Lower product of magnesium × potassium is associated with higher mortality in chronic hemodialysis patients: a cohort study.

This study aimed to investigate the Mg × K product on the mortality risk of hemodialysis patients with concomitant hypokalemia and lower magnesium levels. This was a prospective observational study of patients in a HD center in southern Taiwan. A total of 444 HD patients were divided into 5 groups by the Mg × K product: group 1, bottom quintile, median Mg × K: 7.87, IQR: 7.03-8.12 (n = 89, age: 64 ± 13 years old); group 2, median Mg × K: 9.37, IQR: 8.97-9.86 (n = 89, age:62 ± 13 years old); group 3, median Mg × K: 10.95, IQR: 10.50-11.26 (n = 89, age:64 ± 13 years old); group 4, median Mg × K: 12.30, IQR: 11.87-12.82 (n = 89, 61 ± 12 years old); and group 5, top quintile, median Mg × K: 14.92, IQR:14.07-16.23 (n = 88, 62 ± 11 years old). The patients were followed up for 2 years to determine the risk of all-cause mortality. Patients with a lower Mg × K product had more comorbidities, malnutrition-inflammation status, and a higher mortality risk. Using multivariable Cox regression analysis, a higher Mg × K [HR, 0.89; 95%CI (0.81-0.98)] was found to be an independent predictor of better survival. HD patients with a lower Mg × K product had more comorbidities, a marked malnutrition-inflammation status, and were associated with long-term mortality. A higher Mg × K value is a favorable survival factor.

Albumin to prealbumin ratio in peritoneal dialysis patients: Clinical implication and outcome prediction.

BACKGROUND: Serum prealbumin level is slightly higher, whereas albumin is lower in peritoneal dialysis (PD) than hemodialysis (HD) patients. It is unknown whether albumin to prealbumin ratio (APR) is associated with mortality risk among PD patients. This study aimed to evaluate the clinical implications of APR and its prediction value on long-term outcomes of PD patients. METHODS: The study population were prevalent PD patients at a tertiary hospital. Based on APR, a total of 220 PD patients were divided into 3 groups: group 1: top tertile, median APR: 121.1; IQR:109.5-131.9 (n = 73, male: 37%; age: 59±13); group 2: middle tertile, median APR: 97.1; IQR 93.5-100.0 (n = 73, male:37%; age: 54±14), and group3: bottom tertile, median APR: 81.3; IQR:76.8-85.0 (n = 74, male:38%; 54±11). Patients were followed up for a maximum of 5 years. Outcome of interest was all-cause mortality. RESULTS: Group 1 was characterized by older age, higher prevalence of diabetes, lower nPCR, higher Davies score and hs-CRP level. APR positively correlated to hs-CRP (ß = 0.149, p = 0.045), but negatively correlated to nPCR (ß = -0.161, p = 0.034). Hyperprealbuminemia, accounting for 0%, 23.3%, and 82.4% in groups 1,2, and 3, was associated with a lower risk for mortality (HR:0.41, 95%CI = 0.23-0.73). The cumulative survival is significantly lower in group 1 than the other two groups. By multivariable Cox regression, APR (HR:1.02; 95%CI:1.01-1.03) was found to be an independent predictor of long-term mortality. CONCLUSION: PD patients with high APR are characterized by having more comorbidities and marked malnutrition-inflammation status, and are associated with long-term mortality, whereas hyperprealbuminemia and lower APR are favorable prognostic factors.

Association between hypomagnesemia and mortality among dialysis patients: a systematic review and meta-analysis.

