Association Between Parathyroid Hormone-Related Peptide Levels and Mortality in Patients With Malignancy.

OBJECTIVE: Hypercalcemia of malignancy is a risk factor for mortality in patients with malignancies. Although the parathyroid hormone-related protein (PTHrP) secreted by tumor cells induces hypercalcemia, the association between serum PTHrP levels and mortality remains unclear. This study aimed to investigate the association between serum PTHrP levels and mortality in patients with malignancies. METHODS: We included patients with hypercalcemia (>10 mg/dL) and elevated PTHrP levels (>1.1 pmol/L) and analyzed mortality (overall survival after cancer diagnosis, PTHrP measurement, and 5-year survival rate). Moreover, using Cox proportional hazard model analysis, we investigated the impact of PTHrP levels on survival prognosis, assessing whether this effect varied depending on calcium concentration. RESULTS: We analyzed the data of 183 patients. The median PTHrP level, corrected calcium level, and age were 5.5 (3.0-10.6) pmol/L, 12.5 (11.5-13.4) mg/dl, and 70 (61-76) years, respectively. PTHrP was significantly and linearly associated with serum calcium levels (correlation coefficient, 0.06; 95% CI: 0.039-0.081, t: 5.69; P < .001). The group with the highest PTHrP levels had significantly worse survival rates than the group with the lowest PTHrP levels (hazard ratio: 1.68, 95% CI 1.03-2.77, P = .038). CONCLUSION: This study showed an association between PTHrP and mortality in patients with malignancy after adjusting for serum calcium levels.

The relation between proteinuria and the severity of COVID-19.

BACKGROUND: The association between proteinuria, which is also an indicator of chronic kidney disease (CKD), and coronavirus disease 2019 (COVID-19) severity is unclear. METHODS: We selected 342 hospitalized patients with COVID-19 diagnosed via polymerase chain reaction testing between February 2020 and October 2022 and who had at least one urinalysis 14-365 days before admission. RESULTS: Proteinuria before admission was associated neither with oxygen administration nor developing pneumonia in multivariate analysis (odds ratio [OR] 1.03; 95% confidence interval (CI) 0.44-2.40, p = 0.95 and OR 1.01; 95% CI 0.47-2.17, p = 0.98, respectively). Proteinuria on admission was associated both with oxygen administration and developing pneumonia in multivariate analysis (OR 3.29; 95% CI 1.37-7.88, p < 0.01 and OR 3.81; 95% CI 1.68-8.62, p < 0.01, respectively). The percentage of patients with proteinuria on admission was significantly higher than those before admission (37.4% vs. 17.8%; p < 0.01). In the subgroup analysis, proteinuria on admission among patients with eGFR ≥ 60 mL/min/1.73 m2 was associated with both oxygen administration and developing pneumonia (OR 4.86; 95% CI 1.22-19.38, p = 0.03, OR 3.65; 95% CI 1.06-12.58, p = 0.04, respectively). In contrast, proteinuria on admission among patients with eGFR < 60 mL/min/1.73 m2 was associated with developing pneumonia (OR 6.45; 95%CI 1.78-23.35, p = 0.01), not with oxygen administration (OR 3.28; 95% CI 0.92-11.72, p = 0.07). CONCLUSIONS: Although underlying proteinuria before admission was not associated with COVID-19 severity, proteinuria on admission was associated with oxygen demand and developing pneumonia.

Association between the serum zinc level and nutritional status represented by the geriatric nutritional Rrisk index.

