Fibroblast Growth Factor-23 —::> Insight in CKD (and some bioregulator peptide tips)

by Robin Rose MD (May 27, 2025)

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Sometimes when I read studies (and their conclusions) with a RENOLOGY eye and filter —::> I disagree.

FGF23 is a topic like that.

In another ASN Kidney News (Oct/Nov 2017) a brief description of a study done in England by Shardlow et al suggested that this marker is not “useful” for primary care to order in Stage 3 CKD. Why? Because progression to end stage disease isn’t affected they say.

👉🏿 I BEG TO DISAGREE with this line of thinking. Several reasons.

First of all - remember that the masses of CKD patients in stage 3 often don’t ever arrive at end stage disease. No - they die before that —::> from complications caused by the declined circumstances in earlier disease. The kidney bone is connected to the heart bone: cardiovascular demise takes many kidney patients out long before they arrive at kidney failure.

So to say FGF23 is of no use to my primary care colleagues and I (we who are called upon to manage kidney disease with eGFR greater than 30) well, that isn’t logical or considerate.

Those who know me know that I care about phosphorus levels in early CKD.

And remember that the normal range for serum phosphorus is not normal in ckd (refer to my blog post about lab work). Serum phosphorus over 3.5 mg/dL is already asking for cardiovascular trouble. Calcium leached from the bones and deposited in the arteries is no trivial thing.

So we are obliged to attend to the cardiorenal array of worries that can threaten the wellbeing and actual life of kidney patients.

FGF23 will inform us about many things before the actual lab values begin to shift. That is a marvelous tool!!

And then, this idea that end stage kidney failure is the target for decision making ignores the truth of the matter:. Many many more CKD people die of other related causes (think heart failure, heart attacks, strokes) than kidney failure. We cannot lose track of that fact - I prefer to justify the wisdom of prevention and protection.

So here below is some chat gpt didactic to study - to amplify the skills in your journey of understanding the relationships between Klotho. FGF23, PTH, phosphorus, calcium, and 1,25 vitamin D :: all actionable players in this ckd jamboree.

👉🏿Fibroblast Growth Factor 23 (FGF23) plays a central role in phosphate homeostasis, especially in the early stages of chronic kidney disease.

Here’s a concise yet detailed review of how FGF23 and phosphorus interact in early CKD, with references.

👉🏿FGF23 and Phosphorus in Early CKD

1. Role of FGF23

FGF23 is a hormone secreted by osteocytes and osteoblasts in response to elevated serum phosphate or increased dietary phosphate intake.

• Primary actions:

  • Reduces renal phosphate reabsorption by downregulating NaPi-2a/2c cotransporters in the proximal tubule.

  • Suppresses 1α-hydroxylase, reducing 1,25(OH)₂D (calcitriol) synthesis, thereby lowering intestinal phosphate and calcium absorption.

  • Requires Klotho as a co-receptor for activity.

  
  

In early CKD (stages 1–3):

FGF23 is the first biomarker to rise, often before hyperphosphatemia appears (Isakova et al., 2011).

2. Phosphate Handling in Early CKD

In early CKD, glomerular filtration rate (GFR) is mildly reduced, but phosphate levels often remain normal due to compensatory increases in FGF23.

• Key adaptation:

  • As nephron number declines, FGF23 increases to enhance phosphate excretion from the remaining nephrons.

  • Serum phosphate may still appear normal due to this hormonal adaptation.

✦ However, chronically elevated FGF23 is not benign — it’s associated with LVH (left ventricular hypertrophy), increased mortality, and progression of CKD (Faul et al., 2011).

3. Clinical Implications

• Elevated FGF23 precedes rises in parathyroid hormone (PTH).

• Even with normal phosphorus levels, elevated FGF23 in early CKD should prompt:

  • Dietary phosphate restriction (especially inorganic sources).

  • Consideration of phosphate binders in select cases.

  • Monitoring of vitamin D metabolism and Klotho expression.

    
    

4. Dietary Phosphate Considerations

• Inorganic phosphate (e.g., from additives) is 90–100% bioavailable. Meat is 80% bioavailabie.

• Organic phosphate from plant sources is less absorbable due to phytate- more in the range of 40% - offering many benefits in ckd

• High phosphate intake can raise FGF23 even in people with normal kidney function.

5. Therapeutic Targeting

Emerging strategies aim to:

• Reduce FGF23 overproduction or block its harmful effects

• Modulate phosphate intake and gut-derived uremic toxins that can stimulate FGF23.

