Why I Know that Stage 2 CKD Is NOT NORMAL

docbinah
Jun 17
7 min read

Updated: Jun 18

by Robin Rose MD - June 17, 2025

🪷Stage 2 Chronic Kidney Disease:

Not Just Aging, But a Call to Action

Sometimes I realize that using the term disease is hard for some people to embrace. Rather than encouraging denial - let’s call it chronic kidney decline. And then we choose to learn what’s going on that can be repaired and how to address it with self loving care and nature.

It’s often assumed —[incorrectly] — that Stage 2 CKD [defined by an estimated glomerular filtration rate (eGFR) from 60 to 89 mL/min/1.73 m²] is an expected “normal” part of aging. Many patients — [and unfortunately, many clinicians] — dismiss this stage as clinically insignificant - unless overt proteinuria is present ( I even had a cardiologist try to humiliate me by demanding that I “repeat after me - I don’t have ckd”- even though I was in stage 3 - but had no proteinuria. Really??!!)

But - this view is not only outdated 👉🏿 it is dangerously misleading. I’ve seen patients in stage 2 get an infection like Covid or a trauma and plummet down wildly in renal function. Knowledge translates to action and preventive adaptation can be life and nephron saving.

Stage 2 CKD is not a benign or merely statistical classification.

It represents a biologically active disordered/disease state that reflects injury, maladaptation, and systemic risk — even in the absence of proteinuria or abnormal lab values. Early intervention at this stage can prevent irreversible nephron loss, halt subclinical inflammation, and reduce long-term cardiovascular and metabolic complications.

🪷The Myth of “Normal” Aging

Yes, GFR may decline with age. Yet the question must be asked: why???

One easy response is that kidney decline is caused by toxin exposures throughout the decades of life - the exposome - and then epigenetic damage results. Until toxin monitoring becomes commonplace, we literally can not say that kidney declines simply due to age. There’s a reason and when it’s sought - and found - and remediated, the story plot changes. Remember that bioregulator peptides play a role in repairing epigenetic damage!

So the presence of an eGFR in the 60–89 range does not mean a person is healthy 👉🏿 and there are also other markers of kidney injury to use.

According KDIGO [international guidelines], patients with Stage 2 CKD must have structural or functional damage — and this damage is often present before creatinine levels rise or albumin-creatinine-ratio (ACR) indicates protein spillage.

In truth, many of the subtle, under-appreciated changes in Stage 2 CKD are actual signs of early pathological processes - rather than “benign aging” (the conversation often includes “well what do you expect at your age” - my own answer is vitality and wellbeing!). These subtle early changes are measurable — if we look for them and listen to early whispers of preclinical symptoms — this is modifiable with the right approach.🔬

Subtle abnormalities in urine pH, citrate, or concentrating capacity can also signal early nephron stress. Think tubules.

Some patients with Stage 2 CKD fall into the non-proteinuric phenotype — a group shown to have increased cardiovascular mortality and faster CKD progression, especially among elders and those with metabolic syndrome.

🪷The Hidden Pathology of Stage 2 CKD

Even when albuminuria is absent or minimal, Stage 2 CKD can involve significant pathophysiological changes, including:

🧬Tubulointerstitial inflammation and fibrosis:

Early cytokine signaling (ie.TGF-β, IL-6) begins before creatinine rises. Studies show elevated tubular markers like NGAL and KIM-1 can predict progression, and urinary beta-2 microglobulin testing suggests early tubular dysfunction ( and that is key ! Not to be ignored). The tubules are the core of biochemical discernment in the body- what to keep and what to excrete: when this goes awry it’s truly a tragedy of metabolic chaos in evolution.

🧬Endothelial dysfunction:

Subclinical vascular inflammation and impaired nitric oxide signaling are common in early CKD and contribute to systemic hypertension and cardiac risk. Understanding that statistically, more CKD patients die from cardiovascular failure than kidney failure - this means we are really obliged to intervene and reverse what’s possible as early as possible.

🧬Metabolic acid-base imbalance:

Subtle acidosis may be present even when bicarbonate levels appear “normal,” driving atherosclerosis, bone loss and muscle wasting.

Intervening can improve potassium, phosphorus, uric acid, and parathyroid hormone abnormalities - the earlier the better, as over time, damages occur that can cause a long haul of misery for patients in decline. Optimizing the serum CO2 over 25 and closer to 30 can be useful.

🧬Early mineral metabolism disruption:

FGF-23 and PTH elevations often precede phosphate shifts, contributing to cardiovascular risk. Of critical importance is realizing that serum phosphorus #1 is often not even ordered and #2 is only “normal” in ckd when it’s below 3.5 mg/dL ( the so called normal range is 2.5-4.5 mg/dL - and is deceptive if it’s used for ckd ).

🧬Renal senescence and maladaptation:

Molecular aging markers like p16 and mTOR rise early, promoting tubular stress and glomerular hypertrophy. There are many ways to approach senescence and remediate it in CKD. Bioregulator peptides play an important role in this regard. See Renology Peptides.

🧬Mitochondrial Dysfunction

Mitochondria — our cellular “power plants” —critically maintain renal tubular cell function through ATP production, redox balance, and apoptotic signaling.

