TUBULAR STRESS - a kidney drama

By Robin Rose MD January 15, 2026

👉🏿🌿🌿 Kidney Tubules are where the action is!!

Even in glomerular diseases, declining tubule status is critically important and often precedes the other damages that harm kidney and disrupt filtration in the glomerulus.

Tubule wisdom has become a passion for me in the RENOLOGY journey - the earlier we can step in with awareness of what’s causing kidney decline the more our regenerative medicine wisdom can shine.

So let’s learn together.

“TS” IS TUBULE STRESS.

🌿👉🏿👉🏿What TS-staging means

(core concept)

TS-stage = Tubular Stress stage.

This is a functional- physiologic- metabolic process and concept that complements (and often precedes) eGFR/albuminuria by focusing on tubulointerstitial biology—where CKD usually begins and accelerates.

✨GFR tells you what’s already lost.

✨TS-stage tells you what’s under attack now—and still salvageable. That is a handle for kidney success.

👉🏿🌿🌿Why TS-staging is needed

Conventional CKD staging:

• Overweighs glomerular filtration

• Misses early tubular injury

• Labels Stage 2 decline as “aging” or “normal”

• Detects disease late (missing windows for regenerative possibilities)

  
  

TS-staging reframes CKD as:

• ✨A toxic–metabolic–hypoxic disorder of tubules

  
  

• ✨Driven by SNS tone, phosphate load, acid stress, inflammation, toxins

  
  

• ✨Often present years before creatinine rises

👉🏿🌿🌿TS-Stage framework

—-::>>> (TS0 → TS4)

🌀TS0 — Tubular Reserve (the Resilient Kidney)

👉🏿Biology

• Intact proximal tubules

• Normal mitochondrial density

• Adequate renal perfusion

  
  

👉🏿Labs / signs

• Normal bicarbonate

• Normal phosphate handling

• Low/normal FGF-23

• No tubular protein markers

👉🏿Clinical

• High renal reserve - healthy!

• Stress-tolerant (capable of handling the trauma of illness, meds, toxins, and dehydration)

🌀TS1 — Early Tubular Stress (Reversible)

👉🏿Biology

• Mitochondrial strain

• Oxidative stress

• Early transporter dysfunction

👉🏿Clues

• Mild non–anion gap metabolic acidosis

• Phosphate creeping up within normal range (remember in RENOLOGY - phosphorus >3.5 mg/dL is already creating metabolic havoc )

• Rising FGF-23 with normal PTH

• Fatigue, cold intolerance, nocturia

👉🏿Key point

• Creatinine often still normal

• This is the sweet spot for prevention

🌀TS2 — Established Tubular Injury

👉🏿Biology

• Brush border injury

• Impaired ammoniagenesis

• SNS-mediated vasoconstriction

👉🏿Markers

• ↓ Bicarbonate

• ↑ FGF-23, ↓ Klotho activity

• Tubular proteins (β2-microglobulin, RBP, NGAL)

• Early phosphate toxicity

  
  

👉🏿Clinical

• eGFR may still be “Stage 2”

• Exercise intolerance

• BP lability

• Increased toxin sensitivity

👉🏿👉🏿👉🏿TS2 ≠ normal aging

👉🏿This is active kidney disease.

🌀TS3 — Tubulointerstitial Fibrosis (Progressive)

👉🏿Biology

• Capillary rarefaction

• Fibroblast activation

• Reduced oxygen diffusion

👉🏿Findings

• Persistent acidosis

• Mineral bone axis distortion

• Worsening SNS tone

• Sarcopenia / visceral fat loss

👉🏿Clinical

• eGFR decline accelerates

• Poor recovery from illness

• Medication intolerance

🌀TS4 — Tubular Exhaustion (Low Recovery Potential)

👉🏿Biology

• Fixed fibrosis

• Loss of adaptive capacity

👉🏿Clinical

• Narrow therapeutic window

• Frequent decompensation

• Focus shifts to preservation and symptom stability

• A patient can be:

  • CKD Stage 2 + TS3 (dangerous, ☠️often missed)

  • CKD Stage 3 + TS1 (salvageable)

  
  
  
  

  👉🏿🌿🌿Key drivers of TS-progression

  • Phosphate load / FGF-23 rise

  • Chronic SNS activation (renalase axis)

  • Low-grade acidosis

  • Visceral fat loss / catabolism

  • Environmental toxins (mold, metals, solvents)

  • Hypoxia / sleep disruption

  
  
  
  

  👉🏿🌿🌿Clinical use:::

  (how TS-staging changes medical care)

  
  

  🌀TS-staging informs:

  • Nutrition (phosphate density, protein timing)

  • Hydration type (not just volume)

  • Peptide / bioregulator selection

  • Exercise dosing and commitment

  • Sleep normalization

  • Medication tolerance

  • Illness risk stratification

  
  

  🌀It answers:

  “How stressed are the tubules right now?”

  —not just “What is the GFR?”

  
  

  

  
  

  👉🏿🌿🌿Practical TS-staging inputs (clinic-ready)

  • Serum bicarbonate trend

  • Phosphate

  • FGF-23

  • Urinary tubular proteins

  • BP variability / orthostasis

  • Body composition (VAT loss)

  • Symptom pattern (fatigue, cold,

  
  

  👉🏿🌿🌿CONCLUSION

  TS-staging reframes CKD as a dynamic, tubular-centric process—::> detectable early, modifiable in mid-course, and preventable from accelerating when addressed correctly. Kidney success!

🔆THAT’S RENOLOGY!!🔆