Renal tissue citrate: independence from citrate utilization, reabsorption, and pH

Area of Science:

• Nephrology
• Renal Physiology
• Biochemistry

Background:

• Alkalosis in vivo leads to increased renal tissue citrate, decreased citrate reabsorption, and utilization.
• Renal citrate handling is complex, influenced by extracellular and intracellular fluid pH and substrate levels.
• In vivo studies are limited in determining maximal citrate transport or utilization rates due to confounding factors like ionized calcium.

Purpose of the Study:

• To investigate renal citrate handling and intracellular citrate concentrations in an isolated perfused rat kidney model under varying pH conditions.
• To determine if alkalosis increases intracellular citrate in the kidney and if maximal rates for citrate utilization and reabsorption exist.
• To elucidate the mechanisms regulating renal citrate metabolism during acid-base balance changes.

Main Methods:

• Isolated rat kidneys were perfused with varying bicarbonate concentrations to achieve extracellular fluid pH of 7.2, 7.4, or 7.6.
• Ionized calcium was maintained at a constant level (2.5 meq/liter) throughout the perfusions.
• Citrate utilization (Qcit) and reabsorption (Tcit) rates were measured, with experiments conducted using citrate as the sole substrate or in the presence of glucose, lactate, and malate.

Main Results:

• When citrate was the only substrate, maximal rates for Qcit and Tcit were observed, with Qcit significantly exceeding Tcit.
• At pH 7.6, both Qcit and Tcit were significantly reduced compared to pH 7.2 or 7.4.
• In the presence of glucose, lactate, and malate, intracellular citrate increased significantly at pH 7.6 compared to pH 7.2, indicating de novo synthesis from precursors.
• Contrary to in vivo findings, intracellular citrate did not significantly increase at high extracellular fluid pH when citrate was the sole substrate.

Conclusions:

• The isolated rat kidney can increase intracellular citrate during alkalosis, deriving it from metabolic precursors rather than extracellular citrate.
• Maximal rates for citrate utilization and reabsorption decrease during alkalosis in the isolated kidney.
• Extracellular fluid pH and bicarbonate levels may directly impact citrate utilization, while high extracellular pH appears to reduce citrate reabsorption capacity.