The effect of orally administered nitrate on renal function and blood pressure in a randomized, placebo-controlled, crossover study in healthy subjects.

BACKGROUND: Several studies have shown inorganic nitrate/nitrite to reduce blood pressure in both healthy subjects and hypertensive patients. An effect presumably caused through bioconversion to nitric oxide. However, studies on inorganic nitrate/nitrite have shown inconsistent results on renal functions such as GFR and sodium excretion. The current study investigated whether orally administered nitrate would decrease blood pressure and increase GFR and urinary sodium excretion. METHODS: In a randomized, placebo-controlled, double-blinded, crossover study, 18 healthy subjects received a daily dose of 24 mmol potassium nitrate and placebo (potassium chloride) during 4 days in a randomized order. Subjects also ingested a standardized diet and completed a 24-h urine collection. GFR was determined by the constant infusion technique and during GFR measurement, brachial blood pressure (BP) and central blood pressure (cBP), heart rate, and arterial stiffness were measured every half hour using the Mobil-O-Graph®. Blood samples was analyzed for nitrate, nitrite, cGMP, vasoactive hormones and electrolytes. Urine was analyzed for nitrate, nitrite, cGMP, electrolytes, ENaCγ, NCC, CrCl, CH2O and UO. RESULTS: No differences in GFR, blood pressure or sodium excretion were found between the treatments with potassium nitrate and placebo. However, both nitrate and nitrite levels in plasma and urine were significantly increased by potassium nitrate intake and the 24-h urinary excretion of sodium and potassium were stable, showing adherence to the standardized diet and the study medication. CONCLUSION: We found no decrease in blood pressure or increase in GFR and sodium excretion of 24 mmol potassium nitrate capsules as compared to placebo after 4 days of treatment. Healthy subjects may be able to compensate the effects of nitrate supplementation during steady state conditions. Future research should focus on long-term studies on the difference in response between healthy subjects and patients with cardiac or renal disease.

Comparison of [18F] NaF PET/CT dynamic analysis methods and a static analysis method including derivation of a semi-population input function for site-specific measurements of bone formation in a population with chronic kidney disease-mineral and bone disorder.

PURPOSE: The purpose of this study is to compare dynamic and static whole-body (WB) [18F]NaF PET/CT scan methods used for analysis of bone plasma clearance in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). METHODS: Seventeen patients with CKD-MBD underwent a 60-min dynamic scan followed by a 30-min static WB scan. Tracer kinetics in four thoracic vertebrae were analysed using nonlinear regression and Patlak analysis using image-derived arterial input functions. The static WB scan was analysed using a simplified Patlak method requiring only a single data point in combination with a fixed y-intercept value (V0), both obtained using a semi-population function. The semi-population function was constructed by combining a previously derived population input function in combination with data from venous blood samples. Static WB scan analysis data, obtained from the semi-population input functions, was compared with paired data obtained using dynamic input functions. RESULTS: Bone plasma clearance (Ki) from Patlak analyses correlated well with nonlinear regression analysis, but Ki results using Patlak analysis were lower than Ki results using nonlinear regression analysis. However, no significant difference was found between Ki obtained by static WB scans and Ki obtained by dynamic scans using nonlinear regression analysis (p = 0.29). CONCLUSION: Bone plasma clearance measured from static WB scans correlates with clearance data measured by dynamic analysis. Static [18F]NaF PET/CT scans can be applied in future studies to measure Ki in patients with CKD-MBD, but the results should not be compared uncritically with results obtained by dynamic scan analysis.

Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects - a randomized controlled trial.

BACKGROUND: Chloride is speculated to have nephrotoxic properties. In healthy subjects we tested the hypothesis that acute chloride loading with 3% saline would induce kidney injury, which could be prevented with the loop-diuretic furosemide. METHODS: The study was designed as a randomized, placebo-controlled, crossover study. Subjects were given 3% saline accompanied by either placebo or furosemide. Before, during and after infusion of 3% saline we measured glomerular filtration rate (GFR), fractional excretion of sodium (FENa), urinary chloride excretion (u-Cl), urinary excretions of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ), neutrophil gelatinase-associated lipocalin (u-NGAL) and kidney injury molecule-1 (u-KIM-1) as marker of kidney injury and vasoactive hormones: renin (PRC), angiotensin II (p-AngII), aldosterone (p-Aldo) and arginine vasopressin (p-AVP). Four days prior to each of the two examinations subjects were given a standardized fluid and diet intake. RESULTS: After 3% saline infusion u-NGAL and KIM-1 excretion increased slightly (u-NGAL: 17 ± 24 during placebo vs. -7 ± 23 ng/min during furosemide, p = 0.039, u-KIM-1: 0.21 ± 0.23 vs - 0.06 ± 0.14 ng/ml, p <  0.001). The increase in u-NGAL was absent when furosemide was given simultaneously, and the responses in u-NGAL were not significantly different from placebo control. Furosemide changed responses in u-KIM-1 where a delayed increase was observed. GFR was increased by 3% saline but decreased when furosemide accompanied the infusion. U-Na, FENa, u-Cl, and u-osmolality increased in response to saline, and the increase was markedly pronounced when furosemide was added. FEK decreased slightly during 3% saline infusion, but simultaneously furosemide increased FEK. U-AQP2 increased after 3% saline and placebo, and the response was further increased by furosemide. U-ENaCγ decreased to the same extent after 3% saline infusion in the two groups. 3% saline significantly reduced PRC, p-AngII and p-Aldo, and responses were attenuated by furosemide. p-AVP was increased by 3% saline, with a larger increase during furosemide. CONCLUSION: This study shows minor increases in markers of kidney injury after 3% saline infusion Furosemide abolished the increase in NGAL and postponed the increase in u-KIM-1. The clinical importance of these findings needs further investigation. TRIAL REGISTRATION: (EU Clinical trials register number: 2015-002585-23 , registered on 5th November 2015).