BACKGROUND: Although it is widely known that patients with chronic kidney disease (CKD) can develop zinc deficiency, in our previous analysis, the estimated glomerular filtration rate (eGFR) was not independently associated with the serum zinc level. Thus, a post hoc analysis was conducted to investigate the involvement of nutritional status. METHODS: A total of 655 subjects not on dialysis (402 males; mean age, 57 ± 18 years) who underwent serum zinc level measurements at Jikei University Hospital between April 2018 and March 2019 were selected using the Standardized Structured Medical Information eXchange2 (SS-MIX2) system. In addition, anthropometric data and the Geriatric Nutritional Risk Index (GNRI) representing nutritional status were obtained, and the relationship between the serum zinc level and nutritional status was investigated by multiple regression analysis. RESULTS: The serum albumin level and the GNRI were lower in the zinc-deficiency group, and both were positively associated with the serum zinc level (rho = 0.44, P < 0.01 and rho = 0.44, P < 0.01, respectively). On multiple regression analysis, the GNRI (t = 3.09, P < 0.01) and serum albumin level (t = 4.75, P < 0.01) were independently associated with the serum zinc level. Although a higher eGFR was associated with a higher serum zinc level, this association disappeared on multivariate analysis. CONCLUSION: In this post hoc analysis, the GNRI, as well as the serum albumin level, were correlated with the serum zinc level, indicating that nutritional status is an important determinant of the zinc level. Further investigations are needed to clarify the effects of nutritional status and kidney function on zinc deficiency.

Upward-directed exit-site of the swan-neck catheter and "Easy-to-disinfect the backside area of exit-site" may prevent PD complications.

BACKGROUND: Upward-directed exit-site has been believed to be the worst for frequent ESI by an old retrospective study using straight catheters. No comparison study of 3 exit-site directions using swan-neck catheter has been performed regarding which direction is the best for our endpoints, Easy-to-see the backside area of exit-site: ESBE, Easy-to-disinfect the backside area of exit-site: EDBE, reduction of both exit-site infection (ESI), symptomatic catheter dislocation and peritonitis. METHODS: We assessed the relationship of exit-site direction with our endpoints in a quantitative cross-sectional, multicentered questionnaire survey. Patients who received either non-surgical catheter implantation or exit-site surgery were excluded. RESULTS: The numbers (percentage) of exit-site directions in included 291 patients were upward 79 (26.0), lateralward 108 (37.5) and downward 105 (36.5). Cochran-Armitage analysis showed a significant step-ladder increase in the prevalence of ESI as the direction changed from upward to lateralward to downward (0.15 ± 0.41, 0.25 ± 0.54, 0.38 ± 0.69 episodes/patient-year, p = 0.03). Multivariable regression analysis revealed the upward exit-site independently associates with both higher frequency of ESBE (OR 5.55, 95% CI 2.23-16.45, p < 0.01) and reduction of prevalence of ESI (OR 0.55, 95%CI 0.27-0.98, p = 0.04). Positive association between the prevalence of symptomatic catheter dislocation and ESI (OR 2.84, 95% CI 1.27-7.82, p = 0.01), and inverse association between EDBE and either prevalence of symptomatic catheter dislocation (OR 0.27, 95% CI 0.11-0.72) or peritonitis (OR 0.48, 95% CI 0.23-0.99) observed. CONCLUSION: Upward-directed swan-neck catheter exit-site may be the best for both ESBE and prevention of ESI. EDBE may reduce catheter dislocation and peritonitis. Symptomatic catheter dislocation may predict ESI.

Zinc deficiency: its prevalence and relationship to renal function in Japan.

BACKGROUND: Although zinc deficiency is common among dialyzed patients, its prevalence among non-dialyzed subjects and its relationship to renal function remain unclear. METHODS: We selected 816 non-dialyzed subjects (495 males; mean age, 56 ± 18 years) who underwent measurement of serum zinc at Jikei University Hospital between April 2018 and March 2019 using the Standardized Structured Medical Information eXchange2 (SS-MIX2) system, a global standard in Japan that enables collection of structured medical records with automatic data transfer to a registry database system. A serum zinc level of 60-80 µg/dL was defined as marginal zinc deficiency and a level of < 60 µg/dL as absolute zinc deficiency. We investigated factors associated with serum zinc using multiple regression analysis. RESULTS: Marginal and absolute zinc deficiency were present in 52.3% and 30.6% of subjects, respectively. Serum zinc levels tended to decrease with increasing stage of chronic kidney disease (CKD) (P = 0.051). Estimated glomerular filtration rate (eGFR) was not independently associated with serum zinc levels. Instead, serum albumin (t = 4.69, P < 0.01), hemoglobin (t = 2.54, P = 0.01) and mean corpuscular volume (MCV) (t = - 2.20, P = 0.03) were independently associated with serum zinc. In sensitivity analyses, serum zinc was not associated with either serum copper- or iron-related parameters. CONCLUSION: This large-scale study clarified the prevalence of zinc deficiency among non-dialyzed Japanese subjects. In addition, eGFR was not independently associated with serum zinc, probably due to confounding factors, such as nutritional status and degree of anemia. Further investigations are needed to clarify the epidemiology of zinc deficiency and its associations with CKD.

