Aetiology

Your Organisational Guidance

ebpracticenet urges you to prioritise the following organisational guidance:

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: 2017

The most common cause in the adult population is diabetes.[6] 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.[12][13]

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.[14]

Often people are given the diagnosis of hypertensive renal 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.[1]

Around one third of adults with CKD have a positive family history of CKD, which suggests genetic causation.[15]

Climate also plays a significant role in some CKD presentations.[16] Heat stress nephropathy may represent one of the first epidemics due to global warming. 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.[17] 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.[16][17]

Pathophysiology

The pathophysiology is complex. Regardless of the method of renal injury (i.e., diabetes, hypertension, or glomerular disorders), once renal damage has occurred, a cascade of events ensues.[18][19]

  • In response to renal 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, 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 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 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 <3 mg/mmol (<30 mg/g): normal to mildly increased

    • A2 AER 30 to 300 mg albumin/24 hours or ACR of 3 to 30 mg/mmol (30 to 300 mg/g): moderately increased

    • A3 AER >300 mg albumin/24 hours or ACR >30 mg/mmol (>300 mg/g): severely increased.

There is substantial existing literature using the term microalbuminuria; however, the KDIGO work group encourages the adoption of the term 'albuminuria', with subsequent quantification of the level or amount.[1]

A urine ACR >220 mg/mmol (>2200 mg/g) may be accompanied by signs and symptoms of nephrotic syndrome (e.g., low serum albumin, oedema, and high serum cholesterol).[1]

However, nephrotic level proteinuria is conventionally defined as >3.5 g proteinuria per 24 hours.[2]

Use of this content is subject to our disclaimer