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Background Acute kidney injury (AKI) is associated with an increased incidence of poor liver graft and renal outcomes in patients who have undergone liver transplantation (LT). To date, no comprehensive study has compared patients with and without post-LT AKI and analyzed patients who recovered from AKI versus those who did not. Methods Patients who received living LT between January 2003 and January 2019 were enrolled. We diagnosed and classified AKI patients based on AKI-KDIGO guidelines by increment of creatinine after surgery when compared with serum creatinine on the day of surgery. The recovered AKI subgroup included recipients whose estimated glomerular filtration rate (eGFR) recovered more than 90% of baseline eGFR within 90 days after surgery. The risk of chronic kidney disease (CKD; eGFR Results A total of 392 patients, 77.3% men and mean ± standard deviation age 54.1 ± 8.4 years, met the eligible criteria and were divided into two groups (AKI vs non-AKI) and 243 (62%) patients developed AKI within 7 days after surgery. Compared with the non-AKI group, the AKI group was associated with an adjusted hazard ratio of 1.55 (95% CI 1.12–2.14) for the risk of incident CKD. Among AKI patients, 160 (65.8%) patients recovered renal function and 83 (34.2%) patients did not. Compared with the non-AKI group, the AKI non-recovery group was associated with an adjusted hazard ratio of 2.87 (95% CI 1.95–4.21) for the risk of incident CKD, while the AKI recovery group had no significant difference in the adjusted risk of incident CKD. Conclusions Post-LT AKI is associated with subsequent risk of CKD development. Taking into account recovery status, AKI was no longer associated with a higher risk of CKD if renal function recovered within 90 days after surgery. Identification and implementation of targeted and individualized therapies for patients at risk for AKI, particularly non-recovery AKI, is of paramount importance to reduce incident CKD during follow-up.

Background Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with an overall 5-year survival rate of 9.3%, and this malignancy is expected to become the second leading cause of cancer-related death by 2030. Gemcitabine resistance develops within weeks of PDAC patient's chemotherapeutic initiation. Statins, including pitavastatin, have been indicated to have anticancer effects in numerous human cancer cell lines. Thus, in this study, we hypothesized that a combination of gemcitabine and pitavastatin may have a greater anticancer effect than gemcitabine alone on the human pancreatic carcinoma cell line MIA PaCa-2. Methods The anticancer effects of gemcitabine with pitavastatin were evaluated using human MIA PaCa-2 cell line in vitro and in vivo Balb/c murine xenograft tumor model. Cell viability was assessed with CCK-8, and cell migration was stained by crystal violet. Cell cycle distribution, apoptosis and mitochondrial membrane potential were examined by flow cytometry. Activation of drug transporters (hENTs, hCNTs), intracellular drug activating (dCK) and inhibition of inactivating enzymes (RRMs) pathways were assessed by Western blotting analysis. Molecular mechanisms and signaling pathways of apoptosis, necrosis and autophagy also were assessed by Western blotting. Results We observed that gemcitabine and pitavastatin synergistically suppressed the proliferation of MIA PaCa-2 cells through causing sub-G1 and S phase cell cycle arrest. Activation of apoptosis/necrosis was confirmed by annexin V/propidium iodide double staining, which showed increasing levels of active caspase 3, cleaved poly(ADP-ribose) polymerase and the RIP1-RIP3-MLKL complex. Moreover, gemcitabine-pitavastatin-mediated S phase arrest downregulated cyclin A2/CDK2 and upregulated p21/p27 in MIA PaCa-2 cells. Furthermore, this combination improved drug cellular metabolism pathway, mitochondria function and activated autophagy as part of the cell death mechanism. In vivo, gemcitabine-pitavastatin effectively inhibited tumor growth in a nude mouse mode of Mia PaCa-2 xenografts without observed adverse effect. Conclusion Combined gemcitabine-pitavastatin may be an effective novel treatment option for pancreatic cancer.

It is unclear how the CHA2DS2-VASc score can predict subsequent chronic kidney disease (CKD) and end-stage renal disease (ESRD) among atrial fibrillation (AF) patients. We identified incident AF patients without CKD between 2000 and 2013 from the National Health Insurance Research Database (NHIRD) of Taiwan and calculated the CHA2DS2-VASc score for each patient. Adjusted hazard ratio (HR) with 95% confidence interval (CI) was estimated from multivariate cause-specific Cox models to assess the risk of CKD and ESRD associated with the CHA2DS2-VASc score. A total of 8764 participants with AF who did not have CKD were included in the analysis. The mean age was 69.63 ± 13.48 years and 4800 (54.8%) were males. The adjusted HR of CKD displayed a stepwise increase with the increase in the CHA2DS2-VASc score. When compared with those with a CHA2DS2-VASc score of 0, the adjusted HRs of CKD were 1.57 (95% CI 1.09–2.26), 2.04 (95% CI 1.42–2.94), 2.48 (95% CI 1.70–3.62), 2.88 (95% CI 1.95–4.26), 3.29 (95% CI 2.18–4.95) and 4.00 (95% CI 2.61–6.13) for the AF patients with a CHA2DS2-VASc score of 1, 2, 3, 4, 5 and ≥ 6, respectively. Similarly, as the CHA2DS2-VASc score increased, the adjusted HR of ESRD showed a gradual increase. Patients with a higher CHA2DS2-VASc score were linked to a higher risk of CKD and ESRD in a dose-dependent effect, i.e. the incidence of CKD/ESRD increased with the increasing CHA2DS2-VASc score.

