Ya-Wen Chuang

Lower Variability of Tacrolimus Trough Concentration After Conversion From Prograf to Advagraf in Stable Kidney Transplant Recipients

Backgrounds. Variability of blood trough concentration (C0) in immunosuppressant leads to rejection and graft loss after kidney transplantation. Methods. The aim of this study is to prospectively investigate the change of within-patient variability among stable kidney transplant recipients with conversion from twice-daily Prograf to the same milligram-for-milligram daily dose of once-daily Advagraf. Results. The mean age of 129 patients was 51.3±12.1 years. The conversion to Advagraf was administrated at 6.3±4.8 years after transplantation. The daily dose was changed from 4.7±2.0 mg to 4.9±2.1 mg after conversion. Only six patients increased daily dose by 16.7% to 25% to maintain target levels. The whole blood C0 of tacrolimus before conversion was 5.9±1.7 ng/mL. The mean C0 was significantly reduced after conversion to Advagraf; it was 4.9±1.5 ng/mL on the seventh day (P<0.001) and 5.4 to 5.5 ng/mL at 1 to 6 months (P<0.05). Forty-one (31.8%) patients have reduced C0 of more than 25% on the seventh day. The percent coefficient of variation of tacrolimus C0 more than 22.5% before conversion is associated with higher risk of reduced C0 after conversion (P<0.05). Compared with before conversion, less kidney transplant recipients have percent coefficient of variation more than 22.5% after conversion (3.1% vs. 17.4% with P<0.01). Conclusions. The results support that conversion from Prograf to Advagraf among kidney transplant recipient leads to a significantly lower C0 and within-patient variability of tacrolimus C0. The within-patient variability of C0 before conversion influences C0 on the sevent day after conversion to Advagraf.

Hypokalaemia: an independent risk factor of enterobacteriaceae peritonitis in CAPD patients

BACKGROUND Hypokalaemia is a relatively common complication in uraemic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The hazards of hypokalaemia are multiple and have been correlated with patient morbidity and mortality. Whether it is associated with increased risk of peritonitis remains to be addressed. METHODS We retrospectively analysed our CAPD patients who had complicating peritonitis in a 2-year period. The influence of hypokalaemia on the clinical features of peritonitis was assessed. From September 2003 to August 2005, 140 unselected patients undergoing CAPD treatment and followed up in our hospital were recruited for the study. Hypokalaemia was defined as a serum potassium level <3.5 mmol/l. The impact of hypokalaemia on several clinical parameters, including the nutrition status, dialysis adequacy, occurrence of peritonitis and the etiologic pathogens, was analysed. RESULTS During the study period, 462 determinations (23.6%) were below quantity <mmol/l. The overall peritonitis rate was 30.6 patient-month per episode (total 64 episodes). The prevalence of peritonitis was significantly higher in patients with hypokalaemia (6.9%) compared to those without hypokalaemia (2.1%, P < 0.001). Hypokalaemia was also associated with lower serum albumin (P < 0.001), serum phosphate (P < 0.001), total serum cholesterol (P = 0.049) and normalized protein nitrogen appearance (P < 0.001). There was no correlation between serum potassium level and daily PD exchange volume, total Kt/V, urine volume or daily ultrafiltration volume. The peritoneal equilibration test was not significantly different between patients with and without hypokalaemia. When the aetiologic organisms of peritonitis were grouped according to their usual site of colonization, Enterobacteriaceae appeared to be much more prevalent than epidermal microorganisms (53.1% versus 18.8%, P = 0.004) in the hypokalaemia group. However, this was not the case in patients with normal serum potassium. CONCLUSION CAPD patients with hypokalaemia are associated with a higher prevalence of peritonitis and poor nutritional status. Enterobacteriaceae were the predominant organisms causing peritonitis in the group with hypokalaemia. This unique and novel finding implies the translocation of these organisms from intestinal mucosa into the peritoneal cavity. A pathogenic mechanism linking malnutrition and hypokalaemia is also proposed.

Risk of cancer in patients with polycystic kidney disease: a propensity-score matched analysis of a nationwide, population-based cohort study.