Background: Malnutrition-inflammation-atherosclerosis (MIA) syndrome is caused by the inflammatory cytokines in end stage renal disease (ESRD) patients, and MIA complex-related factors may be associated with hypomagnesemia and mortality. However, the association between serum magnesium level and mortality for dialysis patients is still not clear. Additionally, no meta-analysis has investigated the impact of serum magnesium on peritoneal dialysis and hemodialysis, separately. Methods: We searched published studies in PubMed, Embase, Cochrane, Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews through April 2022. Studies associated with serum magnesium and all-cause mortality or cardiovascular (CV) mortality in ESRD on kidney replacement therapy (KRT) patients were included. A hazard ratio (HR) with 95% confidence intervals (CI) was used to report the outcomes. Results: Twenty-one studies involving 55,232 patients were included. Overall, there was a significant association between hypomagnesemia and all-cause mortality for dialysis patients (HR: 1.67, 95% CI [1.412-2.00], p < 0.001; certainty of evidence: moderate) using a mixed unadjusted and adjusted HR for analysis. There was also a significantly increased risk of CV mortality for individuals with hypomagnesemia compared with the non-hypomagnesemia group (HR 1.56, 95% CI [1.08-2.25], p < 0.001; certainty of evidence: moderate). In addition, a subgroup analysis demonstrated that hypomagnesemia was associated with a high risk of both all-cause mortality and CV mortality (all-cause mortality, HR:1.80, 95% CI [1.48-2.19]; CV mortality, HR:1.84, 95% CI [1.10-3.07]) in hemodialysis (HD) patients, but not in participants receiving peritoneal dialysis (PD; all-cause mortality, HR:1.26, 95% CI [0.84-1.91]; CV mortality, HR:0.66, 95% CI [0.22-2.00]). The systematic review protocol was prespecified and registered in PROSPERO [CRD42021256187]. Conclusions: Hypomagnesemia may be a significant risk factor for all-cause mortality and CV mortality in KRT patients, especially in those receiving hemodialysis. However, because of the limited certainty of evidence, more studies are required to investigate this association.

Impact of Diabetes Mellitus on the Risk of End-Stage Renal Disease in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) patients are associated with insulin resistance and are at higher risk to develop diabetes mellitus (DM). SLE and DM could lead to renal failure respectively. However, it is unknown whether DM increases the risk of end-stage renal disease (ESRD) in SLE patients. This study aimed to evaluate potential synergistic effect of DM on SLE patients for development of ESRD. We conducted this study by using National Health Insurance Research Database of Taiwan. We recruited SLE patients with newly-diagnosed DM as the study cohort. A comparison cohort at a 1:1 ratio of SLE patients without DM matched by age, sex, age at the diagnosis of SLE, duration between diagnosis of SLE and DM, and various comorbidities through propensity score matching were recruited. After 5.01 ± 3.13 years follow-up, the incidence of ESRD was significantly higher in the DM group than in the non-DM group (Incidence rate ratio: 2.71; 95% CI: 1.70-4.32). After control of confounding factors, DM was not an independent risk factor of ESRD. After starting dialysis, DM patients had a similar mortality rate to those without DM. In summary, SLE patients superimposed with subsequent DM are associated with potentially higher risk to develop ESRD.

Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Accelerates Pathogen Identification and May Confer Benefit in the Outcome of Peritoneal Dialysis-Related Peritonitis.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and conventional standard methods were compared for time to pathogen identification and impact on clinical outcomes in peritoneal dialysis-related peritonitis patients. The MALDI-TOF MS method identified the causative microorganisms earlier (average time saved, 64 h for all pathogens), and patients had a shorter hospital stay (mean ± standard deviation, 5.2 ± 4.8 days versus 8.2 ± 4.5 days, P = 0.001).

Impact of HCV Infection on Diabetes Patients for the Risk of End-Stage Renal Failure.

Both diabetes mellitus (DM) and hepatitis C virus infection (HCVI) are associated with chronic kidney disease (CKD). The aim of this study was to evaluate whether HCVI increases the risk of end-stage renal disease (ESRD) in patients with DM.The National Health Insurance Research database of Taiwan was used to conduct this study. After excluding patients with a prior history of CKD, all patients with a first diagnosis of DM from January 1, 2000 to December 31, 2002 were enrolled. The patients who also had HCVI were defined as index cases (HCV group, n = 9787). A comparison cohort at a 1:1 ratio of random incident patients with DM without HCVI matched by age, sex, age at the diagnosis of DM, duration between the diagnosis of DM and the index date, and various comorbidities through propensity score matching were recruited (non-HCV group, n = 9787). The patients were followed until December 31, 2011.The cumulative incidence rate of developing ESRD was significantly higher in the HCV(+) group than in the non-HCV group (P = 0.008). The incidence rate ratio (IRR) for the risk of ESRD was also significantly higher in the HCV(+) group (IRR: 1.44; 95% CI: 1.09-1.89) than in the non-HCV group, especially for those with a younger age (<50 years; IRR: 2.05; 95% CI: 1.22-3.45) and HCVI within 4 years after the diagnosis of DM (IRR: 1.85; 95% CI: 1.16-2.97). After adjusting for comorbidities in multivariate Cox proportional hazard regression analysis, HCVI (HR: 1.47; 95% CI: 1.11-1.93) was an independent factor for developing ESRD in the patients with DM. After starting dialysis for ESRD, the HCV(+) patients had a similar mortality rate to those without HCVI (P = 0.84).HCVI increases the risk of developing ESRD in patients with DM, especially in younger patients and in those who develop HCVI sooner after a diagnosis of DM.

