Sodium flux during dialysis Sushrut S. Waikar, MD, MPH Renal Division Brigham and Women’s Hospital, Harvard Medical School

Background Kidneys filter the blood, clearing it of waste products 20% of heart’s output is directed to the kidneys, which filter ~180L plasma per day Kidneys also regulate water and salt balance

Background Loss of kidney function leads to death within days Excessive buildup of nitrogenous waste, acid, potassium, sodium, water Kidney function can be partially replaced by hemodialysis (~300,000 patients in United States)

Hemodialysis Kidney function can be partially replaced by hemodialysis First performed by Wilhelm Kolff in early 1940s Procedure is typically performed for 4 hours thrice weekly (e.g., Monday, Wednesday, Friday)

Hemodialysis procedure Blood flows into tubing that divides into thousands of parallel hollow fibers Each fiber is a semipermeable membrane Outside of the fibers runs the “dialysate” solution

Clearance during dialysis Convection Negative pressure applied, water and dissolved small solutes (< 40 kDa) pass across membrane into the dialysate fluid which is then discarded Diffusion Solutes travel across membrane down concentration gradient Blood and dialysate flow in opposite directions, maximizing concentration gradient

Goals of a dialysis procedure Get rid of the water that was ingested and produced (during metabolism) since the last procedure – usually 3 liters Done by convection Get rid of salt (sodium chloride, potassium chloride) Maintain acid-base balance Get rid of nitrogenous waste products (urea)

Plasma versus dialysate Sodium (meq/L) 140 Potassium (meq/L) 5.0 3.0 Chloride (meq/L) 114 110 Bicarbonate (meq/L) 20 35 Calcium (meq/L) 2.5 Urea nitrogen (mg/dL) 40

Urea 70 mg/dL Urea 30 mg/dL

Sodium 142 meq/L Sodium ? meq/L

Sodium in dialysate: 140 meq/L Sodium 142 meq/L Sodium ? meq/L

Sodium in dialysate: 140 meq/L Sodium 142 meq/L Sodium ? meq/L CONVECTIVE CLEARANCE: water and small solutes are removed by negative pressure across membrane DIFFUSIVE CLEARANCE: sodium moves down its concentration gradient (in either direction, depending on plasma concentration; dialysate sodium usually fixed)

Factors that influence sodium flux Dialysate sodium concentration = 140 meq/L Plasma sodium concentration = 142 meq/L, changes during procedure Convection and diffusion occur simultaneously Gibbs Donnan effect Large negatively charged proteins NOT able to pass through membrane; electroneutrality must be maintained Sodium and other cations less “permeable” than anions like chloride, bicarbonate

Sodium 142 meq/L Sodium ? meq/L

Factors that influence Na in plasma Plasma sodium concentration itself has many determinants, not just mass balance of sodium and water Also affected by potassium mass balance Water and sodium flux in various body compartments

Distrbution of salt + water in body Water in a 70 kg man 60% water = 42 liters Intracellular: 28 liters Extracellular: 14 liters Interstitial = 10 liters PLASMA VOLUME = 4 liters Sodium is the primary extracellular cation, 140 meq / liter Intracellular sodium

Dialysis membranes Hollow fibers ~12,000 in parallel 20 – 24cm length, diameter 180 to 220 um, 6 to 15 um thickness Pores: avg diameter 30 Angstroms, 10^9 in number Old: Cellobiose (saccharide) New: synthetic membranes (e.g., polysulfone, polyamide, polymethylmethacrylate) Manufactured polymers classified as thermoplastics

Dialysis procedure Blood flow ~ 400 ml/min Dialysate flow ~ 800 ml/min 40% red blood cells, 60% plasma Plasma: 93% water, 7% protein and lipids Dialysate flow ~ 800 ml/min Typically 2-4 liters of “ultrafiltration” (volume removed during 4h procedure)