Association between phosphate binder pill burden and mortality risk in patients on maintenance hemodialysis: a single-center cohort study with 7-year follow-up of 513 patients.

BACKGROUND: Dialysis patients often take multiple oral medications, leading to a high pill burden. Phosphate binders (PBs) account for a large proportion of this daily pill burden (DPB). The relationship between DPB and mortality risk remains unclear, and we hypothesized that this relationship might be influenced by the proportion of PBs to all medications. METHODS: We divided DPB into those derived from PBs and non-PB drugs and analyzed the association with mortality risk over a 7-year period in 513 chronic hemodialysis patients using a baseline model. RESULTS: The median (interquartile range) DPB from all drugs was 15.8 (11.2-21.0) pills/day/patient, and the median ratio of PB pills to all drug pills was 29.3 (13.7-45.9)% at baseline. During a median observation period of 5.2 years, 161 patients (31.4%) died. Kaplan-Meier analysis showed no significant difference in all-cause mortality between PB users and non-users. However, a significant survival advantage was observed in the highest tertile of DPB from PBs compared to the lowest tertile. Conversely, the highest tertile of DPB from non-PB drugs was associated with worse survival. Consequently, the highest tertile of the ratio of PBs to all pills was associated with better survival. This association remained significant even after adjusting for patient characteristics in the Cox proportional hazards model. However, when serum nutritional parameters were included as covariates, the significant association disappeared. CONCLUSIONS: Dialysis patients prescribed a higher rate of PB pills to all medications exhibited a lower mortality risk, possibly due to their better nutritional status.

Measurement of serum remnant-like lipoprotein particle-triglyceride (RLP-TG) and RLP-TG/total TG ratio using highly sensitive triglyceride assay reagent.

BACKGROUND: Serum concentration of remnant-like lipoprotein particles (RLP) have been measured by cholesterol as RLP-C for clinical diagnostic purpose. However, the measurement of TG in RLP and the ratio of RLP-TG/total TG has not been well established. METHOD: Highly sensitive triglyceride assay reagent (TG-EX) was used for RLP-TG assay and compared with the previously used TG reagent (Determiner LTGII). Sera in health check-up populations, cardiovascular disease, diabetes and oral fat load cases were used for the evaluation of the new RLP-TG assay. Serum TC, TG, HDL-C, LDL-C and RLP-C concentrations were also determined in above cases. RESULTS: The detection limit of new RLP-TG using TG-EX was 2.0mg/dl. The within-run imprecision (n=10) was CV=3.0% (RLP-TG: 4.1 mg ± 0.7 mg/dl), CV = 1.4% (RLP-TG: 42.0 ± 0.6 mg/dl) and CV=0.5% (RLP-TG: 100.6 ± 0.6 mg/dl). Cut-off value (75 percentile) of RLP-TG determined in the fasting Japanese population was 13.1mg/dl in men and 9.9 mg/dl in women. In patients with metabolic syndrome, cardiovascular disease and diabetes, RLP-TG levels were significantly higher than those in normal control subjects. RLP-TG levels increased significantly after an oral fat load and the ratio of RLP-TG/total TG increased > 3-fold compared to the ratio in the fasting state. Approximately 80% of TG increased after an oral fat load was TG derived from remnant lipoproteins. CONCLUSION: Normal range of plasma RLP-TG in the fasting Japanese population was first determined using a highly sensitive TG assay reagent. RLP-TG was shown to be higher in cases with metabolic syndrome, cardiovascular disease, etc and a better marker than RLP-C for the measurement of postprandial remnant lipoproteins, together with total TG for RLP-TG/total TG ratio.

Serum fibroblast growth factor-23 levels and progression of aortic arch calcification in non-diabetic patients on chronic hemodialysis.

AIM: Vascular calcification is a cause of cardiovascular death in hemodialysis (HD) patients. The aim of the present study was to evaluate the relationship between the progression of aortic arch calcification (AoAC) and serum fibroblast growth factor (FGF)-23. METHODS: The enrolled study subjects were 127 (83 men and 44 women) HD patients. Calcification of the aortic arch was semiquantitatively estimated with a score (AoACS) on plain chest radiology. Change in AoACS (ΔAoACS) was obtained by subtracting the baseline AoACS value from the follow-up AoACS value. The second assessment was performed from 5 years after the first determination. RESULTS: The percentage of male gender in non-progressors (58.5%) was lesser than in regressors (60.0%) and progressors (74.6%). In addition, the dialysis duration in regressors (14.1±5.1 years) was shorter than in non-progressors (19.5±7.0 years) and progressors (16.8±7.5 years). Interestingly, the serum FGF-23 level in regressors (39225.5±9247.9 pg/mL) was significantly higher than in non-progressors (12896.5±26323.5 pg/mL) and progressors (14062.4±18456.8 pg/mL). Multi-ple regression analyses showed male gender (ß value=0.969, F=5.092, p=0.0192), serum levels of albumin (ß value=-1.395, F=4.541, p=0.0296) and log FGF-23 (ß value=-0.001, F=7.273, p=0.0115) to be significant independent determinants of ΔAoACS. CONCLUSION: Changes in AoAC evaluated by using a simple chest radiograph are associated with serum FGF-23 levels. Excess accumulation of FGF-23 in serum may enable to inhibit the calcification process in vessel walls in chronic HD patients.

Relation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left atrial volume index to left ventricular function in chronic hemodialysis patients.