Clinical implications and outcome prediction in chronic hemodialysis patients with lower serum potassium×uric acid product.

BACKGROUND: The aims of this study were to evaluate correlations between serum potassium (S[K]) and uric acid (S[UA]) in hemodialysis patients and to determine whether lower levels of both S[K] and S[UA] were associated with poor long-term prognoses in these patients. METHODS: A cohort of 424 maintenance hemodialysis patients (58±13 years of age; 47% male; 39% with diabetes) from a single center were divided into tertiles based on the product of S[K]×S[UA] (K×UA): Group 1: low K×UA: n=141; Group 2: median K×UA: n=141; and Group 3: high K×UA: n=142. The longest observation period was 60 months. RESULTS: S[K] showed a positive linear correlation with S[UA] (r=0.33; p<0.001). In multivariate logistic regression analysis, Group 1 was characterized by hypoalbuminemia (odds ratio [OR]=0.20, 95% confidence interval (CI)=0.11-0.35) and lower levels of normalized protein catabolism [nPCR] (OR=0.10, 95%CI=0.05-0.22) and phosphate levels (OR=0.41, 95%CI=0.33-0.51). In contrast, Group 3 was associated with higher nPCR (OR=6.07, 95%CI=2.93-12.50) and albumin levels (OR=2.12, 95% CI=2.12-7.00). Compared to the reference (Group 1), the hazard ratio (HR) for long-term mortality was significantly lower in Groups 2 (HR=0.65, 95%CI=0.43-0.99) and 3 (HR=0.56, 95%CI=0.36-0.89). In multivariate Cox proportional analysis, the risk of mortality decreased by 2% (HR=0.98; 95%CI=0.96-0.99) per 1 unit increase in K×UA product. CONCLUSION: Hemodialysis patients with lower S[K] and [UA] levels were characterized by hypoalbuminemia and lower nPCR, and they were associated with a long-term mortality risk.

Precedent fluctuation of serum hs-CRP to albumin ratios and mortality risk of clinically stable hemodialysis patients.

BACKGROUND: A high sensitivity C-reactive protein to albumin ratio (hs-CRP/Alb) predicts mortality risk in patients with acute kidney injury. However, it varies dynamically. This study was conducted to evaluate whether a variation of this marker was associated with long-term outcome in clinically stable hemodialysis (HD) patients. METHODS: hs-CRP/Alb was checked bimonthly in 284 clinically stable HD outpatients throughout all of 2008. Based on the "slope" of trend equation derived from 5-6 hs-CRP/alb ratios for each patient, the total number of patients was divided into quartiles--Group 1: ß≦ -0.13, n = 71; group 2: ß>-0.13≦0.003; n = 71, group 3: ß>0.003≦0.20; and group 4: ß>0.20, n = 71. The observation period was from January 1, 2009 to August 31, 2012. RESULTS: Group 1+4 showed a worse long-term survival (p = 0.04) and a longer 5-year hospitalization stay than Group 2+3 (38.7±44.4 vs. 16.7±22.4 days, p<0.001). Group 1+4 were associated with older age (OR = 1.03, 95% CI = 1.01-1.05) and a high prevalence of congestive heart failure (OR = 2.02, 95% CI = 1.00-4.11). Standard deviation (SD) of hs-CRP/Alb was associated with male sex (ß = 0.17, p = 0.003), higher Davies co-morbidity score (ß = 0.16, p = 0.03), and baseline hs-CRP (ß = 0.39, p<0.001). Patients with lower baseline and stable trend of hs-CRP/Alb had a better prognosis. By multivariate Cox proportional methods, SD of hs-CRP/alb (HR: 1.05, 95% CI: 1.01-1.08) rather than baseline hs-CRP/Alb was an independent predictive factor for long-term mortality after adjusting for sex and HD vintage. CONCLUSION: Clinically stable HD patients with a fluctuating variation of hs-CRP/Alb are characterized by old age, and more co-morbidity, and they tend to have longer subsequent hospitalization stay and higher mortality risk.

