Effects of Low Chloride versus High Chloride Infusion on Glomerular Filtration Rate and Renal Plasma Flow in Healthy Volunteers—A Randomized, Controlled, Crossover Study

Background: Previous studies have shown that chloride liberal fluids may be associated with worse renal outcomes. Deterioration of kidney function during hyperchloremia/chloride overload is believed to be induced by disturbances in renal perfusion, but exact mechanisms of chloride nephrotoxicity are unclear. The purpose of this randomized, crossover study was to investigate the effect of chloride loading on renal plasma flow (RPF), filtration fraction (FF) and glomerular filtration rate (GFR) in order to elucidate potential nephrotoxic mechanisms of chloride infusion. Methods: Fifteen healthy males were investigated twice after treatment with 2L isotonic saline and plasma-lyte with a wash-out period of at least 10 days. Within 15 mins after completion of infusion, the kidney parameters (RPF, FF and GFR) were estimated by Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography. Results: 99-mTc-DTPA renography showed reduction in both mean GFR (114 ± 13 ml/min vs.119 ± 12 ml/min, p = 0.04) and RPF (977 ± 272 ml/min vs. 1066 ± 197 ml/min, p = 0.19) and increasing FF (12% ± 2% vs. 11% ± 2%, p = 0.19) after 0.9% saline comparing to Plasmalyte, but only GFR reduction was statistically significant. Reduction in GFR and RPF and increasing in FF after 0.9% saline was observed in 10 subjects while in 5 others the reverse trend was shown. There were no statistically significant differences between mean systolic and diastolic blood pressure (BP) before and after each infusion except baseline diastolic BP. Weight changes (Δ weight) were similar after each infusion. Conclusions: We have demonstrated that high chloride infusion can affect kidney function in healthy subjects and seems to lead to impairment in both RPF and GFR.

Acute Effects of Tolvaptan on Renal Hemodynamics in Autosomal Dominant Polycystic Kidney Disease —A Randomized, Cross-Over, Double Blind, Placebo-Controlled Study of Renal Plasma Flow and Glomerular Filtration Rate

Background: Previous studies have shown that reduced renal plasma flow (RPF) may play a role in progression of renal disease in autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan, a vasopressin 2 antagonist, reduces growth of total kidney volume and slows the decrease in estimated glomerular filtration rate (eGFR) in ADPKD. The purpose of this randomized, cross-over, double-blind, placebo-controlled study was to investigate if acute tolvaptan treatment increases RPF in ADPKD patients. Methods: Eighteen ADPKD patients (chronic kidney disease stages I-III) were investigated twice (min. 10 days apart) after acute treatment with either tolvaptan 60 mg or placebo. Two hours after treatment RPF and GFR were estimated by Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography. During the examination day, central and brachial blood pressures (BP) were measured using Mobil-O-Graph? PWA. We also measured plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin II (p-AngII) and aldosterone (p-Aldo), urine excretion of aquaporin 2 (u-AQP2), urine output (OU), urine osmolality (u-Osm) and fractional excretion of sodium (FENa). Results: 99-mTc-DTPA renography showed a similar RPF (673 ± 262 ml/min after tolvaptan vs. 650 ± 209 ml/min after placebo, p = 0.571) and GFR (78 ± 26 ml/min after tolvaptan vs. 79 ± 21 ml/min after placebo p = 0.774) after tolvaptan and placebo treatment. P-AVP and UO increased and u-Osm decreased after tolvaptan and remained unchanged during placebo. Systolic BP tended to decrease during renography during tolvaptan. Very small or insignificant changes were seen in PRC, p-AngII and p-Aldo. Conclusions: Acute tolvaptan treatment did not change renal hemodynamics in ADPKD.