Acute tubulointerstitial nephritis associated with antineutrophil cytoplasmic antibody following cimetidine treatment: a case report.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis usually induces rapidly progressive glomerulonephritis, including pauci-immune necrotizing crescentic glomerulonephritis. Acute tubulointerstitial nephritis (ATIN), which is often drug-induced, is a frequent cause of kidney injury. However, ATIN associated with ANCA without any glomerular lesions has been rarely reported, and drug-induced ATIN associated with ANCA is not well recognized. Here we present a case of an older woman with ATIN associated with myeloperoxidase-ANCA (MPO-ANCA) following cimetidine treatment. CASE PRESENTATION: A 70-year-old woman was admitted to our hospital due to acute kidney injury and mild proteinuria. She had a one-year history of chronic thyroiditis and dyslipidemia, for which she was taking levothyroxine sodium and atorvastatin, respectively. Two weeks before admission she had started cimetidine, methylmethionine sulfonium chloride, and itopride hydrochloride for gastric discomfort persistent since a month. She had experienced fatigue for two weeks and later appetite loss. The patient demonstrated a positive titer for MPO-ANCA (192 IU/mL) and a positive drug-induced lymphocyte stimulation test for cimetidine. She underwent two kidney biopsies that revealed ATIN without any glomerular lesions. Despite discontinuation of cimetidine on admission, renal injury continued with the presence of high MPO-ANCA titer. Oral steroid treatment was closely related with the recovery of her renal function and disappearance of MPO-ANCA. CONCLUSIONS: In this case, ATIN presented as sustained renal insufficiency and high MPO-ANCA titer despite withdrawal of cimetidine. Therefore, we reason that the development of ANCA-associated ATIN was caused by cimetidine. Serologic follow-up with measurement of MPO-ANCA titers and renal biopsy are recommended when the clinical history is inconsistent with the relatively benign course of drug-induced ATIN.

Factors affecting the relationship between ionized and corrected calcium levels in peritoneal dialysis patients: a retrospective cross-sectional study.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) management in patients with end-stage renal disease is important owing to the risk of cardiovascular diseases. In clinical practice, we manage patients not by monitoring the levels of biologically active ionized calcium (iCa) but by monitoring total serum calcium or corrected calcium (cCa). We previously reported that iCa/cCa ratio was different between patients with hemodialysis and those with peritoneal dialysis (PD). In PD patients, several factors are expected to affect iCa/cCa ratio. Therefore, modifying the strategy to achieve better CKD-MBD management might be necessary; however, no reports have studied this to date. Therefore, we investigated the factors influencing iCa/cCa ratio in PD patients. METHODS: This retrospective cross-sectional study examined background and laboratory data, including iCa, collected at routine outpatient visits. The patients were divided into the first, second, and third tertile of iCa/cCa ratio groups to compare patient background and laboratory data. Multiple regression analysis was used to investigate the factors influencing iCa/cCa ratio. We used multiple imputation to deal with missing covariate data. RESULTS: In total, 169 PD patients were enrolled. In PD patients with lower iCa/cCa ratio, PD duration was longer and pH was higher. Urine volume and weekly renal Kt/V were lower in the patients with lower iCa/cCa ratio than in those with higher iCa/cCa ratio. iCa/cCa ratio and weekly renal Kt/V were directly correlated (r = 0.41, p < 0.01), and weekly renal Kt/V and pH were independent factors affecting iCa/cCa ratio (t = 2.86, p < 0.01 and t = - 5.42, p < 0.01, respectively). CONCLUSIONS: iCa levels were lower in PD patients with lower residual renal function (RRF) even though their cCa levels were equal to those with maintained RRF, warranting caution in the assessment and management of CKD-MBD in PD patients.