Background: Nutrition and inflammation have been implicated in predicting mortality in patients on peritoneal dialysis (PD). Serum albumin and globulin can be regarded for the nutritional and inflammatory status. However, there is lack of data to evaluate the synergistic effect of albumin and globulin on mortality prediction. Methods: In 554 patients initiating PD from January 2001 to July 2016, we divided them into four groups by the combination of two categories of low vs. high albumin and low vs. high globulin. The median values for albumin and globulin were chosen to classify them into low or high groups. Their associations with all-cause and cardiovascular (CV) mortality were examined in Cox regression models adjusted for confounding clinical and laboratory data. Results: Patients, 52.91 ± 15.2 years old and 47.8% men, had a median (interquartile range) value of 3.3 (2.9–3.8) g/dL for albumin and 2.8 (2.5–3.2) g/dL for globulin, respectively. Patients with low albumin and high globulin had the highest all-cause mortality and CV mortality, with adjusted hazard ratios of 3.87 (95% CI 1.83–8.20, p < 0.001) and 5.65 (95% CI 2.23–14.34, p < 0.001), respectively, compared with those with a high albumin and low globulin having the lowest mortality rate. Sensitivity analyses further confirmed this relationship. Conclusions: A patient profile of either low albumin or high globulin is linked to a higher risk for mortality, particularly for a profile of both low albumin and high globulin compared with one without either of them. Further studies are needed to explore the mechanisms underlying this phenomenon and how to improve clinical outcomes in those high-risk patients.

Background: This study aimed to determine the association between episodic or persistent hematuria after liver transplantation and long-term renal outcomes. Methods: Patients who underwent living donor liver transplantation between July 2005 and June 2019 were recruited and divided into two groups based on the finding of microscopic or gross hematuria after transplantation. All patients were followed up from the index date until the end date in May 2020. The risks of chronic kidney disease, death, and 30% and 50% declines in estimated glomerular filtration rate (eGFR) were compared between groups. Results: A total of 295 patients underwent urinalysis for various reasons after undergoing transplantation. Hematuria was detected in 100 patients (group A) but was not present in 195 patients (group B). Compared with group B, group A had a higher risk of renal progression, including eGFR decline &gt, 50% [aHR = 3.447 (95%CI: 2.24~5.30), p &lt, 0.001] and worse survival. In addition, patients who took non-steroidal anti-inflammatory drugs (NSAIDs) continuously for over seven days within six months before transplant surgery had high risks of rapid renal progression, including a &gt, 30% decline in eGFR [aHR = 1.572 (95%CI: 1.12~2.21), p = 0.009)]. Conclusion: Development of hematuria after surgery in patients who underwent living donor liver transplant and were exposed to NSAIDs before surgery were associated with worse long-term renal dysfunction and survival.

(1) Background: Little is known about the subsequent renal function change following incident infectious diseases in living-donor liver transplant (LT) recipients. (2) Methods: We studied patients who underwent living-donor LT from January 2003 to January 2019 to evaluate the association of incident hospitalization with major infections or pneumonia with adverse renal outcomes, including a sustained 40% reduction in estimated glomerular filtration rate (eGFR) and renal composite outcome (a 40% decline in eGFR, end-stage renal disease, or death.). Multivariable-adjusted time-dependent Cox models with infection as a time-varying exposure were used to estimate hazard ratio (HR) with 95% confidence interval (CI) for study outcomes. (3) Results: We identified 435 patients (mean age 54.6 ± 8.4 years and 76.3% men), of whom 102 had hospitalization with major infections during follow-up; the most common cause of infection was pneumonia (38.2%). In multiple Cox models, hospitalization with a major infection was associated with an increased risk of eGFR decline > 40% (HR, 3.32; 95% CI 2.13–5.16) and renal composite outcome (HR, 3.41; 95% CI 2.40–5.24). Likewise, pneumonia was also associated with an increased risk of eGFR decline > 40% (HR, 2.47; 95% CI 1.10–5.56) and renal composite outcome (HR, 4.37; 95% CI 2.39–8.02). (4) Conclusions: Our results illustrated the impact of a single infection episode on the future risk of adverse renal events in LT recipients. Whether preventive and prophylactic care bundles against infection and judicious modification of the immunosuppressive regimen benefit renal outcomes may deserve further study.

Chronic kidney disease (CKD) is a known complication of diabetes mellitus, and insulin resistance is a well-known complication of CKD. However, there is no consensus in the published data on the association of CKD with incident diabetes. A total of 15,403 people with CKD were identified from the Taiwan National Health Insurance Research Database to determine their risk of incident diabetes compared with that of 15,403 matched individuals without CKD. Fine and Gray regression models using death as a competing risk were performed to calculate adjusted HRs and 95% CIs. Risk factors for incident diabetes in people with CKD were also determined. The CKD cohort had a higher incidence rate of diabetes compared with the non-CKD cohort (11.23/1000 person-years vs 8.93/1000 person-years). In the fully adjusted model, CKD was a significant and independent predictor of incident diabetes (adjusted HR 1.204; 95% CI 1.11, 1.31). The influence of CKD on incident diabetes showed consistent results in three levels of sensitivity analysis. In the CKD cohort, the significant risk factors for incident diabetes included increased age, geographical location, hypertension, hyperlipidaemia and gout. Of these, hypertension was associated with the highest risk of developing incident diabetes (adjusted HR 1.682; 95% CI 1.47, 1.93). People with CKD were at higher risk of developing incident diabetes. People with CKD and hypertension, hyperlipidaemia, increased age or gout and who lived in certain geographical regions of Taiwan were more likely to develop diabetes as a complication compared with people without those characteristics.

