Ji Soo Kim (@KimneyJ), Wesley Hayes, Detlef Bockenhauer

Welcome back, I’m glad I didn’t scare you off. Yesterday we discussed how to approach a patient with a suspected tubulopathy, so if you missed it, you can access that here. Today’s mission, understanding the proximal tubule. Let’s go!

The Proximal Tubule

The proximal tubule is where A LOT of everything gets reabsorbed, including water (remember where sodium goes, water follows). So, if something goes wrong in the proximal tubule, not a lot gets reabsorbed and is instead lost in the urine. But, is it the whole proximal tubule? Or part of the proximal tubule?

Fanconi Syndrome

More commonly, when something goes wrong with the proximal tubule, it tends to affect the whole proximal tubule.  The proximal tubule throws all of its babies out with the bathwater. This generalised inadequate reabsorption in the proximal tubule is known as Renal Fanconi Syndrome

History of Fanconi Anemia - Fanconi Anemia South Africa
Guido Fanconi

Findings of Fanconi syndrome include:

  1. Metabolic Acidosis with normal anion gap (from bicarbonate losses)
  2. Urine pH <5.5 (Although you are losing a lot of bicarbonate in the proximal tubule, once the plasma bicarbonate is so low that the sick proximal tubule can’t keep up with the decreased bicarbonate load, bicarbonate wasting stops. And remember, the distal convoluted tubule can still ‘acidify’ by excreting hydrogen ions into the urine. This helps you distinguish ‘proximal’ from ‘distal’ renal tubular acidosis)
  3. Hypokalaemia (impaired potassium reabsorption at the proximal tubule AND secondary hyperaldosteronism from salt loss)
  4. Glycosuria but normoglycaemia
  5. Phosphaturia + Hypophosphataemia
  6. Amino Aciduria / Organic Aciduria / Low Molecular Weight Proteinuria

And then think, “Why is there Renal Fanconi Syndrome in the first place?”

PT – proximal tubule; Loop (of Henle); DCT – distal convoluted tubule; CD – collecting duct

Other Proximal Tubulopathies

So, what about when only part of the proximal tubule is affected? The biochemical (and therefore clinical) condition will depend on which part is malfunctioning:

TOP TIPS

1. Fractional excretion of Sodium (FENa) is normal (<1%) in *almost* all renal salt-wasting disorders because of compensation through the renin-angiotensin axis (hyperaldosteronism). In fact, it must be, because if the kidneys were consistently excreting more sodium than is coming in, the poor patient would become increasingly hypovolaemic. In steady state, the input must be equal to the output.

2. Hyperaldosteronism means sodium reabsorption is encouraged in the distal tubule at the expense of Potassium and Hydrogen ions, unless the renin-angiotensin axis itself is impaired.

Proximal RTA

Here is one way to put proximal renal tubular acidosis in the context of metabolic acidosis:

Management of proximal tubulopathy

Management of a proximal tubulopathy will depend on the underlying problem, but when it comes to replacing those escaping electrolytes, the following rules apply:

  1. Replace electrolytes ENTERALLY if possible and try not to correct them suddenly all at once. (Na+, Cl-, K+, PO4- and Bicarbonate)
  2. Tubular wasting disorders operate 24-7. Replacement should mimic this as much as possible to achieve steady blood levels and avoid big peaks and troughs. Use small, frequent doses and use retard preparations, if available
  3. Normalising blood levels is often impossible:
    – An increase in supplementation leads to a transient increase in blood levels
    – Resulting in a higher filtered load
    – Consequently, in higher tubular losses

4. Rehydrate with fluids – give them free access to water
5. Give activated vitamin D.

Summary Table

I thought it would be useful to build a summary table as we travel along the tubule, to include the key points and act as a reference point for comparison at the end. Each day we’ll add a new line…

And there you go – proximal tubule done. That wasn’t so bad….. was it?

Tomorrow we’re talking thick and thin limbs, counter-currents and renin-angiotensin-aldosterone system as we loop-the-loop of Henle. See you there!

Loop the loop definition and meaning | Collins English Dictionary

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