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USMLE Step 1Renal physiologyEP 04 of 08

Glucose transport maximum, splay and SGLT2

Glucosuria is not a leak in a healthy pipe. It appears when the filtered load exceeds a finite carrier capacity, the glucose transport maximum, and splay makes it start earlier than the simple threshold predicts.

  • 4:55 video
  • 3 min read
  • 4 sources
  • Published 6 Nov 2026
Video lesson · 4:55 · Watch on YouTubeSeries: Renal Physiology: GFR, Filtration and Clearance · @medservatory
Chapters (9)
By the end of this lesson

Explain proximal tubular reabsorption of glucose, the transport maximum and splay, and why glucosuria appears in hyperglycaemia or SGLT2 inhibition.

The short version

  1. Filtered load = GFR × plasma glucose; glucose is freely filtered and normally fully reabsorbed, so the urine is glucose free.
  2. SGLT2 (early proximal tubule, S1–S2) does about 90% of reabsorption with high capacity and low affinity; SGLT1 (late proximal tubule, S3) does the remaining 10% with low capacity and high affinity.
  3. Carriers saturate at the transport maximum (Tm), usually quoted at about 375 mg/min; once the load passes it, excretion = filtered load − Tm.
  4. The theoretical threshold is Tm ÷ GFR (300 mg/dL at a GFR of 125 mL/min), but real glucosuria starts at about 180–200 mg/dL; that gap is splay.
  5. SGLT2 inhibitors lower the Tm and the threshold, so glucose spills at a normal plasma level without needing insulin.

Glucosuria with a normal plasma glucose

A routine dipstick comes back glucose positive, yet the plasma glucose is 98 mg/dL, perfectly normal. So where is the sugar in the urine coming from?

The answer lies in the glucose transport maximum, the finite capacity of the proximal tubule carriers, and in what lowers it. This lesson covers glucose reabsorption, the transport maximum, splay, and why glucosuria appears. It builds on the previous lesson, where a clearance below GFR meant net reabsorption.

Filtered load: how much glucose reaches the tubule

Glucose is the classic case of net reabsorption: it is freely filtered and normally fully reabsorbed, so the urine is glucose free.[1][4]

Filtered load
Filtered load = GFR × plasma glucose

With glucose in mg/dL, express GFR in dL/min (1 dL = 100 mL) to get mg/min

SGLT2 and SGLT1: the glucose carriers

Glucose crosses the luminal membrane by sodium-coupled transport, which is secondary active transport. Two carriers share the work.[1][2]

Luminal glucose carriers in the proximal tubule
CarrierSiteShare of reabsorptionProperties
SGLT2Early proximal tubule, segments S1 and S2About 90%High capacity, low affinity
SGLT1Late proximal tubule, segment S3About 10%Low capacity, high affinity

The transport maximum: when the carriers saturate

Carriers are finite. Raise the filtered load and reabsorption rises with it, until the carriers saturate. That ceiling is the transport maximum (Tm), usually quoted at about 375 mg/min.[2][3]

Past the Tm, every extra milligram filtered is simply excreted.

Excretion above the Tm
Excretion = filtered load − Tm

Applies once the filtered load exceeds the Tm

Renal threshold and splay

The renal threshold is the plasma glucose at which glucose first appears in urine. If every nephron were identical, it would be the Tm divided by GFR. With a GFR of 125 mL/min (1.25 dL/min), that is 375 ÷ 1.25 = 300 mg/dL.[2][3]

But real glucosuria starts earlier, at around 180–200 mg/dL. That gap is splay. Nephrons differ in GFR and carrier number, so some spill glucose early.[2][3]

Worked example: GFR 120 mL/min

Take a GFR of 120 mL/min, which is 1.2 dL/min, and a Tm of 375 mg/min.