Sex difference for urologic malignancy risk in uremic patients after kidney transplantation: a population-based study.

BACKGROUND: High urologic malignancy incidence has been reported in end-stage renal disease (ESRD) patients, especially of female sex. This study was undertaken to evaluate whether female recipients still carry an aggravated risk of this malignancy after kidney transplantation (KT). METHODS: The claims data from the Bureau of National Health Insurance of Taiwan were used for analysis. All KT recipients who developed urologic malignancy from January 1, 1999, to December 31, 2007 (n = 2,245) were enrolled in this study. By means of propensity score, a database of 1:4 ratio random incident ESRD patients with matched age, sex, comorbidity rates, and dialysis to index date was used as control (non-KT group, n = 8,980). The last observation period ended on December 31, 2008. RESULTS: The cumulative urologic malignancy incidence rate was significantly higher in female recipients after KT than their female ESRD counterparts without KT (P < 0.001). This gap became more prominent approximately 2 years after transplantation. No similar trend was detected in male KT patients (P = 0.13). Incidence rate ratio of urologic malignancy was significantly higher in female recipients (incidence rate ratio, 2.13; 95% confidence interval [95% CI], 1.53-2.97) than in their male counterparts (incidence rate ratio, 1.43; 95% CI, 0.90-2.25). From multivariate Cox proportional hazard regression tests, female (hazards ratio, 2.10; 95% CI, 1.52-2.95) but not male sex (hazards ratio, 1.47; 95% CI, 0.93-2.32) was determined to be an independent factor for the development of urologic malignancy after KT. After acquiring this malignancy, KT recipients did not have any advantage in cumulative survival compared to ESRD patients without KT (P = 0.07). CONCLUSION: Compared to males, female recipients tended to have a significantly higher urologic malignancy risk after KT.

Comparison of the impact of "fast decline" in residual renal function and "initial anuria" on long-term outcomes in CAPD patients.

BACKGROUND: Residual renal function (RRF) is pivotal to long-term outcomes, while rapid RRF decline (RRFD) is associated with mortality risk for continuous ambulatory peritoneal dialysis (CAPD) patients. This study was conducted to compare the impact of "initial anuria" and rapid RRFD on the long-term prognosis of CAPD patients. METHOD: According to the timing of anuria and the slope of RRFD, a total of 255 incident CAPD patients were divided into 3 groups. For the "anuria" group, anuria was detected from CAPD initiation and persisted for > 6 months (n = 27). Based on the median of the RRFD slope, the other 228 non-anuric patients were divided into a "slow decliner" group (n = 114), and a "rapid decliner" group (n = 114). The maximal observation period was 120 months. RESULTS: Logistic regression tests indicated that the "anuria" group was associated with previous hemodialysis > 3 months (odds ratio [OR]: 8.52, 95% confidence interval [CI]: 3.12 - 23.28), and female (OR: 0.29, 95% CI: 0.09 - 0.90), while the "fast decliner" group with higher Davies co-morbidity scores (DCS) (OR: 1.52; 95% CI: 1.08 - 2.14), body mass index (BMI) (OR: 1.12; 95% CI: 1.04 - 1.21), and male (OR: 1.12; 95% CI: 1.04 - 1.21). After adjusting for DCS, the "fast decliner" group (hazard ratio [HR]: 0.37; 95% CI: 0.17 - 0.80) showed a better outcome than that of the "anuria" group (reference = 1). Both baseline RRF (ß = -0.24; p < 0.001) and DCS (ß = -3.76; p < 0.001) showed inverse linear correlations to the slope of RRFD. From the Cox proportional analyses, higher baseline RRF (HR: 0.92; 95% CI: 0.88 -.97) and higher slope of RRFD (slower decline in RRF) (HR: 0.90; 95% CI: 0.85 - 0.96) were independent factors for less mortality risk in patients with DCS = 0. However, only a higher slope of RRFD (HR: 0.97; 95% CI: 0.94 - 0.99) was significant for better survival in CAPD patients with DCS > 0. CONCLUSION: Compared to the baseline RRF, CAPD patients with co-morbidities that rapidly deteriorate RRFD are more crucially associated with long-term mortality risk.