Recently, both red cell distribution width (RDW) and mean corpuscular volume (MCV) have been associated with unfavorable outcomes in several medical conditions. Therefore, we conducted this retrospective study of 1075 patients with stage 3–5 chronic kidney disease to investigate whether interactions between RDW and MCV influence the risk of mortality. These patients were divided into four groups: group A (n = 415), RDW ≤ 14.9% and MCV ≤ 91.6 fL; group B (n = 232), RDW > 14.9% and MCV ≤ 91.6 fL; group C (n = 307), RDW ≤ 14.9% and MCV > 91.6 fL; and group D (n = 121), RDW > 14.9% and MCV > 91.6 fL. The adjusted hazard ratio (HR) of all-cause mortality for group B versus group A was 1.44 (95% confidence interval [CI], 1.14–2.12, p = 0.02), group C versus group A 2.14 (95% CI, 1.31–3.48, p = 0.002), and group D versus group A 5.06 (95% CI, 3.06–8.37, p

AIM There is little information on the relationship between uric acid (UA) and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD). The aim of this research is to study the influence of UA on RRF decline in CAPD patients. METHODS A retrospective observational cohort study of 304 patients who started CAPD without anuria between 2001 and 2010 was conducted at a single medical center. The outcomes measured in the study included the rate of RRF decline and anuria. A multiple ordinal logistic regression model with backward elimination was conducted to determine the independent factors of the slope of RRF decline. A Cox proportional hazard model was conducted to determine the independent variables of time to anuria. RESULTS The average rate of RRF decline was -0.12 ± 0.22 mL/min per month. Multivariate analysis showed that lower UA group (

AIM Chronic kidney disease (CKD) is always associated with hyperuricaemia. However, the studies evaluating the clinical implications of hyperuricaemia have shown conflicting results in these patients. METHODS A retrospective observational study was conducted in 2408 stage 3-5 CKD patients. Instead of one baseline uric acid (UA) level, the averaged level of the two consecutive measurements for each participant was used as the predictor for the outcomes of the study, which included mortality, renal outcomes, and hospitalization risk. A multivariate Cox proportional hazards model and logistic regression model were performed to determine the independent risk factor. RESULTS The mean UA level was 0.46 ± 0.106 mmol/L. Of the 2408 patients, there were 563 (23.3%) deaths, 143 (5.9%) cardiovascular deaths, 652 (27%) subjects commencing renal replacement therapy (RRT), 664 (27.5%) subjects with rapid renal progression, 1937 (58%) patients requiring hospitalization and 404 (16.7%) patients with CVD hospitalization during a mean follow-up of approximately 3.03 years. After multivariate adjustments, a 1-mg/dL increase in uric acid level was associated with a hazard ratio (HR) of 1.26 for RRT (P = 0.002), an odds ratio (OR) of 1.27 for rapid renal progression (P = 0.001), an HR of 1.19 for all-cause hospitalization (P

It is unclear how the CHA2DS2-VASc score can predict subsequent chronic kidney disease (CKD) and end-stage renal disease (ESRD) among atrial fibrillation (AF) patients.We identified incident AF patients without CKD between 2000 and 2013 from the National Health Insurance Research Database (NHIRD) of Taiwan and calculated the CHAA total of 8764 participants with AF who did not have CKD were included in the analysis. The mean age was 69.63 ± 13.48 years and 4800 (54.8%) were males. The adjusted HR of CKD displayed a stepwise increase with the increase in the CHAPatients with a higher CHA

Background: Malnutrition and inflammation are highly prevalent and tightly regulated with each other in chronic kidney disease (CKD) patients. Inflammation can lead to malnutrition in patients with sufficient nourishment, while malnutrition may also induce an inflammatory response. This study investigated whether the albumin-globulin ratio (AGR) can predict the mortality risk in CKD patients. Methods: We enrolled 956 stage 3&ndash, 5 CKD patients retrospectively at a medical center. Patients&rsquo, baseline characteristics including demographics, laboratory data, pharmacotherapy, and comorbidities were collected for statistical adjustments. The study patients were stratified into three AGR groups according to similar magnitudes of hazards for mortality as follows: low AGR group, AGR &le, 1.0, moderate AGR group, 1.1 &le, AGR &lt, 1.3, high AGR group, AGR &ge, 1.3. Multivariate Cox proportional hazard analysis was performed to evaluate the association of the AGR with the study outcomes, including overall and cardiovascular disease (CVD) mortality. Results: During a median follow-up duration of 2.44 years, 108 (11.3%) deaths were recorded and 50 patients died from CVD. In adjusted model 1, the moderate AGR group was associated with hazard ratios (HR) of 0.57 (95% CI = 0.36&ndash, 0.90, p = 0.016) and 0.52 (95% CI = 0.28&ndash, 0.98, p = 0.043) for all-cause and CVD mortality compared with the low AGR group, respectively. The high AGR group was associated with HRs of 0.49 (95% CI = 0.27&ndash, 0.90, p = 0.021) and 0.27 (95% CI = 0.1&ndash, 0.74, p = 0.01) for all-cause and CVD mortality compared with the low AGR group, respectively. Similar results were obtained in the adjusted model 2 (inverse probability of the group weighted Cox model). In addition, the association between the AGR and mortality risk remained significant when the AGR was treated as a continuous variable. Conclusion: AGR is a significant biomarker predicting overall and cardiovascular mortality risk independent of various important factors amongst stage 3&ndash, 5 CKD patients. We suggest that the AGR may be a simple and inexpensive measurement for detecting CKD patients at risk of mortality.

Background: Chronic kidney disease (CKD) is a well-known complication of atrial fibrillation (AF) but how the incident CKD affects the clinical outcomes amongst AF patients is not clear. Methods: Our study data were retrieved from National Health Insurance Research Data for the period from 1996 to 2013. Incident AF patients were classified as non-CKD group (n = 7272), prevalent CKD group (n = 2104), and incident CKD group (n = 1507) based on administrative codes. Patients with prevalent CKD were those participants who already had CKD ahead of the index date of AF, whereas patients with incident CKD were those who developed CKD after the index date and the remaining patients were designated as non-CKD. Multivariate-adjusted time-dependent Cox models were conducted to estimate the associations of CKD status with the outcomes of interest, including heart failure (HF), acute myocardial infarction (AMI), stroke or systemic thromboembolism, all-cause mortality, and cardiovascular (CV) mortality, expressed as hazard ratio (HR) and 95% confidence interval (CI). Results: The mean age was 70.8 &plusmn, 13.3 years, and 55.4% of the studied population were men. In Cox models, the adjusted rate of HF, AMI, all-cause mortality, and CV mortality was greater in the prevalent and incident CKD groups, ranging from 1.31-fold to 4.28-fold, compared with non-CKD group. Notably, incident CKD was associated with higher rates of HF (HR, 1.8, 95% CI, 1.67&ndash, 1.93), stroke or systemic thromboembolism (HR, 1.33, 95% CI, 1.22&ndash, 1.45), AMI (HR, 1.46, 95% CI, 1.25&ndash, 1.71), all-cause mortality (HR, 1.76, 95% CI, 1.68&ndash, 1.85), and CV mortality (HR, 2.13, 95% CI, 1.92&ndash, 2.36) compared with prevalent CKD. Conclusion: The presence of CKD was associated with higher risks of subsequent adverse clinical outcomes in patients with AF. Our study was even highlighted by the finding that incident CKD was linked to higher risks of outcome events compared with prevalent CKD.

