Pathophysiology

Background and objectives: Obesity is associated with increased parathyroid hormone (PTH) in the general population and in patients with chronic kidney disease (CKD). A direct effect of adipose tissue on bone turnover through leptin production has been suggested, but such an association has not been explored in kidney transplant recipients.

Background and objectives: We assessed the prevalence of obstructive sleep apnea (OSA) and its clinical correlates in a large sample of patients who received a kidney transplant (Tx). We also compared the prevalence of the disorder between dialysis patients who were on the waiting list for a Tx (WL) and Tx patients.

Introduction Impaired kidney function is common in kidney-transplanted patients and complications of chronic kidney disease (CKD), such as mineral and bone disorders (MBD) are also prevalent in this population. Similarly to other stages of CKD, increasing evidence supports the association between MBD and cardiovascular risk after kidney transplantation as well. Still, little is known about the prevalence, clinical correlates of MBD and its management in transplanted patients. In this study, we aimed to examine the characteristics of MBD and its associations with clinical parameters in a large prevalent cohort of patients after kidney transplantation. Methods Nine hundred and ninety stable patients followed at a single kidney transplant outpatient clinic were included in the study. Detailed medical history, demographic data and routine laboratory results, including Ca, P and intact PTH were collected. Estimated GFR was calculated using the abbreviated MDRD formula, patients were stratified into three groups based on eGFR. Target levels for Ca, P and iPTH were based on CKD stages according to the NKF-K/DOQI guidelines. Standard statistical procedures, binomial and multinomial regressions were used in the analysis.

Introduction To date, only a few, at times conflicting, reports suggested that renal function and mortality are associated in kidney-transplanted patients. In our prevalence cohort study, we tested the hypothesis that renal function is associated with mortality in transplanted patients. Methods Data from 985 transplanted patients were analyzed. Socio-demographic parameters, laboratory data, medical and transplant history, type of immunosuppression and estimated glomerular filtration rate were tabulated at baseline. Data on 5year outcome were collected prospectively. Results In multivariate Cox proportional hazard models, the estimated glomerular filtration rate measured at baseline significantly predicted mortality [hazard ratio (HR) for each 10 ml/min decrease = 1.271; 95% confidence interval (CI): 1.121-1.440] after adjustment for several covariables. Additionally, in multivariate Cox proportional hazard models, chronic kidney disease stage 4-5 (HR = 2.678; 95% CI: 1.494-4.802) significantly increased the mortality hazard compared to chronic kidney disease stage 1-2.

Introduction Dialysis treatment prior to transplantation may contribute to premature mortality and graft loss in kidney-transplanted patients. In this prevalent cohort study (TransQol-HU Study), we analyzed the association between pre-transplant dialysis duration versus mortality and death-censored graft loss in kidney-transplanted patients. Methods Data from 926 kidney-transplanted patients followed at a single outpatient transplant center were analyzed. Socio-demographic parameters, laboratory data, medical history, donor characteristics and information on co-morbidities were collected at baseline. Data on 5-year outcome (graft loss, mortality) were collected.

Background. Past studies identified an association between kidney stone disease (KSD) and hypertension. We recently reported a high occurrence of hypertension in families of patients with hyperuricosuric KSD. As hypercalciura frequently coexists with hyperuricosuria and high urinary excretion of calcium is found in patients with hypertension, we hypothesized that hyperuricosuria that is accompanied by hypercalciuria better describes the familial association between KSD and hypertension. Methods. Four hundred and eighty-six KSD patients, aged 18-50 years, attending a lithotripsy unit collected a 24-h urine sample for metabolic analysis and provided information on family history of hypertension. The familial occurrence of hypertension was compared among four groups of patients: those who had combined elevation of both urinary calcium and uric acid excretions ('combined' abnormality, ns 56), those who had hyperuricosuria without concomitant hypercalciuria ('pure' hyperuricosuria, n s 67), those who had hypercalciuria without concomitant hyperuricosuira ('pure' hypercalciuria, ns 52), and a control KSD patient group ('other' abnormality, n s 311). The prevalence of treated hypertension in patients from the four groups was 16%, 12%, 2%, 10%, respectively. Results. Thirty-four per cent of the patients with the 'combined' abnormality had a positive family history of hypertension, defined as two or more first-degree relatives with treated hypertension, that was significantly higher than in patients with either 'pure' hyperuricosuira (15%, P-0.02), 'pure' hypercalciuria (8%, P-0.001), or patients with 'other' abnormality (10%, P-0.001). The adjusted OR for positive family history of hypertension in the 'combined' abnormality group compared to the control KSD patient group was 5.6 (2.39-13.30). The prevalence of hypertension in siblings of patients with the 'combined' abnormality (13%) was significantly higher than in siblings of patients with either 'pure' hyperuricosuria (3%, P-0.001), 'pure' hypercalciuria (1%, P-0.001), or siblings of control patients with 'other' abnormality (4%, P-0.001). The adjusted OR for hypertension in siblings of a patient with 'combined' abnormality compared to a control KSD patient was 3.4 (1.97-5.91). Patients in the 'combined' abnormality group were also characterized by significantly elevated urinary sodium, phosphorus, citrate and potassium excretions. Conclusions. Our data suggest that there is a strong, independent association between familial occurrence of hypertension and the phenotype characterized by combined elevation of both urinary uric acid and calcium excretions. The association is not present in those with 'pure' hyperuricosuria or 'pure' hypercalciuria. Ascertainment of patients based on this phenotype may identify more homogeneous populations for genetic analysis of hypertension.

Background: Chronic renal failure (CRF) is frequently accompanied by systemic vascular alterations which further increase the morbidity and mortality of these patients. However, the nature and the underlying mechanisms of vascular dysfunction are not completely understood. We hypothesized that -in addition to other factors -CRF alters local vasomotor mechanisms that are intrinsic to the vascular wall. Methods: Changes in the diameter of isolated, pressurized (at 80 mm Hg) gracilis skeletal muscle arterioles (diameter approximately 150 Ìm) of female Wistar rats were investigated by videomicroscopy. Arteriolar responses to an increase in flow and vasoactive agents in partially nephrectomized (NX) and sham-operated (control) rats were compared. Results: In NX rats, serum creatinine and urine protein excretion were increased. Compared to controls, increases in intraluminal flow (from 0 to 40 Ìl/min) resulted in significantly reduced dilation in arterioles of NX rats (maximum: 32 B 4 vs. 15 B 4 Ìm, p ! 0.05). Inhibition of nitric oxide (NO) synthesis with L-NAME reduced the dilation of control arterioles but did not affect responses of NX arterioles. Also, dilations in response to histamine were significantly reduced in arterioles from NX rats as compared to control rats. L-NAME significantly decreased histamine-induced dilations of control arterioles, but it did not affect responses of NX arterioles. Dilations in response to the NO donor sodium nitroprusside were also significantly decreased in NX arterioles as compared to responses of control vessels, whereas responses to adenosine and norepinephrine were not significantly different in the two groups. Conclusions: We conclude that in rat skeletal muscle arterioles, CRF induced by renal mass reduction alters the mechanosensitive and agonist-induced responses of peripheral arterioles, in part by interfering with NO-signaling mechanisms. These alterations could contribute to increased peripheral vascular resistance and further aggravate the cardiovascular complications in CRF.