradox.

Non-insulin-based insulin resistance (IR) indices serve as the indicators of metabolic syndrome (MetS) but have limited value for predicting clinical outcomes. Whether the obesity paradox affects the predictive value of these indicators in patients with chronic kidney disease (CKD) remains unknown. We investigated whether MetS and non-insulin-based IR indices can predict all-cause mortality and renal outcomes in a prospective observational study with stage 1-4 CKD Asians (N = 2,457). These IR indices were associated with MetS. A Cox regression model including body mass index (BMI) revealed an association between MetS and renal outcomes. Among the IR indices, only high triglyceride-glucose (TyG) index was associated with adverse renal outcomes: the hazard ratio of Q4 quartile of the TyG index was 1.38 (1.12-1.70). All-cause mortality was marginally associated with MetS but not high IR indices. Low TyG and TyG-BMI indices as well as low BMI and triglyceride were paradoxically associated with increased risks of clinical outcomes. The triglyceride-to-high-density lipoprotein cholesterol ratio and metabolic score for IR indices were not associated with clinical outcomes. In conclusion, MetS and TyG index predict renal outcome and obesity paradox affects the prediction of IR indices in patients with stage 1-4 CKD.

The prognostic value of URR equals that of Kt/V for all-cause mortality in Taiwan after 10-year follow-up.

Kt/V and URR (urea reduction ratio) measurements represent dialysis adequacy. Single-pool Kt/V is theoretically a superior method and is recommended by the Kidney Disease Outcomes Quality Initiative guidelines. However, the prognostic value of URR compared with Kt/V for all-cause mortality is unknown. The effect modifiers and cut-off values of the two parameters have not been compared. We investigated 2615 incident hemodialysis patients with URR of 72% and Kt/V (Daugirdas) of 1.6. The average patient age was 59 years, 50.7% were female, and 1113 (40.2%) died within 10 years. URR and Kt/V were both positively associated with nutrition factors and female sex and negatively associated with body weight and heart failure. In Cox regression mod-els for all-cause mortality, the hazard ratios (HRs) of high URR groups (65-70%, 70-75%, and > 75%) and the URR < 65% group were 0.748 (0.623-0.898), 0.693 (0.578-0.829), and 0.640 (0.519-0.788), respectively. The HRs of high Kt/V groups (Kt/V 1.2-1.4, 1.4-1.7, and > 1.7) and the Kt/V < 1.2 group were 0.711 (0.580-0.873), 0.656 (0.540-0.799), and 0.623 (0.498-0.779), respec-tively. In subgroup analysis, Kt/V was not associated with all-cause mortality in women. The prognostic value of URR for all-cause mortality is as great as that of Kt/V. URR > 70% and Kt/V > 1.4 were associated with a higher survival rate. Kt/V may have weaker prognostic value for women.

Therapy as prevention toward HCV elimination in maintenance hemodialysis: a multi-center, prospective cohort study.

Background: The World Health Organization has established interim guidance for hepatitis C virus (HCV) elimination. We aimed to prove the concept of "treatment as prevention" by conducting a prospective HCV elimination program for hemodialysis (HD) patients. Methods: A universal HCV screen was launched in 22 HD centers in 2019. HCV-viremic patients were linked to care with direct-acting antivirals (DAAs). The second screen was performed in 2021 to evaluate the effect of link-to-care in lowering the prevalence of HCV viremia and the incidence of HCV new/re-infections. Results: Of 2336 patients enrolled in the first screening in 2019, 320 (13.7%) were seropositive for anti-HCV and 181 (7.7%) were HCV-viremic. Of 152 patients successfully linked to treat with DAA, 140 (92.1%) patients achieved a sustained virological response. Of them, 1733 patients participated in the second surveillance. Five anti-HCV-negative patients experienced anti-HCV seroconversion. Of 119 DAA-cured patients and 102 spontaneous HCV clearance patients, none had HCV reinfection. The annual incidence of HCV new infection was 0.1%. Sixty-one of the 620 (9.8%) newly enrolled patients were anti-HCV-seropositive in the second survey. The overall HCV-viremic rate decreased from 7.7% in 2019 to 0.6% (15/2353) in 2021. At the institutional level, 45.5% (10/22) eradicated HCV and 82% (18/22) of HD units had no HCV new infections or reinfections. Conclusions: The link-to-care project proved the concept of "treatment as prevention" by which HCV microelimination helps to prevent reinfection and new infections in the HD population.Trial registration: ClinicalTrials.gov identifier: NCT03803410 and NCT03891550.

High Ultrafiltration Rate Is Associated with Increased All-Cause Mortality in Incident Hemodialysis Patients with a High Cardiothoracic Ratio.

A high ultrafiltration rate (UFR) is associated with increased mortality in hemodialysis patients. However, whether a high UFR itself or heart failure with fluid overload followed by a high UFR causes mortality remains unknown. In this study, 2615 incident hemodialysis patients were categorized according to their initial cardiothoracic ratios (CTRs) to assess whether UFR was associated with mortality in patients with high or low CTRs. In total, 1317 patients (50.4%) were women and 1261 (48.2%) were diabetic. During 2246 (1087−3596) days of follow-up, 1247 (47.7%) cases of all-cause mortality were noted. UFR quintiles 4 and 5 were associated with higher risks of all-cause mortality than UFR quintile 2 in fully adjusted Cox regression analysis. As the UFR increased by 1 mL/kg/h, the risk of all-cause mortality increased 1.6%. Subgroup analysis revealed that in UFR quintile 5, hazard ratios (HRs) for all-cause mortality were 1.91, 1.48, 1.22, and 1.10 for CTRs of >55%, 50−55%, 45−50%, and <45%, respectively. HRs for all-cause mortality were higher in women and patients with high body weight. Thus, high UFRs may be associated with increased all-cause mortality in incident hemodialysis patients with a high CTR, but not in those with a low CTR.

