The most common cause in the adult population is diabetes. It is estimated that one third of patients with diabetes will develop kidney disease, as defined by albuminuria and/or a reduction in the glomerular filtration rate within 15 years after the diagnosis of diabetes.
Often people are given the diagnosis of hypertensive renal disease if no other identifiable etiology is evident.
Less frequent causes include cystic disorders of the kidney (polycystic kidney disease), obstructive uropathy, glomerular nephrotic and nephritic syndromes such as focal segmental glomerulosclerosis, membranous nephropathy, lupus nephritis, amyloidosis, and rapidly progressive glomerulonephritis.
In response to renal injury, there is thought to be an increase in intraglomerular pressure with glomerular hypertrophy, as the kidney attempts to adapt to nephron loss to maintain constant glomerular filtration.
An increase in glomerular permeability to macromolecules such as transforming growth factor-beta (TGF-beta), fatty acids, proinflammatory markers of oxidant stress, and protein may result in toxicity to the mesangial matrix, causing mesangial cell expansion, inflammation, fibrosis, and glomerular scarring.
Additionally, renal injury results in an increase in angiotensin II production, causing an upregulation of TGF-beta, contributing to collagen synthesis and renal scarring within the glomerulus.
Both the structural alterations and accompanying biochemical, cellular, and molecular changes seem to account for progressive renal scarring and loss of kidney function.
All forms of CKD are also associated with tubulointerstitial disease; the exact mechanism of injury is not known but is thought to be secondary to a reduction in blood supply in addition to an infiltration of lymphocytes and inflammatory mediators that result in interstitial fibrosis and tubular atrophy.
Kidney Disease: Improving Global Outcomes (KDIGO) classification
KDIGO classifies CKD based on cause (C), glomerular filtration rate category (G), and albuminuria category (A).
Cause is ascertained from history (e.g., diabetic kidney disease, hypertensive nephrosclerosis).
Glomerular filtration rate (GFR) category is based on GFR (mL/minute/1.73 m²):
G1 GFR ≥90: normal or high
G2 GFR 60 to 89: mildly decreased
G3a GFR 45 to 59: mildly to moderately decreased
G3b GFR 30 to 44: moderately to severely decreased
G4 GFR 15 to 29: severely decreased
G5 GFR <15: kidney failure.
Albuminuria category is based on albumin excretion rate (AER) or albumin to creatinine ratio (ACR):
A1 AER <30 mg albumin/24 hours or ACR <30 mg/g: normal to mildly increased
A2 AER 30 to 300 mg albumin/24 hours or ACR of 30 to 300 mg/g: moderately increased
A3 AER >300 mg albumin/24 hours or ACR >300 mg/g: severely increased.
There is substantial existing literature using the term microalbuminuria; however, the KDIGO work group encourages adoption of the term ‘albuminuria’, with subsequent quantification of the level or amount.
A urine ACR >2200 mg/g may be accompanied by signs and symptoms of nephrotic syndrome (e.g., low serum albumin, edema, and high serum cholesterol).
However, nephrotic level proteinuria is conventionally defined as >3.5 g proteinuria per 24 hours.
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