Background: The incidence rates of diabetes mellitus (DM) and chronic kidney disease (CKD) are increasing worldwide and their coexistence can have a large negative impact on clinical outcomes. However, it is unclear how incident DM affects CKD patients. Methods: Incident CKD patients between 2000 and 2013 were identified from the National Health Insurance Research Database of Taiwan, they were classified as non-DM (n = 10,356), pre-existing DM (n = 6982), and incident DM (n = 1103). Non-DM cases were patients who did not develop DM before the end of the observation period. The outcomes of interest were end-stage renal disease (ESRD), mortality, and composite outcome (ESRD or death). The association between the DM groups and clinical outcomes was estimated using the inverse probability of group-weighted (IPW) multivariate-adjusted time-dependent Cox regression models. Results: During the study period of 14 years, 1735 (16.6%) patients in the non-DM group reached ESRD compared with 2168 (31.05%) in the pre-existing DM group and 111 (11.03%) in the incident DM group (p &lt, 0.001). Moreover, 2219 (21.43%) patients in the non-DM group died compared with 1895 (27.14%) in the pre-existing DM group and 303 (27.47%) in the incident DM group (p &lt, 0.001). Compared with the non-DM group, the pre-existing DM group was associated with a higher risk of ESRD [hazard ratio (HR) 2.54, 95% confidence interval (CI 2.43–2.65), death (HR 2.23, 95% CI 2.14–2.33), and a composite outcome (HR 2.29, 95% CI 2.21–2.36). Similarly, incident DM was also associated with a higher risk of ESRD (HR 1.12, 95% CI 1.06–1.19), death (HR 2.48, 95% CI 2.37–2.60), and a composite outcome (HR 1.77, 95% CI 1.70–1.84) compared with the non-DM group. Factors contributing to incident DM included old age, low monthly income, and having hypertension, hyperlipidemia, and ischemic heart disease, while pentoxifylline reduced the risk of incident DM. Conclusion: Similarly to pre-existing DM, CKD patients with incident DM carried a higher risk of ESRD, mortality, and a composite outcome compared with those with non-DM. For those at risk of incident DM, strict monitoring and intervention strategies must be adopted to help improve their clinical outcomes.

Background: Spironolactone, a non-selective mineralocorticoid receptor antagonist, can protect against cardiac fibrosis and left ventricular dysfunction, and improve endothelial dysfunction and proteinuria. However, the safety and effects of spironolactone on patient-centered cardiovascular and renal endpoints remain unclear. Methods: We identified predialysis stage 3&ndash, 4 chronic kidney disease (CKD) patients between 2000 and 2013 from the Longitudinal Health Insurance Database 2005 (LHID 2005). The outcomes of interest were end-stage renal disease (ESRD), major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), hyperkalemia-associated hospitalization (HKAH), all-cause mortality and cardiovascular mortality. The Fine and Gray sub-distribution hazards approach was adopted to adjust for the competing risk of death. Results: After the propensity score matching, 693 patients with stage 3&ndash, 4 CKD were spironolactone users and 1386 were nonusers. During the follow-up period, spironolactone users had a lower incidence rate for ESRD than spironolactone non-users (39.2 vs. 53.69 per 1000 person-years) and a higher incidence rate for HKAH (54.79 vs. 18.57 per 1000 person-years). The adjusted hazard ratios for ESRD of spironolactone users versus non-users were 0.66 (95% CI, 0.51&ndash, 0.84, p value &lt, 0.001) and 3.17 (95% CI, 2.41&ndash, 4.17, 0.001) for HKAH. A dose-response relationship was found between spironolactone use and risk of ESRD and HKAH. There were no statistical differences in MACE, HHF, all-cause mortality and cardiovascular mortality between spironolactone users and non-users. Conclusion: Spironolactone represented a promising treatment option to retard CKD progression to ESRD amongst stage 3&ndash, 4 CKD patients, but strategic treatments to prevent hyperkalemia should be enforced.

