Browsing by Subject "Kidney disease"

Now showing 1 - 3 of 3
  • Thumbnail Image
    ItemOpen Access
    Effects of Proximal Tubule Angiotensin II Signaling on Energy Metabolism in the Kidney
    (2017-12-12) Jimenez Contreras, Fabian
    Chronic kidney disease (CKD) affects over 26 million adults in the United States, thus it is imperative that we deduce more about the pathogenesis of the disease. CKD is generally multi-factorial, and loss of renal function can result from a number of diseases and pathologic processes. For example, propagation of kidney injury and renal fibrosis can result from abnormal regulation of energy metabolism in kidney cells. In renal proximal tubule epithelial cells, a key segment of the nephron, fatty acids are a major fuel source. As the proximal tubule is responsible for the bulk of sodium reabsorption by the kidney, maintaining adequate energy balance is crucial to this function; therefore, alterations in fatty acid oxidation in the renal proximal tubule may lead to renal dysfunction. Our hypothesis is that angiotensin II (Ang II) signaling, a major effector of the powerful renin-angiotensin system (RAS), alters fatty acid oxidation and this becomes exaggerated in states of renal injury such as hypertension and diabetes where the RAS can be dysregulated. Therefore, we sought to explore the metabolic changes linked to Ang II signaling in the renal proximal tubule. Increased levels of Ang II have previously been shown to induce renal fibrosis and hypertension. For our studies, we used a novel mouse line, one lacking AT1a receptors in renal proximal tubule cells (PTKO mice) and expected that the lack of AT1a receptors helps to maintain normal fatty acid oxidation in disease states. To model pathology which might stress the renal proximal tubule cells, we induced two diseases: hypertension, by infusing Ang II via osmotic mini pumps and diabetes, by employing a genetic model of type 1 diabetes, the Akita model. Our major outcome was the assessment of gene expression of several key metabolic pathways, using a quantitative PCR analysis of samples from mouse renal cortex, which is rich in proximal tubules. We aimed to measure genetic biomarkers in the fatty acid oxidation pathway, glucose oxidation pathway, markers of renal injury and fibrosis. These studies demonstrate how two clinically-relevant diseases influence metabolism in the kidney and how leveraging the RAS may lead to solutions against this disruption, and potentially alter CKD progression.
  • Thumbnail Image
    ItemOpen Access
    Impact of Kidney Function on Effects of the Dietary Approaches to Stop Hypertension (Dash) Diet.
    (J Hypertens (Los Angel)) Tyson, Crystal C; Kuchibhatla, Maragatha; Patel, Uptal D; Pun, Patrick H; Chang, Alex; Nwankwo, Chinazo; Joseph, Michael A; Svetkey, Laura P
    OBJECTIVES: Although the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure in adults with hypertension, how kidney function impacts this effect is not known. We evaluated whether Estimated Glomerular Filtration Rate (eGFR) modifies the effect of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function. METHODS: Secondary analysis of the DASH-Sodium trial, a multicenter, randomized, controlled human feeding study that evaluated the blood pressure lowering effect of the DASH diet at three levels of sodium intake. Data from 92 participants with pre-hypertension or stage 1 hypertension during the 3450 mg /day sodium diet assignment contributed to this analysis. Stored frozen plasma and urine specimens were used to measure kidney related laboratory outcomes. RESULTS: Effects of the DASH diet on blood pressure, phosphorus, intact parathyroid hormone, creatinine, and albuminuria were not modified by baseline eGFR (mean 84.5 ± 18.0 ml/min/1.73 m(2), range 44.1 to 138.6 ml/min/1.73 m(2)) or the presence of chronic kidney disease (N=13%). CONCLUSIONS: The impact of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function does not appear to be modified by eGFR in this small subset of DASH-Sodium trial participants with relatively preserved kidney function. Whether greater reduction in eGFR modifies the effects of DASH on kidney related measures is yet to be determined. A larger study in individuals with more advanced kidney disease is needed to establish the efficacy and safety of the DASH diet in this patient population.
  • Thumbnail Image
    ItemOpen Access
    The Role of Traditional Medicine in the Etiology and Management of Chronic Kidney Disease in Moshi, Tanzania
    (2015) Lunyera, Joseph

    Background: Traditional medicine use is increasingly recognized as a common and important component of healthcare globally. Our study aim was therefore to identify the commonly used traditional medicines in Moshi, Tanzania, the factors influencing their use and associations between traditional medicine use & prevalence of chronic diseases. Methods: We performed a secondary data analysis of a mixed methods study in Moshi, comprising 42 extended interviews and 5 focus group discussions with key informants, and cross-sectional household survey using interviewer-administered questionnaires and field-based diagnostic tests for CKD, diabetes, hypertension and HIV. Results: We identified 168 traditional medicines, of which 15 (8.9%) and 5 (3%) were used to treat chronic diseases and CKD, respectively. Participants reported seeking healthcare advice from medical doctors (97%), family members (52%), pharmacists (24%) and friends or neighbors (14%). In a fully adjusted model, CKD patients were more likely than the non-CKD population to report a history of traditional medicine use (AOR=1.99; p=0.04), and family tradition (OR=1.97), difficulty finding a medical doctor (OR=2.07) and fewer side effects with traditional medicines (OR=2.07) as their reasons for preferring traditional medicines to hospital medicines. Conclusions: Traditional medicine use is high in Moshi, and more so among the CKD population. A history of traditional medicine use is associated with the prevalence of CKD in Moshi. Most of these traditional medicines have biologically active substances that could potentially be developed into therapeutic and prophylactic therapies for CKD, and CKD-associated co-morbidities.