Renal metabolism and oxygen consumption: Under physiological steady-state conditions, the O2 supply to renal tissues is well in excess of O2 demand. In a healthy kidney, renal O2 extraction is only 10-15%. Most renal oxygen consumption is driven by reabsorption of about 99.5% of filtered sodium (Na+).
The medullary thick ascending limbs of the Henle loop (mTALs) are the major O2-consuming site because of the Na±K±2Cl− transporter. PO2 is normally lower in the medulla than in the cortex.
Renal oxygen consumption is directly related to GFR because GFR determines the filtered sodium load. If GFR increases, the kidneys must reabsorb more sodium, so their work increases and oxygen requirements rise. Sustained intrarenal hypoxia is an underlying cause of chronic kidney disease (CKD). Renal tubular hypertrophy, especially in the medulla, can also predispose to hypoxia and CKD.
The kidney shows highly efficient autoregulation through myogenic and tubuloglomerular feedback mechanisms. This helps keep blood flow and glomerular ultrafiltration relatively constant.
Prostaglandin E2, adenosine, and nitric oxide regulate local medullary oxygen balance.
Prostaglandin E2 (PGE2) is produced mainly by collecting duct cells and interstitial cells of the papilla. It inhibits active transport in the medullary thick limb, which reduces transport-related oxygen consumption by mTAL cells. PGE2 also increases medullary blood flow.
Inhibition of PGE2 production with indomethacin reduces medullary PO2. This reduction is presumed to contribute to the chronic interstitial nephritis seen in analgesic nephropathy, which is characterized by fibrosis that is especially marked in the renal medulla and papilla and can progress to papillary necrosis.
Adenosine activates inhibitory receptors that reduce adenylate cyclase activity. Adenosine analogues active at the A1 receptor inhibit active transport in thick ascending limbs and reduce anoxic injury to the mTAL. Adenosine and its analogues also markedly enhance tubuloglomerular feedback and increase oxygen supply by improving vasa recta flow.
Nitric oxide (NO) is produced from arginine by nitric oxide synthase, which is heavily concentrated in the renal medulla. NO likely has a dual effect: it increases vasa recta flow and decreases active transport by the mTAL.
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