Definition

• Abnormalities of kidney structure or function, present for > 3 months, with implications for health. Most cases of CKD are irreversible, but some cases may be partially or even entirely reversible.

 • Abnormalities of kidney function/ structure include decreased GFR (< 60 ml/ min per 1.73 m²) ), increased albuminuria, urinary sediment abnormalities, electrolyte, and other abnormalities due to tubular disorders, abnormalities detected by histology, and structural abnormalities detected by imaging.

 • CKD is classified based on the cause, GFR category, and albuminuria category.

Epidemiology

 • Common, with a significant impact on health worldwide.

 Aetiology

 • Diabetic nephropathy and hypertensive nephropathy are the most common causes, particularly in developed countries.

 • As for AKI, diseases affecting any of the three renal compartments (glomeruli, tubulointerstitium, arteries) can cause CKD. Examples: adult polycystic kidney disease (APKD), dysplastic kidneys, reflux nephropathy, obstructive nephropathy, infections, drugs, systemic diseases that affect the kidney (e.g. systemic lupus erythematosus (SLE), amyloidosis, monoclonal gammopathy, gout), and intrinsic renal diseases (e.g. glomerulonephritis or focal segmental glomerulosclerosis (FSGS)).

 • A kidney biopsy may be required to establish the cause of CKD and inform the treatment plan, for example in cases that present with a rapid elevation in serum creatinine on a background of early stage CKD, or new- onset haematuria or proteinuria.

Pathogenesis

• Injury may primarily affect glomeruli, vessels, or the tubulo- interstitium, eventually leading to loss of nephrons.

 • Loss of nephrons is visible in a biopsy as globally sclerosed glomeruli and atrophy or loss of the associated tubule, with expansion of the interstitium by fibrous tissue.

• Nephron loss is associated with an attendant reduction in GFR.

 • Nephron loss leads to haemodynamic stress in remaining nephrons, leading to further nephron loss.

Presentation

 • Early disease is asymptomatic and can only be picked up if GFR is measured, in particular in at- risk patients (e.g. diabetics, hypertension).

 • With progression, patients feel tired and develop bony pain.

 • Some patients present with high- risk CKD requiring immediate renal replacement therapy (‘end- stage renal failure’), with fluid overload and metabolic derangement.

Biochemistry

• ↑ urea and creatinine due to impaired excretion of waste products.

 • ↓ calcium due to lack of active calcitriol.

• ↑ phosphate due to impaired excretion of phosphate.

• Secondary hyperparathyroidism due to hypocalcaemia.

• ↓ haemoglobin (Hb) due to reduced erythropoietin secretion.

 * Note that loss of acid- base and sodium/ potassium balance occurs late in CKD.

Prognosis

• CKD is classified based on the cause, GFR category, and albuminuria category. Albuminuria and GFR are used to group cases into four risk categories, according to their associations with risks for various outcomes (all- cause and cardiovascular mortality, kidney failure requiring replacement therapy, AKI, and CKD progression).

 Complications

 • High incidence of cardiovascular disease due to a combination of hypertension, vascular calcification, and hyperlipidaemia.

• Derangement of calcium and phosphate metabolism leads to renal bone disease, which is a complex mixture of hyperparathyroid bone disease, osteomalacia, and osteoporosis (Fig. 1).

Fig1. Symptoms and signs of advanced chronic renal failure. Reproduced with permission from Clinical Pathology (Oxford Core Texts), Carton, james, Daly, Richard, and Ramani, Pramila, Oxford university Press (2006), p. 208, Figure 10.4.