Sclerostin as a new key player in arteriovenous fistula calcification.

BACKGROUND: The osteocyte-derived sclerostin has been shown to play a key inhibitor role in determining the normal extent of bone formation, and it consequently protects against the deleterious effects of uncontrolled bone growth. Sclerostin has been demonstrated to be upregulated during vascular smooth muscle cell calcification in vitro and has recently been identified in the human aorta at the protein level. Whether the effects of sclerostin on bone turnover and its vascular expression also translate into clinically significant changes in arteriovenous fistula patency is unknown. PATIENTS AND METHODS: The primary outcome was loss of unassisted arteriovenous fistula patency, defined as arteriovenous fistula thrombosis or need for intervention. In this prospective cohort study, 350 prevalent hemodialysis patients were followed up for 12 months. Serum sclerostin levels were measured and arteriovenous fistula calcification was detected using a 64-detector computerized tomographic scanner. RESULTS: Patients with calcified arteriovenous fistula had higher serum sclerostin levels than patients without. Overall, 26 % of the patients reached the outcome during the follow-up. The 12-month arteriovenous fistula survival was reduced in patients with calcified arteriovenous fistulas. Patients with serum sclerostin levels above median levels at the start of the observation period had a worse arteriovenous fistula survival. Multivariable-adjusted Cox regression analyses revealed that only presence of arteriovenous fistula calcification and serum C-reactive protein level independently predicted loss of unassisted arteriovenous fistula patency. CONCLUSION: Our study suggests that the detection of arteriovenous fistula calcification and serum C-reactive protein levels might be useful for identifying patients at an increased risk for loss of unassisted arteriovenous fistula patency.

Proton pump inhibitor omeprazole use is associated with low bone mineral density in maintenance haemodialysis patients.

OBJECTIVE: Limited studies have shown that proton pump inhibitor (PPI) therapy may decrease bone density or insoluble calcium reabsorption through induction of hypochlorhydria. However, PPI therapy may also reduce bone resorption via inhibition of osteoclastic vacuolar proton pumps. The aim of this study was to determine whether the opposing effects of PPI therapy may cause clinically important alterations in bone mineral densitometry (BMD) parameters in maintenance haemodialysis patients. METHODS: Sixty-eight maintenance haemodialysis patients were enrolled in this study. Patients were classified into two groups involving users of PPI therapy (omeprazole 20 mg/day, group 1, n = 36 patients) and non-users of acid suppression drugs (group 2, n = 32 patients). Patients had radius, hip and spine BMD assessed by dual-energy X-ray absorptiometry. RESULTS: The mean duration of PPI therapy with omeprazole was 27 +/- 5 months. The users of PPI therapy had lower values of bone mineral density and T-scores at the anatomical regions than non-users of acid suppression drugs. Serum calcium and phosphate levels, calcium-phosphate product and serum intact parathormone levels and the ratio of users of vitamin D therapy were similar among groups. A mutivariable adjusted odds ratio for lower bone density associated with more than 18 months of omeprazole, when all the potential confounders were considered, was 1.31 in the proximal radius, 0.982 in the femur neck, 0.939 in the trochanter and 1.192 in the lumbal spine. CONCLUSION: The present data suggest that PPI therapy should be cautiously prescribed in maintenance haemodialysis patients, especially with lower BMD values.

Utility of the Doppler ultrasound parameter, resistive index, in renal transplant histopathology.

BACKGROUND: Doppler ultrasonography is routinely used by many clinicians during long-term follow-up to identify high-risk patients without diagnosing the exact cause of graft dysfunction. Despite a number of studies showing a correlation between intrarenal resistive index (RI) and renal function in patients with kidney diseases, correlations between RI and renal histopathologic characteristics have not been sufficiently evaluated in renal transplant recipients. The aim of this study was to examine this relationship in grafted kidneys. PATIENTS AND METHODS: The intrarenal RI was retrospectively compared with biopsy findings in 28 kidney recipients. All renal biopsy specimens were reviewed by light microscopy and immunofluorescence staining. For glomerulosclerosis, we considered the percentage of glomeruli showing this change; for interstitial fibrosis/tubular atrophy and interstitial infiltration, we graded abnormalities according to the methods of Kliem et al (Kidney Int 49:666, 1996). RESULTS: The percentage of globally sclerosed glomeruli was significantly greater among patients with RI values higher than 0.75 than below this level (23% vs 47%; P = .022). Patients with grade 1 interstitial fibrosis and tubular atrophy (n = 14) showed lower RI values (0.68 +/- 0.03 vs 0.74 +/- 0.06; P = .047) than those with grade 3 fibrosis (n = 12). Similarly, lower RI values (0.66 +/- 0.02 vs 0.73 +/- 0.05; P = .014) were observed among patients with grade 1 (n = 13) compared with grade 3 interstitial infiltration (n = 13). CONCLUSION: RI seemed to provide a prognostic marker for the graft rather than yielding an exact diagnosis of renal graft dysfunction.