Plasma glucose 300 mg/dL, then 500 mg/dL
  1. At 300 mg/dL: filtered load = 1.2 × 300 = 360 mg/min
  2. 360 is below the Tm of 375, so the simple model predicts no glucose in the urine
  3. At 500 mg/dL: filtered load = 1.2 × 500 = 600 mg/min
  4. 600 is above the Tm, so excretion = 600 − 375 = 225 mg/min

SGLT2 inhibitors and glucosuria

Back to the dipstick. SGLT2 inhibitors block the main carrier, so the Tm falls and the threshold drops sharply. In studies the threshold fell from roughly 180–200 mg/dL to under 100 mg/dL.[1][2][3]

So glucose spills at a normal plasma level, and it does so without needing insulin.

Glucosuria means the filtered load exceeded reabsorptive capacity, either because plasma glucose is high or because the capacity is lowered.

Practice question

Original · USMLE style
Your turnQB-MS-S1-REN-026-01

A 46-year-old man with type 2 diabetes mellitus is brought to the emergency department after 3 days of polyuria and poor oral intake. He is volume depleted. His glomerular filtration rate is 80 mL/min and his plasma glucose concentration is 700 mg/dL. Assume that the renal tubular transport maximum for glucose is 375 mg/min and that splay can be ignored.

Which of the following is closest to this patient's rate of urinary glucose excretion?
Pick one option. Your answers stay on this device.

Common questions

What is the glucose transport maximum (Tm)?

It is the ceiling of glucose reabsorption, reached when the proximal tubule carriers saturate. It is usually quoted at about 375 mg/min.

How do you calculate urinary glucose excretion?

Filtered load is GFR × plasma glucose. Once the load passes the Tm, excretion = filtered load − Tm, because every extra milligram filtered is simply excreted.

What is splay in renal glucose handling?

Splay is the gap between the theoretical threshold (Tm ÷ GFR, 300 mg/dL at a GFR of 125 mL/min) and the real threshold of about 180–200 mg/dL. Nephrons differ in GFR and carrier number, so some spill glucose early.

What do SGLT2 and SGLT1 do?

Both reabsorb glucose with sodium. SGLT2, in the early proximal tubule, does about 90% of the work with high capacity and low affinity; SGLT1, in the late proximal tubule, picks up the remaining 10% with low capacity and high affinity.

Why do SGLT2 inhibitors cause glucosuria at a normal plasma glucose?

They block the main carrier, so the Tm falls and the threshold drops sharply, from roughly 180–200 mg/dL to under 100 mg/dL in studies. Glucose therefore spills at a normal plasma level, without needing insulin.

Transcript

Read the full narration, by chapter594 words

0:00A positive dipstick, normal plasma glucose

A routine dipstick comes back glucose positive. The patient's plasma glucose is 98 milligrams per decilitre, perfectly normal. So where is the sugar in the urine coming from? Today: glucose reabsorption, the transport maximum, splay, and why glucosuria appears.

0:19The mental model: filtered load

First, the mental model. Last time, clearance below GFR meant net reabsorption. Glucose is the classic case: freely filtered, and normally fully reabsorbed, so the urine is glucose free. Filtered load is GFR times plasma concentration. Now the carriers.

0:38SGLT2 and SGLT1: the carriers

Glucose crosses the luminal membrane by sodium coupled transport, which is secondary active transport. SGLT two, in the early proximal tubule, segments one and two, does about 90% of the work. It has high capacity and low affinity. SGLT one, in the late proximal tubule, segment three, picks up the remaining 10%. It has low capacity and high affinity.

1:07The transport maximum and the titration curve

But carriers are finite. Raise the filtered load and reabsorption rises with it, until the carriers saturate. That ceiling is the transport maximum, T m, usually quoted at about 375 milligrams per minute. Past the T m, every extra milligram filtered is simply excreted. Excretion equals filtered load minus T m.

1:31The renal threshold and splay

Now the threshold: the plasma glucose at which glucose first appears in urine. If every nephron were identical, it would be the T m divided by GFR. With a GFR of 125, that is 375 over 1.25, 300 mg/dL. But real glucosuria starts earlier, around 180 to 200. That gap is splay. Nephrons differ in GFR and carrier number, so some spill glucose early.