Rapid identification of bacteria and Candida pathogens in peritoneal dialysis effluent from patients with peritoneal dialysis-related peritonitis by use of multilocus PCR coupled with electrospray ionization mass spectrometry.

PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was compared with culture for pathogen detection in peritoneal dialysis (PD)-related peritonitis. Of 21 samples of PD effluent, PCR/ESI-MS identified microorganisms in 18 (86%) samples, including Mycobacterium tuberculosis in 1 culture-negative sample. Of 15 double-positive samples, PCR/ESI-MS and culture reached levels of agreement of 100% (15/15) and 87.5% (7/8) at the genus and species levels, respectively. PCR/ESI-MS can be used for rapid pathogen detection in PD-related peritonitis.

Lower serum potassium combined with lower sodium concentrations predict long-term mortality risk in hemodialysis patients.

BACKGROUND: The purpose of this study was to evaluate the combined effect of different pre-hemodialysis (HD) serum sodium (S[Na]) and potassium (S[K]) concentrations on the long-term prognosis of HD patients. METHODS: A cohort of 424 maintenance HD patients (age: 58 ± 13 years, male: 47%, diabetes: 39%) from a single center were divided into four groups based on both medians of S[Na] (138.4 mmol/L) and S[K] (4.4 mmol/L): Group 1: lower S[Na] & lower S[K]: n = 92; Group 2: lower S[Na] & higher S[K]: n =113; Group 3: higher S[Na] & lower S[K]: n =123; Group 4: higher S[Na] & higher S[K]: n =96. The median observation period was 21 months. RESULT: By multivariate logistic regression analysis, Group 1 was characterized by hypoalbuminemia (OR = 0.37, 95%CI = 0.20-0.67), and lower normalized protein catabolism rate (nPCR) (OR = 0.37, 95% CI = 0.16-0.83). In contrast, Group 4 was characterized by higher nPCR (OR = 2.26, 95% CI = 1.05-4.86) and albumin level (OR = 2.26, 95% CI = 1.17-4.39). As compared to the reference (group 1), the HR for long-term mortality was significantly lower in Groups 3 (HR = 0.54, 95% CI = 0.34- 0.86) and 4 (HR = 0.49, 95% CI = 0.28-0.84). By multivariate Cox proportional analysis, Group 1 was an independent factor (HR = 1.74, 95% CI = 1.18-2.58) associated with long-term mortality. CONCLUSION: HD patients combined with lower S[K] and lower S[Na] were characterized by hypoalbuminemia, lower nPCR and a high prevalence of co-morbidity. They were associated with long-term mortality risk. On the other hand, those patients with higher levels of S[Na] and S[K] tended to have better clinical outcomes.

Increased risk of mortality among haemodialysis patients with or without prior stroke: a nationwide population-based study in Taiwan.

