Asymptomatic atherosclerosis and hypertension in nondiabetic patients with chronic kidney disease.

Atherosclerosis is accelerated in dialysis patients, but less is known about asymptomatic atherosclerosis and major risk factors in patients with different stages of chronic kidney disease (CKD). We compared intima media thickness (IMT) and plaque occurrence in the carotid arteries in 104 nondiabetic patients (stages 1-5 of CKD; mean age: 51.6 years) with those in 40 healthy control subjects. The IMT values (0.69 vs. 0.59 mm; P < 0.002) were higher in patients. More patients had plaques (46.2 vs. 17.5%; P < 0.002), and number of plaques was higher (P < 0.003). Negative correlation between IMT (P < 0.0001), presence of plaques (P < 0.0001), their number (P < 0.040), and chromium 51-labeled ethylenediaminetetraacetate ((51)Cr-EDTA) clearance were found in patients. With multiple regression analysis, relationship between IMT and (51)Cr-EDTA clearance (P < 0.001) and presence of hypertension (P < 0.001) was found. Nondiabetic patients with CKD showed advanced atherosclerosis and IMT, plaque occurrence, and number increased directly with the level of renal dysfunction. Another important risk factor was hypertension.

Cardiac troponin T (cTnT) in hemodialysis patients with asymptomatic and symptomatic atherosclerosis.

BACKGROUND: Cardiovascular mortality is higher in hemodialysis (HD) patients than in the general population. Cardiac troponin T (cTnT) is established as a sensitive marker of myocardial injury in the general population. Less is known about the association between cTnT and intima-media thickness (IMT) and presence of plaques in carotid arteries (asymptomatic atherosclerosis) and prognostic value of cTnT for cardiovascular mortality (symptomatic atherosclerosis) in HD patients. METHODS: In our study 90 HD patients (mean age 56.2 +/- 13.3 years) were followed after determination of cTnT level. Outcome after 21 months was chosen as the end point. In 52 randomly selected HD patients, IMT was measured with B-mode ultrasonography. Plaque occurrence and their numbers were also determined. RESULTS: In 24 (26.6%) patients, cTnT values were >0.1 microg/L (positive test for myocardial injury). During follow-up, 13 patients died from cardiovascular causes and their cTnT values were significantly higher (0.12 vs. 0.06 microg/L; p <0.001) than in those who survived. Correlation between cardiovascular mortality and cTnT was found (p <0.001). The cut-off level of 0.1 microg/L resulted in survival rates of 92% and 64% (p=0.0006). The IMT values of carotid artery were significantly higher (0.85 vs. 0.70 mm; p <0.011) in patients with elevated cTnT. All patients with elevated cTnT had plaques and the number of plaques was significantly higher in these patients (p <0.0001). CONCLUSIONS: cTnT was frequently elevated in our HD patients and was associated with higher cardiovascular mortality and a predictor of cardiovascular outcome. Patients with elevated cTnT showed advanced asymptomatic atherosclerosis in carotid arteries.

Paricalcitol reduces proteinuria in non-dialysis chronic kidney disease patients.

Existing treatment of proteinuria is not sufficient to halt the chronic kidney disease (CKD) epidemic. Therefore the aim of our study was to evaluate the effect of paricalcitol on proteinuria in non-dialysis CKD patients with secondary hyperparathyroidism treated according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Forty-one non-dialysis CKD patients with secondary hyperparathyroidism (iPTH >65 pg/mL), serum calcium <2.6 mmol/L, serum phosphate <1.8 mmol/L and proteinuria (>150 mg/day) were treated with paricalcitol 1 µg/day. Most were treated for 6 months, with the exception of three patients having iPTH <30 pg/mL after 3 months, in whom therapy was stopped. All patients were followed for 6 months. 24-h ambulatory blood pressure (24hABP) monitoring was performed at 0 and 6 months. Fixed doses of ACE inhibitors and/or ARBs and/or statins were kept for 3 months before and during the study. Forty-one patients (30 men, 11 women; age 62.44 ± 11.93 years) with different primary causes of CKD were enrolled in the study. Urinary albumin/creatinine ratio (UACR), 24-h urinary albuminuria (24hUA) and 24-h urinary quantitative proteinuria (24hUQP) were measured. Values at 0 and 6 months of these parameters were log-transformed for statistical analysis. After treatment with paricalcitol, statistically significant reduction (paired t-test) in 24hUA (P < 0.011) and 24hUQP (P < 0.0001) were found. The reduction of UACR was not significant (P = 0.074). In the observational period no statistically significant reduction in 24hABP was found. Treatment with 1 µg paricalcitol daily according to clinical practice in non-dialysis CKD patients with secondary hyperparathyroidism and proteinuria significantly reduces 24hUA and 24hUQP without significant change in 24hABP.

Radiographic assessment of vascular calcification, aortic pulse wave velocity, ankle-brachial index and fibroblast growth factor-23 in chronic hemodialysis patients.

