AKI and chronic kidney disease

Acute Kidney Injury, Chronic Kidney Disease & Fluid/Electrolyte Emergencies

Renal parenchymal integrity and fluid-electrolyte equilibrium are essential for systemic haemodynamic stability. Acute deterioration in renal function and severe electrolyte derangements—predominantly hyperkalaemia and dysnatraemias—account for a major proportion of emergency admissions and inpatient medical consultations in Australian hospitals.

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Acute Kidney Injury (AKI): Staging & Aetiology

The Kidney Disease: Improving Global Outcomes (KDIGO) criteria standardize the clinical definition and staging of acute kidney injury.

KDIGO Diagnostic Staging of AKI

• Stage 1: Serum Creatinine Criteria: Increase $\ge 26.5\ \mu\text{mol/L}$ within 48 hours, or $1.5 - 1.9 \times$ baseline within 7 days; Urine Output Criteria: $< 0.5\text{ mL/kg/hour}$ for 6 to 12 hours
• Stage 2: Serum Creatinine Criteria: $2.0 - 2.9 \times$ baseline serum creatinine; Urine Output Criteria: $< 0.5\text{ mL/kg/hour}$ for $\ge 12$ hours
• Stage 3: Serum Creatinine Criteria: $\ge 3.0 \times$ baseline, or serum creatinine $\ge 353.6\ \mu\text{mol/L}$, or initiation of renal replacement therapy; Urine Output Criteria: $< 0.3\text{ mL/kg/hour}$ for $\ge 24$ hours, or anuria for $\ge 12$ hours

Aetiological Classification of AKI

1. Prerenal Azotaemia ($55-60\%$):

   • Decreased effective arterial blood volume and renal hypoperfusion with preserved parenchymal and tubular architecture.
   • Common Precipitants: Dehydration, haemorrhage, septic shock, congestive heart failure (cardiorenal syndrome), liver cirrhosis (hepatorenal syndrome).
   • The 'Triple Whammy' Drug Interaction: The combination of an ACE inhibitor or ARB (blocks angiotensin II-mediated efferent arteriolar vasoconstriction), an NSAID (blocks prostaglandin-mediated afferent arteriolar vasodilation), and a diuretic (induces intravascular hypovolaemia). This trio cripples intraglomerular hydrostatic pressure, precipitating acute prerenal failure.

2. Intrinsic Renal Injury ($35-40\%$):

   • Direct structural damage to glomeruli, tubules, interstitium, or renal microvasculature.
   • Acute Tubular Necrosis (ATN, $85\%$ of intrinsic):
     • Ischaemic ATN: Prolonged, severe prerenal hypoperfusion leading to tubular epithelial hypoxia and necrosis.
     • Nephrotoxic ATN: Aminoglycosides (gentamicin), iodinated radiocontrast media, cisplatin, amphotericin B, or endogenous pigments (myoglobin from rhabdomyolysis [elevated serum creatine kinase, dipstick positive for 'blood' with zero RBCs on microscopy], haemoglobin from massive intravascular haemolysis, light chains in multiple myeloma).
   • Acute Interstitial Nephritis (AIN): Drug-induced allergic hypersensitivity ($> 75\%$ of cases: penicillins, cephalosporins, sulfonamides, proton pump inhibitors, NSAIDs). Classic clinical triad: low-grade fever, maculopapular rash, and arthralgia/eosinophilia (present in $< 30\%$). Urine microscopy shows sterile pyuria, white blood cell casts, and eosinophiluria. Managed by prompt drug cessation $\pm$ oral corticosteroids.
   • Acute Glomerulonephritis (Nephritic Syndrome): Immune-complex deposition or ANCA vasculitis; characterized by hypertension, oliguria, dysmorphic red blood cells, and red blood cell casts.

3. Postrenal / Obstructive Uropathy ($5-10\%$):

   • Mechanical blockage of urinary flow from the renal pelvis to the urethral meatus.
   • Bladder outlet obstruction (benign prostatic hyperplasia, prostate adenocarcinoma, neurogenic bladder, blocked urinary catheter) or bilateral ureteric obstruction.
   • First-Line Investigation: Urgent renal tract ultrasound to evaluate for hydronephrosis and assess post-void residual bladder volume.