BACKGROUND & OBJECTIVES: Patients with prior stroke (PS) undergoing chronic dialysis are at a high risk of mortality. However, little is known about the cumulative risk and survival rate of dialysis patients with long-term follow up. The aim of this study was to assess risks for mortality between patients with and without PS undergoing chronic haemodialysis (HD). METHODS: The Taiwan National Health Insurance Research Database (NHRI-NHIRD-99182) was used and all adult patients (≥18 yr) with end stage renal disease (ESRD) who started maintenance HD between January 1, 1999, and December 31, 1999, were selected. The patients were followed from the first reported date of HD to the date of death, end of dialysis or December 31, 2008. A Cox's proportional hazard model was applied to identify the risk factors for all-cause mortality. RESULTS: Among 5672 HD patients, 650 patients (11.5%) had PS. A higher proportion of stroke history at baseline was found in men (52.8%) and those aged ≥ 55 yr (80.9%). After adjusting for age, sex and other covariates, the patients with PS were found to have a 36 per cent increased risk of mortality compared to those without PS (HR 1.36, 95% CI: 1.22-1.52). The cumulative survival rates among HD patients without PS were 96.0 per cent at the first year, 68.4 per cent at the fifth year, and 46.7 per cent at the ninth year, and 92.9, 47.3 and 23.6 per cent, respectively, in those with PS (log-rank: P<0.001). INTERPRETATION & CONCLUSIONS: Our findings showed that PS was an important predictor for all-cause mortality and poor outcome in patients undergoing chronic HD.

Increasing high-sensitive C-reactive protein level predicts peritonitis risk in chronic peritoneal dialysis patients.

BACKGROUND: The aim of this study was to evaluate whether a high baseline level of high-sensitivity C-reactive protein (hs-CRP) or changes in the level predicts the risk of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: A prospective, cross-sectional, case-control study was conducted in a single hospital-based PD unit. A total of 327 patients were included in the study. Serum hs-CRP was measured annually for 2 years. Patients were divided into 4 groups according to the changes in annual hs-CRP levels (at baseline and at 1 year intervals): group 1 (from <5 mg/L to <5 mg/L, n = 171), group 2 (from <5 mg/L to ≥5 mg/L, n = 45), group 3 (from ≥5 mg/L to <5 mg/L, n = 45), and group 4 (from ≥5 mg/L to ≥5 mg/L, n = 80). Demographics, biochemistry results, PD adequacy indices, and peritonitis risk were compared between the groups. RESULTS: The initial serum albumin level was similar in the 4 groups (p = 0.12). There was a negative linear correlation between the serial albumin change (∆alb) and serial hs-CRP change (∆hs-CRP; r = -0.154, p = 0.005). The hazard ratio (HR) for peritonitis was significantly higher in group 2 (HR = 1, reference) than in group 4 (HR = 0.401, 95% CI 0.209 - 0.769). Group 2 had a greater serum albumin decline rate (∆alb: -3% ± 9%) and hs-CRP elevation rate (∆hs-CRP: 835% ± 1232%) compared to those for the other groups. CONCLUSIONS: A progressive increase in the hs-CRP level was associated with a corresponding decline in the serum albumin level. Progressive rather than persistently high levels of serum hs-CRP predicted peritonitis risk in CAPD patients.

Association of fatty liver disease with nonfatal cardiovascular events in patients undergoing maintenance hemodialysis.

BACKGROUND/AIMS: The prevalence of cardiovascular (CV) disease in patients undergoing maintenance hemodialysis (HD) is reportedly higher than that in healthy individuals. In the present study, we aimed to investigate whether ultrasonographically documented fatty liver disease (FLD) is an independent risk factor for nonfatal CV events in patients undergoing HD. METHODS: A retrospective cohort study was conducted in a medical center in southern Taiwan. The medical records of 490 patients undergoing HD who were enrolled between July 1998 and October 2012 were screened. Finally, 278 patients who had undergone hepatic ultrasonography and had available data were recruited in the present study. The patients included 130 men and 148 women; their mean age was 59.9 years. The primary endpoint was nonfatal CV events in the observation period. The comparable data included epidemiological, hematological, and biochemical profiles. A time-dependent statistical method was used to analyze the associated factors. RESULTS: The prevalence of nonfatal CV events was significantly increased in the patients with FLD compared with those without FLD (CV events: 32 vs. 18%, respectively; p = 0.008). After adjusting for associated risk factors (sex, age, body mass index, smoking, diabetes, hypertension, dyslipidemia, and Kt/V), multivariate analyses identified FLD (CV events: hazard ratio 2.84, 95% confidence interval 1.52-5.28, p = 0.001), advanced age, and diabetes to be independently associated with nonfatal CV events. CONCLUSION: The study suggests that FLD was an independent risk factor for nonfatal CV events in patients undergoing maintenance HD.