Association between Body Mass Index and Renal Outcomes Modified by Chronic Kidney Disease and Anemia: The Obesity Paradox for Renal Outcomes.

Obesity-related nephropathy is associated with renal function progression. However, some studies have associated a high body mass index (BMI) with improved renal outcomes­this is referred to as the obesity paradox for renal outcomes, especially in relation to advanced chronic kidney disease (CKD). Central obesity can explain the obesity paradox in all-cause mortality. However, whether obesity or central obesity is associated with renal outcomes (renal replacement therapy or a 50% decline in the estimated glomerular filtration rate) in patients with advanced CKD remains unclear. Our study included 3605 Asian patients with CKD stages 1−5 divided into six groups according to their BMI (between 15 and 35 kg/m2). Through linear regression, BMI was positively associated with hemoglobin and albumin at CKD stages 4 and 5. In the competing risk Cox regression model, a high BMI (27.5−35 kg/m2) was associated with renal outcomes at CKD stages 1−3, but not stages 4 and 5. A high BMI was associated with renal outcomes in patients with hemoglobin ≥11 g/dL, but not <11 g/dL. A high waist-to-hip ratio was not associated with renal outcomes. We conclude that the CKD stage and anemia may explain the obesity paradox in renal outcomes in patients with CKD.

Hyperuricemia, a Non-Independent Component of Metabolic Syndrome, Only Predicts Renal Outcome in Chronic Kidney Disease Patients without Metabolic Syndrome or Diabetes.

Uric acid (UA) is elevated in metabolic syndrome (MS) and diabetes (DM). UA is associated with central obesity and blood glucose and is proposed as a criterion of MS. Previous reports showed that UA could predict renal outcome in CKD. However, recent clinical trials did not demonstrate the benefits of urate-lowering agents (ULA) for renal outcome. Whether the prognostic value of UA for renal outcome is independent of MS or secondary to MS in CKD patients is unknown. Our study included 2500 CKD stage 1−4 Asian patients divided by UA tertiles and MS/DM. In linear regression, UA was associated with obesity, C-reactive protein, and renal function. In Cox regression, high UA was associated with worse renal outcome in non-MS/DM, but not in MS/DM: hazard ratio (95% confidence interval) of UA tertile 3 was 3.86 (1.87−7.97) in non-MS/DM and 1.00 (0.77−1.30) in MS/DM (p for interaction < 0.05). MS was associated with worse renal outcome, but redefined MS (including hyperuricemia as the 6th criteria) was not. In conclusion, hyperuricemia is associated with worse renal outcome in non-MS/DM and is not an independent component of MS in CKD stage 1−4 patients. Hyperuricemia secondary to MS could not predict renal outcome.

Association between the risk of heart failure hospitalization and end-stage renal disease with digoxin usage in patients with cardiorenal syndrome: A population-based study.

Background: The management of the coexistence of heart disease and kidney disease is increasingly challenging for clinicians. Chronic kidney disease (CKD) is not only a prevalent comorbidity of patients with heart failure but has also been identified as a noteworthy risk factor for all-cause mortality and poor clinical outcomes. Digoxin is one of the commonest treatments for heart disease. There are few trials investigating the role of digoxin in patients with cardiorenal syndrome (CRS). This study aims to examine the association between digoxin usage and clinical outcomes in patients with CRS in a nationwide cohort. Method: We conducted a population-based study that included 705 digoxin users with CRS; each patient was age, sex, comorbidities, and medications matched with three non-users who were randomly selected from the CRS population. Cox proportional hazards regression analysis was conducted to estimate the effects of digoxin on the incidence of all-cause mortality, congestive heart failure (CHF) hospitalization, coronary artery disease (CAD) hospitalization, and end-stage renal disease (ESRD). Results: The all-cause mortality rate was significantly higher in digoxin users than in non-users (adjusted hazard ratio [aHR] = 1.26; 95% confidence interval [CI] = 1.09-1.46, p = 0.002). In a subgroup analysis, there was significantly high mortality in the 0.26-0.75 defined daily dose (DDD) subgroup of digoxin users (aHR = 1.49; 95% CI = 1.23-1.82, p<0.001). Thus, the p for trend was 0.013. With digoxin prescription, the CHF hospitalization was significantly higher [subdistribution HR (sHR) = 1.17; 95% CI = 1.05-1.30, p = 0.004], especially in the >0.75 DDD subgroup (sHR = 1.19; 95% CI = 1.01-1.41, p = 0.046; p for trend = 0.006). The digoxin usage lowered the coronary artery disease (CAD) hospitalization in the > 0.75 DDD subgroup (sHR = 0.79; 95% CI = 0.63-0.99, p = 0.048). In renal function progression, more patients with CRS entered ESRD with digoxin usage (sHR = 1.34; 95% CI = 1.16-1.54, p<0.001). There was a significantly greater incidence of ESRD in the < 0.26 DDD and 0.26-0.75 DDD subgroups of digoxin users (sHR = 1.32; 95% CI = 1.06-1.66, p = 0.015; sHR = 1.44; 95% CI = 1.18-1.75; p for trend<0.001). Conclusion: Digoxin should be prescribed with caution to patients with CRS.