Background: The results have been inconsistent with regards to the impact of uric acid (UA) on clinical outcomes both in the general population and in patients with chronic kidney disease. The aim of this study was to study the influence of serum UA levels on mortality in patients undergoing continuous ambulatory peritoneal dialysis. Methods: Data on 492 patients from a single peritoneal dialysis unit were retrospectively analyzed. The mean age of the patients was 53.5 &plusmn, 15.3 years, with 52% being female (n = 255). The concomitant comorbidities at the start of continuous ambulatory peritoneal dialysis (CAPD) encompassed diabetes mellitus (n = 179, 34.6%), hypertension (n = 419, 85.2%), and cardiovascular disease (n = 186, 37.9%). The study cohort was divided into sex-specific tertiles according to baseline UA level. A Cox proportional hazard model was used to calculate hazard ratios (HRs) of all-cause, cardiovascular, and infection-associated mortality with adjustments for demographic and laboratory data, medications, and comorbidities. Results: Multivariate Cox regression analysis showed that, using UA tertile 1 as the reference, the adjusted HR of all-cause, cardiovascular, and infection-associated mortality for tertile 3 was 0.4 (95% confidence interval (CI) 0.24&ndash, 0.68, p = 0.001), 0.4 (95% CI 0.2&ndash, 0.81, p = 0.01), and 0.47 (95% CI 0.19&ndash, 1.08, p = 0.1). In the fully adjusted model, the adjusted HRs of all-cause, cardiovascular, and infection-associated mortality for each 1-mg/dL increase in UA level were 0.84 (95% CI, 0.69&ndash, 0.9, p = 0.07), 0.79 (95% CI, 0.61&ndash, 1.01, p = 0.06), and 0.79 (95% CI, 0.48&ndash, 1.21, p = 0.32) for men and 0.57 (95% CI, 0.44&ndash, 0.73, p &lt, 0.001), 0.6 (95% CI, 0.41&ndash, 0.87, p = 0.006), and 0.41 (95% CI, 0.26&ndash, 0.6, p &lt, 0.001) for women, respectively. Conclusions: Higher UA levels are associated with lower risks of all-cause, cardiovascular and infection-associated mortality in women treated with continuous ambulatory peritoneal dialysis.

There is increasing evidence showing that albumin–globulin ratio (AGR) can predict the survival of patients in many types of malignancies. However, no study was done to explore the value of AGR in peritoneal dialysis (PD) patients. A total of 554 incident patients undergoing PD from January 2001 through July 2016 were enrolled for this retrospective observational study. The outcomes of interest were all-cause mortality and cardiovascular disease (CVD) mortality. Baseline patient’s socio-demographic data, pharmacotherapy, comorbidities, laboratory and PD-related parameters were collected and used in the multivariate Cox models. The predictive value of AGR on mortality risk was compared with other markers using area under the receiver operating characteristic curve (AUC) analysis. Among the study participants, there were 265 (47.83%) men and the mean follow-up time was 3.87 ± 3.15 years. Univariate Cox analysis showed that low AGR was significantly associated with worse outcomes in terms of all-cause and CVD mortality and it remained an independent predictor in the multivariate models. The fully adjusted hazard ratios for the low AGR group versus high AGR group were 2.12 (95% CI 1.34–3.35, p = 0.001) and 2.58 (95% CI 1.42–4.7, p = 0.002) for all-cause and CVD mortality, respectively. The predictive ability of AGR for mortality risk was superior to that of other biomarkers based on AUC calculations. In conclusion, low AGR was independently associated with higher all-cause and CVD mortality risks in patients undergoing PD.

Although red cell distribution width (RDW) has emerged as a biomarker of clinical prognostic value across a variety of clinical settings in the last two decades, limited evidence is available for its role in end-stage renal disease. We enrolled 313 incident patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in this retrospective observational study from 2006 to 2015. In the fully adjusted model of Cox regression analysis, the adjusted hazard ratios for the high RDW group versus the low RDW group were 2.58 (95% confidence interval (CI) = 1.31–5.09, p = 0.006) and 3.48 (95% CI = 1.44–8.34, p = 0.006) for all-cause and cardiovascular disease (CVD)-related mortality, respectively. Based on area under the receiver operating characteristic curve (AUC) analysis, RDW (AUC = 0.699) had a stronger predictive value for all-cause and CVD-related mortality than other biological markers including hemoglobin (AUC = 0.51), ferritin (AUC = 0.584), iron saturation (AUC = 0.535), albumin (AUC = 0.683) and white blood cell count (AUC = 0.588). Given that RDW is a readily available hematological parameter without the need for additional cost, we suggest that it can be used as a valuable index to stratify the risk of mortality beyond a diagnosis of anemia.

BackgroundPeritonitis rate has been reported to be associated with technique failure and overall mortality in previous literatures. However, information on the impact of the timing of the first peritonitis episode on continuous ambulatory peritoneal dialysis (CAPD) patients is sparse. The aim of this research is to study the influence of time to first peritonitis on clinical outcomes, including technique failure, patient mortality and dropout from peritoneal dialysis (PD).MethodsA retrospective observational cohort study was conducted over 10 years at a single PD unit in Taiwan. A total of 124 patients on CAPD with at least one peritonitis episode comprised the study subjects, which were dichotomized by the median of time to first peritonitis into either early peritonitis patients or late peritonitis patients. Cox proportional hazard model was used to analyze the correlation of the timing of first peritonitis with clinical outcomes.ResultsEarly peritonitis patients were older, more diabetic and had lower serum levels of creatinine than the late peritonitis patients. Early peritonitis patients were associated with worse technique survival, patient survival and stay on PD than late peritonitis patients, as indicated by Kaplan-Meier analysis (log-rank test, p = 0.04, p < 0.001, p < 0.001, respectively). In the multivariate Cox regression model, early peritonitis was still a significant predictor for technique failure (hazard ratio (HR), 0.54; 95% confidence interval (CI), 0.30 – 0.98), patient mortality (HR, 0.34; 95% CI, 0.13 – 0.92) and dropout from PD (HR, 0.50; 95% CI, 0.30 – 0.82). In continuous analyses, a 1-month increase in the time to the first peritonitis episode was associated with a 2% decreased risk of technique failure (HR, 0.98; 95% CI, 0.97 – 0.99), a 3% decreased risk of patient mortality (HR, 0.97; 95% CI, 0.95 – 0.99), and a 2% decreased risk of dropout from PD (HR, 98%; 95% CI, 0.97 – 0.99). Peritonitis rate was inversely correlated with time to first peritonitis according to the Spearman analysis (r = –0.64, p < 0.001).ConclusionsTime to first peritonitis is significantly correlated with clinical outcomes of peritonitis patients with early peritonitis patients having poor prognosis. Patients with shorter time to first peritonitis were prone to having a higher peritonitis rate.

