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Proximal tubule: sodium-coupled glucose and amino acid reabsorption

Proximal tubule · SGLT2 Tm 375 mg/min SGLT2 inhibitors

Secondary active transport in the early proximal tubule (S1/S2) couples the inward sodium gradient to reabsorption of virtually all filtered glucose, amino acids, lactate and phosphate. It is a saturable, transport-maximum-limited system.

Traced from the start

  1. Glomerular filtration barrier
  2. Proximal tubule: sodium-coupled glucose and amino acid reabsorption

Detail

Reabsorbs
~100% of filtered glucose (SGLT2 in S1/S2 takes 80-90%, high-affinity SGLT1 in S3 the remainder) and amino acids; lactate, citrate, phosphate
Transporter
Apical SGLT2 (1 Na+ : 1 glucose) with basolateral GLUT2; apical SGLT1 (2 Na+ : 1 glucose) with GLUT1 in S3
Kinetics
Tm glucose ~375 mg/min (men, ~300 women); renal threshold ~10-11 mmol/L (180-200 mg/dL); splay from nephron heterogeneity means glycosuria begins just below Tm
Hormone
No direct control; angiotensin II and insulin upregulate SGLT2; PTH governs phosphate via NaPi-IIa
Diuretic
SGLT2 inhibitors (empagliflozin, dapagliflozin): glycosuria of ~60-80 g/day with mild natriuresis and osmotic diuresis; lower the renal threshold so glucose appears at normal plasma levels

When it goes wrong

Plasma glucose above ~10-11 mmol/L (diabetes)

Glycosuria with osmotic diuresis: polyuria, polydipsia, volume depletion

SGLT2 inhibitor

Euglycaemic diabetic ketoacidosis (ketosis with glucose under 14 mmol/L), genital candidiasis, volume depletion and postural hypotension; withhold when fasting, peri-operatively or acutely unwell

Generalised proximal tubular failure (Fanconi syndrome: myeloma, cystinosis, tenofovir, cisplatin, Wilson disease)

Glycosuria with normal plasma glucose, aminoaciduria, phosphaturia with rickets or osteomalacia, proximal RTA

Pregnancy (higher GFR and lower threshold)

Benign renal glycosuria with normal plasma glucose

Practise this structure

2 questions in the bank tagged Tubular Transport.

A 7-year-old boy has passed large volumes of urine and craved salty food since infancy, and he is small for his age. His blood pressure is 92/56 mmHg and he has…

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A healthy adult receives an intravenous glucose load. Plasma glucose is 12 mmol/L (reference 3.5–7.8 mmol/L), the measured glomerular filtration rate is 120 mL/…

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