Aetiology
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Chronisch nierlijden (multidisciplinaire aanpak)Published by: WORELLast published: 2017GPC pluridisciplinaire sur la néphropathie chronique (IRC)Published by: Groupe de travail Développement de recommandations de première ligneLast published: 2017The most common cause of chronic kidney disease (CKD) in the adult population is diabetes.[6] It is estimated that 20% to 40% of people with diabetes will develop kidney disease, as defined by albuminuria and/or a reduction in the glomerular filtration rate, within the 15-year period following the diagnosis of diabetes.[15][16]
Hypertension is the second most common cause.[6] The interaction between hypertension and CKD is complex, with hypertension a cause and a consequence of CKD.[17]
Often people are given the diagnosis of hypertensive kidney disease if no other identifiable aetiology 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.
People who have a close family member with the disease are at a higher risk themselves of developing CKD.[18][19] Monogenic disorders may account for up to 30% of non-diabetic CKD in adults and up to 50% in children.[20] The most common monogenic disorder is autosomal dominant polycystic kidney disease (caused by genetic variants in PKD1 and PKD2 genes).[21] Genes associated with complex kidney diseases (where risk of disease depends on both genotype and environment) have been described, such as the apolipoprotein L1 (APOL1) gene. People of African ethnic origin are more likely to have an APOL1 risk variant than people of other ethnic origins.[21]
Climate also plays a significant role in some CKD presentations.[22] Heat stress nephropathy may represent one of the first epidemics due to climate change. Various presentations in different parts of the world, such as Mesoamerican nephropathy, Sri Lankan nephropathy, and CKD of unknown origin (CKDu), may all be related to the climate.[23] The mechanisms implicated are hyperthermia, dehydration, and toxin and heavy metal concentration in drinking water and soil, in addition to worsening poverty with climate change leading to poor harvests.[22][23]
Pathophysiology
The pathophysiology is complex. Regardless of the method of kidney injury (i.e., diabetes, hypertension, or glomerular disorders), once kidney damage has occurred, a cascade of events ensues.[24][25]
In response to kidney injury, there is thought to be an increase in intra-glomerular pressure with glomerular hypertrophy, as the kidney attempts to adapt to nephron loss to maintain constant glomerular filtration.
An increase in glomerular permeability to macro-molecules such as transforming growth factor-beta (TGF-beta), fatty acids, pro-inflammatory markers of oxidant stress, and protein may result in toxicity to the mesangial matrix, causing mesangial cell expansion, inflammation, fibrosis, and glomerular scarring.
Additionally, kidney injury results in an increase in angiotensin II production, causing an upregulation of TGF-beta, contributing to collagen synthesis and kidney scarring within the glomerulus.
Both the structural alterations and accompanying biochemical, cellular, and molecular changes seem to account for progressive kidney scarring and loss of kidney function.
All forms of CKD are also associated with tubulo-interstitial diseases; 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.
Classification
Kidney Disease: Improving Global Outcomes (KDIGO) classification[1]
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 60-89: mildly decreased
G3a GFR 45-59: mildly to moderately decreased
G3b GFR 30-44: moderately to severely decreased
G4 GFR 15-29: 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 <3 mg/mmol (<30 mg/g): normal to mildly increased
A2 AER 30-300 mg albumin/24 hours or ACR of 3-30 mg/mmol (30-300 mg/g): moderately increased
A3 AER >300 mg albumin/24 hours or ACR >30 mg/mmol (>300 mg/g): severely increased.
In the absence of evidence of kidney damage, neither G1 nor G2 fulfils the criteria for CKD.
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