Association of intrarenal blood flow with renal function and target organ damage in hypertensive patients with fibromuscular dysplasia: the ARCADIA-POL study.

INTRODUCTION Data on the assessment of intrarenal blood flow parameters in patients with renal fibromuscular dysplasia (FMD) are scarce. OBJECTIVES The aim of the study was to evaluate intrarenal blood flow parameters in patients with FMD and significant or nonsignificant renal artery stenosis (RAS). PATIENTS AND METHODS We evaluated intrarenal blood flow parameters by Doppler ultrasonography in 153 patients with renal FMD enrolled in the ARCADIA­POL study: 32 and 121 patients with and without significant RAS, respectively, compared with 60 matched patients with essential hypertension and 60 healthy controls. RESULTS Patients with FMD and significant RAS had a lower renal resistive index (RRI) compared with patients with FMD without significant RAS, patients with essential hypertension, and normotensive controls (mean [SD], 0.51 [0.08] vs 0.60 [0.07], 0.62 [0.06], and 0.61 [0.06], respectively; P <0.001). In patients with nonsignificant RAS, RRI correlated significantly with carotid intima-media thickness, 24­hour diastolic blood pressure, 24­hour pulse pressure, left ventricular diastolic function, known duration time of hypertension, and age. In patients with significant RAS, there was a significant correlation between RRI and known duration time of hypertension, left ventricular diastolic function, and age. In a separate, "per­kidney" analysis, renal arteries with FMD and significant RAS were characterized by lower RRI values, higher maximal blood flow velocity, higher renal aortic ratio, and longer acceleration time compared with renal arteries with FMD and nonsignificant RAS as well as renal arteries without FMD. CONCLUSIONS In contrast to atherosclerotic RAS, intrarenal blood flow in patients with FMD and RAS is preserved, confirming that renal vasculature is relatively intact in these patients.

Influence of candidate polymorphisms on the dipeptidyl peptidase IV and µ-opioid receptor genes expression in aspect of the ß-casomorphin-7 modulation functions in autism.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with population prevalence of approximately 60-70 per 10,000. Data shows that both opioid system function enhancement and opiate administration can result in autistic-like symptoms. Cow milk opioid peptides, including ß-casomorphin-7 (BCM7, Tyr-Pro-Phe-Pro-Gly-Pro-Ile), affect the µ-opioid receptor (MOR) and are subjected to degradation resulting from the proline dipeptidyl peptidase IV (DPPIV, EC 3.4.14.5) enzyme activity. The presence of MOR and DPPIV activity are crucial factors determining biological activity of BCM7 in the human body. Our study examined the effect of ß-casomorphin-7 on the MOR and DPPIV genes expression according to specific point mutations in these genes. In addition, we investigated frequency of A118G SNP in the MOR gene and rs7608798 of the DPPIV (A/G) gene in healthy and autistic children. Our research indicated correlation in DPPIV gene expression under the influence of BCM7 and hydrolyzed milk between healthy and ASD-affected children with genotype GG (P<0.0001). We also observed increased MOR gene expression in healthy children with genotype AG at polymorphic site A118G under influence of BCM7 and hydrolyzed milk. The G allele frequency was 0.09 in MOR gene and 0.68 in the DPPIV gene. But our results suggest no association between presence of the alleles G and A at position rs7608798 in DPPIV gene nor alleles A and G at position A118G of the MOR and increased incidence of ASD. Our studies emphasize the compulsion for genetic analysis in correlation with genetic factors affecting development and enhancement of autism symptoms.

Relationship between hemodynamic parameters of renal artery stenosis and the changes of kidney function after renal artery stenting in patients with hypertension and preserved renal function.

