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Inflammation in renal insufficiency

Csaba P Kovesdy, MD, FASN
Joel D Kopple, MD
Kamyar Kalantar-Zadeh, MD, MPH, PhD
Section Editor
Jeffrey S Berns, MD
Deputy Editor
Alice M Sheridan, MD


Recurrent or chronic inflammatory processes are common in individuals with chronic renal disease (CKD), including those with chronic renal failure (CRF) and especially end-stage renal disease (ESRD). This is due to many underlying factors, including the uremic milieu, elevated levels of circulating proinflammatory cytokines, oxidative stress, carbonyl stress, protein-energy wasting (PEW), enhanced incidence of infections (especially dialysis-access related), and others. Although the definition of inflammation is unclear in this setting, CRF-associated chronic inflammation, as assessed by increased C-reactive protein (CRP) levels above 5 mg/L over at least three months, has been reported in 30 to 60 percent of North American and European dialysis patients, with dialysis patients in Asian countries possibly having a lower prevalence [1-7].

The acute-phase response is a major pathophysiologic phenomenon that accompanies inflammation. With this reaction, normal homeostatic mechanisms are replaced by new set points that presumably contribute to defensive or adaptive capabilities.

Acute-phase proteins are defined as those proteins whose plasma concentrations increase (positive acute-phase proteins), such as CRP, or decrease (negative acute-phase proteins), such as albumin, during inflammatory states. Measurement of the levels of these proteins is frequently utilized to define the presence and/or degree of inflammation in a given patient. A number of inflammatory markers have been studied in patients with CKD (table 1). (See "Acute phase reactants".)

Despite its name, the "acute"-phase response can persist over months to years and become chronic. In such states of chronic inflammation, positive acute-phase proteins including CRP (normal range <1 mg/L) may be slightly but persistently increased, which can predispose to an increased risk of atherosclerotic cardiovascular disease (CVD; CRP 1 to 3 mg/L) [8]. However, in many CKD patients, especially in maintenance dialysis patients, serum CRP levels are persistently between 5 and 50 mg/L, although they may fluctuate widely [8]. During acute and fulminant infections, such as acute osteomyelitis, serum CRP is usually above 50 mg/dL (table 2).

Among patients with CKD, the presence of an inflammatory state may also be closely related to accelerated atherogenesis, protein-energy malnutrition (PEM, also referred to as PEW), and anemia [9-11]:


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