Hypercholesterolemia promotes early renal dysfunction in apolipoprotein E-deficient mice  

Camille M Balarini, Mariana ZT Oliveira, Thiago MC Pereira, Nyam F Silva, Elisardo C Vasquez, Silvana S Meyrelles andAgata L Gava

Published: 26 November 2011   Lipids in Health and Disease 2011, 10:22doi:10.1186/1476-511X-10-220

Abstract

Background

Aging and dyslipidemia are processes which can lead to deleterious consequences to renal function. Therefore, the aim of this study was to determine the effects of both hypercholesterolemia and aging on renal function in mice.

Methods

Male hypercholesterolemic apolipoprotein E-deficient mice (ApoE, n=13) and age-matched C57BL/6 control mice (C57, n=15) were studied at 2 (young) and 8 (adult) month-old. At each time point, animals were placed in metabolic cages for 24 hours to urine volume and urinary creatinine quantification. Blood samples were collected for serum cholesterol, urea and creatinine measurements. Glomerular filtration rate (GFR) was estimated through creatinine clearance determination. Mesangial expansion was evaluated by Periodic Acid Schiff staining, renal fibrosis was determined through Masson's trichrome staining and neuronal nitric oxide synthase (nNOS) expression in the kidney was performed by Western Blotting. To statistical analysis two- way ANOVA followed by Fisher's post hoc test was used.

Results

Total plasma cholesterol was increased about 5-fold in ApoE mice at both time points compared to C57 animals. At 2-month-old, GFR was already markedly reduced in ApoE compared to C57 mice (187 +/- 28 vs 358 +/- 92 uL/min, p<0.05). Adult C57 (-77%) and ApoE (-50%) mice also presented a significant reduction of GFR. In addition, serum urea was significantly increased in young ApoE animals compared to C57 mice (11 +/- 1.3 vs 7 +/- 0.9 mmol/L, p<0.01). A significant mesangial expansion was observed at 2-month old ApoE mice compared to C57 mice (35 +/- 0.6 vs 30 +/- 0.9 %, respectively, p<0.05), which was aggravated at 8-month old animals (40 +/- 3 and 35 +/- 3 %, respectively). Tubulointersticial fibrosis was augmented at both young (17 +/- 2%, p<0.05) and adult (20 +/- 1 %, p<0.05) ApoE mice compared to respective C57 age controls (8 +/- 1 and 12 +/- 2%, respectively). The expression of nNOS was markedly reduced in a time-dependent manner in both strains.

Conclusions

These data show that both hypercholesterolemia and aging contribute to the loss of renal function in mice.

Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis

Dimitrios Daoussis¹, Vasileios Panoulas¹, Tracey Toms¹, Holly John¹, Ioannis Antonopoulos¹, Peter Nightingale², Karen MJ Douglas¹, Rainer Klocke¹ and George D Kitas^1,3*

¹Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Pensnett Road, Dudley, West Midlands, DY1 2HQ, UK

²Wolfson Laboratory, Department of Medical Statistics, School of Medicine, University of Birmingham, Queen Elizabeth Medical Centre, Edgbaston, Birmingham, B15 2TH, UK

Arthritis Research & Therapy 2009, 11:R116 doi:10.1186/ar2775


Introduction


Arthritis Research Campaign Epidemiology Unit, University of Manchester, Oxford Road, Stopford Building, Manchester, M13 9PT, UKRecent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment.

Methods

Renal function was assessed in 350 consecutive RA patients by estimated glomerular filtration rate (GFR) using the six-variable Modification of Diet in Renal Disease equation. Risk factors for renal dysfunction were recorded or measured in all participants. Linear regression was used to test the independence of the association between GFR and UA.

Results

Univariable analysis revealed significant associations between GFR and age, systolic blood pressure, total cholesterol, triglycerides, RA duration and UA. UA had the most powerful association with renal dysfunction (r = -0.45, P < 0.001). A basic model was created, incorporating all of the above parameters along with body mass index and gender. UA ranked as the first correlate of GFR (P < 0.001) followed by age. Adjustments for the use of medications (diuretics, low-dose aspirin, cyclooxygenase II inhibitors and nonsteroidal anti-inflammatory drugs) and further adjustment for markers of inflammation and insulin resistance did not change the results.

Conclusions

UA is a strong correlate of renal dysfunction in RA patients. Further studies are needed to address the exact causes and clinical implications of this new finding. RA patients with elevated UA may require screening for renal dysfunction and appropriate management

The Effect of High-Flux Hemodialysis on Hemoglobin Concentrations in Patients with CKD: Results of the MINOXIS Study.

Schneider A, Drechsler C, Krane V, Krieter DH, Scharnagl H, Schneider MP, Wanner C; for the MINOXIS Study Investigators.

Source

Division of Nephrology, University Hospital Würzburg, Würzburg, Germany;

Abstract

Background and objectivesHemodialysis treatment induces markers of inflammation and oxidative stress, which could affect hemoglobin levels and the response to erythropoietin use. This study sought to determine whether high-flux dialysis would help improve markers of renal anemia, inflammation, and oxidative stress compared with low-flux dialysis.Design, settings, participants, &amp; measurementsIn a prospective, controlled study, 221 patients undergoing maintenance hemodialysis and receiving darbepoetin-alfa treatment (mean age, 66 years; 55% male) from 19 centers were screened in a 20-week run-in period of low-flux hemodialysis with a synthetic dialysis membrane. Thereafter, 166 patients were enrolled and randomly assigned to receive a synthetic high-flux membrane or to continue on low-flux dialysis for 52 weeks. Data on myeloperoxidase, oxidized LDL, high-sensitivity C-reactive protein, and the Malnutrition Inflammation Score were collected at baseline and after 52 weeks; routine laboratory data, such as hemoglobin, ferritin, and albumin, and the use of darbepoetin-alfa, were also measured in the run-in period.

