Measuring Glomerular Filtration Rate and Renal Blood Flow

Measuring GFR

• GFR - the amount of plasma ultrafiltrate formed each minute
• Measured using the plasma level of a substance and the amount of that substance that is excreted
• Substances used to measure GFR must be freely filtered through glomeruli, and neither secreted nor reabsorbed by the tubules, as well as nontoxic and not metabolised in the body
• Inulin is commonly used in measuring GFR because it has complete clearance at the glomeruli, and neither secreted or reabsorbed, therefore it's renal plasma clearance = GFR
• Renal plasma clearance - the volume of plasma from which a substance is completely removed by the kidney per minute. Unit is ml/min.

• This is a "virtual volume" which does not actually exist, because there is not actually two different fractions of plasma, one with and one without the tracer

• Free-water - the amount of water present in excess (usually in urine) of that required to produce a solution with the same osmolality as plasma
• A loading dose of inulin is given IV, then a sustained infusion given to keep arterial plasma level constant
• Once the inulin has equilibrated with body fluids, urine and plasma samples are collected and used to determine clearance
• U_IN = 35mg/mL, V = 0.9 ml/min, P_IN = 0.25 mg/ml, C_IN = U_INV/P_IN = 35 x 9 / 0.25 = 126ml/min

(assuming - constant plasma concentration of tracer, tracer does not cause physiological resistance eg. changing what it is used to measure, is not broken down in tubular fluid. Peripheral venous blood can be used to estimate arterial concentration if the venous blood is draining a tissue with no extraction of the substance.)

• Clearance of creatinine C_Cr can also be used, although some creatinine is secreted by tubules, therefore creatinine clearance is slightly higher than inulin

Measuring Renal Blood Flow

• Renal plasma flow (RPF) = the amount of a substance excreted per unit of time divided by the renal A-V difference
• (rearranged from amount excreted = A-V difference x RPF)
• Any substance can be used for this equation, as long as its concentration in arterial and renal venous plasma can be measured, on the condition that

• The amount contained in red cells is unaltered on passage through the kidney
• It is not metabolised, stored or produced by the kidney, and does not affect blood flow

• P-aminohippuric acid (PAH) is often used - this is both filtered by the glomeruli and secreted by tubular cells, so its extraction ratio is high
• When infused at low doses, 90% of PAH in arterial blood is removed in a single kidney circulation, therefore RPF is calculated by dividing the amount of PAH in urine by the plasma PAH level, ignoring the level in renal venous blood
• Peripheral venous plasma PAH level is virtually the same as arterial plasma, therefore this can be used
• Effective renal plasma flow (ERPF) = U_PAHV / P_PAH = Clearance of PAH (C_PAH)
• So for U_PAH (conc of PAH in urine): 14mg/ml, urine flow V: 0.9ml/min, concentration of PAH in plasma P_PAH: 0.02mg/ml
• ERPF = 14x0.9/0.02 = 630mL/min
• This gives the clearance of PAH, that is, the amount of plasma which PAH is cleared from per minute
• Knowing the average PAH extraction ratio 0.9 means that the actual RPF can be calculated (rather than the effective RPF):
• ERPF/extraction ration = 630/0.9 = Actual RPF = 700mL/min
• From this, renal blood flow can be calculated by dividing by (1-Hct)