Renal Physiology

Educational Objectives

The goal of this program is to improve the perioperative management of patients with acute or chronic renal injury. After hearing and assimilating this program, the clinician will be better able to:

1. Elaborate on the physiology of renal filtrate formation.

2. Select appropriate tests to assess renal function.

Summary

Renal anatomy: kidneys located retroperitoneal at ≈T12 to L2; composed of renal cortex and medulla; nephron (functional unit) composed of glomerulus surrounded by Bowman capsule and tubules; parasympathetic innervation via vagus nerve; sympathetic innervation arises from T8 to L1; pain relayed through spinal cord from T10 to L1; kidneys receive ≈20% to 25% of cardiac output; filter ≈180 L/day of fluid (99% reabsorbed); urine output 1 to 2 L/day

Nephron: all ultrafiltration occurs in glomerulus; filtrate moves through proximal convoluted tubule, loop of Henle, distal tubule, and collecting duct; cortical nephrons receive ≤90% of renal blood flow; juxtamedullary nephrons receive less blood flow and fewer in number; most secretion and absorption occurs deeper in medulla; vasa recta provide capillary supply to tubules (only supply of oxygen for nephrons deep in medulla)

Filtration: glomerular filtration rate (GFR) measures filter rate per minute; Starling forces (hydrostatic and oncotic pressures) provide driving force for ultrafiltration; affected by renal arterial pressure and tone of afferent and efferent arterioles; filtration occurs if glomerular capillary pressure greater than glomerular oncotic pressure; contents of plasma (minus some plasma proteins) filtered through glomerulus and transported to proximal convoluted tubule

Autoregulation of renal blood flow and GFR: tubuloglomerular feedback involves local vascular tone of afferent and efferent arterioles; fast response; primary mechanism for autoregulation initially; renin secreted by kidney eventually leads to slower, more systemic response; renal blood flow and GFR essentially unchanged if mean arterial pressures 50 to 150 mm Hg

Tubuloglomerular feedback: macula densa on ascending loop of Henle monitors Na and Cl as surrogates for GFR; decreased flow leads to stimulation of cyclooxygenase-2 and prostaglandin E2, suppression of adenosine, and release of renin into systemic circulation; overall effect to dilate afferent arteriole

Renin system: release of renin stimulated by hypotension, decreased Na, or sympathetic stimulation; renin converts angiotensinogen to angiotensin; angiotensin converted to angiotensin II in lungs; leads to release of aldosterone; antidiuretic hormone (ADH) also plays role; ultimate effect vasoconstriction of efferent arterioles; reabsorption of Na and H20 increases in proximal convoluted tubule; increase of GFR leads to negative feedback on renin

Antidiuretic hormone: release of ADH from posterior pituitary stimulated by hypernatremia, hyperosmolality, presence of angiotensin II, hypovolemia, or sympathetic activity; ADH increases reabsorption of water, intravascular volume, and blood pressure (ideally), leads to systemic vasoconstriction through different receptor, activates increase in reabsorption of Na in ascending loop of Henle, and increases water reabsorption in collecting duct

Modification of ultrafiltrate: reabsorption and secretion occur in proximal tubule; more reabsorption (predominantly water) occurs in descending loop of Henle; additional reabsorption (predominantly Na and Cl) occurs in ascending loop of Henle; Na-K-Cl pump located in ascending loop; reabsorption and secretion occur in distal convoluted tubule; 65% of all solutes and 100% of glucose reabsorbed in proximal convoluted tubule; ≈15% of solutes absorbed in loop of Henle and ≈20% in distal convoluted tubule; sites of action for aldosterone include distal convoluted tubule and collecting duct; ADH works on collecting duct

Cellular regulation: energy-dependent process; junctions between cells of collecting duct tight to regulate what can pass through; Na and K channels on luminal side regulated by diffusion; adenosine triphosphate — dependent Na-K pump located in interstitium; energy used to regulate intracellular K leading to K loss, Na reabsorption, change in interstitial fluid osmolality, and increased reabsorption of water

Evaluation of renal function: evaluation of glomerular function (production of ultrafiltrate) and tubular function (reabsorption and modification of ultrafiltrate and secretion of waste products) necessary; can assess GFR with creatinine clearance and serum creatinine; can assess tubular function with fractional Na excretion, serum to urine osmolality ratio, or urine Na concentration; urine output primary method of assessment in operating room

Creatinine clearance: volume of plasma cleared of creatinine per unit of time; creatinine made by skeletal muscles and broken down at relatively constant rate; filtered and secreted in kidneys; creatinine clearance overestimates GFR because of secretion; normal GFR 120 to 130 mL/min/1.73 m2 for young adult; muscle mass decreases with age; 80 mL/min/1.73 m2 considered normal for mature adults; GFR of 15 to 25 mL/min/1.73 m2 raises concern about acute kidney injury or chronic kidney disease; relationship of serum creatinine to GFR inverse and exponential

Serum urea nitrogen (BUN): has inverse relationship with GFR, similar to creatinine; less useful; levels can be altered with diets high or low in protein or with steroids; ≈50% passively reabsorbed in proximal convoluted tubule; reabsorption increases with increased sodium and water reabsorption; BUN rises out of proportion in hypovolemic states; ratio of BUN to creatinine >20:1 in prerenal patients

Assessment of tubular function: most common causes of acute kidney injury prerenal, renal, and acute tubular necrosis; urine Na, fractional excretion of Na, or fractional excretion of urea can be measured; low values for all 3 indicate likely prerenal cause; cause likely not prerenal if values elevated

Anesthetic considerations: most anesthetic agents considered safe; antibiotics (particularly aminoglycosides) could potentially lead to kidney injury; renal effects of anesthetics typically related to hemodynamic changes; hypotension must be avoided; renal dysfunction might lead to decreased excretion of some medications

Neuromuscular blockers and impaired renal function: succinylcholine can be used if no preexisting hyperkalemia; cisatracurium and atracurium likely best choices because of their metabolism; pancuronium has largest decrease in excretion (more than vecuronium and rocuronium)

Other drugs: anticholinesterases (eg, neostigmine) have prolonged effect, but recurarization typically does not occur; metabolites of some opioids (eg, morphine-6-glucuronide, hydromorphone-3-glucuronide, normeperidine) raise concern; benzodiazepines typically have prolonged effect; digoxin may have increased toxicity; potential for increased toxicity with thiocyanate (byproduct of sodium nitroprusside); adjustment of doses of antibiotics necessary

Readings

Goren O et al: Perioperative acute kidney injury. Br J Anaesth 2015 Dec;115 Suppl 2:ii3-14; Hobson C et al: Perioperative acute kidney injury: risk factors and predictive strategies. Crit Care Clin 2017 Apr;33(2):379-96.

 

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Caswell was recorded at Comprehensive Anesthesiology Review, held April 24-28, 2019, in Cleveland, OH, and presented by the Cleveland Clinic Foundation. For information about upcoming CME opportunities from the Cleveland Clinic, please visit www.ccfcme.org. The Audio Digest Foundation thanks the speakers and sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

AN614702

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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