Candida albicans infections in renal transplant recipients: effect of caspofungin on polymorphonuclear cells.

This study aimed to compare the caspofungin immunomodulating activities against Candida albicans on polymorphonuclear cells (PMNs) from renal transplant recipients (RTRs) and healthy subjects (HSs). RTR PMNs showed a significantly reduced fungicidal activity compared with that of HS PMNs. Addition of caspofungin to RTR PMNs significantly potentiated the yeast intracellular killing rate, achieving values similar to those observed for HS PMNs. These data show that caspofungin is suitable for invasive candidiasis treatment in patients with immune system-impaired components

Increased urine semaphorin-3A is associated with renal damage in hypertensive patients with chronic kidney disease: a nested case-control study

BACKGROUND: Semaphorins are guidance proteins implicated in several processes such as angiogenesis, organogenesis, cell migration, and cytokine release. Experimental studies showed that semaphorin-3a (SEMA3A) administration induces transient massive proteinuria, podocyte foot process effacement and endothelial cell damage in healthy animals. While SEMA3A signaling has been demonstrated to be mechanistically involved in experimental diabetic glomerulopathy and in acute kidney injury, to date its role in human chronic kidney disease (CKD) has not been investigated. METHODS: To test the hypothesis that SEMA3A may play a role in human CKD, we performed a cross-sectional, nested, case–control study on 151 matched hypertensive patients with and without CKD. SEMA3A was quantified in the urine (USEMA) by ELISA. Glomerular filtration rate was estimated (eGFR) by the CKD-EPI formula and albuminuria was measured as albumin-to-creatinine ratio (ACR). RESULTS: USEMA levels were positively correlated with urine ACR (p = 0.001) and serum creatinine (p < 0.001). USEMA was higher in patients with both components of renal damage as compared to those with only one and those with normal renal function (p < 0.007 and <0.001, respectively). The presence of increased USEMA levels (i.e. top quartile) entailed a fourfold higher risk of combined renal damage (p < 0.001) and an almost twofold higher risk of macroalbuminuria (p = 0.005) or of reduced eGFR, even adjusting for confounding factors (p = 0.002). CONCLUSIONS: USEMA is independently associated with CKD in both diabetic and non diabetic hypertensive patients. Further studies may help clarify the mechanisms underlying this association and possibly the pathogenic changes leading to the development of CKD

Left ventricular dilatation and subclinical renal damage in primary hypertension

Objective: A new classification of left ventricular geometry based on left ventricular dilatation and concentricity has recently been developed. This classification identifies subgroups differing with regard to systemic haemodynamics, left ventricular function and cardiovascular prognosis. We investigated the relationship between the new classification of left ventricular geometry and subclinical renal damage, namely urine albumin excretion and early intrarenal vascular changes in primary hypertensive patients. Methods: A total of 449 untreated hypertensive patients were studied. Four different patterns of left ventricular hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. Albuminuria was measured as the albumin-to-creatinine ratio. Early intrarenal vascular changes, expressed as the renal volume to resistive index ratio, were evaluated by ultrasound and Doppler scan. Results: Patients with concentric dilated left ventricular hypertrophy had higher albumin excretion rates (P = 0.0258) and prevalence of microalbuminuria (P &lt; 0.0001) and lower renal volume to resistive index ratio than patients with concentric nondilated hypertrophy (P = 0.0093). Patients with eccentric dilated hypertrophy showed a higher prevalence of microalbuminuria than patients with eccentric nondilated hypertrophy (P &lt; 0.0001). Moreover, patients with chamber dilatation showed a higher prevalence of microalbuminuria (P = 0.0002) and lower renal volume to resistive index ratio (P = 0.0107) than patients without chamber dilatation. After adjusting for potentially confounding variables, left ventricular chamber dilatation was an independent predictor of subclinical renal damage. Conclusion: Left ventricular dilatation is associated with subclinical renal damage in hypertension. These findings extend previous reports and provide a pathophysiological rationale for the observed unfavourable prognosis in patients with left ventricular dilatation

Serum uric acid and its relationship with metabolic syndrome and cardiovascular risk profile in patients with hypertension: Insights from the I-DEMAND study

BACKGROUND AND AIMS: The independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes. METHODS AND RESULTS: A total of 2429 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi) <60 ml/min/1.73 m(2) or as the presence of microalbuminuria (albumin-to-creatinine ratio ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women). The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03-1.18; P = 0.0060; OR 1.28, 95% CI 1.15-1.42; P < 0.0001). These associations were stronger in patients without diabetes and with normal renal function. CONCLUSIONS: Mild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk