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Secondary factors and progression of chronic kidney disease

George L Bakris, MD
John P Forman, MD, MSc
Section Editor
Gary C Curhan, MD, ScD
Deputy Editor
Alice M Sheridan, MD


A variety of chronic kidney diseases (CKDs) progress to end-stage renal disease (ESRD), including chronic glomerulonephritis, diabetic nephropathy, and polycystic kidney disease. Although the underlying problem often cannot be treated, extensive studies in experimental animals and humans suggest that progression in CKD may be largely due to secondary factors that are sometimes unrelated to the activity of the initial disease. These include systemic and intraglomerular hypertension, glomerular hypertrophy, the intrarenal precipitation of calcium phosphate, hyperlipidemia, and altered prostanoid metabolism (table 1) [1-5].

The major histologic manifestation of these secondary causes of renal injury is focal segmental glomerulosclerosis, which is called secondary FSGS [2]. Thus, glomerular damage and proteinuria typically occur with progressive renal failure, even in primary tubulointerstitial diseases such as chronic pyelonephritis due to reflux nephropathy. (See "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis", section on 'Pathogenesis of secondary FSGS'.)

The use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptors blockers to treat some of these secondary mechanisms and slow disease progression are discussed separately. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults".)


A large amount of data exist concerning the general clinical characteristics of patients in whom the progression of renal dysfunction is accelerated.

Major factors include increased proteinuria, hypertension, hyperglycemia, and black race (see "Overview of the management of chronic kidney disease in adults" and "Definition and staging of chronic kidney disease in adults" and "Overview of diabetic nephropathy", section on 'Risk factors'). Lower levels of high-density lipoprotein (HDL) and transferrin may also be risk factors.

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Literature review current through: Nov 2017. | This topic last updated: Apr 21, 2017.
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