Clinical outcome of incident peritoneal dialysis patients with diabetic kidney disease.

BACKGROUND: Although peritoneal dialysis (PD) is becoming more widespread, PD among diabetic patients carries some concerns, such as worsened glycemic control due to constant exposure to glucose and operational errors due to diabetic complications. However, several technical advances could overcome these disadvantages. We, therefore, aimed to compare technical and patient survival between diabetic and non-diabetic PD patients. METHODS: We conducted a historical cohort study of 103 patients (mean age, 57 ± 16 years; 75 males, 32 diabetic patients) who started PD between January 2011 and January 2016. Kaplan-Meier survival analysis was used to compare technical and patient survivals between diabetic and non-diabetic patients. Multivariate Cox regression analysis was used to estimate the effects of the presence of diabetes on these outcomes. RESULTS: Technical and patient survivals did not differ significantly between groups (P = 0.62, P = 0.34, respectively). In addition, presence of diabetes affected neither technical nor patient survival in multivariate analysis (hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.58-2.82 and HR 0.80; 95% CI 0.22-2.68, respectively). CONCLUSIONS: Technical and patient survivals of diabetic PD patients were not inferior to those of non-diabetic PD patients. These results suggest that no hesitation is warranted in initiating PD for diabetic patients with end-stage renal disease.

Interventional nephrology: current status and clinical impact in Japan.

BACKGROUND: Current status and clinical significance of interventional nephrology has not been reported from Japan. METHODS: Questionnaires were mailed twice to the directors of all 534 Japanese certificated nephrology training institutions in 2014. The main questions were current performance, categorized annual procedure volume and managers of peritoneal dialysis (PD) access, vascular access (VA) surgery, endovascular intervention, and kidney biopsy. Frequencies of nephrologist involvement between high volume center and low volume center and association between the level of nephrologists' involvement to each procedure and annual procedure volume were examined. RESULTS: 332 (62.2%) institutions answered performance of all procedures and 328 (61.4%) institutions answered all procedure volume. Kidney biopsy, VA surgery, endovascular intervention and PD access surgery were performed by any doctors in 94.2, 96.3, 88.4, and 76.2% and each involvement of nephrologist was 93.9, 54.1, 53.1 and 47.6%, respectively. Cochran-Armitage analyses demonstrated significant increases in all 4 procedure volume with greater management by nephrologists (p < 0.01). Nephrologists involvement to VA surgery associated with procedure volume increase in not only VA surgery, but also PD catheter insertion (p < 0.01) and kidney biopsy (p < 0.05). And nephrologists involvement to PD catheter insertion also associated with surgical volume increase in both VA surgery (p < 0.01) and endovascular intervention (p < 0.05). CONCLUSIONS: Main manager of all 4 procedures was nephrologist in Japan. Each procedure volume increased as nephrologists become more involved. Acquisition of one specific procedure by nephrologist associated with increase not only in this specific procedure volume, but also the other procedure volume.

Gender interaction of uric acid in the development of hypertension.

AIM: The present study explored the gender interaction on the risk of uric acid in the new development of hypertension. STUDY DESIGN: A longitudinal retrospective cohort. SUBJECTS & METHODS: A total of 5,807 individuals with an average age of 38 ± 7 years old were recruited. Individuals whose blood pressure rose more than 140/90mmHg or those who newly commenced antihypertensive treatment were defined as a new onset of hypertension. Cox regression analysis was employed for the analysis. RESULTS: During the 10-years follow-up, 42.8% of men and 22.2% of women had developed hypertension. Factors to predict the hypertension development were male gender, older age, higher BMI, higher uric acid, and higher mean blood pressure. An association between higher uric acid levels and higher incidence of hypertension remained statistically significant in women in a multivariate model adjusted for various clinical variables (Hazard ration (HR), 1.180; 95%CI, 1.018 to 1.369), whereas such association was not found in men (HR, 1.034; 95%CI, 0.994 to 1.075). The interaction between the two genders reached statistical significance (p for interaction = 0.007). CONCLUSION: Higher uric acid is associated with the incident hypertension in the both genders. Women are more susceptible to the development of hypertension than men.