In early CKD, mitochondrial dysfunction is a key pathogenic driver, even before measurable glomerular decline [meaning normal GFR may not illuminate the true picture]. We see:

Decreased mitochondrial biogenesis
Increased reactive oxygen species (ROS) production
Loss of mitochondrial membrane potential
Apoptosis of renal tubular epithelial cells

These disruptions reduce nephron energy efficiency, worsen oxidative stress, and contribute to progressive fibrosis 👉🏿 especially strong in diabetic nephropathy and hypertensive nephrosclerosis.

🧬 Heavy metals and toxins [a major conversation]

A foundational flaw in CKD thinking is the assumption that declining GFR is an inevitable part of aging. But we now realize that it is not a cause — it's a context.

What truly accumulates with time in most individuals is toxic load: heavy metals, pesticides, pharmaceuticals, plasticizers, air pollutants, and uremic solutes. This is called the exposome - a rich topic for another blog post! These are nephrotoxic by nature. They promote mitochondrial dysfunction, tubular inflammation, oxidative stress, fibrosis, and immune dysregulation — the very hallmarks of early CKD [sadly conventional medicine rarely screens for them, let alone addresses them] .

Exposure to heavy metals like cadmium, lead, arsenic, gadolinium, aluminum, and mercury is a well-documented risk factor for early kidney injury. These metals:

Accumulate/damage in proximal tubular cells
Disrupt mitochondrial electron transport
Induce oxidative and nitrosative stress
Trigger cell death and interstitial fibrosis

Chronic low-dose exposure (ie from contaminated water, rice, fish, or industrial emissions) may lead to subclinical nephrotoxicity, which progresses insidiously to CKD.

Environmental nephrotoxins [such as pesticides, solvents, and bisphenol A (BPA) etc] also contribute to early renal damage via mitochondrial damage and proinflammatory cytokine activation.

Until we systematically measure, reduce, and support the exposure history/exposome of each patient and then actively seek to clear environmental and metabolic toxins, we cannot accurately speak about “normal aging” in relation to the kidneys. Chronic kidney disease is not simply a disease of age. It is a disease of accumulated injury — and injury is modifiable.

🧬Gut Dysbiosis in CKD [also major]:

Gut dysbiosis — an imbalance in the intestinal microbiome — is already present in many patients with Stage 2 CKD. Even modest declines in kidney function are associated with shifts in microbial composition that favor undesirable uremic toxin producers such as Clostridia and Enterobacteriaceae, 👉🏿 while beneficial butyrate-producing species decline.

Dysbiosis contributes to increased intestinal permeability (“leaky gut”), systemic inflammation, and elevated levels of harmful gut-derived uremic toxins [like indoxyl sulfate and p-cresyl sulfate - both are toxic to renal tubules and promote oxidative stress and fibrosis].

Dysbiosis alters bile acid metabolism, impairs short-chain fatty acid (SCFA) signaling, and disrupts immune regulation. These changes further burden the kidneys and accelerate metabolic and vascular complications.

Supporting microbial diversity and gut integrity through diet, probiotics, prebiotics, peptides, and reduced use pharmaceutical gut stressors (like PPIs, antibiotics, steroids) can offer critical early intervention in CKD care. Being proactive and protective trumps treating overt distress/decline/disease.

🪷Functional Markers Beyond Proteinuria

So Stage 2 CKD is often overlooked and under diagnosed because most aren’t looking beyond albuminuria and creatinine. Yet even when ACR is normal, markers like urinary β2-microglobulin, retinol-binding protein (RBP), and NGAL reveal early tubular damage.

🪷Stage 2 CKD Is Treatable

Intervening at Stage 2 is not just possible — it’s a clinical opportunity to offer regenerative vitality. To me it is obligatory and considerate. Strategies that support mitochondrial function, reduce tubular load, improve nitric oxide signaling, and lower glomerular pressure can significantly improve outcomes. Diet, exercise, sleep, hydration, stress reduction, toxin reduction, nature engagement. social balance are all Medicine [the proverbial low hanging fruit] that re-routes abnormal pathways

Before using the array of pharmaceuticals we have, there are many ways to harvest the low hanging fruit from the tree of lifestyle.

• RAAS [Renin-Angiotensin-Aldosterone System] modulation with botanicals and peptides.

•Uric acid reduction through lifestyle, diet, herbals, supplements and peptides.

•Alkali therapy with bicarbonate or citrate, plant dominant diet, vagus practices, breath practices (all truly medicinal).

•Nutritional and lifestyle interventions including hydration, plant-based diet, and avoidance of nephrotoxins.

•Bioregulatory supports like carnosine, glycine, CoQ10, and low-dose lithium orotate (for early not late ckd)

🪷Toxins, Not Time: The Real Driver of “Age-Related” CKD

Chronic kidney disease is not simply a disease of age. It is a disorder of accumulated injury — and injury is modifiable.

It’s true - understanding kidney calls for a notable learning curve. Once it becomes part of day to day health awareness, it becomes possible to chip away at the huge swath of people enduring the consequence that declined kidney causes.

First things first: recognize the patterns of decline in early ckd and commit to peeling away the layers to identify each individual’s collage of issues. Knowing there are tools for reversal of damages offers us hope and motivation to take the next step, turn the next stone, pave the path to optimal kidney success.

Repeat after me: stage 2 ckd is not normal.

Now let’s reverse this kidneydemic!