INTRODUCTION: The role of physiological assessment of renal artery stenosis (RAS) using renal fractional flow reserve (rFFR) and resting translesional pressures ratio (Pd/Pa ratio) in the prediction of benefit from revascularization is still unknown. OBJECTIVES: The aim of the study was to assess the relationship between hemodynamic data and the change in kidney function after renal artery stenting in secondary hypertension. PATIENTS AND METHODS: 34 hypertensive patients (50% males, median age 65 years) with at least 60% RAS, underwent stenting and were followed up for 6 months. Pd/Pa ratio (ratio of mean distal to lesion to proximal pressure) and hyperemic rFFR (after papaverine) were measured before the procedure. At baseline and after 6 months, the glomerular filtration rate (eGFR), serum cystatin C and albuminuria were determined. In receiver operating characteristic curves, two previously established cut-off values with the highest accuracy of identifying severe RAS were used: 0.93 for the Pd/Pa ratio and 0.8 for the rFFR. RESULTS: No significant difference in eGFR was found between patients with decreased and normal Pd/Pa ratio (1.4 vs 7.9 ml/min, p = ns). Similarly, minor changes in eGFR were observed in patients with decreased vs normal rFFR (2.4 vs 4.1 ml/min, p = ns). In patients with decreased Pd/Pa ratio, albuminuria remained stable (change 1.4 mg/24 h) compared with an increase of 12.6 mg/24 h in the subgroup with Pd/Pa ≥ 0.93(p < 0.05). However, after exclusion of two outliers with significant baseline proteinuria (425 and 1095 mg/24 h, respectively), the difference in albuminuria change according to the baseline Pd/Pa ratio was no longer maintained. CONCLUSIONS: Hemodynamic parameters of RAS do not distinguish the patients who may benefit from renal artery stenting in terms of kidney function improvement in short-term follow-up.

ß-casomorphin-7 alters µ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with heterogeneous clinical phenotypes reflecting genetic predisposition and exposure to environmental factors. Reactions to food may play a significant role especially in young children. Milk proteins are particularly strong allergens and are additional source of bioactive peptides including ß-casomorphin-7 (BCM7, Tyr-Pro-Phe-Pro-Gly-Pro-Ile). BCM7 exerts its influence on nervous, digestive, and immune functions via the µ-opioid receptor (MOR). Proline dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) appears to be the primary degrading enzyme of BCM7. Moreover, DPPIV is known to restrict activity of proinflammatory peptides. BCM7 is considered to modulate an immune response by affecting MOR and DPPIV genes expression. In this study, we determined the MOR and DPPIV genes expression in children diagnosed with a severe form of AD. 40 healthy children and 62 children diagnosed with severe AD (AD score ≥60) were included in the study. Peripheral blood mononuclear cells (PBMCs) from the studied subjects were incubated with the peptide extracts of raw and hydrolysed cow milk with defined ß-casein genotypes (A1A1, A2A2 and A1A2) and MOR and DPPIV genes expression was determined with real-time PCR. Incubation PBMCs with peptide extracts from cow milk caused an increase of the MOR gene expression (p<0.05; p<0.001) in AD children with a simultaneous decrease in the DPPIV gene expression (p<0.001). The obtained results supplement the knowledge on the BCM7 participation in AD etiology and provide an important diagnostic tool.

Relationship between renal resistive index and early target organ damage in patients with never-treated essential hypertension.

The aim of our study was to evaluate renal resistive index (RI) value in never treated hypertensive patients in relation to ambulatory blood pressure measurement (ABPM) values and early target organ damage. The study included 318 subjects: 223 patients with never treated essential hypertension (mean age 37.1 years) and 95 normotensive healthy subjects (mean age 37.9 years). ABPM, echocardiography and carotid and renal arteries duplex color Doppler examinations were performed. RI values in patients with never treated essential hypertension were no different from the normotensive control group (0.59 +/- 0.05 vs 0.59 +/- 0.05; NS). In the untreated patients RI correlated significantly with 24-h pulse pressure (r=0.234; p<0.01) and ambulatory arterial stiffness index (AASI) values (r=0.274; p<0.001), intima-media thickness (IMT) (r=0.249; p<0.001), E'/A' (rho= -0.279; p<0.001) and relative wall thickness (RWT; r=0.185; p<0.01). In the multivariate stepwise analysis, RI values correlated independently with carotid IMT (beta=0.272; p=0.020) and 24-h AASI values (beta=0.305; p=0.009). In normotensive healthy controls, significant independent correlation between RI and carotid IMT and 24-h AASI values were also found. Our study may indicate limited value of RI in differentiating patients with uncomplicated hypertension with healthy controls. Renal resistive values were independently correlated with carotid IMT and AASI. These may suggest that renal vascular resistance is related to two markers for cardiovascular events both in the hypertensive and normotensive subjects.