Usefulness of combination therapy with Daclatasvir plus Asunaprevir in chronic hepatitis C patients with chronic kidney disease.

AIM: Combination therapy with Daclatasvir (DCV) plus Asunaprevir (ASV) has been proven effective in patients with chronic hepatitis C virus (HCV) infection. However, little is known as to the effect of this therapy in patients with reduced renal function. Focusing on CKD patients whose renal function has declined, the present trial addresses the efficacy and safety of this combination therapy in CKD patients with reduced estimated glomerular filtration rate (eGFR). MATERIALS AND METHODS: The study design is a single-center, retrospective longitudinal observational study enrolling 106 patients with (n = 29) or without (n = 77) CKD. After the treatment with combined DCV with ASV for chronic HCV genotype 1b, patients were followed for a total of 48 weeks and the comparison was made in clinical parameters between the two groups. RESULTS: (1) The majority of patients in both groups achieved sustained virological response at 24 weeks (90.8 % in the non-CKD group, and 93.1 % in the CKD). (2)The reduction rate in HCV-RNA levels 2 weeks after commencing the treatment was faster in the CKD group than that in the non-CKD group (81.8 vs. 79.2 %, p < 0.01). (3) Three patients in the CKD group and 6 patients in the non-CKD group withdrew from the treatment because of the adverse events. CONCLUSION: Combination therapy with DCV plus ASV for chronic HCV genotype 1b infection is useful and tolerable, not only in patients with normal eGFR, but also in those with CKD with declined eGFR. Viral eradication at an early phase of the treatment appears to be faster in CKD patients.

Possible prevention of uremic nausea by vitamin D receptor activators in non-dialysis patients with stage 5 chronic kidney disease.

BACKGROUND: Nausea is a major uremic symptom and a frequent indication for starting dialysis. However, preventive medication for uremic nausea has not yet been identified. Vitamin D receptor activators (VDRAs) may prevent uremic nausea via their pleiotropic actions. The objective of this study was to explore whether VDRA administration during the predialysis period is associated with a reduced prevalence of uremic nausea just prior to beginning dialysis. METHODS: A multicenter, retrospective, cross-sectional study was performed to identify a medication to prevent uremic nausea. Patients with stage 5 CKD who were followed-up over 3 months were included. The primary outcomes examined were the prevalence of uremic nausea, congestive heart failure (CHF), and intractable edema at dialysis commencement. The predictor variable was VDRA use during the predialysis period. RESULTS: One thousand five hundred and thirty six patients who had just begun dialysis in nine Japanese facilities between January 2006 and October 2013 were included. Two hundred and thirty (15.0%) patients had commenced dialysis because of uremic nausea, and three hundred and ninety two (25.5%) patients had been using VDRAs before initiating dialysis. Logistic regression analysis showed that, among the medications examined in this study, only VDRA use was independently associated with a lower frequency of uremic nausea (OR 0.512, 95% CI 0.347-0.738, P = 0.0003). On the other hand, CHF and intractable edema were not associated with VDRA administration. CONCLUSION: Use of VDRAs during the predialysis period was the only factor associated with a lower prevalence of uremic nausea, suggesting that VDRAs may prevent uremic nausea in patients with advanced CKD.

Risk factors for encapsulating peritoneal sclerosis: Analysis of a 36-year experience in a University Hospital.

AIM: Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication that occurs in peritoneal dialysis (PD) therapy. The present study aimed to identify the risk factors, especially peritonitis and biocompatible PD fluid. METHODS: The study included 703 patients who received PD between January 1980 and March 2015 at two centres. The patients were divided into two groups: those who had developed EPS (EPS group: n = 44) and those who had no documentary evidence of EPS (non-EPS group: n = 659). The independent risks of EPS were determined by univariate and multivariate logistic models. RESULTS: Encapsulating peritoneal sclerosis occurred in 44/703 (6.3%) patients between January 1980 and March 2015. In multivariate logistic models of risk factors correlated with EPS, dialysate to plasma creatinine ratio (D/P Cr) by peritoneal equilibration test (PET) and history of peritonitis were risk factors for EPS development (P < 0.01, respectively) in addition to PD duration. Especially, total duration of peritonitis, defined by period between onset and resolution of peritonitis, was an important risk factor for EPS development in patients with a history of peritonitis. Receiver operating characteristic (ROC) curve analysis revealed that cut-off point for EPS development was 36 days. Moreover, biocompatible PD fluid contributed to decreased EPS development. CONCLUSION: Both the longer duration of peritonitis and higher D/P Cr, as well as the longer PD duration, were risk factors for EPS development. Furthermore, use of biocompatible PD fluid contributed to the decrease in EPS development.

Influence of Left Ventricular Ejection Fraction on the Effects of Supplemental Use of Angiotensin Receptor Blocker Olmesartan in Hypertensive Patients With Heart Failure.

BACKGROUND: There is no robust evidence of pharmacological interventions to improve mortality in heart failure (HF) patients with preserved left ventricular ejection fraction (LVEF) (HFpEF). In this subanalysis study of the SUPPORT Trial, we addressed the influence of LVEF on the effects of olmesartan in HF. METHODS AND RESULTS: Among 1,147 patients enrolled in the SUPPORT Trial, we examined 429 patients with reduced LVEF (HFrEF, LVEF <50%) and 709 with HFpEF (LVEF ≥50%). During a median follow-up of 4.4 years, 21.9% and 12.5% patients died in the HFrEF and HFpEF groups, respectively. In HFrEF patients, the addition of olmesartan to the combination of angiotensin-converting enzyme inhibitor (ACEI) and ß-blocker (BB) was associated with increased incidence of death (hazard ratio (HR) 2.26, P=0.002) and worsening renal function (HR 2.01, P=0.01), whereas its addition to ACEI or BB alone was not. In contrast, in HFpEF patients, the addition of olmesartan to BB alone was significantly associated with reduced mortality (HR 0.32, P=0.03), whereas with ACEIs alone or in combination with BB and ACEI was not. The linear mixed-effect model showed that in HFpEF, the urinary albumin/creatinine ratio was unaltered when BB were combined with olmesartan, but significantly increased when not combined with olmesartan (P=0.01). CONCLUSIONS: LVEF substantially influences the effects of additive use of olmesartan, with beneficial effects noted when combined with BB in hypertensive HFpEF patients. (Circ J 2016; 80: 2155-2164).

The differences in acid-base status and the calcium parathyroid axis between peritoneal dialysis and hemodialysis.

BACKGROUND: Several guidelines have set the target levels of serum Ca, phosphorus, and parathyroid hormone (PTH) for better management of chronic kidney disease-mineral and bone disorders (CKDMBD) in dialysis patients. Although serum ionized Ca (iCa) is a biologically active component, corrected Ca (cCa) is used in clinical settings. However, the association between iCa and cCa is affected by acid-base status. We investigated the difference in acid-base and the calcium-parathyroid status between hemodialysis (HD) and peritoneal dialysis (PD). METHODS: The markers associated with CKD-MBD were measured in 142 patients receiving chronic dialysis (69 on PD and 73 on HD). RESULTS: Serum bicarbonate levels were significantly higher in the PD group than in the HD group (26.6 ± 2.8 vs. 22.9 ± 2.0 mEq/L, p < 0.01). The serum iCa levels and the iCa/cCa ratio were significantly lower in the PD group than in the HD group (iCa 1.07 ± 0.08 vs. 1.14 ± 0.08 mmol/L, p < 0.01; iCa/cCa ratio 45.5 ± 3.1% vs. 49.7 ± 3.2%, p < 0.01). The cCa levels were significantly higher in the PD group than in the HD group (9.4 ± 0.4 vs. 9.1 ± 0.4 mg/dL, p < 0.01). Intact PTH levels were significantly higher in the PD group than in the HD group (220 (40 - 581) vs. 133 (30 - 666) pg/mL, p < 0.01). CONCLUSIONS: We found that PD patients had lower iCa and higher PTH levels despite higher cCa levels as compared to HD patients. These results suggested that the assessment of both Ca and PTH should be different between PD and HD.

Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial.

We examined whether an additive treatment with an angiotensin receptor blocker, olmesartan, reduces the mortality and morbidity in hypertensive patients with chronic heart failure (CHF) treated with angiotensin-converting enzyme (ACE) inhibitors, ß-blockers, or both. In this prospective, randomized, open-label, blinded endpoint study, a total of 1147 hypertensive patients with symptomatic CHF (mean age 66 years, 75% male) were randomized to the addition of olmesartan (n = 578) to baseline therapy vs. control (n = 569). The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, non-fatal stroke, and hospitalization for worsening heart failure. During a median follow-up of 4.4 years, the primary endpoint occurred in 192 patients (33.2%) in the olmesartan group and in 166 patients (29.2%) in the control group [hazard ratio (HR) 1.18; 95% confidence interval (CI), 0.96-1.46, P = 0.112], while renal dysfunction developed more frequently in the olmesartan group (16.8 vs. 10.7%, HR 1.64; 95% CI 1.19-2.26, P = 0.003). Subgroup analysis revealed that addition of olmesartan to combination of ACE inhibitors and ß-blockers was associated with increased incidence of the primary endpoint (38.1 vs. 28.2%, HR 1.47; 95% CI 1.11-1.95, P = 0.006), all-cause death (19.4 vs. 13.5%, HR 1.50; 95% CI 1.01-2.23, P = 0.046), and renal dysfunction (21.1 vs. 12.5%, HR 1.85; 95% CI 1.24-2.76, P = 0.003). Additive use of olmesartan did not improve clinical outcomes but worsened renal function in hypertensive CHF patients treated with evidence-based medications. Particularly, the triple combination therapy with olmesartan, ACE inhibitors and ß-blockers was associated with increased adverse cardiac events. This study is registered at clinicaltrials.gov-NCT00417222.

Serum uric acid and the incidence of CKD and hypertension.

BACKGROUND: Uric acid (UA) levels correlate positively with the prevalence of chronic kidney disease (CKD) and/or hypertension. We tested the hypothesis that UA may also have a link to a new incidence of CKD and hypertension. METHODS: Study design is a cohort study and the predictor is UA levels. Of the 15,470 screened cases, 8223 participants without CKD were eligible for the analysis of the incidence of CKD. Among these CKD candidates, 7569 participants were eligible for the analysis of the new development of hypertension. The observation period was 4 years. RESULTS: Relationship of UA with new cases of CKD. Higher UA levels had a closer association with the new development of CKD; 1.1 % (UA < 5 mg/dL), 1.5 % (5.0-5.9 mg/dL), 1.7 % (6.0-6.9 mg/dL), and 3.4 % (≧7 mg/dL), respectively (p < 0.001 by the Chi-square test). Cox proportional hazard analysis showed that the estimates of the CKD development were eGFR [Hazard Ratio (HR) 0.816, 95 % confidence intervals (CI) 0.791-0.840] and male gender (HR 0.562, 95 % CI 0.322-0.982). UA levels and new development of hypertension. Higher UA levels had a closer association with the new development of hypertension; 5.0 % (UA < 5 mg/dL), 8.9 % (5.0-5.9 mg/dL), 10.6 % (6.0-6.9 mg/dL), and 11.8 % (≧7 mg/dL), respectively (p < 0.001 by the Chi-square test). Cox proportional hazard analysis showed that the estimates of the hypertension development were BMI (HR 1.190, 95 % CI 1.155-1.226), age (HR 1.021, 95 % CI 1.010-1.032), HDL-cholesterol (HR 1.013, 95 % CI 1.007-1.019), male gender (HR 1.791, 95 % CI 1.338-2.395), UA level (HR 1.112, 95 % CI 1.024-1.207), and eGFR (HR 1008, 95 % CI 1.002-1.013). Furthermore, the logistic analysis showed that the odds ratio (OR) to estimate hypertension in the high UA group (UA ≧ 7 mg/dL; OR 1.33, 95 % CI 1.01-1.80) was greater than that in the low UA group (UA < 5 mg/dL). Kaplan-Meier analysis also confirmed the finding that the higher the UA levels the greater the hypertension development (p < 0.001 by the Log-rank test and Cox proportional hazard analysis). CONCLUSION: High UA levels are associated with the new development of hypertension, but not with the incidence of CKD.