2:05Worked example: GFR 120 mL/min

Let's run it. GFR 120 mL a minute, which is 1.2 decilitres a minute. Plasma glucose 300 milligrams per decilitre. Filtered load: 1.2 times 300, 360 milligrams a minute. That is below the T m of 375, so a simple model predicts no glucose in the urine. At 500, the load is 600, so 225 milligrams a minute are excreted.

2:36SGLT2 inhibitors and glucosuria

Back to the dipstick: SGLT two inhibitors block the main carrier, so the T m falls and the threshold drops sharply. In studies the threshold fell from roughly 180 to 200 to under 100 milligrams per decilitre. So glucose spills at a normal plasma level, and it does so without needing insulin. Glucosuria means the filtered load exceeded reabsorptive capacity, either because plasma glucose is high or because the capacity is lowered.

3:08Practice question

Your turn. A 46-year-old man with type two diabetes is volume depleted, with a GFR of 80 mL per minute. His plasma glucose is 700 milligrams per decilitre. Assume a transport maximum of 375 milligrams per minute, and ignore splay. Which is closest to his rate of urinary glucose excretion? A, zero. B, 185 milligrams per minute. C, 375. D, 560. E, 935. Pause here and decide. Filtered load first: point eight decilitres a minute times 700 is 560 milligrams a minute. A is out: zero would mean the load stayed under the T m, and it does not. C is out: 375 is the most that is reabsorbed, not the amount excreted. D is out: that is the whole filtered load, as if nothing were reabsorbed. E is out: it adds the T m to the load, instead of subtracting it. So the answer is B: 560 minus 375 leaves 185.

4:26High-yield recap and next lesson

Three things to keep. One: excretion is filtered load minus the T m, once the load passes the T m. Two: splay rounds the curve, so glucosuria starts below the theoretical threshold. Three: SGLT two inhibitors lower the threshold, so glucose appears even at normal plasma levels. Next up: the countercurrent mechanism, and how the kidney concentrates urine.

Sources

Numbers in the text, e.g. [1], point here
  1. Kalra S. Diabetes Ther 2014;5:355-366 (SGLT2 and SGLT1 sites and shares of glucose reabsorption). PMC4269649. pmc.ncbi.nlm.nih.gov/articles/PMC4269649
  2. Andrianesis V et al. Ther Adv Endocrinol Metab 2016;7:212-228 (transport maximum, renal threshold, splay, SGLT2 inhibition). PMC5298360. pmc.ncbi.nlm.nih.gov/articles/PMC5298360
  3. DeFronzo RA et al. Diabetes Care 2013;36:3169-3176 (titration curve, threshold, splay, effect of SGLT2 inhibition on the threshold). PMC3781504. pmc.ncbi.nlm.nih.gov/articles/PMC3781504
  4. Perry RJ, Shulman GI. J Biol Chem 2020;295:14379-14390 (SGLT2 in the early proximal tubule; limits of SGLT2 inhibition). PMC7573269. pmc.ncbi.nlm.nih.gov/articles/PMC7573269

Transport maximum and threshold figures are textbook conventions; measured values vary between studies. The splay rounding and the inhibitor curves drawn in the video are illustrative.

The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.

Image credits. All video diagrams are original (code-drawn); no third-party artwork is used in the video. Thumbnail: kidney/nephron illustration from Servier Medical Art (smart.servier.com), licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/); adapted (recoloured, outlined, resized). Example lab values are illustrative.

Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-REN-026.

For exam study only, not medical advice. Read the medical disclaimer.

In this series

Playlist on YouTube
← Previous · EP 03Renal clearance: inulin, creatinine and PAH
  1. EP 01GFR and Starling forces at the glomerulus5:25
  2. EP 02Afferent vs efferent arteriole: GFR, RPF and filtration fraction5:16
  3. EP 03Renal clearance: inulin, creatinine and PAH5:20
  4. EP 04Glucose transport maximum, splay and SGLT24:55
  5. EP 05Countercurrent multiplier: how the kidney concentrates urine5:02
  6. EP 06Aldosterone and ADH in the distal nephron5:20
  7. EP 07Diuretics by nephron segment: loop, thiazide and more5:53
  8. EP 08RAAS explained: renin, angiotensin II and aldosterone5:23