Cardiovascular disease is the major cause of death in hemodialysis (HD) patients. We investigated the relation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left atrial volume index (LAVi) to left ventricular function in chronic HD patients. A total of 117 patients were enrolled as subjects (74 men and 43 women). Echocardiography was performed to evaluate the left atrial volume index (LAVi) and left ventricular mass index (LVMI). Diastolic left ventricular function was estimated as E/E' by tissue Doppler imaging with cardiac ultrasonography. Serum NT-proBNP was measured at the time of echocardiographic measurements. Multiple regression analysis showed that LAVi (F = 24.372, p < 0.0001) and E/E' (F = 23.473, p < 0.0116) were significant predictors for serum NT-proBNP levels, and LVMI (F = 46.807, p < 0.0001) was a best predictor for LAVi among associated factors. These findings suggest that serum NT-proBNP and LAVi are both good biomarkers for predicting the LV remodeling in chronic HD patients.

Relationship of high-molecular-weight adiponectin levels to visceral fat accumulation in hemodialysis patients.

OBJECTIVE: High molecular weight adiponectin (HMW ADPN) plays an important role in the regulation of insulin resistance and atherogenic processes. However, the role of HMW ADPN remains to be determined in hemodialysis (HD) patients. PATIENTS AND METHODS: We measured serum HMW ADPN in 49 HD patients (age: 62.4+/-12.0 years, time on HD: 8.4+/-6.4 years, male/female=30/19), and examined the association between HMW ADPN and visceral fat area (VFA) estimated by abdominal CT scans. RESULTS: Serum HMW ADPN concentrations were weakly and inversely correlated with serum TG (r=-0.271, p=0.0598), but significantly and positively correlated with HDL cholesterol (r=0.392, p=0.0050). Serum HMW ADPN levels were positively correlated with BMI (r=0.472, p=0.0084) in male patients, and the HMW ADPN levels were positively correlated with serum levels of HDL cholesterol (r=0.514, p=0.0243) and TG (r=0.605, p=0.0061).The regression coefficient between VFA and HMW ADPN was -0.491 (p<0.003). Multiple stepwise regression analyses showed that VFA was the most significant and independent determinant of serum HMW ADPN concentration. CONCLUSION: These findings suggest that HMW ADPN may be inversely associated with visceral fat accumulation in HD patients.

Ruptured arterial aneurysm of the kidney in a patient with microscopic polyangiitis.

We present the case of a 55-year-old man with ruptured arterial aneurysm accompanied by microscopic polyangiitis in the kidney. He was admitted to our hospital because of general fatigue, fever and serious numbness of his extremities. Microscopic polyangiitis (MPA) was diagnosed on the basis of cardinal symptoms, including rapidly progressive glomerular nephritis, peripheral nerve disorder and the lung abnormality, as well as positive MPO-ANCA findings. Hemodialysis had to be started on admission because of renal failure. Renal biopsy demonstrated necrotizing glomeruli, crescent formation with interstitial infiltrates. There were no immune deposits on immunofluorescence study or electron micrographs. The pathological diagnosis was necrotizing glomerulonephritis involving small and medium-sized arteries. He was treated with intravenous semi-pulse methylprednisolone therapy because of the intensely pathological renal activation and the abnormal shadow on chest X-ray. The inflammatory reaction subsequently improved, MPO-ANCA decreased and the lung lesions diminished. He complained of sharp pain of sudden onset on his left side. His hemoglobin dropped from 9.8 g/dl to 6.0 g/dl developed in the subsequent hours, but there were no sign of hemorrhage. Abdominal CT scan showed a large left-sided perinephric, intracapsular hematoma. Selective arterial angiography showed multiple aneurysms in renal and hepatic arteries. No active bleeding was present and he recovered with transfusion, supportive therapy and monitoring alone. Multiple aneurysms detected by angiography in the renal and hepatic arteries showed improvement. He is currently stable on regular hemodialysis treatment with a low dose of oral prednisolone.

Anti-glomerular basement membrane antibody disease with granulomatous lesions on renal biopsy.

We present the case of a 56-year-old woman with anti-glomerular basement membrane (anti-GBM) antibody disease accompanied by granulomatous reaction in the kidney. Three months prior to admission to our kidney center, she had suffered from interstitial pneumonia and had a slightly elevated level of MPO-ANCA (13 EU). Her serum level of creatinine was normal (0.72 mg/dl) but proteinuria (1+) and hematuria (2+, 1-4/HF) were present. She was admitted to our hospital because of general fatigue, loss of appetite, high fever (over 38.5 degrees C) and a rapid decline in renal function (creatinine 8.50 mg/dl). Hemodialysis therapy was started immediately after admission. The serological study was negative for MPO-ANCA and PR3-ANCA but positive for anti-GBM antibody (139 EU). Renal biopsy demonstrated necrotizing glomeruli, cellular crescents and grauloma formation with multinucleated giant cells. Immunofluorescence microscopy revealed linear staining of IgG and C3. We diagnosed graulomatous, crescentic and necrotizing glomerulonephritis, patho-logically. She was diagnosed as having anti-GBM antibody disease because alveolar hemorrhage was absent. Steroid therapy including methylprednisolone pulse therapy (500 mg/day, 3 days) and 2 courses of plasma exchange were effective in reducing the fever, anti-GBM antibody titer and C-reactive protein level. Her renal function recovered and she was able to quit hemodialysis therapy 68 days after the start of hemodialysis and she has shown no signs of pulmonary alveolar hemorrhage to date. The present case suggests that intensive therapy may restore renal function in anti-GBM disease even though renal function was sufficiently damaged and required hemodialysis therapy and active pathological changes were observed in renal biopsy specimens.