High incidence of hepatocellular carcinoma in ESRD patients: caused by high hepatitis rate or 'uremia'? a population-based study.

OBJECTIVE: A high incidence of hepatocellular carcinoma has been reported in end-stage renal disease patients. This study was undertaken to evaluate whether this was caused by a high rate hepatitis or 'uremia' per se. METHODS: We used claims data of the Bureau of National Health Insurance of Taiwan for analysis. All patients diagnosed with end-stage renal disease having received their first dialysis between 1 January 2003 and 31 December 2007 (n = 38 714) were enrolled for the study. A database of 1 million randomly selected subjects matched for age, gender, hepatitis B and C infection, and liver cirrhosis for the same period was used as control (n = 38 714). The longest observation period was up to 31 December 2008. RESULTS: There was no significant difference in the incidence of hepatocellular carcinoma between end-stage renal disease patients and their non-end-stage renal disease counterparts (2.03 per 1000 person-years vs. 2.10 per 1000 person-years, rate ratio = 0.947; 95% confidence interval: 0.792-1.132). End-stage renal disease patients with hepatocellular carcinoma had higher percentages of diabetes mellitus, hypertension, heart failure and gout (all P < 0.001), and they presented with a worse cumulative survival rate than the non-end-stage renal disease group (P < 0.001). End-stage renal disease patients developing hepatocellular carcinoma were younger, and had more comorbidities than their non-end-stage renal disease counterparts. End-stage renal disease (hazard ratio = 1.61) and diabetes mellitus (hazard ratio = 1.55) were found to be independent factors for mortality in hepatocellular carcinoma patients. CONCLUSIONS: After matching for hepatitis and liver cirrhosis, end-stage renal disease is not associated with a higher incidence of hepatocellular carcinoma than the general population. The high incidence of hepatocellular carcinoma in end-stage renal disease patients was caused by a high viral hepatitis rate rather than 'uremia' per se. Owing to increased comorbidity, end-stage renal disease patients developing hepatocellular carcinoma had worse long-term survival than non-end-stage renal disease patients.

Long-term survival and predictors for mortality among dialysis patients in an endemic area for chronic liver disease: a national cohort study in Taiwan.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at a higher risk for chronic hepatitis, liver cirrhosis (LC) and mortality than the general population. Optimal modalities of renal replacement therapy for ESRD patients with concomitant end-stage liver disease remain controversial. We investigated the long-term outcome for chronic liver disease among dialysis patients in an endemic area. METHODS: Using Taiwan's National Health Insurance claim data (NHRI-NHIRD-99182), We performed a longitudinal cohort study to investigate the impact of comorbidities on mortality in dialysis patients. We followed up 11293 incident hemodialysis (HD) and 761 peritoneal dialysis (PD) patients from the start of dialysis until the date of death or the end of database period (December 31, 2008). A Cox proportional hazards model was used to identify the risk factors for all-cause mortality. RESULTS: Patients receiving PD tended to be younger and less likely to have comorbidities than those receiving HD. At the beginning of dialysis, a high prevalence rate (6.16 %) of LC was found. Other than well-known risk factors, LC (hazard ratio [HR] 1.473, 95 % CI: 1.329-1.634) and dementia (HR 1.376, 95 % CI: 1.083-1.750) were also independent predictors of mortality. Hypertension and mortality were inversely associated. Dialysis modality and three individual comorbidities (diabetes mellitus, chronic lung disease, and dementia) interacted significantly on mortality risk. CONCLUSIONS: LC is an important predictor of mortality; however, the effect on mortality was not different between HD and PD patients.

Cyclin D1 expression in podocytes: regulated by mitogens in collaboration with integrin-extracellular matrix interaction through extracellular signal-regulated kinase.