Vascular calcification is a frequent complication of chronic kidney disease and end stage renal disease. In both the general population and patients with end stage renal disease, vascular calcification is related to arterial stiffness and is a predictor of cardiovascular morbidity and mortality. Various diagnostic methods are currently used to assess vascular calcification. There is a preference for simple, reliable methods that can be used in daily practice. Therefore, several imaging and laboratory methods are investigated. Twenty-eight patients with mean age of 62 years on chronic hemodialysis were enrolled in the study. The mean duration of hemodialysis treatment was 70 months (range 3 to 350 months). Vascular calcification was assessed with coronary computed tomography and lateral lumbar, pelvic and hand radiographs. Vascular stiffness was evaluated using aortic pulse wave velocity and ankle-brachial index measurements, and finally serum levels of fibroblast growth factor-23 were followed. A statistically significant correlation was demonstrated between all the following parameters: coronary artery calcification score, aortic pulse wave velocity, abdominal aortic calcification score, simple vascular calcification scores in pelvis and hand. A statistically significant correlation of ankle-brachial index >1.3 to coronary artery calcification score was found. There was no correlation between the previous parameters and fibroblast growth factor-23. The results of our study indicate that simple imaging methods could provide confident vascular damage assessment and therefore potentially guide therapy adjustments. An association between fibroblast growth factor-23 and the other diagnostic modalities in our study was not found.

Gangrenous appendicitis presenting as acute abdominal pain in a patient on automated peritoneal dialysis: a case report.

INTRODUCTION: Presentations of abdominal pain in patients on peritoneal dialysis deserve maximal attention and careful differential diagnosis on admittance to medical care. In this case report a gangrenous appendicitis in a patient on automated peritoneal dialysis is presented. CASE PRESENTATION: We report the case of a 38-year-old Caucasian man with end-stage renal disease who was on automated peritoneal dialysis and developed acute abdominal pain and cloudy peritoneal dialysate. Negative microbiological cultures of the peritoneal dialysis fluid and an abdominal ultrasonography misleadingly led to a diagnosis of culture negative peritonitis. It was decided to remove the peritoneal catheter but the clinical situation of the patient did not improve. An explorative laparotomy was then carried out; diffuse peritonitis and gangrenous appendicitis were found. An appendectomy was performed. Myocardial infarction and sepsis developed, and the outcome was fatal. CONCLUSION: A peritoneal dialysis patient with abdominal pain that persists for more than 48 hours after the usual antibiotic protocol for peritoneal dialysis-related peritonitis should immediately alert the physician to the possibility of peritonitis caused by intra-abdominal pathology. Not only peritoneal catheter removal is indicated in patients whose clinical features worsen or fail to resolve with the established intra-peritoneal antibiotic therapy but, after 72 hours, an early laparoscopy should be done and in a case of correct indication (intra-abdominal pathology) an early explorative laparotomy.

Forty-eight-hour ambulatory blood pressure and carotid-femoral pulse wave velocity in hemodialysis patients.

Carotid-femoral pulse wave velocity (cfPWV) is an important predictor of cardiovascular events in the general population and also in hemodialysis (HD) patients. In the general population, cfPWV is strongly associated with age and blood pressure (BP). The best timing and method of BP measurement in HD patients is uncertain. Ambulatory blood pressure measurements (ABPM) have been used to better define the relationship between BP, target organ damage, and outcomes in HD patients. The aim of this study was to determine the possible association between cfPWV, cardiovascular risk factors, single BP measurements, and 48-hour ABPM in chronic HD patients. Thirty-three HD patients (22 men, 11 women) were included. After the end of the mid-week HD session, BP was measured, arterial stiffness was estimated by cfPWV, and 48-hour ABPM was performed. The mean systolic and diastolic BP readings before cfPWV measurement were 136/79 mmn Hg, and the mean 48-hour systolic and diastolic BP readings were 131/76 mm Hg. The mean and range of the cfPWV measurements were 8.31 ± 2.35 m/s and 5.18-16.53 m/s, respectively. Using regression analysis, no association between cfPWV and BP before PWV measurements was found. A statistically significant correlation between cfPWV and 48-hour systolic and diastolic ABPM was found. Using multiple regression analysis (including age, sex, smoking, diabetes, body mass index, total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides, C-reactive protein, albumin, phosphorus, calcium, and iPTH) 48-hour systolic (P < 0.001) and diastolic ABPM (P < 0.005) still remain significantly associated with cfPWV. Only 48-hour ABPM was associated with cfPWV in HD patients in our study. We found no relationship between cfPWV and other cardiovascular risk factors.

Predictive value of carotid intima media thickness in hemodialysis patients.

