Effect of Hypertonic Sodium Chloride on Urinary Biomarkers in Healthy Subjects and Patients With Chronic Kidney Disease (CASE)

Effect of Hypertonic Sodium Chloride on Urinary Biomarkers in Healthy Subjects and Patients With Chronic Kidney Disease

Effect of Intravenous Sodium Chloride on Urinary Biomarkers for Measurement of Sodium- and Water Channel Activity in the Nephron in Healthy Subject an Patients With Chronic Kidney Disease. A Case Control Study

Patients with chronic kidney disease (CKD) have a defect in the tubular reabsorption of sodium, and therefore the ability to excrete a sodium load is diminished compared to healthy subjects. Urinary biomarkers reflects the water- and sodium-channel activity in the kidney and may be measured after an infusion with hypertonic saline in CKD patients and healthy subjects.

The fractional sodium excretion is elevated as high as 10-20% In patients with chronic kidney disease (CKD) Changes in the sodium intake results in a slower expansion and/or reduction in extracellular fluid in CKD patients. Urinary biomarkers reflects the kidneys transport of sodium and water in the nephron. Changes in the sodium-and water channel activity is induced by intervention with hypertonic Saline (3.0%) The change in sodium-and water channel activity is followed by change in extracellular and intracellular fluid compartments and the plasma concentration of vasoactive hormones. The purpose of this study is to investigate the changes in urinary biomarkers (u-NKCC2, u-ENaC-gamma and u-AQP2), the activity of the sodium-and water channels, the extra- and intracellular fluid compartments and the plasma concentration of Vasoactive hormones in patients with CKD and in healthy subjects. Subjects and patients are examined during one examination day. Four days prior to the examination day the subjects consume a standardized diet based on the amount of sodium and calories. On the examination day the subjects receive an infusion with hypertonic saline. Renal function is measured by renal clearance of 51Cr-EDTA. Urinary biomarkers (u-NKCC2, u-ENaC-gamma and u-AQP2) are measured to evaluate the activity of sodium channels in the nephron and changes in fluid compartments are measured by body composition monitor.

Urinary epithelial sodium channels (ENaC), Sodium-potassium-2chloride transporters (NKCC) and aquaporin2 channels (AQP2) before, during and after fluid infusion

plasma concentrations of: renin, Angiotensin II, aldosterone, Vasopressin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)

Inclusion Criteria: healthy subjects healthy males and females age 18-70 BMI range 18,5-30,0 kg/m2 Patients with CKD age 18-70 eGFR 15-60 ml/min BMI range 18.5 - 30.0 kg/m2 Exclusion Criteria: healthy subjects hypertension (ie ambulatory BP >130 mmHg systolic or/and >80 mmHg diastolic) history or clinical significant signs of heart, lung, liver, kidney, endocrine, brain or neoplastic disease. alcohol abuse drug abuse smoking pregnancy or nursing blood donation within a month prior to examination Medical treatment apart from oral contraception Patients with chronic kidney disease clinical significant signs of heart, lung, liver, endocrine, brain or neoplastic disease. diabetes immunosuppressive medications smoking alcohol abuse drug abuse pregnancy or nursing

Jensen JM, Mose FH, Kulik AE, Bech JN, Fenton RA, Pedersen EB. Abnormal urinary excretion of NKCC2 and AQP2 in response to hypertonic saline in chronic kidney disease: an intervention study in patients with chronic kidney disease and healthy controls. BMC Nephrol. 2014 Jun 26;15:101. doi: 10.1186/1471-2369-15-101.