Abnormal tubular permeability in hypothermic perfused kidneys

Area of Science:

• Nephrology
• Physiology
• Renal Function Studies

Background:

• Isolated canine kidneys perfused at hypothermic conditions (15°C) demonstrate lower than expected inulin and creatinine clearance rates.
• Clearance values for inulin, creatinine, and p-aminohippurate (PAH) correlate linearly with urine flow rate in these perfused kidneys.

Purpose of the Study:

• To investigate the reasons for unexpectedly low inulin and creatinine clearance in isolated, hypothermic canine kidneys.
• To determine if solute loss from tubular fluid contributes to reduced clearance measurements.

Main Methods:

• Isolated canine kidneys were perfused with cryoprecipitated plasma.
• Retrograde intraureteral injection (RII) was used to introduce fluids containing dextran, inulin, and PAH into the tubular system, followed by ureteral occlusion and fluid collection.
• Measurements of solute recovery in renal venous perfusate were performed.

Main Results:

• Inulin and PAH were found to be lost from distal tubular fluid in isolated kidneys, unlike in situ kidneys.
• Recovery percentages in renal venous perfusate after RII were: dextran (9.22%), inulin (11.0%), and PAH (22.0%).
• Solute loss was observed to be dependent on urine flow rate, which could be manipulated by perfusion pressure or mannitol addition.

Conclusions:

• The reduced measured glomerular filtration rate in hypothermic perfused kidneys is partly attributed to the diffusion of inulin and creatinine out of the tubular lumen.
• This tubular leakage affects clearance measurements in isolated kidney preparations.
• Findings highlight the importance of considering tubular solute transport in interpreting renal clearance data, especially under hypothermic conditions.