Cyclin D1 plays significant roles in cell cycle entry and migration. We have documented that both integrin α3ß1 expressions and the number of podocytes were reduced in focal segmental glomerulosclerosis. We wondered whether integrin-extracellular matrix (ECM) interaction was involved in the regulation of cyclin D1 expression, and the possible signaling pathways in mitogen-stimulating podocytes. Cultured podocytes were divided into serum (mitogens/growth factors)-starved and serum-stimulated groups. Reverse transcription polymerase chain reaction was used to detect cyclin D1 mRNA, and Western blot analysis was used to measure protein concentrations of cyclin D1 and extracellular signal-regulated kinase (ERK) activation (p-ERK/ERK). The integrin-ECM interaction was blocked by anti-ß1-integrin monoclonal antibody or RGDS (Arg-Gly-Asp-Ser). The MEK inhibitor, U0126, was used to inhibit ERK activation. The results showed that there was little cyclin D1 protein in serum-starved groups, but it was abundant in serum-stimulated groups. Both cyclin D1 mRNA and protein levels were reduced in serum-stimulated podocytes after blocking integrin-ECM interaction. ERK activation in serum-stimulated podocytes was significantly decreased after blocking integrin-ECM interaction. Cyclin D1 mRNA and protein concentrations in serum-stimulated podocytes were reduced after blocking ERK activation by U0126. We demonstrate that integrin-ECM interaction collaborates with mitogens to activate ERK/mitogen-activated protein kinase pathways which are essential for cyclin D1 expression in podocytes.

Reverse epidemiology of hypertension-mortality associations in hemodialysis patients: a long-term population-based study.

BACKGROUND: Although hypertension (HTN) is a predictor of mortality, recent data have questioned the link between baseline HTN and mortality in incident hemodialysis (HD) patients. We used Taiwan's National Health Insurance claim data (NHRI-NHIRD-99182) to investigate the association. METHODS: In 1999, this longitudinal cohort study enrolled 5752 new HD patients. Follow-up began from the initiation of HD until death, the end of HD, or the end of 2008. A Kaplan-Meier survival analysis was done. Cox proportional hazard analysis was used to identify the risk factors for mortality. RESULTS: The prevalence of baseline HTN was 75.47%. Patients with HTN had a higher prevalence of diabetic mellitus (DM) and cardiovascular diseases. The 1-, 5-, and 9-year cumulative survival rates were 95.5, 63.7 and 41.8% in patients with HTN, and 95.5, 71.0, and 52.0% in those without HTN (log-rank test: P <0.001). Multivariate analysis showed that patients with baseline HTN may have a higher survival rate (hazard ratio (HR) 0.901, 95% confidence interval (CI): 0.819-0.992). After stratification by age and DM, only elderly (≥65) patients without DM had a significantly higher survival rate (HR 0.769, 95% CI: 0.637-0.927). HTN predicts lower mortality with increasing age in patients with congestive heart failure (CHF) or coronary artery disease (CAD). CONCLUSIONS: There is a reverse (counterintuitive) association between baseline HTN and mortality in elderly HD patients without DM and a clear tendency for a reverse association with increasing age in patients with CHF or CAD. Further study of the association between HTN and mortality in older HD patients may be warranted.

Effects of Extract from Solid-State Fermented Cordyceps sinensis on Type 2 Diabetes Mellitus.

Diabetes mellitus is the most common chronic disease in the world, and a wide range of drugs, including Chinese herbs, have been evaluated for the treatment of associated metabolic disorders. This study investigated the potential hypoglycemic and renoprotective effects of an extract from the solid-state fermented mycelium of Cordyceps sinensis (CS). We employed the KK/HIJ diabetic mouse model, in which the mice were provided with a high-fat diet for 8 weeks to induce hyperglycemia, followed by the administration of CS or rosiglitazone for 4 consecutive weeks. Several parameters were evaluated, including changes in body weight, plasma lipid profiles, oral glucose tolerance tests, insulin tolerance tests, and plasma insulin concentrations. Our results show that the CS extract significantly elevated HDL/LDL ratios at 4 weeks and decreased body weight gain at 8 weeks. Interestingly, CS treatment did not lead to obvious improvements in hyperglycemia or resistance to insulin, while in vitro MTT assays indicated that CS protects pancreatic beta cells against the toxic effects of STZ. CS also enhanced renal NKA activity and reduced the accumulation of mesangial matrix and collagen deposition. In conclusion, CS extract can potentially preserve ß-cell function and offer renoprotection, which may afford a promising therapy for DM.