A higher serum alkaline phosphatase is associated with the incidence of hip fracture and mortality among patients receiving hemodialysis in Japan.

BACKGROUND: Monitoring of serum alkaline phosphatase (ALP) is recommended in the management of chronic kidney disease-mineral and bone disorder (CKD-MBD). However, unlike calcium, phosphate or parathyroid hormone, the relationship between serum ALP and patient outcome receiving hemodialysis (HD) in Japan is unknown. METHODS: Baseline data of 185 277 HD patients with duration >90 days (66 ± 12 years, males 61.9%, and median HD duration of 5.8 years) were extracted from a nationwide dialysis registry at the end of 2009 in Japan. Outcomes were then evaluated using the registry at the end of 2010 using a multivariate logistic regression analysis. RESULTS: During 1-year follow-up, 14 230 (7.9%) patients died of all causes, including 6396 (3.6%) cardiovascular deaths. In addition, 1586 patients (1.0%) were newly diagnosed as hip fractures. All-cause and cardiovascular mortality and the incidence of hip fracture were higher in line with the increase in baseline serum ALP. On multivariate analysis, patients with the highest ALP quartile had higher all-cause and cardiovascular mortalities and a higher incidence of hip fracture than those with the lowest quartile [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.33-1.60; OR 1.25, 95% CI 1.10-1.42; and OR 1.71, 95% CI 1.33-2.18, respectively]. CONCLUSIONS: In this large cohort study, higher serum ALP levels were independently associated not only with mortality but also with the incidence of hip fracture in Japanese HD patients. Further study is needed to test whether serum ALP measurements could improve the patient outcomes.

Combined therapy with peritoneal dialysis and hemodialysis: a multicenter retrospective observational cohort study in Japan.

BACKGROUND/AIMS: Combining peritoneal dialysis (PD) and hemodialysis (HD) has been common treatment option in Japan. METHODS: In this retrospective, multicenter, observational study, the clinical characteristics and outcomes of 104 patients (57 ± 11 years, males 72%) who had switched from PD alone to combined therapy with PD and HD were studied. Clinical parameters were measured at baseline and after 3 months of combined therapy. RESULTS: At baseline, urine volume, dialysate-to-plasma ratio of creatinine (D/P Cr), and total Kt/V were 150 ml/day (range: 0-2,000 ml/day), 0.67 ± 0.11, and 1.8 ± 0.4, respectively. During the first 3 months of combined therapy, body weight, urine volume, serum creatinine level, and D/P Cr decreased, whereas hemoglobin levels increased. CONCLUSIONS: In patients where PD does not result in acceptable outcomes, combined therapy with PD and HD may have potential benefits in terms of dialysis adequacy and hydration status. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=368389

HGPD: Human Gene and Protein Database, 2012 update.

The Human Gene and Protein Database (HGPD; http://www.HGPD.jp/) is a unique database that stores information on a set of human Gateway entry clones in addition to protein expression and protein synthesis data. The HGPD was launched in November 2008, and 33,275 human Gateway entry clones have been constructed from the open reading frames (ORFs) of full-length cDNA, thus representing the largest collection in the world. Recently, research objectives have focused on the development of new medicines and the establishment of novel diagnostic methods and medical treatments. And, studies using proteins and protein information, which are closely related to gene function, have been undertaken. For this update, we constructed an additional 9974 human Gateway entry clones, giving a total of 43,249. This set of human Gateway entry clones was named the Human Proteome Expression Resource, known as the 'HuPEX'. In addition, we also classified the clones into 10 groups according to protein function. Moreover, in vivo cellular localization data of proteins for 32,651 human Gateway entry clones were included for retrieval from the HGPD. In 'Information Overview', which presents the search results, the ORF region of each cDNA is now displayed allowing the Gateway entry clones to be searched more easily.