☀️A RENOLOGY PEPTIDE TUTORIAL☀️

💫Bonothyrk is a peptide bioregulator derived from the parathyroid gland - it supports the trophic regulation of parathyroid tissue function.

In the context of CKD with elevated FGF23 and phosphorus imbalance, using Bonothyrk can be rationalized as follows:

👉🏿Rationale for Bonothyrk Use in CKD with Hyperphosphatemia and High FGF23

☀️Modulation of Parathyroid Function

• CKD disrupts the calcium-phosphorus-PTH-FGF23 axis, often leading to secondary hyperparathyroidism (sHPT).

• Elevated FGF23 suppresses calcitriol, reducing calcium absorption and stimulating PTH secretion.

• Bonothyrk may help normalize PTH secretion by supporting the regeneration and peptide expression of parathyroid cells, potentially reducing maladaptive PTH responses.

☀️Downstream Effects on Phosphorus Metabolism

• Balanced PTH activity supports phosphaturia (urinary phosphate excretion), especially early in CKD.

• By stabilizing parathyroid tone, Bonothyrk can indirectly help to moderate phosphorus levels and reduce the feedback pressure on FGF23 secretion.

☀️FGF23 Overcompensation and Bonothyrk’s Possible Mitigation Role

• In early CKD, FGF23 elevation precedes PTH as a compensatory mechanism.

• Chronic FGF23 elevation is associated with left ventricular hypertrophy (LVH) and increased mortality.

• By assisting PTH balance, Bonothyrk could alleviate the need for excessive FGF23 upregulation, helping to rebalance the regulatory loop.

☀️Bonothyrk is a peptide bioregulator derived from the parathyroid gland (by the Russian peptide school, marketed by companies like Peptides or Khavinson’s institutes). It contains short peptides thought to support the trophic regulation of parathyroid tissue function.

In the context of CKD with elevated FGF23 and phosphorus imbalance, using Bonothyrk can be rationalized as follows:

☀️Klotho and Vitamin D Crosstalk

• FGF23 suppresses 1α-hydroxylase, reducing active vitamin D.

• A well-regulated parathyroid system, supported by Bonothyrk, may help maintain vitamin D receptor signaling, indirectly aiding phosphate and calcium balance.

☀️Peptide Bioregulation in CKD

• In peptide theory, Bonothyrk may support gene expression and repair of damaged parathyroid cells without hyperstimulation.

• This is not a hormone therapy, but a low-dose peptide support aimed at restoring physiological feedback loops.

☀️ Supporting Evidence (Theoretical and Empirical)

• While peer-reviewed Western trials are limited, studies from St. Petersburg Institute of Bioregulation (Khavinson et al.) have shown that:

  • Parathyroid-derived peptides can normalize PTH levels in aged or stressed animals.

  • They have a low risk of overstimulation, acting more as epigenetic modulators than direct agonists

    
    

☀️ Vitamin D Crosstalk

• FGF23 suppresses 1α-hydroxylase, reducing active vitamin D.

• A well-regulated parathyroid system, supported by Bonothyrk, may help maintain vitamin D receptor signaling, indirectly aiding phosphate and calcium balance.

☀️Peptide Bioregulation in CKD

• In peptide theory, Bonothyrk may support gene expression and repair of damaged parathyroid cells without hyperstimulation.

• This is not a hormone therapy, but a low-dose peptide support aimed at restoring physiological feedback loops.

• A knowledgeable RENOLOGY clinician can guide patients in choosing and using these strategies.

☀️RENOLOGY PEPTIDES, FOLLOWING THE HARVEST OF LOW HANGING FRUIT FROM THE TREE of LIFESTYLE 👉🏿 a path to Kidney Success ☀️

Key References

• Isakova T, Wahl P, et al. Fibroblast growth factor 23 is a novel early marker of mineral metabolism disruption in CKD. Kidney Int. 2011;79(12):1370–1378. doi:10.1038/ki.2011.47

• Faul C, Amaral AP, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121(11):4393–4408. doi:10.1172/JCI46122

• Scialla JJ, Wolf M. Roles of phosphate and FGF23 in cardiovascular disease. Nat Rev Nephrol. 2014;10(5):268–278. doi:10.1038/nrneph.2014.49

• Khavinson V. Kh. et al. “Peptide regulation of age-related dysfunction of parathyroid gland in rats.” Bulletin of Experimental Biology and Medicine, 2003.

• IsakovaT. et al. “FGF23 and adverse outcomes in CKD.” J Am Soc Nephrol, 2011.

• FaulC. et al. “FGF23 induces LVH.” J Clin Invest, 2011