🩺 When the Filters Fail: A review of reduced renal function

Your kidneys filter over 180 litres of blood a day, removing waste, balancing electrolytes, and regulating blood pressure. But what happens when renal function starts to decline?

👩‍⚕️ Meet Karen, a 54-year-old woman with Type 2 Diabetes and longstanding hypertension. She’s noticed some ankle swelling, increasing fatigue, and mild nausea. Her GP runs bloods— her eGFR is 38 mL/min/1.73m², her creatinine is up, and there’s proteinuria.

Beneath those swelling ankles lies a story of pressure, filtration failure, and systemic fallout. This is where physiology meets clinical reality, and small changes start to snowball.

1. The Hidden Cost of Nephrons Lost: Glomerular Dysfunction & Uraemia

Reduced kidney function means your body can't effectively excrete waste products like urea and creatinine.

In early kidney impairment, remaining nephrons hyperfiltrate to compensate—this adaptive response eventually becomes maladaptive. Why? The increased glomerular capillary pressure accelerates glomerulosclerosis, leading to further nephron loss. In Karen’s case, chronic hypertension and diabetic nephropathy are the culprits behind this insidious process.

As GFR declines, metabolic waste (like urea, creatinine, and middle molecules) accumulates. This manifests clinically as uraemia, with its nonspecific but increasingly debilitating symptoms: fatigue, anorexia, cognitive clouding, and pruritus. If unaddressed, it progresses to pericarditis or encephalopathy.

2. Volume Overload & Electrolyte Chaos

Without proper filtration, the body may retain fluid, leading to edema, especially in the legs and around the eyes.

Why does Karen have ankle swelling? Her kidneys are no longer excreting sodium effectively, leading to volume expansion. The ensuing oedema results from increased hydrostatic pressure and reduced oncotic pressure (thanks to urinary protein losses).

Now let’s talk potassium. The kidneys are key for K⁺ homeostasis, particularly in the distal nephron. With reduced GFR, hyperkalaemia can develop—especially if exacerbated by ACE inhibitors or spironolactone. This isn’t just a lab abnormality; it’s a potential arrhythmic time bomb.

3. Hypertension: The Chicken and the Egg

The kidneys help regulate blood pressure through the renin-angiotensin-aldosterone system. With reduced function, hypertension often develops.

Chronic kidney disease (CKD) can both cause and worsen hypertension. Mechanistically, sodium retention and activation of the renin-angiotensin-aldosterone system (RAAS) raise systemic vascular resistance. Karen’s elevated BP not only contributes to her CKD but is also a target for aggressive management to slow progression. 

It’s a vicious cycle, and understanding that feedback loop is critical for treatment decisions.

4. Anaemia and Renal Bone Disease: The Silent Strikes

The kidneys produce erythropoietin, a hormone essential for red blood cell production.

Erythropoietin is synthesised by peritubular interstitial fibroblasts in the renal cortex. Karen’s reduced renal mass = reduced erythropoietin = normocytic, normochromic anaemia. She’s tired not just from uraemia, but also from low haemoglobin and reduced oxygen carrying capacity.

And because they also play a role in activating vitamin D, calcium and phosphate imbalances can lead to bone demineralization. Phosphate retention and impaired 1α-hydroxylation of vitamin D disrupt calcium/phosphate homeostasis. Result? Secondary hyperparathyroidism → increased bone turnover → renal osteodystrophy. These changes are often subclinical until fractures or bone pain emerge.

5. Cardiovascular Risk: Death by Association

CKD isn’t just a renal problem—it’s a cardiovascular risk amplifier. Endothelial dysfunction, chronic inflammation, calcium-phosphate dysregulation, and LVH from volume overload all contribute. In fact, Karen is more likely to die of a cardiovascular event than reach end-stage renal disease.

🎓 Understanding the domino effect of declining renal function is a must for any med student. It’s not just about the kidneys—it’s about the entire body responding to the chaos of internal imbalance.

📘 AKI vs CKD: Different Stories, Shared Impact

Acute kidney injury (AKI) and chronic kidney disease (CKD) both involve loss of renal function, but their stories are quite different.

AKI is a sudden and usually reversible decline in kidney function, often triggered by events like dehydration, infection, medications (think NSAIDs or contrast), or obstruction. It develops over hours to days and is often recognised by a rapid rise in serum creatinine or a marked drop in urine output. If treated early and the underlying cause is addressed, kidney function often recovers.

In contrast, CKD is a progressive and largely irreversible condition where kidney function declines over months to years. The most common culprits are long-term conditions like diabetes and hypertension. It’s often silent until well advanced, which is why routine screening in high-risk patients is so important. The kidneys slowly lose their filtering capacity, and once the nephron loss crosses a certain threshold, complications like anaemia, bone disease, and cardiovascular events begin to appear.

Physiologically, AKI involves abrupt injury to the nephrons, but the architecture of the kidney may remain largely intact if the cause is reversed quickly. CKD, however, features chronic scarring and loss of nephrons, often with evidence of small, shrunken kidneys on imaging.

💡 Clinical Pearl: Patients with CKD are at higher risk of developing AKI, particularly when exposed to additional stressors — creating what we call acute-on-chronic kidney injury, a situation that can push someone rapidly toward dialysis if not recognised and managed promptly.