Utility of c2 monitoring in prediction of diastolic dysfunction in renal transplant recipients.

BACKGROUND: A number of experimental studies have suggested that cyclosporine (CsA) toxicity induces cardiac modifications which may cause diastolic dysfunction over the course of time. Doppler echocardiography with tissue Doppler imaging (TDI) could consistently detect diastolic dysfunction. The purpose of this study was to assess diastolic dysfunction using C2 monitoring of CsA exposure in stable renal transplant patients. PATIENTS AND METHODS: Seventy-eight kidney recipients including 42 men and 36 women of overall mean age of 52 +/- 9 years were obtained in 47 living and in 31 cases from cadaveric donations over 12 or more months after transplantation using cases from CsA, mycophenolate mofetil, and steroid. C2 levels were measured by an enzyme multi-immune assay technique. The patients underwent conventional and Doppler echocardiography with TDI. RESULTS: The patients were divided into 2 groups according to C2 levels less than 500 mug/L (group 1, n = 40) versus greater than 500 mug/L (group 2, n = 38). The demographic parameters, serum creatinine and lipid levels, systolic and diastolic blood pressures, number and type of antihypertensive medications, and conventional echocardiographic parameters did not differ significantly between the groups. However, group 1 patients showed significantly higher isovolumic relaxation time (109 +/- 27 vs 86 +/- 14 ms), early diastolic deceleration time (189 +/- 52 vs 137 +/- 59 ms), and lower values of E velocity (56 +/- 32 vs 92 +/- 27 cm/s) and E/A ratios (0.81 +/- 0.23 vs 1.15 +/- 0.46) than group 2. TDI studies revealed significantly lower E'/A' (0.76 +/- 0.25 vs 1.09 +/- 0.32, P < .05) in group 1 versus group 2. CONCLUSION: The data suggested that the higher C2 levels may induce diastolic dysfunction in the hearts of kidney recipients without impairment of contractile performance.

Gingival health status in renal transplant recipients: relationship between systemic inflammation and atherosclerosis.

Cardiovascular disease (CVD) is the leading cause of mortality in renal transplant recipients (RTR). Systemic and periodontal inflammation has been suggested to have a possible role in the development of atherosclerosis. In the present study, we aimed to investigate the relationship between gingival health status, inflammation and atherosclerosis in RTRs. Eighty-three RTR (50 male, 33 female) were enrolled in the study. Routine biochemical analyses, serum lipoproteins, C-reactive protein, fibrinogen, homocystein, parathyroid hormone (PTH) and cyclosporin A (CsA) trough levels were studied. All patients had 24-h ambulatory blood pressure monitoring and B-mode ultrasound of the common carotid arteries. Gingival status was evaluated by the Löe and Silness gingival index (GI). Mean GI value was 2.3 +/- 0.5. Fifty patients (60.3%) had GI value >or= 2.1 (severe gingivitis; group A). Thirty-three patients (39.7%) had GI value < 2.1 (no or moderate gingivitis; group B). Age, carotid intima-media thickness (CIMT) and mean time on dialysis before transplantation were significantly higher in group A than in B. Systemic inflammation markers were not different between group A and group B. Mean CIMT was positively correlated with GI (r = 0.425; p = 0.001) and negatively correlated with high-density lipoprotein cholesterol (r = -0.256; p = 0.023). After the correction for confounding variables, mean CIMT was still significantly correlated with GI (r = 0.376, p = 0.02). In RTR, gingival inflammation seems to be associated with CIMT in the absence of systemic inflammation. Thus, gingivitis may, in part, play a role in the development of systemic atherosclerosis without causing any aggravation in systemic inflammatory response.