BACKGROUND Data for the risk of any solid cancer in patients with polycystic kidney disease are scarce. Therefore, we did a nationwide cohort study in Taiwan to establish the risk of cancer in patients with polycystic kidney disease without either chronic kidney disease or end-stage renal disease. METHODS From inpatient claims of the Taiwan National Health Insurance Research Database, we included patients aged 20 years and older and diagnosed with polycystic kidney disease between January, 1998 and December, 2010, in the polycystic kidney disease cohort. Patients with a history of cancer, a history of chronic kidney disease or of end-stage renal disease (recorded from the Registry of Catastrophic Illness Patient Database) were excluded. For each patient with polycystic kidney disease, one patient aged older than 20 years with no history of polycystic kidney disease or cancer was randomly selected from the National Health Insurance Research Database, matched 1:1 on the basis of the propensity score calculated by logistic regression, and was included in the control non-polycystic kidney disease cohort. The follow-up period for each patient was estimated from the index date to the date of diagnosis of cancer, or the patient was censored due to withdrawal from the insurance programme (eg, death, immigration, or imprisonment) or on Dec 31, 2011. The primary outcome of interest was a diagnosis of cancer during a 14-year follow-up period. The risk of cancer was represented as a hazard ratio (HR) calculated in Cox proportional hazard regression models. FINDINGS 4346 patients with polycystic kidney disease and 4346 without were enrolled in the study. The median follow-up period in the polycystic kidney disease cohort was 3·72 years (IQR 1·25-7·31) and in the non-polycystic kidney disease cohort was 4·96 years (2·29-8·38). The overall incidence of cancer was higher in the polycystic kidney disease cohort than in the control cohort (20·1 [95% CI 18·3-21·9] per 1000 person-years vs 10·9 [10·1-11·8] per 1000 person-years; crude hazard ratio (HR) 1·77 [95% CI 1·52-2·07]; HR adjusted for age, sex, frequency of medical visits, and comorbidities was 1·83 [1·57-2·15]). The specific risks (adjusted subhazard ratios) were significantly higher in the polycystic kidney disease cohort than that in the non-polycystic kidney disease cohort for liver cancer (1·49 [95% CI 1·04-2·13]; p=0·030), colon cancer (1·63 [1·15-2·30]; p=0·006), and kidney cancer (2·45 [1·29-4·65]; p=0·006). INTERPRETATION To our knowledge, this is the first report of the association of polycystic kidney disease without end-stage renal disease with the risk of liver, colon, and kidney cancer. Health-care professionals should be aware of this risk, when treating patients with polycystic kidney disease. FUNDING Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence, Academia Sinica Taiwan Biobank, Stroke Biosignature Project, NRPB Stroke Clinical Trial Consortium, Tseng-Lien Lin Foundation, Taiwan Brain Disease Foundation, Katsuzo and Kiyo Aoshima Memorial Funds, China Medical University Hospital, and Taiwan Ministry of Education.

Systemic inflammation is associated with pulmonary hypertension in patients undergoing haemodialysis

BACKGROUND Pulmonary hypertension (PH) is an overlooked cardiovascular morbidity in patients undergoing haemodialysis. Inflammation has been demonstrated to play a significant role with certain types of PH in non-uraemic patients, but studies analysing the mechanisms in dialyzed patients with PH are rare. Hence, we investigated systemic and local inflammation biomarkers associated with PH in uraemia patients to elucidate the potential mechanism. METHODS A cross-sectional study was conducted in which 97 haemodialysis patients were initially evaluated in our hospital. Twelve inflammatory cytokines were measured using a cytometric beads assay in patients with and without PH. FE(NO) (fractional exhaled nitric oxide) was checked by a chemiluminescence analyser in patients with and without PH as well as by normal controls. RESULTS Thirty-nine eligible patients were enrolled. Compared to patients without PH (group A), patients with PH (group B) had significantly higher serum levels of hs-CRP, IL-1beta, TNF-alpha and IL-6. FE(NO) was also measured. Though the pre-dialysis FE(NO) levels were elevated in both groups; group B patients had significantly higher pre-dialysis FE(NO) levels than group A patients (39.9 +/- 16.7 versus 31.8 +/- 10.3, P = 0.045). The post-dialysis FE(NO) levels returned to normal in group A while the remaining were significantly higher in group B (30.3 +/- 10.3 versus 20.1 +/- 10.9, P = 0.003). CONCLUSIONS Our study revealed that dialyzed patients with PH had a significantly higher level of airway FE(NO) as well as serum levels of acute phase reactive protein and cytokines, including IL-1beta, TNF-alpha and IL-6. A chronic inflammation might play an important role in the pathogenesis of PH in patients undergoing haemodialysis.