💡Clinical Reasoning Pearls:

• Always think “reversible contributors”: volume depletion, nephrotoxic meds, obstructive uropathy.
• Interpret creatinine in context—it varies with muscle mass, age, and sex.
• Proteinuria is more than a number: it’s a marker of glomerular injury and predictor of progression.
• eGFR doesn’t drop linearly—it’s silent until late stages, so screening in high-risk patients (like Karen) is key.

🩺 Managing Karen: A Clinical Walkthrough of Reduced Renal Function

1. Confirm the diagnosis and stage the CKD

Before jumping to treatment:

• Why eGFR? It’s our estimate of global kidney function but it’s based on creatinine, which is affected by muscle mass and other factors.
• Karen’s eGFR of 38 mL/min/1.73m² = CKD Stage 3b.
• Why proteinuria matters: Urinary albumin/protein quantification (e.g. ACR or PCR) tells us about glomerular integrity—the more protein in the urine, the more “leaky” the glomeruli, and the worse the prognosis.
• First question: Is this acute, chronic, or acute-on-chronic? Her long history and stable derangement favour chronicity, but always rule out reversible causes like urinary obstruction or volume depletion.

2. Lifestyle, comorbidity and medication review

Let’s address the why behind each recommendation:

• Salt and fluid restriction: Reduce volume overload and help with BP control.
• Glycaemic control: High glucose damages glomerular basement membranes (via advanced glycation end-products).
• Review meds: Stop nephrotoxic agents (NSAIDs, certain antibiotics). Consider ACE inhibitors/ARBs for both BP control and reduction in proteinuria—but monitor for hyperkalaemia.
• Smoking cessation: Slows CKD progression and lowers CV risk.

3. Blood pressure: Target and treatment

• Target BP? Usually <130/80, stricter if proteinuria present.
• How RAAS inhibition helps: Beyond BP lowering, ACE inhibitors/ARBs reduce glomerular capillary pressure → less proteinuria → slower scarring.
• Why caution with volume status? Starting RAAS blockers in a dehydrated or heavily diuresed patient can precipitate AKI.

4. Correcting anaemia and bone metabolism

• Anaemia: Check iron studies (many CKD patients are iron-deficient) and haemoglobin.
• If EPO is the issue, consider erythropoiesis-stimulating agents—but not too early. Overcorrection increases stroke risk.
• CKD–mineral bone disease (CKD-MBD):

• Manage phosphate with dietary restriction and binders.
• Replace active vitamin D (calcitriol) to suppress secondary hyperparathyroidism.
• Why it matters: Imbalanced Ca/PO₄ and high PTH → vascular calcification, fractures, tendon rupture—slow, silent complications unless actively managed.

5. Cardiovascular disease prevention

• CKD is a risk multiplier. Statins are often indicated if eGFR <60 and aged >50.
• Why? Chronic inflammation, oxidative stress, and dyslipidaemia all contribute to accelerated atherosclerosis.
• If Karen has albuminuria, she’s likely also got endothelial dysfunction. It’s not just about the kidneys.

6. Planning ahead: When to refer and when to talk about dialysis

• Refer to nephrology when: eGFR <30, rapid decline in function, resistant hypertension, or heavy proteinuria.
• Start laying the groundwork for renal replacement discussions well before end-stage disease. Karen’s not there yet—but educating her early improves outcomes.
📦 What’s the Deal with Dialysis?
Dialysis is a form of renal replacement therapy, used when the kidneys can no longer maintain balance of fluid, electrolytes, and waste products — typically when chronic kidney disease progresses to end-stage.

There are two main types:
• Haemodialysis: Blood is diverted through an external machine (a dialyser) where it’s filtered and returned. Most patients attend a dialysis centre, usually 3 times per week for around 4 hours per session.
• Peritoneal dialysis: Dialysis fluid is introduced into the peritoneal cavity via a catheter. The peritoneal membrane acts as the filter. Patients can do this at home, often overnight (automated peritoneal dialysis).
When is it needed? Dialysis is considered when kidney function drops below the threshold required to:
• Control persistent fluid overload not responsive to medication
• Correct severe electrolyte imbalances (e.g. refractory hyperkalaemia)
• Clear accumulating toxins and waste products when symptoms of uraemia develop (e.g. nausea, pruritus, pericarditis, encephalopathy)
• Manage complications that can't be addressed conservatively, such as severe acidosis
  
  
  


🧠 The key concept: Dialysis doesn't cure CKD — it substitutes part of the kidney’s function. It buys time, alleviates symptoms, and improves quality of life. But it's complex, life-altering, and the decision to initiate it is never taken lightly.

👩‍⚕️ Clinical follow-up for Karen:

• 3–6 monthly review depending on stability.
• Monitor: BP, eGFR, electrolytes, Hb, iron studies, PTH, phosphate, albumin:creatinine ratio.
• Vaccinations! Influenza, pneumococcal, and COVID boosters—CKD = immunocompromised.

Summary

In Karen’s story, we’ve seen how reduced renal function doesn’t just stay in the kidneys—it echoes through every system, every symptom, and every blood test. For clinicians and students alike, recognising these early shifts isn’t just about preserving GFR—it’s about understanding the physiology, respecting the complexity, and meeting patients where they are. Because in the end, managing chronic kidney disease is less about chasing numbers, and more about anticipating consequences—and acting before they cascade.