Smoking and hyperparathyroidism in patients with end-stage renal disease (ESRD).

Background And Methods: Smoking is associated with hyperparathyroidism in the elderly general population and nicotine, the main component of tobacco smoke, stimulates PTH release in experimental models. Although smoking is a persisting problem in patients with end-stage renal disease (ESRD), the association between smoking and PTH has never been specifically examined in these patients. We investigated the relationship between smoking and hyperparathyroidism in a well-characterized group of 161 nondiabetic dialysis patients.

Circulating soluble receptor for advanced glycation end product (sRAGE) and left ventricular hypertrophy in patients with chronic kidney disease (CKD).

Background And Aim: A decoy receptor for advanced glycation end product (soluble RAGE or sRAGE) is involved in left ventricular hypertrophy (LVH), and cardiomyopathy myocardial damage in experimental models and observational studies in patients with heart failure support the hypothesis that sRAGE attenuates the progression of heart disease and prevents death. Since sRAGE accumulates in patients with chronic kidney disease (CKD) we studied the relationship between plasma sRAGE with LVH in CKD patients.

Methods And Results: We enrolled 142 patients with an average estimated glomerular filtration rate (eGFR) of 32 ml/min/1.

How to deal with continuous and dichotomic outcomes in epidemiological research: linear and logistic regression analyses.

Because of some limitations of stratification methods, epidemiologists frequently use multiple linear and logistic regression analyses to address specific epidemiological questions. If the dependent variable is a continuous one (for example, systolic pressure and serum creatinine), the researcher will use linear regression analysis. Otherwise, if the dependent variable is dichotomic (for example, presence/absence of microalbuminuria), one could use logistic regression analysis.

Ranolazine can markedly increase tacrolimus blood levels.

We report the case of a renal transplant patient on tacrolimus who developed a fully reversible renal failure and a doubling in serum tacrolimus closely associated with initiation of ranolazine (Ranexa) treatment, a new anti-angina drug recently introduced in Europe.

Severe hyponatraemia during sepsis and marijuana addiction.

The authors report a 29-year-old kidney transplant patient who presented, four episodes of severe hyponatraemia associated with sepsis from 2006 to 2010. He was a long-term user of marijuana. The association between severe recurrent hyponatraemia during sepsis and marijuana addiction might not be casual, since experimental data show that vasopressin release induced by sepsis is modulated by the endocannabinoid system.

Vasopressin beyond water: implications for renal diseases.

Purpose Of Review: This review aims to analyze the relationships between arginine vasopressin (AVP) and chronic kidney disease (CKD) and to define the potential of vasopressin receptor antagonists beyond the treatment of water metabolism disorders.

Recent Findings: Experimental studies in rat and observational studies in humans suggest that AVP may play a role in the genesis and exacerbation of renal damage and chronic renal insufficiency.

Summary: A sustained stimulation of vasopressin receptors induces intrarenal renin-angiotensin system activation, podocyte alterations, glomerular hyperfiltration and hypertrophy eventuating in proteinuria and kidney damage.

Stratification for confounding--part 2: direct and indirect standardization.

Standardization is a method used to compare observed and expected rates of a given disease/outcome by removing the influence of factors that may confound the comparison. There are two major standardization methods: one is used when the 'standard' is the structure of a population (direct method) and the other when the 'standard' is a set of specific event rates (indirect method). The direct standardization is commonly used for large populations while the indirect one is applied to populations of relatively small dimensions.

Stratification for confounding--part 1: the Mantel-Haenszel formula.

Stratification allows to control for confounding by creating two or more categories or subgroups in which the confounding variable either does not vary or does not vary very much. The Mantel-Haenszel formula is applied in cohort and in case-control studies to calculate an overall, unconfounded, effect estimate of a given exposure for a specific outcome by combining stratum-specific relative risks (RR) or odds ratios (OR). Stratum-specific RRs or ORs are calculated within each stratum of the confounding variable and compared with the corresponding effect estimates in the whole group (that is, with the unstratified RR or OR).

Neuropeptide Y receptor Y2 gene polymorphism interacts with plasma neuropeptide Y levels in predicting left ventricular hypertrophy in dialysis patients.

Background: Neuropeptide Y (NPY) is a sympathetic neurotransmitter that acts on multiple receptors involved in cardiovascular remodelling and angiogenesis. Plasma levels of NPY are increased in patients with end-stage renal disease (ESRD) and are independently related to left ventricular hypertrophy (LVH) and incident cardiovascular events in these patients.

Objective: To investigate the relationship between NPY receptor Y2 gene polymorphism and left ventricular mass index (LVMI) as well as the interaction between this polymorphism and plasma NPY in determining LVH in 189 ESRD patients.

Selection bias and information bias in clinical research.

The internal validity of an epidemiological study can be affected by random error and systematic error. Random error reflects a problem of precision in assessing a given exposure-disease relationship and can be reduced by increasing the sample size. On the other hand, systematic error or bias reflects a problem of validity of the study and arises because of any error resulting from methods used by the investigator when recruiting individuals for the study, from factors affecting the study participation (selection bias) or from systematic distortions when collecting information about exposures and outcomes (information bias).

Measures of effect in epidemiological research.

The study of the relationship between risk factors and outcomes is important both in etiological and prognostic research. To assess the strength of a given risk factor-outcome relationship we use measures that are calculated in relative and absolute terms. Risk ratio, incidence rate ratio and odds ratio are relative measures of this relationship.

Statistical methods for the assessment of prognostic biomarkers(part II): calibration and re-classification.

