Measurement of glomerular filtration rate in obese patients: pitfalls and potential consequences on drug therapy.

Epidemiological studies have shown that obesity is associated with chronic kidney disease and end stage renal disease. These studies have used creatinine derived equations to estimate glomerular filtration rate (GFR) and have indexed GFR to body surface area (BSA). However, the use of equations using creatinine as a surrogate marker of glomerular filtration and the indexation of GFR for BSA can be questioned in the obese population. First, these equations lack precision when they are compared to gold standard GFR measurements such as inulin clearances; secondly, the indexation of GFR for 1.73 m(2) of BSA leads to a systematic underestimation of GFR compared to absolute GFR in obese patients who have BSA that usually exceed 1.73 m(2). Obesity is also associated with pathophysiological changes that can affect the pharmacokinetics of drugs. The effect of obesity on both renal function and drug pharmacokinetics raises the issue of correct drug dosage in obese individuals. This may be particularly relevant for drugs known to have a narrow therapeutic range or excreted by the kidney.

Comparisons of serum vitamin d levels, status, and determinants in populations with and without chronic kidney disease not requiring renal dialysis: a 24-hour urine collection population-based study.

OBJECTIVE: Vitamin D deficiency is frequent in the general population and might be even more prevalent among populations with kidney failure. We compared serum vitamin D levels, vitamin D insufficiency/deficiency status, and vitamin D level determinants in populations without chronic kidney disease (CKD) and with CKD not requiring renal dialysis. DESIGN AND METHODS: This was a cross-sectional, multicenter, population-based study conducted from 2010 to 2011. Participants were from 10 centers that represent the geographical and cultural diversity of the Swiss adult population (≥15 years old). INTERVENTION: CKD was defined using estimated glomerular filtration rate and 24-hour albuminuria. Serum vitamin D was measured by liquid chromatography-tandem mass spectrometry. Statistical procedures adapted for survey data were used. MAIN OUTCOME MEASURE: We compared 25-hydroxy-vitamin D (25(OH)D) levels and the prevalence of vitamin D insufficiency/deficiency (serum 25(OH)D < 30 ng/mL) in participants with and without CKD. We tested the interaction of CKD status with 6 a priori defined attributes (age, sex, body mass index, walking activity, serum albumin-corrected calcium, and altitude) on serum vitamin D level or insufficiency/deficiency status taking into account potential confounders. RESULTS: Overall, 11.8% (135 of 1,145) participants had CKD. The 25(OH)D adjusted means (95% confidence interval [CI]) were 23.1 (22.6-23.7) and 23.5 (21.7-25.3) ng/mL in participants without and with CKD, respectively (P = .70). Vitamin D insufficiency or deficiency was frequent among participants without and with CKD (75.3% [95% CI 69.3-81.5] and 69.1 [95% CI 53.9-86.1], P = .054). CKD status did not interact with major determinants of vitamin D, including age, sex, BMI, walking minutes, serum albumin-corrected calcium, or altitude for its effect on vitamin D status or levels. CONCLUSION: Vitamin D concentration and insufficiency/deficiency status are similar in people with or without CKD not requiring renal dialysis.

Genetic loci influencing kidney function and chronic kidney disease.

Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.

Frequency and impact of autosomal dominant polycystic kidney disease in the Seychelles (Indian Ocean).

BACKGROUND: As little such data is available in African populations, we investigated the prevalence of ADPKD and the impact of the disease in the Seychelles islands, where approximately 65% of the population is of African descent and 30% of Caucasian or mixed descent. METHODS: Prevalent cases were identified over a 3-year period by requesting all the doctors in the country (most of them are employed within a national health system) to refer all presumed or confirmed cases and by systematically examining the family members of all confirmed cases. The diagnosis was based on standard criteria including ultrasonographic findings and family history. RESULTS: Forty-two cases were identified in this population of 74,331 inhabitants, a total prevalence (per 100,000 total population) of 57 (95% CI, 41-76). All but one of the cases were of Caucasian descent so that the prevalence rates of the disease in the populations of Black and Caucasian descents were respectively 2 (0-11) and 184 (132-249). The prevalence rates of the gene(s) carriers were estimated to be 75 (45-117) in the total population respectively 6 (0-33) and 236 (140-372) in the Black and Caucasian populations. Haplotype analysis in 58 cases from three families showed a common DNA fragment in all affected individuals. Cases had significantly higher blood pressure compared to the general population and 21% had serum creatinine higher than 120 mumol/l. Among the established pedigrees, mean age of death between 1960 and 1995 (haemodialysis was introduced in 1992) was younger in subjects with than those without ADPKD (50.5 vs 67.7 years; P < 0.001). CONCLUSIONS: In the Seychelles, ADPKD clusters in the Caucasian population (possibly a founder effect), is rare in individuals of black descent, and is associated with substantial clinical and survival impact.