Background: Little is known about how incident atrial fibrillation (AF) affects the clinical outcomes in chronic kidney disease (CKD) patients and whether there is a different influence between pre-existing and incident AF. Methods: Incident CKD patients from 2000 to 2013 were retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan and they were classified as non-AF (n = 15,251), prevalent AF (n = 612), and incident AF (n = 588). The outcomes of interest were end-stage renal disease (ESRD) requiring dialysis, all-cause mortality, cardiovascular (CV) mortality, acute myocardial infarction (AMI), stroke or systemic thromboembolism. Results: Compared with CKD patients without AF, those with prevalent or incident AF were associated with higher adjusted rates of ESRD (hazard ratio (HR), 1.40, 95% confidence interval (CI), 1.32&ndash, 1.48, HR, 2.91, 95% CI, 2.74&ndash, 3.09, respectively), stroke or systemic thromboembolism (HR, 1.89, 95% CI, 1.77&ndash, 2.03, HR, 1.67, 95% CI, 1.54&ndash, 1.81, respectively), AMI (HR, 1.24, 95% CI, 1.09&ndash, 1.41, HR, 1.99, 95% CI, 1.75&ndash, 2.27, respectively), all-cause mortality (HR, 1.64, 95% CI, 1.56&ndash, 1.72, HR, 2.17, 95% CI, 2.06&ndash, 2.29, respectively), and CV mortality (HR, 2.95, 95% CI, 2.62&ndash, 3.32, HR, 4.61, 95% CI, 4.09&ndash, 5.20, respectively). Intriguingly, CKD patients with prevalent AF were associated with lower adjusted rates of ESRD, AMI, all-cause mortality, and CV mortality compared with those with incident AF. Conclusion: Both incident and prevalent AF were independently associated with greater risks of AMI, all-cause mortality, CV mortality, ESRD, and stroke or systemic thromboembolism. Our findings are novel in that, compared with prevalent AF, incident AF possessed an even higher risk of some clinical consequences, including ESRD, all-cause mortality, CV mortality, and AMI.

Objective Peritoneal dialysis (PD) has become more prevalent as a treatment modality for end-stage renal disease, and peritonitis remains one of its most devastating complications. The aim of the present investigation was to examine the frequency and predictors of peritonitis and the impact of peritonitis on clinical outcomes. Methods Our retrospective observational cohort study enrolled 391 patients who had been treated with continuous ambulatory PD (CAPD) for at least 90 days. Relevant demographic, biochemical, and clinical data were collected for an analysis of CAPD-associated peritonitis, technique failure, drop-out from PD, and patient mortality. Results The peritonitis rate was 0.196 episodes per patient–year. Older age (>65 years) was the only identified risk factor associated with peritonitis. A multivariate Cox regression model demonstrated that technique failure occurred more often in patients experiencing peritonitis than in those free of peritonitis ( p < 0.001). Kaplan–Meier analysis revealed that the group experiencing peritonitis tended to survive longer than the group that was peritonitis-free ( p = 0.11). After multivariate adjustment, the survival advantage reached significance (hazard ratio: 0.64; 95% confidence interval: 0.46 to 0.89; p = 0.006). Compared with the peritonitis-free group, the group experiencing peritonitis also had more drop-out from PD ( p = 0.03). Conclusions The peritonitis rate was relatively low in the present investigation. Elderly patients were at higher risk of peritonitis episodes. Peritonitis independently predicted technique failure, in agreement with other reports. However, contrary to previous studies, all-cause mortality was better in patients experiencing peritonitis than in those free of peritonitis. The underlying mechanisms of this presumptive “peritonitis paradox” remain to be clarified.

A 66-year-old man with uremia and on hemodialysis was referred to our hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure accompanied by hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). Circulating IgG anti-GBM antibody was not detected. Because the findings of renal biopsy suggested anti-GBM disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture submitted on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immunosuppressive agents were discontinued and antituberculous agents were administrated. No relapse of pulmonary hemorrhage occurred during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.

Background: Glucose is one of the constituents in hemodialysates and peritoneal dialysates. How the dialysis associates with the incident diabetes mellitus (DM) remains to be assessed. Methods: The claim data of end-stage renal disease (ESRD) patients who initiated dialysis from and a cohort of matched non-dialysis individuals from 2000 to 2013 were retrieved from the Taiwan National Health Insurance Research Database to examine the risk of incident DM among patients on hemodialysis (HD) and peritoneal dialysis (PD). Predictors of incident DM were determined for HD and PD patients using Fine and Gray models to treat death as a competing event, respectively. Results: A total of 2228 patients on dialysis (2092 HD and 136 PD) and 8912 non-dialysis individuals were the study population. The PD and HD patients had 12 and 97 new-onset of DM (incidence rates of 15.98 and 8.69 per 1000 patient-years, respectively), while the comparison cohort had 869 DM events with the incidence rate of 15.88 per 1000 patient-years. The multivariable-adjusted Cox models of Fine and Gray method showed that the dialysis cohort was associated with an adjusted hazard ratio (HR) of 0.49 (95% CI 0.39&ndash, 0.61, p value &lt, 0.0001) for incident DM compared with the comparison cohort. The adjusted HR of incident DM was 0.46 (95% CI 0.37&ndash, 0.58, p value &lt, 0.0001) for HD and 0.84 (95% CI 0.47&ndash, 1.51, p value = 0.56) for PD. Conclusions: ESRD patients were associated with a lower risk of incident DM. HD was associated with a lower risk of incident DM, whereas PD was not.