Intestinal bacterial overgrowth in CAPD patients with hypokalaemia

OBJECTIVE We have previously demonstrated that hypokalaemia is a risk factor for enteric peritonitis in CAPD patients. The underlying mechanism is unclear, and there have been no similar reports. We hypothesized that hypokalaemia may result in dysmotility of the intestinal tract and in turn cause bacterial overgrowth and subclinical translocation of enteral bacteria. METHODS Uraemic patients undergoing CAPD in our hospital were enrolled in the study. Hypokalaemia was defined as a serum potassium (K) level < or = 3.5 mEq/L despite treatment for 1 month. A breath hydrogen test (BHT) was performed to detect if intestinal bacterial overgrowth was present. Blood samples were also collected for the study of inflammatory cytokines, including interleukin 1 (IL1), IL2, IL6, IL8, TNF-alpha and gamma-IFN. RESULTS A total of 68 patients were recruited. Hypokalaemia was present in 18 cases (26.5%, group 1), while 50 cases (group 2) had normal serum K levels. A higher prevalence of abnormal BHT was found in group 1 (27.8%), compared with group 2 (8.0%, P = 0.048). There was a trend towards a higher prevalence of abnormal BHT in diabetes mellitus (DM) patients with hypokalaemia (80.0%) compared with normal kalaemia (22.2%, P = 0.09), while no similar trends were found in non-DM hypokalaemic patients (7.7 versus 4.9%). When comparisons were made among different subgroups, patients with DM and hypokalaemia had a significantly higher prevalence of abnormal BHT compared to non-DM, normokalaemic patients (P < 0.0004) and non-DM, hypokalaemic patients (P = 0.008). Multivariate logistic regression analysis revealed that DM was an independent risk factor for abnormal BHT (odds ratio: 12.39, 95% CI: 2.25-68.20, P = 0.004). There was no significant difference in serum albumin, Kt/V, weekly creatinine clearance, pattern of peritoneal equilibrium test, C-reactive protein and various inflammatory cytokines between the two groups. CONCLUSION CAPD patients with hypokalaemia may have intestinal bacterial overgrowth. While both DM and hypokalaemia might contribute to this abnormality, only DM appeared to be the independent risk factor.

In-hospital mortality risk estimation in patients with acute nonvariceal upper gastrointestinal bleeding undergoing hemodialysis: a retrospective cohort study.

Background: Upper gastrointestinal bleeding (UGIB) is a major cause of clinical bleeding among patients with end-stage renal disease (ESRD). This study aimed to investigate the association between mortality and UGIB in patients with uremia. Methods: From 2004 to 2010, a tertiary hospital-based retrospective cohort comprising 322 patients undergoing hemodialysis was investigated. All the patients were diagnosed with UGIB according to the International Classification of Diseases, 9th Revision (ICD-9) that included peptic ulcer bleeding, duodenal ulcer bleeding, and other symptoms. UGIB was required to be one of the first three discharge diagnoses. Rehospitalization within 3 days after discharge was regarded as the same course. Exclusion criteria were age <20 years, previous gastric resection or vagotomy, esophageal and gastric variceal bleeding, or gastric cancer within the first 2 years of the index hospitalization. Results: The all-cause in-hospital mortality rate of patients with UGIB undergoing hemodialysis was high, with the first-month mortality rate of 13.7%, sixth-month mortality rate of 26.7%, and first-year mortality rate of 27.0%. Using Cox regression models, we found that the high mortality rate of the UGIB group was significantly correlated with older age [adjusted hazard ratio (HR) = 1.02, 95% confidence interval (CI) = 1.01–1.04], female sex (adjusted HR = 1.62, 95% CI = 1.05–2.51), infection during hospitalization (adjusted HR = 1.85, 95% CI = 1.13–3.03), single episodic UGIB (adjusted HR = 2.00, 95% CI = 1.08–3.70), abnormal white blood cell (WBC) count (adjusted HR = 1.59, 95% CI = 1.03–2.45), and albumin level ≤3 g/dL (adjusted HR = 2.67, 95% CI = 1.51–4.72). Conclusion: In conclusion, patients with ESRD who are admitted with primary UGIB have a profoundly increased risk of all-cause in-hospital mortality during the follow-up period.

Clinical outcome of elderly peritoneal dialysis patients with assisted care in a single medical centre: a 25 year experience.

Peritoneal dialysis (PD) is an alternative treatment for elderly patients with end‐stage renal disease (ESRD). In Taiwan, non‐professional personnel are employed to provide assisted care for elderly patients. Whether assisted care is appropriate for elderly patients is unknown. The aim of this paper is to evaluate the outcomes of assisted care in a single centre.

