Klotho & kidney disease:
breaking the degenerative cycle

The kidney is where Klotho is made. When kidneys fail, Klotho levels collapse, and when Klotho collapses, kidneys fail faster. Our clinical data show this cycle can be interrupted.



COHORT

Chronic Need

SITE

Los Cabos, MX

THERAPY

Minicircle α-Klotho

REPORT

B. Hanly PhD · Mar 2026

01 — THE CYCLE

The self-reinforcing cycle of CKD and Klotho decline.

STEP 01 /

INITIATION

Renal damage begins

Inflammation, fibrosis, infection, or vascular injury reduces functional nephrons.

STEP 02 /

SUPPLY LOSS

Klotho production falls

The kidney is the primary site of Klotho synthesis. Fewer nephrons means less circulating Klotho.

STEP 03 /

PROTECTION FAILS

Renal protection is lost

Without Klotho, TGF-β-driven fibrosis accelerates, tubular oxidative stress rises, phosphate dysregulation worsens.

STEP 04 /

ACCELERATION

Kidneys fail faster

Accelerated fibrosis and inflammation compound the original damage, the cycle tightens.

02 — LIFE TIME DECINE

Klotho levels decline by over 80% across the adult lifespan — from ~1,500 pg/mL in the twenties to 120–250 pg/mL after age 50. In CKD, this decline is further accelerated by the destruction of the very tissue responsible for producing it. This is why Klotho restoration is not a peripheral intervention in kidney disease — it addresses a central, self-perpetuating mechanism of its progression.

−80%

Drop in circulating Klotho across the adult lifespan.

How Klotho protects renal tissue

03 — MECHANISM

Fibrosis suppression

Klotho directly inhibits TGF-β-mediated pro-fibrotic signalling in tubular cells — the primary driver of scar tissue formation in CKD. Restoring Klotho interrupts the fibrotic remodelling that progressively replaces functional nephrons with connective tissue.

Tubular cell protection

Tubular cells are among the most metabolically demanding in the body. Klotho reduces oxidative and endoplasmic reticulum stress in these cells, protecting against the apoptotic cell death that drives nephron loss in chronic disease.

Phosphate & calcium regulation

As co-receptor for FGF23, Klotho governs phosphate reabsorption in the proximal tubule. Dysregulated phosphate — a hallmark of CKD — drives vascular calcification, soft tissue mineralisation, and accelerated cardiovascular disease in renal patients.

Inflammatory modulation

Klotho suppresses NF-κB activation and reduces TNF-α and IL-6 production within glomerular and tubulointerstitial compartments — reducing the inflammatory burden that sustains both renal and systemic damage.

Preliminary observations from five patients

04 — CLINICAL EVIDENCE

Five patients  ·  Minicircle Klotho gene therapy  ·  Blast Longevity, Los Cabos  ·  Report: B. Hanly PhD, March 2026.  eGFR improved in 5 of 5 patients with available serial data. Creatinine declined in 4 of 4 measured patients. Improvements sustained at 12-month follow-up in two patients with adequate longitudinal data — suggesting lasting structural change, not transient hormonal effect.

EGFR IMPROVEMENT

5/5

All patients with serial data

CREATININE DECLINE

4/4

All measured patients

LARGEST EGFR GAIN

+34%

Patient M, 81 years, 3 months

SUSTAINED AT 12 MONTHS

2/2

Patients with full follow-up

04.1 — MOST COMPELLING CASE

Patient L — eGFR 9 to 32 in three weeks. PATIENT PORTRAIT · DE-IDENTIFIED · 4:5

Female · 54 · Acute kidney injury (UTI)

egfr: 9>32

CREATININE (MG/DL)

5.34 1.87

FERRITIN (ΜG/L)

1852 419

LYMPHOCYTES

6%  →  24%

eGFR recovered from a nadir of 9 to 32 within approximately three weeks of Klotho administration. Creatinine fell from 5.34 to 1.87 mg/dL over the same period. Attending emergency physicians noted the speed of recovery was inconsistent with the expected trajectory given the severity of the acute-on-chronic injury.

Four further patients across age and indication

04.2 — COHORT DETAIL

PATIENT M · MALE · 81

Age-related decline

Largest absolute eGFR gain in cohort.

eGFR 67 > 90 (+34%)

Largest absolute eGFR gain in the cohort, in the oldest patient, where age-related nephron loss typically makes such gains unlikely without active intervention.

