I-Wen Ting

The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial.

Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 10(9) cfu Bifobacterium bifidum A218, 10(9) cfu Bifidobacterium catenulatum A302, 10(9) cfu Bifidobacterium longum A101, and 10(9) cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.

Hypertensive Disorders in Pregnancy and Subsequent Diabetes Mellitus: A Retrospective Cohort Study

BACKGROUND Cohort study on the association between hypertensive disorders in pregnancy (HDP) and postpartum diabetes is limited. This retrospective cohort study investigated the incidence of diabetes mellitus after delivery among women with HDP using claims data of a universal insurance system. METHODS We defined the HDP group as women aged 19-40 years with their first HDP in 2003, excluding those with a history of gestational diabetes mellitus, diabetes mellitus, or hypertension before the date of diagnosis with HDP. Women who had normal pregnancy without HDP were randomly chosen as our comparison group, frequency matched with age and index year of the HDP group. Both groups were followed until December 31, 2008 to evaluate the occurrence of diabetes. RESULTS This study consisted of 1139 women with HDP cases and 4527 non-HDP pregnant women. Overall, the subsequent incidence of diabetes mellitus was 5.08-fold higher in the HDP group than in the non-HDP group, with an adjusted hazard ratio of 3.42 (95% confidence interval [CI], 2.07-5.64) after controlling for age, occupation, income, and comorbidity. The hazard ratio of developing diabetes increased to 39.5 (95% CI, 13.0-120.6) for women having HDP, hyperlipidemia, and obesity simultaneously. CONCLUSIONS Women with HDP have a high risk of subsequent diabetes. HDP women with obesity and hyperlipidemia are at an extremely high risk of diabetes mellitus. Early identification of women with HDP is needed for prevention, particularly those with other comorbidities.

Multidisciplinary care in patients with chronic kidney disease: A systematic review and meta-analysis

BACKGROUND Multidisciplinary care (MDC) was widely used in multiple chronic illnesses but the effectiveness of MDC in patients with chronic kidney disease (CKD) was inconclusive. The aim of this meta-analysis is to estimate the effectiveness of MDC for CKD. METHODS We searched PubMed, Web of Science, Google Scholar, Cochrane Library, and China Journal Full-text Database for relevant articles published in English or Chinese. Studies investigating MDC and non-MDC in patients with CKD were included. Random effect model was used to compare all-cause mortality, dialysis, risk of temporal catheterization, and hospitalization in the two treatment entities. RESULTS We analyzed 8853 patients of 18 studies in patients with CKD stages 3-5, aged 63±12 years. MDC was associated with lower risk of all-cause mortality with an odds ratio (OR) of 0.52 [95% confidence interval (CI): 0.44-0.88, p=0.01], mainly in cohort studies. MDC was associated with a lower risk of starting dialysis (p=0.02) and lower risk of temporal catheterization for dialysis (p<0.01). MDC was not associated with a higher chance of choosing peritoneal dialysis (p=0.18) or a lower chance of hospitalization for dialysis (p=0.13). CONCLUSIONS Limited evidence from randomized controlled trials is currently available to support the benefit of MDC in patients with CKD. MDC is associated with lower all-cause mortality, lower risk of starting dialysis, and lower risk of temporal catheterization for dialysis in cohort studies. MDC is not associated with a higher chance of choosing peritoneal dialysis or a lower chance of hospitalization for dialysis. More studies are needed to determine the optimal professional that should be included in MDC.

Comparing Survival between Peritoneal Dialysis and Hemodialysis Patients with Subclinical Peripheral Artery Disease: a 6-Year Follow-Up

Peripheral artery disease (PAD) is known to be an increased mortality risk in patients with end-stage renal disease (ESRD). The aim of this study was to compare patient survival between patients with subclinical PAD undergoing peritoneal dialysis (PD) and hemodialysis (HD). Subclinical peripheral artery was defined as an ankle-brachial index of less than 0.9. This study was conducted from April 2005, and the observation period ended on 30 June 2011. At the end of the follow-up, the status of all patients was assessed and data on mortality were obtained for the entire cohort. A total of 91 patients (61 HD and 30 PD) were included for analyses in this study. Mortality rate was 60.0% (18/30) for PD and 52.5% (32/61) for HD. Kaplan-Meier estimate demonstrate that PD patients had a higher mortality rate than those underwent HD (log-rank p = 0.0039). Cox regression model demonstrated that PD was an independent predictor for further mortality in ESRD patients with subclinical peripheral artery disease.(p = 0.012, HR: 1.776, 95% CI: 1.136-2.775). In multivariate analysis, the HD group still had a greater survival than PD group (p = 0.005, HR:1.916, 95% CI: 1.218-3.015). In patients with subclinical peripheral artery disease, the patient survival is better in HD patients as compared with PD patients.

