Chronic Kidney Disease (CKD) 

Definition (KDIGO 2024)

Chronic Kidney Disease is defined as:

Abnormalities of kidney structure or function present for ≥3 months, with health implications

Diagnostic Criteria (ANY ONE for ≥3 months):

  1. ↓ GFR < 60 mL/min/1.73 m²
  2. Markers of kidney damage:
    • Albuminuria (ACR ≥30 mg/g)
    • Urine sediment abnormalities
    • Electrolyte abnormalities due to tubular disorders
    • Structural abnormalities (imaging)
    • Histological abnormalities
    • Post-transplant state

Epidemiology

  • Global prevalence: ~10–13%
  • India: rising due to:
    • Diabetes epidemic
    • Hypertension
    • Aging population
  • Leading causes:
    • Diabetic kidney disease (DKD)
    • Hypertensive nephrosclerosis
    • Glomerulonephritis

Etiology 

1. Systemic Diseases

  • Diabetes mellitus (most common worldwide)
  • Hypertension
  • SLE, vasculitis
  • Amyloidosis

2. Primary Renal Diseases

  • Glomerular: IgA nephropathy, FSGS
  • Tubulointerstitial: chronic pyelonephritis
  • Cystic: ADPKD

3. Obstructive Uropathy

  • BPH
  • Stones
  • Malignancy

4. Drug-induced

  • NSAIDs
  • Calcineurin inhibitors
  • Lithium

Pathophysiology 

1. Nephron Loss → Hyperfiltration

  • Surviving nephrons undergo:
    • ↑ Glomerular capillary pressure
    • ↑ Single nephron GFR

 Leads to glomerulosclerosis


2. RAAS Activation

  • Angiotensin II:
    • Efferent arteriole constriction
    • ↑ intraglomerular pressure
    • Fibrosis

3. Tubulointerstitial Fibrosis

  • Final common pathway:
    • Inflammation
    • Fibroblast activation
    • Collagen deposition

4. Uremic Toxin Accumulation

  • Middle molecules
  • Protein-bound toxins
  • Leads to:
    • Endothelial dysfunction
    • Immune dysregulation

5. CKD-MBD (Mineral Bone Disorder)

  • ↓ GFR → phosphate retention
  • ↓ Vitamin D activation
  • ↑ PTH (secondary hyperparathyroidism)


Staging (KDIGO Classification)

GFR Stages (G)

Stage

GFR (mL/min/1.73 m²)

G1

≥90

G2

60–89

G3a

45–59

G3b

30–44

G4

15–29

G5

<15 (ESRD)


Albuminuria Stages (A)

Stage

ACR (mg/g)

A1

<30

A2

30–300

A3

>300

Risk Stratification

  • Combine GFR + Albuminuria → Prognosis
  • High risk: G4/G5 + A3


Clinical Features

Early CKD

  • Asymptomatic
  • Mild HTN
  • Nocturia

Feature

 Pathophysiology 

Fatigue

Multifactorial: anemia (↓ erythropoietin), uremic toxins → mitochondrial dysfunction, chronic inflammation

Anorexia

Uremic toxins act on hypothalamus + altered taste sensation + cytokine-mediated appetite suppression

Weight loss

Protein-energy wasting (PEW), chronic inflammation, metabolic acidosis → muscle catabolism

Hypertension

Sodium & water retention + Renin-Angiotensin-Aldosterone System activation → vasoconstriction

LVH

Chronic pressure overload (HTN) + volume overload + anemia → high cardiac output state

Heart failure

Volume overload + LVH → diastolic dysfunction; uremic cardiomyopathy + ischemia

Encephalopathy

Accumulation of uremic toxins (guanidino compounds) → neurotransmitter imbalance + cerebral edema

Peripheral neuropathy

Distal symmetric polyneuropathy due to toxin-mediated axonal degeneration (“dying-back neuropathy”)

Nausea, vomiting

Uremic toxins stimulate chemoreceptor trigger zone (CTZ) + delayed gastric emptying

Uremic gastritis

Ammonia production from urea → mucosal irritation + ↑ gastric acid + platelet dysfunction → bleeding risk

Anemia (↓ EPO)

↓ Erythropoietin production + iron deficiency + chronic inflammation → normocytic normochromic anemia

Pruritus

Multifactorial: hyperphosphatemia, Ca-P deposition in skin, mast cell activation, uremic toxins

Uremic frost (late)

Severe uremia → urea crystallizes in sweat after evaporation (seen in very high BUN, rare now)


Investigations

1. Core Diagnostic Panel (Must for ALL patients)

Investigation

Why Order? (Pathophysiology / Clinical Reason)

Serum creatinine + eGFR

Diagnose CKD (GFR <60 for ≥3 months); trend progression; staging (KDIGO)

Blood urea (BUN)

Reflects uremic toxin load → correlates with symptoms (uremia, encephalopathy)

Urine routine + microscopy

Detect proteinuria, hematuria, casts → helps identify glomerular vs tubular disease

Urine ACR (Albumin/Creatinine ratio)

Earliest marker of kidney damage; prognostic (KDIGO A staging)

Serum electrolytes (Na⁺, K⁺, Cl⁻)

Detect life-threatening abnormalities (esp. hyperkalemia → arrhythmias)

Serum bicarbonate (HCO₃⁻) / ABG

Detect metabolic acidosis due to ↓ acid excretion

Complete blood count (CBC)

Detect anemia due to ↓ Erythropoietin


2. Etiology Workup (To Identify Cause of CKD)

Investigation

Why Order?

Blood glucose / HbA1c

Diagnose diabetic kidney disease (most common cause)

Lipid profile

CKD → accelerated atherosclerosis; baseline CV risk

ANA, dsDNA, complements

Suspect lupus nephritis or autoimmune GN

ANCA

Vasculitis-related renal disease

Serum protein electrophoresis

Multiple myeloma (light chain nephropathy)

Viral markers (HBV, HCV, HIV)

Secondary causes of CKD + transplant planning

Urine culture

Chronic infection → reflux nephropathy / pyelonephritis


3. Imaging

Investigation

Why Order? 

Ultrasound KUB

Differentiate AKI vs CKD: small shrunken kidneys → CKD; large kidneys → DM, amyloidosis, PKD

Doppler renal vessels

Suspected renal artery stenosis

CT / MRI (selected cases)

Structural abnormalities, obstruction, tumors


4. CKD Complication Assessment

Investigation

Why Order?

Serum calcium, phosphate

Detect CKD-MBD (mineral bone disorder)

PTH levels

Secondary hyperparathyroidism due to phosphate retention

Vitamin D levels

↓ activation in CKD → contributes to bone disease

Iron studies (ferritin, TSAT)

Differentiate iron deficiency vs anemia of CKD

ECG

Detect hyperkalemia changes (peaked T waves, arrhythmias)

Chest X-ray

Volume overload → pulmonary edema

Echocardiography

LVH, heart failure (major cause of mortality)