Mean corpuscular volume is the measure of the average size of the circulatory erythrocyte, and it is principally used as an index for the differential diagnosis of anemia. Recently, mean corpuscular volume has been associated with mortality in many clinical settings. However, the association of mean corpuscular volume with mortality in patients with CKD has not been fully addressed.We conducted a retrospective observational cohort study of 1439 patients with stages 3-5 CKD and baseline mean corpuscular volume values from 2004 to 2012 in a medical center. The study cohort was divided into the high-mean corpuscular volume group and the low-mean corpuscular volume group by the median value (90.8 fl) of mean corpuscular volume. The baseline patient information included demographic data, laboratory parameters, medications, and comorbid conditions. The independent association of mean corpuscular volume with mortality was examined using multivariate Cox regression analysis.Of the 1439 participants, 234 patients (16.2%) died during a median follow-up of 1.9 years (interquartile range, 1.1-3.8 years). The crude overall mortality rate was significantly higher in the high-mean corpuscular volume group (high-mean corpuscular volume group, 22.7%; low-mean corpuscular volume group, 9.7%; P0.001). In the fully adjusted models, the high-mean corpuscular volume group was associated with higher risks of all-cause mortality (hazard ratio, 2.19; 95% confidence interval, 1.62 to 2.96; P0.001), cardiovascular mortality (hazard ratio, 3.57; 95% confidence interval, 1.80 to 7.06; P0.001), and infection-related mortality (hazard ratio, 2.22; 95% confidence interval, 1.41 to 3.49; P=0.001) compared with the low-mean corpuscular volume group.In patients with stages 3-5 CKD, mean corpuscular volume was associated with all-cause mortality, cardiovascular disease mortality, and infection-associated mortality, independent of other factors. The underlying pathophysiologic mechanisms warrant additional investigation.

Chronic kidney disease (CKD) is always associated with hyperuricaemia. However, the studies evaluating the clinical implications of hyperuricaemia have shown conflicting results in these patients.A retrospective observational study was conducted in 2408 stage 3-5 CKD patients. Instead of one baseline uric acid (UA) level, the averaged level of the two consecutive measurements for each participant was used as the predictor for the outcomes of the study, which included mortality, renal outcomes, and hospitalization risk. A multivariate Cox proportional hazards model and logistic regression model were performed to determine the independent risk factor.The mean UA level was 0.46 ± 0.106 mmol/L. Of the 2408 patients, there were 563 (23.3%) deaths, 143 (5.9%) cardiovascular deaths, 652 (27%) subjects commencing renal replacement therapy (RRT), 664 (27.5%) subjects with rapid renal progression, 1937 (58%) patients requiring hospitalization and 404 (16.7%) patients with CVD hospitalization during a mean follow-up of approximately 3.03 years. After multivariate adjustments, a 1-mg/dL increase in uric acid level was associated with a hazard ratio (HR) of 1.26 for RRT (P = 0.002), an odds ratio (OR) of 1.27 for rapid renal progression (P = 0.001), an HR of 1.19 for all-cause hospitalization (P 0.001), and an HR of 1.12 for cardiovascular disease (CVD) hospitalization (P = 0.02), but not significantly with all-cause mortality and cardiovascular death at the end of follow-up.In stage 3-5 CKD patients, hyperuricaemia was associated with a higher risk of renal replacement therapy, rapid renal progression and hospitalization for all causes or CVD, but not with all-cause mortality or cardiovascular mortality.

There is little information on the relationship between uric acid (UA) and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD). The aim of this research is to study the influence of UA on RRF decline in CAPD patients.A retrospective observational cohort study of 304 patients who started CAPD without anuria between 2001 and 2010 was conducted at a single medical center. The outcomes measured in the study included the rate of RRF decline and anuria. A multiple ordinal logistic regression model with backward elimination was conducted to determine the independent factors of the slope of RRF decline. A Cox proportional hazard model was conducted to determine the independent variables of time to anuria.The average rate of RRF decline was -0.12 ± 0.22 mL/min per month. Multivariate analysis showed that lower UA group (0.372 mmol/L), higher UA group (≧0.421 mmol/L), male gender, diabetes mellitus (DM), the use of calcium channel blocker (CCB), and RRF at baseline were linked positively with the rate of RRF decline; on the other hand, independence in dialysate exchanges and BUN were negatively associated with the risk of RRF decline. In addition, male gender, DM, diuretics, and CCB were associated with a higher risk of progression to anuria, whereas 24-h urine amount at baseline conferred a protective role in the development of anuria.A U-shaped relationship was found between UA levels and the rate of RRF decline in patients on CAPD, with a faster decline rate in those of higher and lower UA groups.

Objectives Uric acid (UA) is the product of purine or nucleotide metabolism via the pathway of xanthine oxidase or xanthine dehydrogenase. Although epidemiological studies assessing the role of UA in cardiovascular disease or mortality have produced inconsistent results, the correlation between UA and technique failure in patients on continuous ambulatory peritoneal dialysis (CAPD) remains to be assessed. Design A retrospective cohort study. Setting Patients starting CAPD between 2001 and 2009 in a single centre in Taiwan. Participants A total of 371 patients on CAPD. Primary outcome measures All-cause and peritonitis-related technique failure. Results A cohort of 371 participants (43.9% male) was enrolled in the study with a mean age of 55.7±15.9 years at the start of CAPD. During the study period, technique failure occurred in 41 (34.4%) patients in the hyperuricaemia group compared with 49 (19.4%) in the normouricaemia group (p=0.003). In the multivariate Cox regression models, hyperuricaemia at baseline was significantly associated with both a higher risk of technique failure (HR 1.24; 95% CI 1.09 to 1.42, p=0.001) and peritonitis-related technique failure (HR 1.29; 95% CI 1.07 to 1.57, p=0.008). Conclusions UA was shown to be associated with all-cause and peritonitis-related technique failure in our study. Patients on CAPD with hyperuricaemia should be closely monitored and strategies of increasing survival on CAPD should be taken.

