Anaes · Applied cardiovascular & respiratory physiology
Renal: GFR & tubular function
Also known as Glomerular filtration rate · Filtration fraction · Clearance · Tubuloglomerular feedback · Proximal tubule · NHE3
The kidney filters plasma at the glomerulus and then selectively reabsorbs and secretes along the nephron, and the glomerular filtration rate (textbook about 125 mL per minute, not measured in [1]) is the single best measure of kidney function in textbook teaching. GFR/FF/RBF/autoregulation/Starling/clearance/65-percent/diuretic-site numbers below are standard textbook framework carried with explicit honesty notes; the retrieved abstracts own only the narrowed points cited inline. Built on the renoprotective acute-eGFR-decline physiology review with myogenic/TGF/neurohormonal arteriolar mechanisms and GLP-1 nonhemodynamic distinction (Ayub 2026), the macula-densa NOS1-knockout ischaemic-AKI mouse study with enhanced TGF and GFR 236 to 24 microlitres per min (Li 2026), the kidney-specific NHE3-knockout K-restriction mouse study with exacerbated hypokalaemia/acidosis and 60 percent lower glutamine synthetase (Nogueira Coelho 2026), the HUNT-3 proximal-tubule-dysfunction cohort with A1M HR 1.33 and B2M HR 1.28 for CV death (Ikeme 2026), the SGLT2-for-cirrhotic-ascites mechanistic review with NHE3-SGLT2 coupling and TGF/RAAS modulation and limited early clinical data (Gao 2026), and the n-147-dog serum-chloride-RAAS study with inverse angiotensin/aldosterone associations (Adin 2026).
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Red flags
- GFR is about 125 mL per minute and filtration fraction about 20 percent; a fall in GFR is the hallmark of kidney injury, and a small rise in serum creatinine reflects a large fall in GFR because of the curved creatinine-GFR relationship.
- NSAIDs (constrict the afferent arteriole), ACE inhibitors and angiotensin receptor blockers (dilate the efferent arteriole) each lower glomerular capillary pressure and GFR — the mechanism of functional, reversible acute kidney injury, and the basis of the 'double whammy' when combined with hypovolaemia.
- Tubuloglomerular feedback (the macula densa sensing tubular NaCl and adjusting the afferent arteriole) links tubular reabsorption to filtration, so a damaged tubule (less reabsorption) signals the glomerulus to constrict, lowering GFR — a feature of acute tubular necrosis.
- The proximal tubule reabsorbs about 65 percent of filtered sodium and water and essentially all glucose and amino acids; SGLT2 inhibitors block proximal glucose reabsorption, and loss of proximal NHE3 disrupts sodium, bicarbonate and potassium handling.
- Autoregulation holds GFR constant from a mean arterial pressure of about 80 to 180 mmHg, but it is abolished by hypovolaemia and overridden by sympathetic vasoconstriction (shock, stress response), which is why the perioperative kidney is vulnerable.
Meet the patient
A 74-year-old hypertensive diabetic presents for bowel surgery. He takes ramipril, furosemide and, for his back, ibuprofen. He has been fasting and bowel-prepped overnight. At induction his pressure drops, and by morning his urine output is 10 mL per hour and his creatinine has risen. The kidney that filtered fine yesterday now does not.[1]
The question this topic answers is the one his kidney is failing on: what holds glomerular filtration pressure up when the patient is dry? The answer is afferent prostaglandin dilation and efferent angiotensin-II constriction — exactly the two defences his three drugs and his fast have dismantled. That is the triple whammy, and it is the most examinable idea in renal physiology.[1]
References6ShowHide
- [1]Ayub F, Juncos LA The Physiologic Basis of Acute Glomerular Filtration Rate Decline With Renoprotective Therapies Mayo Clin Proc, 2026.PMID 42336099
- [2]Li M, et al. Macula densa-specific NOS1 knockout determines susceptibility to ischemic acute kidney injury Clin Sci (Lond), 2026.PMID 41837645
- [3]Nogueira Coelho J, et al. Renal NHE3 is required to limit hypokalemia and metabolic acidosis during dietary potassium deficiency Pflugers Arch, 2026.PMID 42260191
- [4]Ikeme JC, et al. Proximal tubule reabsorptive dysfunction and risk of cardiovascular death among community-living adults: the HUNT-3 cohort Eur Heart J Open, 2026.PMID 42291457
- [5]Gao Y, et al. Repurposing SGLT2 Inhibitors for Cirrhotic Ascites: From Mechanistic Research to Clinical Exploration J Clin Transl Hepatol, 2026.PMID 41810110
- [6]Adin D, et al. Influence of serum chloride concentrations on the renin-angiotensin-aldosterone system in dogs with congestive heart failure Am J Physiol Renal Physiol, 2026.PMID 42324236