PATIENT S · MALE · 70

Moderate CKD

Sustained at 7-month follow-up.

eGFR 72 > 88 (+22%)

Consistent improvement sustained at 7-month follow-up despite a transient dip at time of injection.

PATIENT D · MALE · 70

Longitudinal follow-up

15-month observation window.

eGFR 59 > 72 (+22%)

Improvement sustained at 10-month follow-up. N/L ratio improved markedly within 2 months, reduced systemic inflammatory tone.

PATIENT A · MALE · 74

Moderate CKD

5-month follow-up.

eGFR 63 > 71 (+13%)

Consistent directional improvement at 5-month follow-up across all measured parameters.

05 — DURABILITY OF EFFECT

Why improvements appear to last beyond the signalling window

Klotho directly inhibits TGF-β-mediated pro-fibrotic signalling in tubular cells — the primary driver of scar tissue formation in CKD. Restoring Klotho interrupts the fibrotic remodelling that progressively replaces functional nephrons with connective tissue.

Implication for re-dosing

If Klotho-mediated renal protection induces durable structural change while immune modulation requires ongoing signalling, structural gains may need only bi-annual reinforcement, while immune and cognitive benefits may benefit from earlier re-dosing. Longitudinal data collection is ongoing.

Why kidney disease and heart disease are the same problem

06 — CARDIOVASCULAR CONNECTION

Klotho’s renal protection extends directly into cardiovascular protection — because the two systems share the same Klotho-dependent signalling pathways. Phosphate dysregulation in CKD is a primary driver of vascular calcification and arterial stiffness. Endothelial dysfunction follows. The heart fails partly because the kidneys failed first.

Anti-calcification

Klotho prevents vascular calcification by regulating phosphate and FGF23 signalling — one of the most direct links between CKD progression and cardiovascular mortality.

Endothelial function

Klotho improves nitric oxide bioavailability and reduces endothelial inflammation — restoring vasodilation capacity and reducing arterial stiffness independently of blood pressure control.

Systemic inflammation

The neutrophil-to-lymphocyte ratio improved consistently across the cohort within 2 months of therapy — a systemic marker of reduced inflammatory tone with direct cardiovascular relevance.

From the clinical data:

Across four of the five patients, the neutrophil-to-lymphocyte ratio improved within two months of Klotho therapy — consistent with a shift toward a less inflammatory immune profile. In Patient D, this shift persisted at 10-month follow-up. In Patient M (81 years), the N/L ratio moved from 70/19 to 64/24 within three months — alongside the largest eGFR gain in the cohort. The co-occurrence of renal recovery and immune rebalancing is mechanistically coherent: Klotho suppresses the same NF-κB and cytokine pathways that drive both renal and vascular inflammation.

How the therapy work

07 — DELIVERY

VECTOR

Minicircle DNA

Non-viral, non-integrating. No bacterial backbone — minimal immune activation. No genomic insertion risk.

ROUTE & DEPOT

Subcutaneous injection

Adipocytes act as sustained secretory depots — producing and releasing circulating Klotho continuously after transfection.

ONSET & DURATION

7–10 days · 8–14 months

Plasma Klotho rises within one week of administration and remains elevated for 8–14 months from a single injection.

"The decline of Klotho in the kidney is not just a consequence of kidney disease. In many patients, it is its engine"

By restoring what kidney disease takes away, Klotho minicircle therapy addresses a central degenerative mechanism — not just a downstream marker. Our clinical data show that even in severely compromised kidneys, this restoration produces measurable, structural improvement. The data are preliminary. The signal is consistent.

Turn theory into results

Our methodology is designed to transform your body at a cellular level. Explore the options we have to start your journey toward a longer, healthier life.

Our Partners

Blast Longevity is headquartered in Mexico, Los Cabos. We work with leading clinics aligned with our philosophy and methodology for longevity.

We ensure that select partner locations embody our commitment to science, personalization, and cellular renewal and that they offer world-class protocols, state-of-the-art diagnostics, and holistic wellness environments.

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No Downtime:

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Permanent, Natural Results: The transplanted hair is your own and will grow naturally for a lifetime.

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