Inflammation and Progression of CKD: The CRIC Study

Abstract

Background and objectives CKD is a global public health problem with significant mortality and morbidity.Design, setting, participants, & measurements We examined the multivariable association of plasma levels of IL-1, IL-1 receptor antagonist, IL-6, TNF-a, TGF-b, high-sensitivity C-reactive protein, fibrinogen, and serum albumin with progression of CKD in 3430 Chronic Renal Insufficiency Cohort study participants.Results Over a median follow-up time of 6.3 years, 899 participants reached the composite end point of $50% decline in eGFR from baseline or onset of ESRD. Elevated plasma levels of fibrinogen, IL-6, and TNF-a and lower serum albumin were associated with a greater decline in eGFR over time. After adjusting for demographics, BP, laboratory variables, medication use, and baseline eGFR, hazard ratios for the composite outcome were greater for the patients in the highest quartile of fibrinogen (hazard ratio, 2.05; 95% confidence interval, 1.64 to 2.55; P,0.001), IL-6 (hazard ratio, 1.44; 95% confidence interval, 1.17 to 1.77; P,0.01), and TNF-a (hazard ratio, 1.94; 95% confidence interval, 1.52 to 2.47; P,0.001) compared with those in the respective lowest quartiles. The hazard ratio was 3.48 (95% confidence interval, 2.88 to 4.21; P,0.001) for patients in the lowest serum albumin quartile relative to those in the highest quartile. When also adjusted for albuminuria, the associations of fibrinogen (hazard ratio, 1.49; 95% confidence interval, 1.20 to 1.86; P,0.001), serum albumin (hazard ratio, 1.52; 95% confidence interval, 1.24 to 1.87; P,0.001), and TNF-a (hazard ratio, 1.42; 95% confidence interval, 1.11 to 1.81; P,0.001) with outcome were attenuated but remained significant.Conclusions Elevated plasma levels of fibrinogen and TNF-a and decreased serum albumin are associated with rapid loss of kidney function in patients with CKD.

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

“…Patients with CVD tend to have greater multimorbidity than individuals who are free from CVD 195 . Diseases most often associated with multimorbidity are diabetes, chronic kidney disease, anaemia, chronic pulmonary disease, depression, and dementia, which all involve inflammageing as an important risk factor 3,138,139,142,143,196 . The presence of comorbid diseases is well established to affect both the response to treatment and the prognosis for hard clinical outcomes, such as cardiovascular and all-cause mortality, as well as hospitalization and health-care utilization 197 .…”

“…Therefore, the coexistence of CVD, diabetes, and frailty might be just one example of a general phenomenon that involves multiple diseases, as exemplified by the following observations. Low-grade chronic inflammation is a primary contributor to the onset and progression of chronic kidney disease 11,142,209,210 . Inflammation is a causal factor for cancer initiation, promotion, malignancy, and metastatic dissemination 211,212 .…”

“…The collective evidence suggests that chronic inflammation is a risk factor across multiple diseases, some of which are traditionally viewed as pathophysiologically unrelated, such as CVD 157,159,160,220 , diabetes 138,180,221 , chronic kidney disease 11,142,209 , cancer 211,212,222 , depression 13,143,217 , and dementia 12,139,223 . In addition, higher levels of inflammatory markers in blood are associated with a greater loss of muscle mass and strength, accelerated loss of mobility, lower-extremity performance and physical activity, and depression in older individuals 224–228 , all of which are essential elements for defining frailty on the basis of the criteria most often used in the literature 229 .…”

Inflammation: A Key Contributor to the Genesis and Progression of Chronic Kidney Disease

“…A state of sustained systemic inflammation, commonly observed as elevated Creactive protein or erythrocyte sedimentation rate, is a prominent feature in patients with CKD [48] . Altered intestinal tract microbiome profile, present even in the early stages of CKD [49,50] , represents an important source of inflammation.…”

Influential factors on serum albumin concentration in hospitalized chronic kidney disease patients

“…Decreased serum albumin is associated with rapid loss of kidney function in patients with chronic kidney disease (CKD) all over the world (2,3). Therefore, the increase of SAC is one of the therapeutic goals in the management of CKD patients (4).…”