Longitudinal change in estimated GFR among CKD patients: A 10-year follow-up study of an integrated kidney disease care program in Taiwan

Background This study examined the progression of chronic kidney disease (CKD) by using average annual decline in estimated GFR (eGFR) and its risk factors in a 10-year follow-up CKD cohort. Methods A prospective, observational cohort study, 4600 individuals fulfilled the definition of CKD, with or without proteinuria, were followed for 10 years. The eGFR was estimated by the MDRD equation. Linear regression was used to estimate participants’ annual decline rate in eGFR. We defined subjects with annual eGFR decline rate <1 ml/min/1.73 m2 as non-progression and the decline rate over 3 ml/min/1.73 m2 as rapid progression. Results During the follow-up period, 2870 (62.4%) individuals had annual eGFR decline rate greater than 1 ml/min/1.73 m2. The eGFR decline rate was slower in individuals with CKD diagnosed over the age of 60 years than those with onset at a younger age. Comparing to subjects with decline rate <1 ml/min/1.73 m2/year, the odds ratio (OR) of developing rapid CKD progression for diabetes, proteinuria and late onset of CKD was 1.72 (95% CI: 1.48–2.00), 1.89(1.63–2.20) and 0.68 (0.56–0.81), respectively. When the model was adjusted for the latest CKD stage, comparing to those with CKD stage 1, patients with stage 4 and stage 5 have significantly higher risks for rapid progression (OR, 5.17 (2.60–10.25), 19.83 (10.05–39.10), respectively). However, such risk was not observed among patients with the latest CKD stage 2 and 3. The risk for incident ESRD was 17% higher for each 1 ml/min/1.73 m2 increasing in annual decline rate. Conclusions Not everyone with CKD develops ESRD after a 10-year follow-up. Absolute annual eGFR decline rate can help clinicians to better predict the progression of CKD. Individuals with renal function decline rate over 3 ml/min/1.73 m2/year require intensive CKD care.

Association Between Periodontitis Needing Surgical Treatment and Subsequent Diabetes Risk: A Population-Based Cohort Study

BACKGROUND It is well known that patients with diabetes have higher extent and severity of periodontitis, but the backward relationship is little investigated. The relationship between periodontitis needing dental surgery and subsequent type 2 diabetes mellitus (DMT2) in those individuals without diabetes was assessed. METHODS This is a retrospective cohort study using data from the national health insurance system of Taiwan. The periodontitis cohort involved 22,299 patients, excluding those with diabetes already or those diagnosed with diabetes within 1 year from baseline. Each study participant was randomly frequency matched by age, sex, and index year with one individual from the general population without periodontitis. Cox proportional hazards regression analysis was used to estimate the influence of periodontitis on the risk of diabetes. RESULTS The mean follow-up period is 5.47 ± 3.54 years. Overall, the subsequent incidence of DMT2 was 1.24-fold higher in the periodontitis cohort than in the control cohort, with an adjusted hazard ratio of 1.19 (95% confidence interval = 1.10 to 1.29) after controlling for sex, age, and comorbidities. CONCLUSIONS This is the largest nation-based study examining the risk of diabetes in Asian patients with periodontitis. Those patients with periodontitis needing dental surgery have increased risk of future diabetes within 2 years compared with those participants with periodontitis not requiring dental surgery.