The influence of high peritonitis rate (HPR) on clinical outcomes of continuous ambulatory peritoneal dialysis (CAPD) patients has been far less studied in the Chinese population than in those of the USA, Australia and Europe. Furthermore, concerning the peritonitis risk, most studies primarily examined the risk of developing the first peritonitis episode, rather than a HPR. A single-center, retrospective, observational study was carried out over 10 years in Taiwan. A total of 124 patients with at least one peritonitis episode were the study subjects. The Cox proportional hazard model was used to assess the impact of HPR on clinical outcomes. Multivariate logistic regression was conducted to determine the independent factors associated with a HPR. In the multivariate Cox regression model, HPR was still a significant predictor for technique failure, patient mortality and dropout from peritoneal dialysis (PD). Factors independently associated with a HPR were peritonitis occurrence during the first year after the start of CAPD and the first peritonitis infected with streptococcus species. Peritonitis during the first year after PD commencement and the first peritonitis infected by streptococcus species were significantly associated with an increased risk of a HPR. Our data also indicate that HPR was correlated with technique failure, patient mortality and dropout from PD, thus highlighting the need and role of future studies to reduce this complication.

Background Iron is essential not only for erythropoisis but also for several bioenergetics’ processes in myocardium. Hepcidin is a well-known regulator of iron homeostasis. Recently, researchers identified low hepcidin was independently associated with increased 3-year mortality among systolic heart failure patients. In addition, our previous in vivo study revealed that the left ventricular mass index increased in chronic kidney disease patients with lower serum hepcidin. We hypothesize that hepcidin interacts with the apoptotic pathway of cardiomyocytes during oxidative stress conditions. Methods To test this hypothesis, human cardiomyocytes were cultured and treated with ferrous iron. The possible underlying signaling pathways of cardiotoxicity were examined following knockdown studies using siRNAs of hepcidin (siRNA1 was used as a negative control and siRNA2 was used to silence hepcidin). Results We found that ferrous iron induces apoptosis in human cardiomyocytes in a dose-dependent manner. This iron-induced apoptosis was linked to enhanced caspase 8, reduced Bcl-2, Bcl-xL, phosphorylated Akt and GATA-4. Hepcidin levels increased in human cardiomyocytes pretreated with ferrous iron and returned to non-iron treated levels following siRNA2 transfection. In iron pretreated cardiomyocytes, the siRNA2 transfection further increased caspase 8 expression and decreased the expression of GATA-4, Bcl-2, Bcl-xL and phosphorylated Akt than iron pretreatment alone, but caspase 9 levels remained unchanged. Conclusions Our findings suggest that hepcidin can rescue human cardiomyocytes from iron-induced apoptosis through the regulation of GATA-4/Bcl-2 and the extrinsic apoptotic pathway.

There is a broad spectrum of glomerular histological findings in postinfectious glomerulonephritis (PIGN). We conducted this retrospective study to compare the clinicopathological features between two distinct morphology of PIGN.Thirteen patients with typical endocapillary proliferation and eight patients with atypical mesangial proliferation were enrolled in this study. The patients' records were reviewed with respect to clinical presentation, microbiology, serology, morphology of renal biopsy, and clinical course.In comparison of histological parameters, glomerular neutrophil infiltration was more commonly present in typical endocapillary proliferation group (p = 0.018). Glomerular IgA dominant or co-dominant deposition was more frequently seen in atypical mesangial proliferation group (p = 0.032). In a comparison of clinical parameters, atypical mesangial proliferation group had lesser degrees of proteinuria, higher serum levels of complement, and higher rates of staphylococcal infection, although none of the differences was statistically significant. Glomerular morphology did not seem to affect the renal outcome. Moreover, our data suggested that the percentage of patients with atypical mesangial proliferation significantly increased over time (p0.001).Atypical mesangial proliferation may represent a resolution stage of PIGN. The nature of subclinical infection with a more protracted course may contribute to the increasing recognition of this resolving PIGN at the time of renal biopsy. Another possible explanation is that the atypical morphology may be a peculiar pattern of post-staphylococcal glomerulonephritis, which was increasingly identified in PIGN over the past 10 years.

AIM: To assess the correlation between the serum hepcidin-25 level and left ventricular mass index. METHODS: This study was a cross-sectional study conducted between March 2009 and April 2010. Demographic and biochemical data, including the serum hepcidin-25 level, were collected for chronic kidney disease (CKD) patients. Two-dimensional echocardiography was performed to determine the left ventricle mass (LVM), left ventricular mass index (LVMI), interventricular septum thickness (IVSd), left ventricle posterior wall thickness (LVPW), right ventricular dimension (RVD), left atrium (LA) and ejection fraction (EF). RESULTS: A total of 146 patients with stage 1 to 5 CKD were enrolled. Serum hepcidin-25 levels were 16.51 ± 5.2, 17.59 ± 5.32, 17.38 ± 6.47, 19.98 ± 4.98 and 22.03 ± 4.8 ng/mL for stage 1 to 5 CKD patients, respectively. Hepcidin-25 level was independently predicted by the serum ferritin level (β = 0.6, P = 0.002) and the estimated glomerular filtration rate (β = -0.48, P = 0.04). There were negative correlations between the serum hepcidin level and the LVM and LVMI (P = 0.04 and P = 0.005, respectively). Systolic blood pressure (BP) was positively correlated with the LVMI (P = 0.005). In the multivariate analysis, a decreased serum hepcidin-25 level was independently associated with a higher LVMI (β = -0.28, 95%CI: -0.48 - -0.02, P = 0.006) after adjusting for body mass index, age and systolic BP. CONCLUSION: A lower serum hepcidin level is associated with a higher LVMI in CKD patients. Low hepcidin levels may be independently correlated with unfavorable cardiovascular outcomes in this population.

Background Stroke and low heart rate variability (HRV) are both associated with an unfavorable prognosis in hemodialysis patients. The relationship between stroke and changes in HRV during hemodialysis remains unclear. Methods This study measured differences between predialysis and postdialysis HRV (△HRV) in 182 maintenance hemodialysis patients, including 30 patients with stroke, to assess changes in HRV during hemodialysis, and also to compare results to 114 healthy controls. Results All predialysis HRV measurements had no differences between stroke patients and those without stroke, but were lower than healthy controls. Postdialysis very low frequency (VLF) (P