Urinary Indices: Prerenal vs ATN

$$\text{Fractional Excretion of Sodium (FeNa)} = \frac{\text{Urine Na} \times \text{Serum Creatinine}}{\text{Serum Na} \times \text{Urine Creatinine}} \times 100$$

• Urine Sodium ($\text{U}_{\text{Na}}$): Prerenal Azotaemia: $< 20\text{ mmol/L}$ (avidity to conserve sodium); Acute Tubular Necrosis (ATN): $> 40\text{ mmol/L}$ (impaired tubular reabsorption)
• Fractional Excretion of Sodium (FeNa): Prerenal Azotaemia: $< 1\%$; Acute Tubular Necrosis (ATN): $> 2\%$
• Fractional Excretion of Urea (FeUrea): Prerenal Azotaemia: $< 35\%$ (preferred if patient takes loop diuretics); Acute Tubular Necrosis (ATN): $> 50\%$
• Urine Osmolality: Prerenal Azotaemia: $> 500\text{ mOsm/kg}$ (intact concentrating ability); Acute Tubular Necrosis (ATN): $< 350\text{ mOsm/kg}$ (isosthenuria)
• Urea/creatinine: Interpret each result in its own units and clinical context. Do not apply a ratio of unconverted mmol/L urea and micromol/L creatinine as if dimensionless. Dehydration, GI bleeding, diet and kidney function all affect the pattern.
• Urine Sediment Microscopy: Prerenal Azotaemia: Normal or Hyaline casts; Acute Tubular Necrosis (ATN): 'Muddy brown' granular casts, epithelial cells

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Chronic Kidney Disease (CKD) Staging & Complications

Chronic kidney disease is defined by persistent kidney damage or an estimated glomerular filtration rate (eGFR) $< 60\text{ mL/min/1.73 m}^2$ present for $\ge 3\text{ months}$.

The KDIGO GFR and Albuminuria Matrix

• G1: eGFR ($\text{mL/min/1.73 m}^2$): $\ge 90$; Description: Normal or high (with other kidney damage); Albuminuria Stage: A1; Urine ACR ($\text{mg/mmol}$): $< 3.0$; Description: Normal to mildly increased
• G2: eGFR ($\text{mL/min/1.73 m}^2$): $60 - 89$; Description: Mildly decreased; Albuminuria Stage: A2; Urine ACR ($\text{mg/mmol}$): $3.0 - 30.0$; Description: Moderately increased (microalbuminuria)
• G3a: eGFR ($\text{mL/min/1.73 m}^2$): $45 - 54$; Description: Mild-to-moderately decreased; Albuminuria Stage: A3; Urine ACR ($\text{mg/mmol}$): $> 30.0$; Description: Severely increased (macroalbuminuria)
• G3b: eGFR ($\text{mL/min/1.73 m}^2$): $30 - 44$; Description: Moderately-to-severely decreased; Albuminuria Stage: —; Urine ACR ($\text{mg/mmol}$): —; Description: —
• G4: eGFR ($\text{mL/min/1.73 m}^2$): $15 - 29$; Description: Severely decreased; Albuminuria Stage: —; Urine ACR ($\text{mg/mmol}$): —; Description: —
• G5: eGFR ($\text{mL/min/1.73 m}^2$): $< 15$; Description: Kidney failure (End-stage kidney disease); Albuminuria Stage: —; Urine ACR ($\text{mg/mmol}$): —; Description: —

Complications of Advanced CKD & Management

1. Anaemia of CKD:
   • Primarily driven by deficient erythropoietin (EPO) synthesis by renal peritubular interstitial fibroblasts. Normocytic, normochromic anaemia.
   • CKD anaemia: Check iron status and other correctable causes before choosing treatment. KDIGO 2026 iron criteria vary by dialysis status: do not use one universal ferritin target for every patient. Select oral or intravenous iron according to circumstances and response. ESA initiation considers symptoms, haemoglobin, transfusion risk and adverse effects; when used in adults, keep the haemoglobin target below 115 g/L rather than normalising it. Monitor iron indices, blood pressure and response.
2. CKD-Mineral and Bone Disorder (CKD-MBD):
   • CKD mineral/bone disorder: Phosphate retention and reduced active vitamin D contribute to altered calcium/PTH and bone turnover. Interpret serial calcium, phosphate and PTH together. Calciphylaxis is a distinct severe multifactorial disorder, not synonymous with ordinary vascular calcification.

• Secondary hyperparathyroidism: Cinacalcet increases calcium-sensing receptor sensitivity, suppressing PTH; it does not inhibit that receptor. In non-dialysis CKD, trends in calcium, phosphate and PTH guide management. Routine calcitriol for every stage 3–5 patient or a normal-laboratory PTH target for stage 4 is inappropriate.
• CKD acidosis: KDIGO 2024 advises considering treatment when acidosis has potential clinical consequences, for example bicarbonate below 18 mmol/L. Dose and monitor to avoid hypertension, fluid overload or excessive correction; 22 is not a universal mandatory drug-treatment threshold.

1. Cardiovascular Risk Reduction: Cardiovascular disease is the single leading cause of death in CKD. Blood pressure targets $< 130/80\text{ mmHg}$ using an ACE inhibitor or ARB (reduces intraglomerular pressure and proteinuria) plus an SGLT2 inhibitor (empagliflozin/dapagliflozin) for cardiovascular and renal protection.

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Primary references (checked 7 October 2026): KDIGO CKD guidance.

KDIGO 2026 anaemia guideline updates iron and ESA decisions.