Renal Glucose Handling & Glycosuria

Glomerular filtration

• Glucose is small (~180 Da), water soluble and essentially not protein bound, therefore it is freely filtered at the glomerulus.
• There is no significant renal secretion of glucose.

Filtered glucose load = GFR × plasma glucose concentration

At a normal GFR of about 125 mL/min and plasma glucose of about 5 mmol/L, filtered glucose load is approximately 0.625 mmol/min.

Proximal tubular reabsorption

Normally, virtually all filtered glucose is reabsorbed in the proximal tubule, so essentially none appears in urine.

Transport maximum and renal threshold

• Glucose reabsorption is carrier-mediated and therefore saturable.
• As plasma glucose rises, filtered glucose load rises linearly.
• Initially, reabsorbed load matches filtered load, so urinary glucose is negligible.
• Renal threshold: plasma glucose concentration at which glucose first begins to appear in urine, typically around 10–11 mmol/L, although variable.
• Splay: glucose begins appearing in urine before the whole-kidney transport maximum is reached because nephrons differ in transport capacity and transporter saturation is gradual.
• Transport maximum (TmG): maximum rate of tubular glucose reabsorption; classically about 375 mg/min (~2.1 mmol/min) in an adult.
• Beyond TmG, further filtered glucose cannot be reabsorbed and urinary glucose excretion rises approximately in parallel with filtered load.

Glucose excretion = filtered load − reabsorbed load

Factors causing glycosuria

• Increased plasma glucose: e.g. diabetes mellitus, where filtered glucose load exceeds tubular reabsorptive capacity.
• Reduced tubular glucose reabsorption: e.g. SGLT2 inhibition or proximal tubular dysfunction, which may produce glycosuria despite normal plasma glucose.

Renal consequences of glycosuria

1. Osmotic diuresis

• Glucose remaining within tubular fluid acts as an effective non-reabsorbed osmole.
• It increases tubular fluid osmolality, reduces water reabsorption and increases urine volume.
• High ADH levels cannot fully overcome this diuresis because glucose continues to retain water within the tubular lumen.

2. Volume loss

• Polyuria causes extracellular fluid loss, reduced circulating blood volume, dehydration and hypovolaemia.
• If severe, reduced renal perfusion may reduce GFR.

3. Electrolyte loss

• Sodium: natriuresis accompanies osmotic diuresis.
• Potassium: increased distal tubular flow and distal Na⁺ delivery promote K⁺ secretion.
• Other electrolytes may also be lost with severe or prolonged osmotic diuresis.

4. Other consequences

• Urinary glucose represents loss of an energy substrate/calories.
• Persistent glycosuria may predispose to genitourinary infection, although this is secondary to the core renal physiology being examined.

Summary: glucose is freely filtered, almost completely reabsorbed in the proximal tubule via SGLT2 and SGLT1, and becomes glycosuric when transport capacity is exceeded or tubular reabsorption is reduced. Glycosuria produces an osmotic diuresis with water and electrolyte loss that cannot be fully overcome by ADH.