Upregulation in Inflammation and Collagen Expression in Perirenal but Not in Mesenteric Adipose Tissue from Diabetic Munich Wistar Frömter Rats.

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment-insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-ß was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain.

Imbalance in Bone Morphogenic Proteins 2 and 7 Is Associated with Renal and Cardiovascular Damage in Chronic Kidney Disease.

Arterial stiffness is a major vascular complication of chronic kidney disease (CKD). The development of renal damage, hypertension, and increased pulse wave velocity (PWV) in CKD might be associated with an imbalance in bone morphogenetic proteins (BMP)-2 and BMP-7. Plasma BMP-2 and BMP-7 were determined by ELISA in CKD patients (stages I-III; n = 95) and Munich Wistar Frömter (MWF) rats. Age-matched Wistar rats were used as a control. The expression of BMP-2, BMP-7, and profibrotic and calcification factors was determined in kidney and perivascular adipose tissues (PVAT). BMP-2 was higher in stage III CKD patients compared to control subjects. BMP-7 was lower at any CKD stage compared to controls, with a significant further reduction in stage III patients. A similar imbalance was observed in MWF rats together with the increase in systolic (SBP) and diastolic blood pressure (DBP), or pulse wave velocity (PWV). MWF exhibited elevated urinary albumin excretion (UAE) and renal expression of BMP-2 or kidney damage markers, Kim-1 and Ngal, whereas renal BMP-7 was significantly lower than in Wistar rats. SBP, DBP, PWV, UAE, and plasma creatinine positively correlated with the plasma BMP-2/BMP-7 ratio. Periaortic and mesenteric PVAT from MWF rats showed an increased expression of BMP-2 and profibrotic and calcification markers compared to Wistar rats, together with a reduced BMP-7 expression. BMP-2 and BMP-7 imbalance in plasma, kidney, and PVATs is associated with vascular damage, suggesting a profibrotic/pro-calcifying propensity associated with progressive CKD. Thus, their combined analysis stratified by CKD stages might be of clinical interest to provide information about the degree of renal and vascular damage in CKD.

Impact of pharmacist's intervention on reducing cardiovascular risk in obese patients.

Background Obesity is a risk factor for cardiovascular disease, the leading cause of death. Health education, nutritional follow-up, and life style habits modification are key for cardiovascular risk reduction in obese patients. Objective To measure the impact of pharmacist's intervention on cardiovascular risk in obese patients. Setting A Spanish community pharmacy. Method Obese patients (BMI ≥ 30) with (group A, n = 30) and without (group B, n = 14) comorbidities were selected. Variables determined in first visit on-site: anthropometric values (weight, height, waist circumference), blood pressure, glycemic (glucose, HbA1c) and lipid parameters (total cholesterol, HDL-c, LDL-c, triglycerides). The PharmaFit Protocol consisted in a 24-month follow-up focusing (i) monthly on adherence to nutritional guidelines and modification of life style habits, and (ii) bi-monthly on anthropometric variables, blood pressure, and biochemical determinations. Feedback was provided to the primary care physician or specialist. Main ouitcome measure Cardiovascular risk estimated by REGICOR score. Results Anthropometric variables significantly decreased in all groups. Plasma glucose levels were significantly reduced in group A without changes in HbA1c. Lipid parameters significantly improved in group A, whereas HDL-c significantly raised in all groups. REGICOR score was significantly reduced in group A female (13.8 ± 1.6 vs. 5.8 ± 1, p < 0.0001) and male (12.7 ± 1.7 vs. 4.4. ± 0.6, p < 0.005) patients, and in group B female patients (3.5 ± 0.7 vs. 1.9 ± 0.4, p < 0.001). Conclusion Community pharmacist intervention, delivered as a 24-month follow-up and combining health and dietary education, has a highly positive impact on the reduction of cardiovascular risk in obese patients.