Results. After 52 weeks, the low-flux and the high-flux groups did not differ with respect to hemoglobin (mean ± SD, 11.7±0.9 g/dl versus 11.7±1.1 g/dl; P=0.62) or use of darbepoetin-alfa (mean dosage ± SD, 29.8±24.8 μg/wk versus 26.0±31.1 μg/wk; P=0.85). Markers of inflammation, oxidative stress, or nutritional status also did not differ between groups.

Conclusion. Over 1 year, high-flux dialysis had no superior effects on hemoglobin levels or markers of inflammation, oxidative stress, and nutritional status. These data do not support the hypothesis that enhanced convective toxin removal would improve patient outcome.

Clin J Am Soc Nephrol. 2011 Nov 17. [Epub ahead of print]: http://www.ncbi.nlm.nih.gov/pubmed/22096040

Handgrip strength is an independent predictor of renal outcomes in patients with chronic kidney diseases

1. Yu-Tzu Chang1,*, 
2. Hung-Lien Wu2,*, 
3. How-Ran Guo3, 
4. Ya-Yun Cheng3, 
5. Chin-Chung Tseng1,
6. Ming-Cheng Wang1, 
7. Ching-Yuang Lin4 and 
8. Junne-Ming Sung1

1. ¹Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
2. ²Department of Nutrition, National Cheng Kung University Hospital, Tainan, Taiwan
3. ³Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
4. ⁴Children's Medical Center, China Medical University Hospital, Taichung, Taiwan

http://ndt.oxfordjournals.org/content/26/11/3588.

Abstract

Background. In dialysis patients, protein-energy wasting (PEW) is associated with high mortality, and some indicators of PEW, such as serum albumin value, subjective global assessment (SGA) score and handgrip strength (HGS), may predict mortality. However, whether PEW is associated with poor renal outcomes and whether the indicators of PEW can predict renal outcomes in patients with non-dialysis-dependent chronic kidney disease (CKD-ND) is still unclear.

Methods. We enrolled 128 clinically stable patients with CKD-ND and followed up for 33.8 ± 9.2 months. Baseline characteristics, echocardiographic information, laboratory data, HGS, SGA scores, anthropometric parameters, bioimpedance analyses and other indicators of PEW were examined in relation to the risk of reaching renal composite end points of pre-dialysis mortality or dialysis-dependent end-stage renal disease.

Results. Twenty-six patients reached composite renal end points. Multivariate Cox regression analyses showed that HGS was an independent predictor of renal outcome in patients with CKD-ND of Stages 1–5 [CKD_1–5, hazard ratio (HR) = 0.90, P = 0.004] or advanced CKD-ND of Stages 3b [defined as estimated glomerular filtration rate (eGFR) of 30–44 mL/min/1.73m²] to 5 (CKD_3b–5, HR = 0.91, P = 0.031), but not serum albumin, SGA score or other indicators of PEW. When the cutoffs were set at 24.65 kg in men with CKD_1–5, 20.15 kg in men with CKD_3b–5 and 10.15 kg in women with CKD_1–5 or CKD_3b–5, which were deduced from receiver-operating characteristics analyses, patients with lower HGS had significantly poor renal outcomes in Kaplan–Meier survival analyses in all subgroups and higher HR for reaching renal end points in multivariate Cox regression analyses in all subgroups except for women with CKD_3b–5, whose HR had marginal significance (HR = 3.78, P = 0.068) after adjusting for age and eGFR.

Conclusions. This is the first study demonstrating that HGS is an independent predictor of composite renal outcomes in CKD-ND patients. HGS can be incorporated to clinical practice for assessing nutrition status and renal prognosis in patients with CKD-ND

Effect of intradialytic resistance band exercise on physical function in patients on maintenance hemodialysis: a pilot study.

Bullani R, El-Housseini Y, Giordano F, Larcinese A, Ciutto L, Bertrand PC, Wuerzner G, Burnier M, Teta D.

Source

Department of Nephrology, University Hospital (CHUV), Rue du Bugnon 17, Lausanne, Switzerland. Roberto.Bullani@chuv.ch

Abstract

Although physical activity is recommended in patients on maintenance hemodialysis (MHD), randomized controlled trials testing the effects of exercise in this population have given conflicting results. In general, aerobic exercises mostly failed to produce improvements in physical function, whereas resistance exercises, although less studied, appeared to be more promising. The use of sophisticated materials such as leg press and free weights may preclude widespread application of resistance training in patients on MHD. Simple and cheap elastic bands may thus be an attractive alternative. We tested the feasibility of a supervised intradialytic resistance band exercise training program, and its effects on physical function, in patients on MHD. A total of 11 unselected adult patients on MHD from our center, aged 70 ± 10.7 (mean ± standard deviation) years, including 8 men and 3 women, accepted to follow the program under the supervision of qualified physiotherapists. Thirty-six exercise sessions of moderate intensity (twice a week, mean duration 40 minutes each, during 4.5 to 6 months), mainly involving leg muscles against an elastic resistance, were performed. The exercise program was well tolerated and all patients completed it. Statistically significant improvements were observed in the following tests: Tinetti test, 23.9 ± 3.9 points before versus 25.7 ± 3.5 points after the program (P = .022); the Timed Up and Go test, 12.1 ± 6.6 versus 10 ± 5.8 seconds (P = .0156). Improvements in the 6-minute walk distance and in the one-leg balance tests just failed to reach statistical significance. In this single-center pilot study, an intradialytic resistance band exercise program was feasible, well tolerated, and showed encouraging results on physical function.

Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

PMID:

 

21195922

 

[PubMed - indexed for MEDLINE]