Atherosclerosis is accelerated in hemodialysis patients. Intima media thickness (IMT) is a strong predictor for cardiovascular events in the general population. Using B-mode ultrasonography, IMT in the common carotid arteries was measured in 99 nondiabetic hemodialysis patients (44 women and 55 men, mean age 53.1 years and mean dialysis duration 45.8 months). During a follow-up of 42.4 +/- 19.5 months, 33 patients died, 19 (57.6%) of them of cardiovascular causes. In these 19 patients IMT was significantly higher (0.89 vs. 0.69 mm) than in those who survived. Correlation between cardiovascular mortality and IMT was found. Patients were divided in relationship to the tertiles of IMT and the risk for cardiovascular death was progressively higher from the first tertile of IMT onward (P < 0.0006). IMT turned out to be an independent predictor of cardiovascular death (P < 0.025). According to our results IMT may be usefully applied for cardiovascular mortality risk stratification in nondiabetic hemodialysis patients.

Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis?

BACKGROUND: The receptor activator of nuclear factor kappaB ligand (RANKL), produced by osteoblasts/stromal cells, is a member of the RANK/RANKL/OPG system, which regulates bone resorption by osteoclasts. Since RANKL and osteoprotegerin (OPG) production in bone is influenced by parathyroid hormone (PTH), we measured serum RANKL and OPG concentrations in haemodialysis (HD) patients, who commonly hypersecrete PTH. We aimed to determine if clinically demonstrated PTH-enhanced bone resorption is a consequence of increased RANKL synthesis. METHODS: RANKL, OPG, osteocalcin, intact PTH, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase 5b and beta-CrossLaps (CTx) were measured in blood samples from 80 HD patients and 50 age-matched controls. HD patients were stratified to tertiles according to their serum PTH levels: 29.3-103.0, 109.7-263.0 and 262.0-1700.0 pg/ml in the first, second and third tertiles, respectively. RESULTS: Mean serum RANKL levels were 1.6 times higher in HD patients than in age-matched controls (1.36+/-0.39 vs 0.83+/-0.70 pmol/l; P<0.001). All the measured bone markers significantly differed between patients and controls (P<0.001). Spearman's tests of correlation showed a statistically significant association of RANKL with PTH, osteocalcin and CTx (r=0.322, P=0.004; r=0.231, P=0.039; and r=0.230, P=0.040, respectively). Mean serum RANKL levels were significantly different between PTH tertiles (P = 0.003), but serum OPG levels were not (P=0.144). The highest RANKL levels were measured in the upper PTH tertile (1.54+/-0.39 pmol/l) and were significantly higher than in the middle or lower tertiles (1.27+/-0.42 and 1.23+/-0.26 pmol/l, respectively; P=0.003). Both of the measured bone-resorption markers, tartarate-resistant acid phosphatase 5b and CTx, as well as both bone formation markers, osteocalcin and bone-specific alkaline phosphatase were also significantly higher in the upper tertile, indicating that whole-bone remodelling is activated at high PTH and RANKL levels. CONCLUSIONS: Serum RANKL levels were significantly higher in HD patients than in healthy age-matched controls. Moreover, RANKL levels were significantly higher in the upper PTH tertile, indicating enhanced RANKL synthesis in a PTH-dependent fashion. Thus, our clinical findings clearly support published in vitro studies that demonstrated a stimulating effect of PTH on RANKL synthesis. Therefore, the hypothesis that PTH increases bone resorption in HD patients through RANKL appears valid.

Atherosclerosis in patients with end-stage renal failure prior to initiation of hemodialysis.

BACKGROUND: In dialysis patients cardiovascular mortality is 10 to 20 times higher than in general population. It remains uncertain whether atherosclerosis of dialysis patients is effectively accelerated because many of dialysis patients have more or less marked vascular lesions already at the start of dialysis treatment. SUBJECTS AND METHODS. Using B-mode ultrasonography (ATL HDI 3000), we compared intima-media thickness (IMT) and plaque occurrence (indicators of atherosclerosis) in the common carotid arteries (CC), in the area of bifurcation (CB) and in the proximal part of internal carotid arteries (CI) in 28 hemodialysis patients (14 men and 14 women; mean age 49.4 years; mean duration of HD treatment 66.6 months) with that in 28 age-sex matched patients prior to initiation of hemodialysis. We also investigated possible differences in atherosclerotic risk factors in both groups. RESULTS: The IMT values of CC (0.71 vs. 0.70 mm; p = 0.937), CB (0.81 vs. 0.77 mm; p = 0,423) and CI (0.72 vs. 0.71 mm; p = 0.935) were not significantly different in dialysis patients and patients starting dialysis treatment. We also found no difference in plaque occurrence (61% vs. 54%; p = 0.787) and in atherosclerotic risk factors (hypertension, smoking, lipids) between both groups. CONCLUSIONS: In our study we found no difference in atherosclerotic lesions in carotid arteries between dialysis patients and patients with end-stage renal failure starting dialysis treatment. Patients with chronic renal failure are at high risk for cardiovascular diseases so we should intervene earlier and more actively long before dialysis treatment in order to reduce the atherosclerotic risk factors.