Bicarbonate de sodium pour ralentir la progression de la maladie rénale chronique [Sodium bicarbonate to slow the progression of chronic kidney disease].

Metabolic acidosis is a prevalent complication in moderate and late stages of chronic kidney disease (CKD). It is established that the correction of metabolic acidosis may improve metabolic bone disorders and protein degradation in the skeletal muscle, two characteristic complications of patients with advanced CKD. In the last 18 months, three randomized controlled trials have drawn the attention on a novel indication to correct metabolic acidosis in these patients, i.e., halting CKD progression. These data show that sodium bicarbonate, a cheap and easily manageable treatment, may delay the progression of CKD and the need of a renal replacement therapy such as dialysis or kidney transplantation.

Nouvelles techniques radiologiques pour les patients insuffisants rénaux [New radiological techniques to investigate patients suffering from chronic kidney disease].

Radiological investigations using gadolinium or intravenous iodinated contrast products are used cautiously in patients suffering from chronic kidney disease because of their risk of acute kidney injury and systemic nephrogenic fibrosis. In this article, we review several radiological alternatives that can be useful to obtain renal anatomical and/or functional information in this patient population. The basic principles, indications, and advantages and limitations of Doppler ultrasound with measurement of the resistance index, contrast-enhanced ultrasound, and a technique called BOLD-MRI (blood-oxygenation level dependent-MRI) are discussed.

Polykystose hépatorénale: développements récents [Recent insights into polycystic kidney disease]

Autosomal dominant polycystic kidney disease is one of the most prevalent genetic diseases and every general practitioner may have to counsel these patients. The follow-up of the patients carrying the trait has changed substantially lately and new treatments have been developed and are close to get approval. We review here the new ultrasound diagnostic criteria, the place of the renal volumetry by MRI in the follow-up, the place of the genetic molecular diagnosis and we discuss the pathogenesis and the future treatment that are in phase III clinical studies and will soon change completely the outcome of the disease.

Calcifications vasculaires et déficit en vitamine K: un facteur de risque modifiable dans l'insuffisance rénale chronique [Vascular calcifications and vitamin K deficiency: a modifiable risk factor in chronic kidney disease].

The mechanisms of vascular calcifications in chronic renal failure are complex. Apart for clotting factors, vitamin K-dependent proteins include matrix Gla protein. Glutamic acid residues in matrix Gla protein are carboxylated by vitamin K-dependent gamma-carboxylase, which enables it to inhibit calcification. The purpose of this review is to discuss available evidence implicating vitamin K as a modifiable risk factor in the pathogenesis of vascular calcification in renal diseases.

Renal tissue oxygenation in essential hypertension and chronic kidney disease.

Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD). In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system) or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.

Anemia and chronic kidney disease are potential risk factors for mortality in stroke patients : a historic cohort study

Rapport de synthèseApproche et objectifL'objectif de la recherche était de préciser les relations existant entre l'insuffisance rénale chronique, l'anémie et l'accident vasculaire cérébral parmi des patients hospitalisés au Centre Hospitalier Universitaire Vaudois (CHUV) pour un accident vasculaire cérébral (AVC). Les auteurs ont déterminé la prévalence de l'anémie et de l'insuffisance rénale chronique parmi ces patients et examiné s'ils sont des facteurs de risque indépendants de la mortalité suite à un AVC.L'insuffisance rénale chronique est associée à un risque élevé de développer un AVC. L'anémie est une complication et une conséquence fréquente qui découle de l'insuffisance rénale chronique et est également un facteur de risque pour les maladies cérébro- et cardiovasculaires.MéthodeLa présente étude de cohorte rétrospective se base sur le registre des AVC du CHUV et inclut tous les patients traités suite à un premier AVC au service de neurologie du CHUV entre les années 2000 et 2003.Les variables utilisées pour l'analyse sont les caractéristiques démographiques, l'insuffisance rénale chronique, le débit de filtration glomérulaire.(GFR), l'anémie et d'autres facteurs de risque d'AVC. Ils ont été récoltés au moyen du système informatique du laboratoire du CHUV, d'entretiens téléphoniques (patients ou proches) et du registre des AVC du CHUV.L'insuffisance rénale chronique a été calculée sur base de la ,,Kidney Disease Outcomes Quality Initiative (K/DOQI)-CKD Classification", laquelle est divisée en cinq stades. L'anémie a été définie par une hémoglobine de < 120g/L pour les femmes et < 130g/L pour les hommes.Les analyses statistiques réalisées sont des tests Chi-carré, des tests de Τ ainsi que des courbes de Kaplan-Meier et le modèle de régression de Cox.RésultatsParmi 890 patients adultes avec un AVC, le GFR moyen était de 64.3 ml/min/1.73 m2, 17% souffraient d'anémie et 10% sont décédés pendant la première année après la sortie de l'hôpital, suite à l'"AVC index". Parmi ceux-ci, 61% avaient une insuffisance rénale chronique de stade 3-5 et 39% de stade 1 ou 2 selon les critères de K/DOQI.D'autre part un taux d'hémoglobine élevé a pu être associé à un risque moins élevé de mortalité un an après la sortie de l'hôpital.Conclusion et perspectiveNous avons constaté que l'anémie ainsi que l'insuffisance rénale chronique sont fréquents parmi les patients souffrant d'un AVC et qu'ils sont des facteurs de risque d'un taux de mortalité élevé après un an. En conséquence, il pourrait être utile de traiter les patients souffrant d'anémie et d'insuffisance rénale dès que possible afin de diminuer les complications et comorbidités résultants de ces maladies.La perspective est de rendre les cliniciens attentif à l'importance de l'insuffisance rénale et de l'anémie parmi les patients ayants développé un AVC, ainsi que d'initier le traitement approprié afin de diminuer les complications, les comorbidités ainsi que les récidives d'un AVC. L'efficacité et l'économicité des interventions visant à améliorer le pronostic chez les patients présentant un AVC et souffrant d'une insuffisance rénale chronique et / ou d'une anémie doivent être évaluées par des études appropriées.