Calibration is the ability of a prognostic model to correctly estimate the probability of a given event across the whole range of prognostic estimates (for example, 30% probability of death, 40% probability of myocardial infarction, etc.). The key difference between calibration and discrimination is that the latter reflects the ability of a given prognostic biomarker to distinguish a status (died/survived, event/non-event), while calibration measures how much the prognostic estimation of a predictive model matches the real outcome probability (that is, the observed proportion of the event).

Diagnostic methods 2: receiver operating characteristic (ROC) curves.

Clinical practice commonly demands 'yes or no' decisions; and for this reason a clinician frequently needs to convert a continuous diagnostic test into a dichotomous test. Receiver operating characteristic (ROC) curve analysis is an important test for assessing the diagnostic accuracy (or discrimination performance) of quantitative tests throughout the whole range of their possible values, and it helps to identify the optimal cutoff value. The value of this analysis is not confined to diagnosis in that it may also be applied to assess the prognostic value of biomarkers and to compare their predictive value.

Testing for causality and prognosis: etiological and prognostic models.

Etiological research aims to investigate the causal relationship between putative risk factors (or determinants) and a given disease or other outcome. In contrast, prognostic research aims to predict the probability of a given clinical outcome and in this perspective the pathophysiology of the disease is not an issue. Multivariate modeling is a fundamental tool both to infer causality and to investigate prognostic factors in epidemiological research.

Linear and logistic regression analysis.

In previous articles of this series, we focused on relative risks and odds ratios as measures of effect to assess the relationship between exposure to risk factors and clinical outcomes and on control for confounding. In randomized clinical trials, the random allocation of patients is hoped to produce groups similar with respect to risk factors. In observational studies, exposed and unexposed individuals may differ not only for the presence of the risk factor being tested but also for a series of other factors that are potentially related to the study outcome, thus making 'confounding' very likely.

The endothelium as a target in renal diseases.

The endothelium is a fundamental layer in the arterial wall both for the local regulation of flow to critical organs like the heart, brain and kidney, and for the protection of the vascular system from atherogenic insults. Inhibition of nitric oxide (NO) synthesis has profound effects at systemic and renal levels. Low NO bioavailability may occur in essential hypertension and in a variety of conditions associated with high cardiovascular risk.

Neuropeptide Y and markers of osteoblast activity in dialysis patients: a cross-sectional study.

Background: In mice, neuropeptide Y (NPY) decreases bone turnover by means of a parathyroid hormone-independent effect on osteoblast activity.

Study Design: Cross-sectional study.

Setting & Participants: We studied the relationship between levels of NPY and biomarkers of osteoblast activity in 161 nondiabetic patients with end-stage renal disease (131 patients, hemodialysis; 30 patients, continuous ambulatory peritoneal dialysis).

It is important to lower homocysteine in dialysis patients.

Homocysteine has been implicated in atherosclerotic and thrombotic vascular disease in the general and in the end-stage renal disease (ESRD) population as well. Although not strong, the risk associated with raised homocysteine (25% risk excess for a 5 mum increase) is quite consistent across studies in the general population. Likewise, individuals harboring a polymorphism leading to higher homocysteine levels coherently display an increased risk for cardiovascular events in comparison with individuals without such a polymorphism.

Bias in clinical research.

The quality of a clinical study depends on internal and external factors. Studies have internal validity when, random error apart, reported differences between exposed and unexposed individuals can be attributed only to the exposure under investigation. Internal validity may be affected by bias, that is, by any systematic error that occurs in the design or in the conduction of a clinical research.

An additive effect of endothelial nitric oxide synthase gene polymorphisms contributes to the severity of atherosclerosis in patients on dialysis.

Background: Reduced synthesis of nitric oxide (NO) is considered a major proatherogenic mechanism in patients with end-stage renal disease (ESRD), but genetic factors impinging on this mechanism have been little studied in this population.

Methods: We tested the relationship between carotid intima-media thickness (IMT) and three endothelial NO synthase (eNOS) polymorphisms (G894T, T-786C, and 27-bp repeat in intron 4) in an ethnically and geographically homogeneous group of 147 patients with ESRD.

Results: The IMT was significantly thicker (P = .

Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections.

Background And Methods: The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections.

Results: During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine.

Clinical databases in nephrology: research and clinical practice goals and challenges.

In clinical practice we formulate direct questions related to patient management that should be answered on the basis of results of valid studies. Bias problems are dealt with using different approaches in observational studies and in clinical trials. The clinical trial is the standard for assessing the efficacy of treatments while the efficiency of treatments at community level is better captured by observational studies.

Low triiodothyronine and cardiomyopathy in patients with end-stage renal disease.

Objectives And Methods: Low free plasma triiodothyronine (fT3) is associated with inflammation and cardiovascular damage in patients with end-stage renal disease (ESRD). We investigated the relationship between fT3, left ventricular systolic function and left ventricular mass in a group of 234 dialysis patients, and modelled the association between fT3 and cardiomyopathy in statistical analyses including both direct (interleukin-6 and C-reactive protein) and inverse (serum albumin) acute phase inflammation markers.

Results: Plasma fT3 concentration in dialysis patients was significantly (P < 0.

Chronic kidney disease epidemics--a gap in effectiveness: the distance between potential and actual treatment benefits.

Metabolic syndrome is a cluster of traditional risk factors including hypertension, abdominal obesity, hypertriglyceridemia, low HDL cholesterol and fasting hyperglycemia. This syndrome is a noxious condition not only for the cardiovascular (CV) system but also for the kidney. In a recent analysis of the NHANES III study the prevalence rate of chronic kidney disease (CKD) was very low in patients without risk factors, but reached 9% in those with five risk factors.