Aliskiren add-on therapy effectively reduces proteinuria in chronic kidney disease: an open-label prospective trial.

INTRODUCTION: The combination therapy of aliskiren and renin-angiotensin-aldosterone system (RAAS) blocker in chronic kidney disease (CKD) is controversial. Whether such dual blockade can effectively apply to patients with CKD irrespective of stage and amount of proteinuria remains uncertain. METHODS: We added aliskiren at a dosage of 150 mg/day for six months in 103 Chinese CKD patients who had been treated with angiotensin converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) and still had significant proteinuria or uncontrolled hypertension. Blood pressure, serum creatinine, estimated glomerular filtration rate (eGFR), potassium, and spot urine protein-to-creatinine ratio (UPCR) were measured at three and six months after aliskiren add-on therapy and compared with baseline. RESULTS: The combination of aliskiren and ACEi or ARB significantly reduced UPCR by 23% (p=0.001) and mean arterial pressure by 7.9 ± 13.8 mmHg (p<0.001) at six months. Twenty-five percent of subjects had a greater than 50% reduction in UPCR. No significant changes in eGFR and serum potassium level were noted at six months. CONCLUSIONS: Adding aliskiren on ACEi or ARB in CKD patients, both in diabetes and non-diabetes, has a favorable effect on reducing residual proteinuria and inadequately controlled blood pressure.

Albuminuria, proteinuria, and urinary albumin to protein ratio in chronic kidney disease.

BACKGROUND: Both albuminuria and proteinuria are important disease markers of chronic kidney disease (CKD). Their relationship and the ratio between urinary albumin and protein in patients with CKD have not been investigated. Whether clinical features can affect these measurements is not clear. METHODS: We conducted a cross-sectional study in 602 CKD patients. Demographic data, including age, gender, and co-morbidity such as diabetes, hypertension, hyperuricemia, and hyperlipidemia, were reviewed and recorded. Their urinary albumin, total protein, and creatinine were determined and urinary albumin to creatinine ratio (UACR), total protein to creatinine ratio (UPCR), and albumin to total protein ratio (UAPR) were calculated. Their estimated glomerular filtration rate (eGFR) was calculated according to serum creatinine. The correlation between UACR and UPCR was thus analyzed. We also investigated factors associated with these urinary measurements. RESULTS: UACR and UPCR increased progressively as renal function deteriorated, while UAPR increased to a plateau in CKD stage 4. There was direct relationship between UACR and UPCR. UAPR rose exponentially with the increase of both UACR and UPCR when UACR <500 mg/g or UPCR <1,000 mg/g. Multivariate regression analysis revealed diabetes and hyperuricemia were associated with increased UACR and UPCR, while both urinary parameters were inversely related to male gender and eGFR. Diabetes and hyperuricemia were associated with increased UAPR and UAPR was negatively correlated with age and eGFR. CONCLUSION: There was a significant association between UACR and UPCR in patients with CKD. Characteristics of patients, renal function, and co-morbidities all affected UACR, UPCR, and UAPR.

Proinflammatory cytokines, hepatocyte growth factor and adipokines in peritoneal dialysis patients.

Chronic inflammation is a well-recognized complication in dialysis patients and a potential role of the adipose tissue as an important tissue of origin contributing to inflammation has been proposed. Stable peritoneal dialysis (PD) patients were enrolled to investigate the relationship between serum levels of proinflammatory cytokines and adipokines. Our results revealed that there was a strong association between high sensitivity C-reactive protein and interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) but not with IL-10 and IL-18. IL-6 correlated with TNF-alpha, IL-10, and IL-18. No association was found between IL-10 and IL-18. Adiponectin was positively correlated with all proinflammatory cytokines, except IL-10. No significant association was found between resistin and proinflammatory cytokines. Hepatocyte growth factor (HGF) was directly related to proinflammatory cytokines but not with adipokines. The presence of residual kidney function (RKF) affected IL-6, TNF-alpha, and HGF levels. The peritoneal transport property did not influence inflammatory cytokine and adipokine levels. In conclusion, there was a close relationship between proinflammatory cytokines and adipokines. HGF correlated with proinflammatory cytokines but not with adipokines. The PD-related factors such as RKF, peritoneal property and dialysis glucose load affected levels of proinflammatory cytokines. Body mass index was an important determinant of leptin and adiponectin in PD patients.

Clinical interpretation of reticulocyte hemoglobin content, RET-Y, in chronic hemodialysis patients.