Anemia and chronic kidney disease are associated with poor outcomes in heart failure patients.

BACKGROUND: Chronic kidney disease (CKD) has been linked to higher heart failure (HF) risk. Anemia is a common consequence of CKD, and recent evidence suggests that anemia is a risk factor for HF. The purpose of this study was to examine among patients with HF, the association between CKD, anemia and inhospital mortality and early readmission. METHODS: We performed a retrospective cohort study in two Swiss university hospitals. Subjects were selected based the presence of ICD-10 HF codes in 1999. We recorded demographic characteristics and risk factors for HF. CKD was defined as a serum creatinine > or = 124 956;mol/L for women and > or = 133 micromol/L for men. The main outcome measures were inhospital mortality and thirty-day readmissions. RESULTS: Among 955 eligible patients hospitalized with heart failure, 23.0% had CKD. Twenty percent and 6.1% of individuals with and without CKD, respectively, died at the hospital (p < 0.0001). Overall, after adjustment for other patient factors, creatinine and hemoglobin were associated with an increased risk of death at the hospital, and hemoglobin was related to early readmission. CONCLUSION: Both CKD and anemia are frequent among older patients with heart failure and are predictors of adverse outcomes, independent of other known risk factors for heart failure.

Asymptomatic high flow subclavian steal in a patient with hemodialysis access.

Subclavian steal phenomenon due to proximal subclavian artery stenosis or occlusion is not un-common but often remains asymptomatic. We describe the case of a 66-year-old man with end-stage renal disease hemodialysed through a brachio-brachial loop graft of the left forearm. Echo-Doppler precerebral examination showed a high reversed flow of 570 ml/min in the ipsilateral vertebral artery. After successful endovascular recanalization of the subclavian artery, access blood flow increased and vertebral flow decreased to 30 ml/min. Complete neurological examination was normal both before and after endovascular treatment. This case demonstrates how high a subclavian steal can be without causing symptoms and how well precerbral and cerebral circulation can adapt to hemodynamic changes.

High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease.

ABSTRACT: BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIATM HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA <50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.

Surrogate decision making for patients with end-stage dementia.

OBJECTIVE: We aim to explore how health surrogates of patients with dementia proceed in decision making, which considerations are decisive, and whether family surrogates and professional guardians decide differently. METHODS: We conducted an experimental vignette study using think aloud protocol analysis. Thirty-two family surrogates and professional guardians were asked to decide on two hypothetical case vignettes, concerning a feeding tube placement and a cardiac pacemaker implantation in patients with end-stage dementia. They had to verbalize their thoughts while deciding. Verbalizations were audio-recorded, transcribed, and analyzed according to content analysis. By experimentally changing variables in the vignettes, the impact of these variables on the outcome of decision making was calculated. RESULTS: Although only 25% and 31% of the relatives gave their consent to the feeding tube and pacemaker placement, respectively, 56% and 81% of the professional guardians consented to these life-sustaining measures. Relatives decided intuitively, referred to their own preferences, and focused on the patient's age, state of wellbeing, and suffering. Professional guardians showed a deliberative approach, relied on medical and legal authorities, and emphasized patient autonomy. Situational variables such as the patient's current behavior and the views of health care professionals and family members had higher impacts on decisions than the patient's prior statements or life attitudes. CONCLUSIONS: Both the process and outcome of surrogate decision making depend heavily on whether the surrogate is a relative or not. These findings have implications for the physician-surrogate relationship and legal frameworks regarding surrogacy. Copyright © 2011 John Wiley & Sons, Ltd.