Pablo E. Pergola

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BACKGROUND Chronic kidney disease (CKD) associated with type 2 diabetes is the leading cause of kidney failure, with both inflammation and oxidative stress contributing to disease progression. Bardoxolone methyl, an oral antioxidant inflammation modulator, has shown efficacy in patients with CKD and type 2 diabetes in short-term studies, but longer-term(More)
BACKGROUND Rats fed a high fat diet and given a low dose of streptozotocin (STZ) (35 mg/kg) develop type 2 diabetes with insulin resistance, hyperinsulinemia, moderate hyperglycemia, hyperlipidemia, and salt-sensitive hypertension. We postulated that rats with noninsulinopenic (type 2) diabetes develop lesions of diabetic nephropathy significantly more(More)
Oxidative stress and inflammation are mediators in the development and progression of chronic kidney disease (CKD) and its complications, and they are inseparably linked as each begets and amplifies the other. CKD-associated oxidative stress is due to increased production of reactive oxygen species (ROS) and diminished antioxidant capacity. The latter is(More)
BACKGROUND Hyperkalemia (serum potassium level, >5.0 mmol per liter) is associated with increased mortality among patients with heart failure, chronic kidney disease, or diabetes. We investigated whether sodium zirconium cyclosilicate (ZS-9), a novel selective cation exchanger, could lower serum potassium levels in patients with hyperkalemia. METHODS In(More)
The role of adrenergic nerve function in the cutaneous vascular response to changes in local skin temperature in the human forearm was examined using three protocols: 1) blocking release of norepinephrine presynaptically by local iontophoresis of bretylium (BT), 2) altering background adrenergic tone by changing whole body skin temperature, and 3) blocking(More)
BACKGROUND The relationships of anemia, microalbuminuria, and estimated glomerular filtration rate (eGFR) with cardiovascular disease (CVD) and subsequent death are not fully understood. We hypothesized that each of these chronic kidney disease-related measures would have an independent relationship with CVD. METHODS A cohort of 37 153 persons screened in(More)
During heat stress, increases in blood flow in nonglabrous skin in humans are mediated through active vasodilation by an unknown neurotransmitter mechanism. To investigate this mechanism, a three-part study was performed to determine the following: (1) Is muscarinic receptor activation necessary for active cutaneous vasodilation? We iontophoretically(More)
To test for an active vasodilator system in human hand and finger skin, seven subjects had a small area of dorsal hand, palm, or dorsal finger pretreated with bretylium (BT) to block adrenergic vasoconstriction. Skin blood flow was monitored at a BT-treated site, a comparable untreated site, and the forearm by laser-Doppler flowmetry. Cutaneous vascular(More)
BACKGROUND Lowering of blood pressure prevents stroke but optimum target levels to prevent recurrent stroke are unknown. We investigated the effects of different blood-pressure targets on the rate of recurrent stroke in patients with recent lacunar stroke. METHODS In this randomised open-label trial, eligible patients lived in North America, Latin(More)
BACKGROUND/AIMS Bardoxolone methyl, a novel synthetic triterpenoid, induces Nrf2, a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules. METHODS This exploratory multi-center, open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with(More)