“Systemic and renal hemodynamic mechanisms in obesity-related kidney injury“
is funded by UEFISCDI under the PN III – P4 – PCE Programme.
Beneficiary institution: Grigore T. Popa University of Medicine and Pharmacy Iasi
Funding period: 12.07.2017-31.12.2019
Total amount: 832,500 RON
Project code: PN-III-P4-ID-PCE-2016-0126
Obesity is a major independent risk factor for chronic kidney disease (CKD), but the mechanisms leading to obesity-related CKD in theabsence of overt hypertension are unclear. Obesity may increase the transmission of systemic blood pressure (BP) to the glomerular capillaries.
The obese Zucker rats (OZR) develop glomerular injury despite similar BP to lean controls (LZR). We have found that OZR have impaired renal autoregulation (AR) and blunted renal myogenic response (MYO). Furthermore, OZR have higher BP variability and exhibit more frequent hypertensive transients than do LZR, which correlate positively with the degree of renal injury. The baroreflex is also blunted in OZR. Obesity is a condition of chronic inflammation, and we found increased levels of TNF-alpha and IL-6 in OZR, while infusion of IL-6 in normal animals blunts the renal myogenic response and the baroreflex. Based on our preliminary data, we hypothesize that
Glomerular injury in obesity is due, in part, to impaired renal AR and increased BP variability which result in enhanced transmission of systemic BP load to the glomerulus. We further propose that chronic increases in inflammatory cytokines, TNF-alpha and/or IL-6, contribute to the attenuation of baroreflex sensitivity and to blunting of the renal MYO response, leading to renal injury in obesity.
We will test these hypotheses using an integrative physiological approach including novel analytical techniques to assess renal AR and baroreflex, as well as molecular, morphological and biochemical techniques, in the following specific aims:
1) Test the hypothesis that impaired renal AR, due to attenuated renal MYO response, and higher BP variability, due
to reduced baroreflex sensitivity, cause renal injury in OZR;
2) Test the hypothesis that increased inflammatory cytokines (specifically, TNF-α and IL-6) cause attenuation of renal MYO response and reduction in baroreflex sensitivity, leading to renal injury in OZR.