High Risk of Renal Failure in Stage 3B Chronic Kidney Disease is Under-recognized in Standard Medical Screening

Background: The objective of this study was to determine the risk of renal failure in patients with under‐recognized chronic kidney disease (CKD) in the self‐pay standard medical screening program of health management centers. Methods: The abbreviated Modification of Diet in Renal Disease equation was used to calculate the estimated glomerular filtration rate (eGFR) of study subjects. Study subjects with eGFR less than 60 mL/min/1.73m2 but with normal results of routine assessment, including serum creatinine, blood urea nitrogen, urinalysis and kidney ultrasound, were defined as having under‐recognized CKD. Episodes of renal failure requiring dialysis within 2 years in subjects with stage 3 to stage 5 CKD were evaluated. Results: A total of 15,817 subjects were recruited and 28.4% of subjects were identified by routine assessments as having a kidney problem. The prevalences of CKD 3A, 3B, 4 and 5 were 8.3%, 1.9%, 0.3% and 0.2%, respectively. All subjects with stages 4 and 5 CKD had abnormal serum creatinine levels, but 48.7% of 1,507 subjects with stage 3 CKD (stage 3A, n = 713; stage 3B, n = 21) had normal routine assessments. Subjects with under‐recognized stage 3B CKD had the highest risk (20%) of developing renal failure compared to subjects with stages 3‐5 CKD and abnormal results of routine assessments. Conclusion: Identifying subjects with CKD stage 3 by the eGFR equation, especially in stage 3B, is advantageous in detecting the risk of renal failure over the routine clinical assessment that is currently carried out by health management institutions in Taiwan.

Risk of Peripheral Arterial Occlusive Disease in Patients With Systemic Lupus Erythematosus: A Nationwide Population-Based Cohort Study

AbstractSystemic lupus erythematosus (SLE) is associated with atherosclerosis, but the relationship between SLE and peripheral arterial occlusive disease (PAOD) remains unclear. We sought to investigate this relationship by comparing cardiovascular complications in patients with and without SLE.Data on patients from 2000 to 2011 were collected from the National Health Insurance Research Database of Taiwan. The SLE cohort was frequency-matched according to age, sex, and history of diabetes mellitus (DM) with patients without SLE (control cohort). We evaluated the risk of cardiovascular complications, including hypertension, DM, stroke, chronic obstructive pulmonary disease, heart failure, coronary artery disease, and hyperlipidemia.The study included 10,144 patients with SLE and 10,144 control patients. The incidence of PAOD was 9.39-fold higher (95% confidence interval [CI] = 7.70–11.15) in the SLE cohort than in the non-SLE cohort. Moreover, SLE was an independent risk factor for PAOD. The adjusted risk of PAOD was highest in patients with SLE who were aged ⩽34 years (hazard ratio = 47.6, 95% CI = 26.8–84.4). The risk of PAOD was highest during the first year of follow-up and decreased over time.Patients with SLE exhibit a higher incidence and an independently higher risk of PAOD compared with the general population. The PAOD risk is markedly elevated in patients with SLE who are young and in whom the disease is at an early stage.

Current Safety of Renal Allograft Biopsy With Indication in Adult Recipients: An Observational Study.

AbstractRenal biopsy remains the golden standard diagnosis of renal function deterioration. The safety in native kidney biopsy is well defined. However, it is a different story in allograft kidney biopsy. We conduct this retrospective study to clarify the safety of allograft kidney biopsy with indication.All variables were grouped by the year of biopsy and they were compared by Mann–Whitney U test (for continuous variables) or Chi-square test (for categorical variables). We collected possible factors associated with complications, including age, gender, body weight, renal function, cause of uremia, status of coagulation, hepatitis, size of needle, and immunosuppressants.We recruited all renal transplant recipients undergoing allograft biopsy between January of 2009 and December of 2014. This is the largest database for allograft kidney biopsy with indication. Of all the 269 biopsies, there was no difference in occurrence among the total 14 complications (5.2%) over these 6 years. There were only 3 cases of hematomas (1.11%), 6 gross hematuria (2.23%), 1 hydronephrosis (0.37%), and 2 hemoglobin decline (0.74%). The outcome of this cohort is the best compared to all other studies, and it is even better than the allograft protocol kidney biopsy. Among all possible factors, patients with pathological report containing “medullary tissue only” were susceptible to complications (P < 0.001, 1.8 of relative risk).In modern era, this study demonstrates the safety of allograft kidney biopsy with indication. Identifying the renal capsule before biopsy to avoid puncture into medulla is the most important element to prevent complications.