Renin-Angiotensin System Blockade Is Not Associated with Hyperkalemia in Chronic Hemodialysis Patients

Background. Serious hyperkalemia was reported in 10% of chronic hemodialysis (HD) patients that could lead to arrhythmia and death. Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) are well accepted for cardio-protective benefits. The relationship between renin-angiotensin system blockade (RASB) and hyperkalemia in chronic HD patients remains controversial. The aim of this study was to find the relationship between RASB and hyperkalemia in these patients. Methods. Pre-dialysis serum potassium, clinical factors, and drugs were evaluated in 200 chronic HD patients in one HD center. Hyperkalemia was defined as serum K ≥ 5.3 meq/L. Finally, multivariate analysis with logistic regression was used to evaluate the risk of hyperkalemia by RASB and other factors. Results. In 200 patients, the mean K was 4.93 ± 0.79 meq/L, and 70 (35%) patients had hyperkalemia. Fifty-eight (29%) patients were prescribed with RASB. Seven variables—non-DM, longer HD duration, lower dialysate calcium, lower serum glucose, higher serum iPTH, not using RASB, and not using furosemide—were more frequent in hyperkalemia group. In logistic regression analysis, RASB was associated with decreased odds for hyperkalemia (OR 0.262, p = 0.001 in model A; OR 0.205, p = 0.001 in model B). In addition, furosemide was associated with decreased odds for hyperkalemia (OR 0.068, p = 0.022 in model B). Conclusions. RASB is not associated with hyperkalemia in chronic HD patients.

The Case ∣ Ascites with oliguric acute renal failure

Hung-Chieh Yeh, I-Wen Ting, Wan-Yi Huang and Jenq-Wen Huang Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Correspondence: Jenq-Wen Huang, Department of Internal Medicine, National Taiwan University Hospital, no. 7, Chung-Shan South Road, Taipei 100, Taiwan. E-mail: jenqwen@ha.mc.ntu.edu.tw

Uric acid predicts adverse outcomes in chronic kidney disease: a novel insight from trajectory analyses

Background Very little is known about longitudinal trajectories of serum uric acid (SUA) over the course of chronic kidney disease (CKD). We aimed to determine whether longitudinal SUA trajectories are associated with the risk of end-stage renal disease (ESRD) and all-cause mortality among CKD patients. Methods We conducted a prospective cohort study from a 13-year multidisciplinary pre-ESRD care registry. The final study population consisted of 5090 CKD patients aged 20-90 years between 2003 and 2015. An individuals SUA trajectory was defined by group-based trajectory modeling in four distinct patterns: high, moderate-high, moderate and low. Time to ESRD and death was analyzed by multiple Cox regression. Results A total of 948 ESRD events and 472 deaths occurred with incidence rates of 57.9 and 28.7 per 1000 person-years, respectively. Compared with those with a low SUA trajectory, the adjusted hazard ratio of patients for incident ESRD was in a dose-response manner as follows: moderate, 1.89 [95% confidence interval (CI), 1.37-2.60]; moderate-high, 2.49 (1.75-3.55); and high, 2.84 (1.81-4.47); after considering the competing risk of death. For all-cause mortality, the corresponding risk estimate of the same SUA trajectory was 1.38 (95% CI, 0.89-2.12), 1.95 (1.22-3.10) and 4.52 (2.48-8.26), respectively. The unfavorable effect of elevated SUA trajectories on progression to ESRD was differentially higher among CKD patients without using urate-lowering agents at baseline (P for interaction = 0.018). Conclusions Elevated SUA trajectories are associated with accelerated kidney failure and all-cause mortality in CKD patients. Adequate experimental evidence is urgently needed to inform when and how to optimize SUA in this population.

Brucellosis in a renal transplant recipient

Brucellosis is one of the most common systemic zoonotic diseases transmitted by consumption of unpasteurized dairy products or by occupational contact with infected animals. Brucellosis is rare in renal transplant recipients. Only 3 cases have been reported in the literature. We report a case of brucellosis with hematologic and hepatobiliary complications in a patient 3 years after renal transplantation. The mean time from transplantation to the diagnosis of brucellosis in these 4 reported patients was 5.1 years (range 17 months to 13 years). All patients had fever and constitutional symptoms, and all attained clinical cure after combination antibiotic therapy. Given the small number of patients, further study is needed to identify the characteristics of brucellosis in renal transplant recipients. Drug interactions and acute renal failure developed in our patient during antibiotic treatment. Therefore, we should monitor the levels of immunosuppressive agents frequently. Several studies have shown in vitro susceptibilities of Brucella melitensis to tigecycline. In our patient, fever finally subsided after tigecycline administration. The minimum inhibitory concentration of tigecycline using Etest was 0.094 μg/mL. Tigecycline may be a potential option for treatment of brucellosis in the setting of transplantation.