BACKGROUND: Iron deficiency is the most common factor associated with erythropoietin (EPO) hyporesponsiveness. Current iron indices are inadequate to demonstrate the status or utility of iron in erythropoiesis. The aims of this study are to investigate the value of the reticulocyte hemoglobin content, RET-Y, in hemodialysis (HD) patients and compare the levels with conventional iron indices. METHODS: HD patients (n = 289) were divided into 4 groups according to serum ferritin (cutoff value 100 ng/ml) and transferrin saturation (TSAT, cutoff value 20%). The RET-Y value, hemogram and biochemical data were determined and compared between groups. Factors associated with RET-Y were examined. RESULTS: The mean RET-Y value was 1,716 +/- 125 AU. Patients with absolute iron deficiency had lower RET-Y levels and mean corpuscular volume (MCV). Patients with functional iron deficiency had a lower reticulocyte production index and serum albumin levels. MCV, mean corpuscular hemoglobin concentration (MCHC) and albumin were independently correlated with the RET-Y level (all p < 0.001). EPO-independent patients had low iron indices and low RET-Y levels, but a higher reticulocyte production index and albumin levels were noted. CONCLUSION: RET-Y levels in HD patients were close to that of the normal population. Low RET-Y levels were observed in patients with absolute iron deficiency and also in EPO-independent patients with low ferritin and low TSAT. There was a strong association between the serum albumin and RET-Y levels in chronic HD patients.

Association between C-reactive protein and biomarkers of bone and mineral metabolism in chronic hemodialysis patients: a cross-sectional study.

OBJECTIVE: Both chronic inflammation and dysregulation of bone and mineral metabolism are closely related with long-term outcomes of dialysis patients. Our objective was to investigate the relationship between these two abnormalities. DESIGN: This was a cross-sectional study. SETTING: This study was performed at a hospital-based hemodialysis center. PATIENTS: We enrolled 448 (male, 198; female, 250) clinically stable hemodialysis patients. Patients with chronic inflammatory disease, malignancy, or viral hepatitis were excluded. Their age (mean +/- SD) was 57.4 +/- 12.5 years. MAIN OUTCOME MEASURES: Biomarkers, including high-sensitivity C-reactive protein (hsCRP), total calcium, phosphate, and intact parathyroid hormone levels, were measured and compared with the recommended range in the K/DOQI guidelines. Correlations between these parameters were analyzed, and factors independently associated with hsCRP and the calcium phosphate product (Ca x P) were identified by regression analysis. RESULTS: Most patients did not achieve the K/DOQI recommended therapeutic range in the four parameters, and only 50 patients (11%) met their treatment goals. The hsCRP level was directly related to calcium, phosphate, and Ca x P. Patients who achieved the guidelines' range had lower hsCRP levels (1.97 mg/L vs. 2.71 mg/L, P < .05). A high hsCRP level (> or = 10 mg/L) was associated with higher calcium, phosphate, and Ca x P levels, and lower albumin levels. Serum albumin, Ca x P, alkaline phosphatase, and diabetes independently predicted hsCRP levels. CONCLUSION: There is a strong association between chronic inflammation and the disturbance of bone mineral metabolism in chronic hemodialysis patients.

Better sleep quality and less daytime symptoms in patients on evening hemodialysis: a questionnaire-based study.

The aims of this study were to investigate the prevalence of sleep disorders in patients with end-stage renal disease (ESRD), and to assess the effect of dialysis schedule on sleep quality and the presence of daytime symptoms. We prospectively selected 150 long-term hemodialysis (HD) patients in three groups (morning, afternoon, and evening dialysis) and gave them a sleep questionnaire, the Epworth sleepiness scale and the Pittsburgh sleep quality index. Snoring was the most common complaint (56%), followed by insomnia (38%) and restless legs syndrome (22.7%). The evening dialysis group experienced more sleep time in bed (P = 0.02), required less hypnotic medication (P = 0.049), had fewer daytime symptoms (P < 0.01), and experienced less daytime sleepiness (P = 0.034). Our study confirms the high prevalence of sleep disorders in ESRD patients, and indicates a beneficial effect of evening HD on sleep quality and reduction of daytime symptoms.

Leukoencephalopathy associated with dialysis disequilibrium syndrome.

Dialysis disequilibrium syndrome (DDS) is usually seen in severely uremic patients who are dialyzed aggressively. DDS mostly appeared within 24 hours after hemodialysis (HD) and may last for a few hours. This diagnosis is made by the exclusion of other causes including metabolic and intracranial events and has been recognized for more than 40 years. Few reports described the cerebral radiographic features associated with DDS. We present an 83-year-old uremic patient experiencing DDS at initial HD. DDS-related cerebral radiographic manifestations reported in the literature are reviewed, along with a discussion of the role of neuroimaging in the diagnosis of DDS.