Chronic kidney disease: pathophysiology and progression
This article is primarily for health professionals.
Pathophysiology
Unlike acute kidney injury (AKI), where the healing process is complete with complete functional kidney recovery, chronic and sustained insults from chronic and progressive nephropathies evolve to progressive kidney fibrosis and destruction of the normal architecture of the kidney.
This affects all the 3 compartments of the kidney, namely the glomeruli, the tubules, the interstitium, and the vessels. It manifests histologically as glomerulosclerosis, tubulointerstitial fibrosis, and vascular sclerosis.
The sequence of events that lead to scarring and fibrosis are complex, overlapping, and multistage phenomena.
- Infiltration of damaged kidneys with extrinsic inflammatory cells
- Activation, proliferation, and loss of intrinsic renal cells (through apoptosis, necrosis, mesangiolysis, and podocytopenia)
- Activation and proliferation of extracellular matrix (ECM) producing cells including myofibroblasts and fibroblasts
- Deposition of ECM replacing the normal architecture.
Mechanisms of accelerated progression of CKD
- Systemic and intraglomerular hypertension
- Glomerular hypertrophy
- Intrarenal precipitation of calcium phosphate
- Altered prostaglandin metabolism.
All these mechanisms lead to a histological entity called ‘focal segmental glomerulosclerosis’.
Clinical risk factors for accelerated progression of CKD are proteinuria, hypertension, black race, and hyperglycemia. Also, environmental exposures such as lead, smoking, metabolic syndrome, possibly some analgesic agents, and obesity have also been linked to accelerated progression of CKD.
Last Reviewed on 27 May 2024