Key Facts

The kidneys regulate fluid balance, electrolyte homeostasis, acid-base balance, blood pressure, and erythropoiesis. They also activate vitamin D (1,25-dihydroxycholecalciferol) and excrete metabolic waste products.

Epidemiology

CKD affects approximately 13% of the UK population (predominantly stages 1-3). Stage 3-5 CKD affects approximately 6%. AKI affects approximately 15% of hospitalised patients. Approximately 65,000 patients receive renal replacement therapy in the UK.

Aetiology

Kidney function depends on:

• Glomerular filtration: Determined by hydrostatic and oncotic pressures across the glomerular capillary
• Tubular function: Reabsorption and secretion along the nephron
• Hormonal regulation: RAAS, ADH, natriuretic peptides, prostaglandins
• Renal blood flow: 20-25% of cardiac output (~1.2 L/min), autoregulated between MAP 80-180 mmHg

Pathophysiology

Glomerular filtration barrier consists of:

1. Fenestrated endothelium (size barrier)
2. Glomerular basement membrane (charge barrier — negative charge repels albumin)
3. Podocyte foot processes with slit diaphragm (final barrier)

Tubuloglomerular feedback: Macula densa senses NaCl delivery → adjusts afferent arteriolar tone → maintains stable GFR

Juxtaglomerular apparatus: Macula densa + juxtaglomerular cells (granular cells) → renin release in response to decreased NaCl, decreased perfusion pressure, or sympathetic activation

Countercurrent mechanism: Loop of Henle creates medullary hypertonicity (up to 1200 mOsm/kg) enabling urine concentration

Acute Kidney Injury

• Oliguria (<0.5 mL/kg/hr), rising creatinine
• Fluid overload, hyperkalaemia, metabolic acidosis, uraemia
• Classified by KDIGO criteria: Stage 1-3 based on creatinine rise or urine output reduction

Chronic Kidney Disease

• Often asymptomatic until advanced (GFR <30)
• Fatigue, nausea, pruritus, restless legs
• Anaemia (erythropoietin deficiency), bone disease (CKD-MBD), acidosis

Nephrotic Syndrome

• Proteinuria >3.5g/24h, hypoalbuminaemia, oedema, hyperlipidaemia
• Podocyte damage — minimal change disease (children), membranous nephropathy (adults)

Nephritic Syndrome

• Haematuria, hypertension, oliguria, mild proteinuria
• Glomerular inflammation — IgA nephropathy, post-streptococcal GN

Red Flags

• Anuria — consider obstructive uropathy (urgent USS)
• Rapidly rising creatinine — consider rapidly progressive glomerulonephritis (urgent renal biopsy)
• Pulmonary-renal syndrome — consider Goodpasture's or ANCA vasculitis

Bedside

• Urine dipstick: Blood (haematuria), protein (proteinuria), leucocytes/nitrites (infection)
• Bladder scan: Post-void residual — exclude urinary retention
• Fluid balance: Strict input/output monitoring

Bloods

• U&Es: Creatinine, urea, eGFR, sodium, potassium
• Urine albumin:creatinine ratio (uACR): Screening for albuminuria (>3 mg/mmol is abnormal)
• Calcium, phosphate, PTH: CKD-mineral bone disease assessment
• FBC: Anaemia of CKD (normocytic, normochromic)
• Autoimmune screen: ANA, ANCA, anti-GBM, complement C3/C4 — if glomerulonephritis suspected

Imaging

• Renal USS: Size, obstruction, cysts, masses (normal kidney 10-12cm)
• CT KUB: Renal stones
• Doppler USS: Renal artery stenosis

Special Tests

• Renal biopsy: Glomerulonephritis, unexplained CKD, nephrotic syndrome
• MAG3 renogram: Differential renal function, obstruction assessment
• Cystatin C: Alternative GFR marker (less affected by muscle mass)

Non-pharmacological

• Dietary: Sodium restriction (<6g/day), potassium restriction if hyperkalaemia, adequate protein but not excessive in CKD
• Fluid management: Guided by volume status
• Nephrotoxin avoidance: NSAIDs, aminoglycosides, contrast media — hold ACEi/ARB in AKI

Pharmacological

• AKI: Treat underlying cause, optimise fluid status, correct electrolytes
• CKD (NICE NG203):
  • ACEi/ARB: Ramipril 1.25-10mg OD if diabetes or uACR >30 mg/mmol or hypertension
  • SGLT2 inhibitors: Dapagliflozin 10mg OD — DAPA-CKD trial showed 39% reduction in kidney disease progression
  • Blood pressure target: <140/90 (or <130/80 if uACR >70 mg/mmol)
  • Anaemia: ESA (epoetin alfa) if Hb <100 g/L and iron replete
  • CKD-MBD: Phosphate binders (calcium acetate, sevelamer), alfacalcidol
  • Sodium bicarbonate: If bicarbonate <20 mmol/L

Surgical

• Renal replacement therapy: Haemodialysis, peritoneal dialysis, or transplantation when eGFR <5-10 or symptomatic
• AV fistula formation: 6 months before anticipated dialysis start

Referral Criteria

• eGFR <30 (G4-G5) — nephrology referral
• Progressive CKD (eGFR decline >5/year)
• uACR >70 mg/mmol (A3)
• Suspected glomerulonephritis or vasculitis

• AKI: In-hospital mortality 20-50% depending on severity and ICU admission; 30% develop CKD within 3 years
• CKD stage 5: Dialysis patients — 5-year survival approximately 40% (worse than many cancers)
• Renal transplant: 5-year graft survival ~90% (living donor), ~85% (deceased donor)
• DAPA-CKD trial: Dapagliflozin reduced kidney disease progression by 39% regardless of diabetes status
• CKD is an independent cardiovascular risk factor — CV death is the leading cause of death in CKD patients

CKD Staging (NICE NG203)

Nephron Segment Functions