New Pharmacologic Agents That Target Inflammation and Fibrosis in Nonalcoholic Steatohepatitis–Related Kidney Disease

Musso, Giovanni; Michieli, Franco De; Bongiovanni, Daria; Parente, Renato; Framarin, L.; Leone, Nicola; Berrutti, M; Gambino, Roberto; Cassader, Maurizio; Cohney, Solomon; Paschetta, Elena

doi:10.1016/j.cgh.2016.08.002

Cited by 29 publications

(20 citation statements)

References 123 publications

(140 reference statements)

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“…Additionally, a number of studies have suggested that the rates of CKD increases in NAFLD according to stage of hepatic fibrosis, as estimated by noninvasive fibrosis biomarkers . In one study, Musso et al reported that NASH and CKD share common proinflammatory and profibrotic mechanisms, which could explain the poor clinical outcomes of NASH patients with cirrhosis as compared to other etiologies after simultaneous liver‐kidney transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…37 Additionally, a number of studies have suggested that the rates of CKD increases in NAFLD according to stage of hepatic fibrosis, as estimated by noninvasive fibrosis biomarkers. 38,39 In one study, Musso et al 40 Because of the multicollinearity between metabolic components and history of CVD, the latter was excluded from multivariable analysis Participants without NAFLD were excluded. NAFLD was defined as moderate to severe hepatic steatosis on ultrasound.…”

Section: Discussionmentioning

confidence: 99%

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Chronic kidney disease is independently associated with increased mortality in patients with nonalcoholic fatty liver disease

Paik

Golabi

Younoszai

et al. 2018

Liver International

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Background & Aims Nonalcoholic fatty liver disease and chronic kidney disease share similar pathophysiologic features. Our aim was to assess the association between different stages of chronic kidney disease and mortality in patients with nonalcoholic fatty liver disease. Methods Third National Health and Nutrition Examination Survey‐linked mortality files were utilized. Nonalcoholic fatty liver disease was diagnosed by hepatic ultrasound and chronic kidney disease was defined according to the Kidney Disease Improving Global outcomes guideline. Multivariable Cox proportional hazard model was used to assess the effect of chronic kidney disease on overall and cardiovascular mortality. Results Total cohort included 11 695 adult participants; mean age 43.3 years, 48.4% male, 76.4% white, 18.6% had nonalcoholic fatty liver disease and 9.3% had chronic kidney disease. 5.6% had diabetes, 21.3% had hypertension, 4.3% had cardiovascular disease. Compared to subjects without chronic kidney disease or nonalcoholic fatty liver disease, nonalcoholic fatty liver disease patients with chronic kidney disease were more likely to be older, had less income, and higher prevalence of comorbidities (all P < 0.001). Prevalence of chronic kidney disease among nonalcoholic fatty liver disease cohort was 11.31%. Compared to non‐nonalcoholic fatty liver disease group, patients with nonalcoholic fatty liver disease had higher rates of stage 1, 2 and 3a chronic kidney disease, but similar rates for stage 3b, 4 and 5. Mortality rate was 18.5% in 17 years. Among nonalcoholic fatty liver disease cohort, the presence of chronic kidney disease stages 2‐3a (HR = 2.31, 95% CI: 1.70‐3.15) and stages 3b‐5 (HR = 4.83, 95% CI: 2.40‐9.71) were independently associated with increased overall mortality. Conclusions Among patients with nonalcoholic fatty liver disease, moderate to advanced stages of chronic kidney disease are associated with overall mortality. Identification of chronic kidney disease in nonalcoholic fatty liver disease has important prognostic implications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chronic kidney disease is independently associated with increased mortality in patients with nonalcoholic fatty liver disease

Paik

Golabi

Younoszai

et al. 2018

Liver International

View full text Add to dashboard Cite

show abstract

“…79 Collectively, NAFLD and CKD share common proinflammatory and profibrotic mechanisms of disease progression. 80,81 Experimental evidence also supports a role of the inflammasome and innate immune system in CKD. 32,82 Therefore, all of these factors and pathways could indicate a causal link between NAFLD and CKD, whereby NAFLD increases the risk of incident CKD.…”

Section: Putative Mechanisms Linking Nafld With Ckd T2dm and Metabolimentioning

confidence: 91%

NAFLD as a driver of chronic kidney disease

Byrne

Targher

2020

Journal of Hepatology

306

263

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Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are worldwide public health problems, affecting up to 25-30% (NAFLD), and up to 10-15% (CKD) of the general population. Recently, it has also been established that there is a strong association between NAFLD and CKD, regardless of the presence of potential confounding diseases such as obesity, hypertension and type 2 diabetes. Since NAFLD and CKD are both common diseases that often occur alongside other metabolic conditions, such as type 2 diabetes or metabolic syndrome, elucidating the relative impact of NAFLD on the risk of incident CKD presents a substantial challenge for investigators working in this research field. A growing body of epidemiological evidence suggests that NAFLD is an independent risk factor for CKD and recent evidence also suggests that associated factors such as metabolic syndrome, dysbiosis, unhealthy diets, platelet activation and processes associated with ageing could also contribute mechanisms linking NAFLD and CKD. This narrative review provides an overview of the literature on: a) the evidence for an association and causal link between NAFLD and CKD and b) the underlying mechanisms by which NAFLD (and factors strongly linked with NAFLD) may increase the risk of developing CKD.

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“…The NLRP3 inflammasome is the best studied among the inflammasomes, multiprotein cytosolic complexes that form part of the NLR family of PRR [88,89]. NLRP3 is involved in chronic kidney disease pathogenesis [90,91].…”

Section: Macrophages Phenotype Under the Control Of Bioactive Moleculmentioning

confidence: 99%

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Calle

Hotter

2020

IJMS

137

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Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction, but its progression is due to different pathological mechanisms, including oxidative stress, inflammatory cells infiltration, inflammation and fibrosis. Macrophages (Mφ) accumulation in kidneys correlates strongly with serum creatinine, interstitial myofibroblast accumulation and interstitial fibrosis scores. However, whether or not Mφ polarization is involved in the progression of DN has not been adequately defined. The prevalence of the different phenotypes during the course of DN, the existence of hybrid phenotypes and the plasticity of these cells depending of the environment have led to inconclusive results. In the same sense the role of the different macrophage phenotype in fibrosis associated or not to DN warrants additional investigation into Mφ polarization and its role in fibrosis. Due to the association between fibrosis and the progressive decline of renal function in DN, and the role of the different phenotypes of Mφ in fibrosis, in this review we examine the role of macrophage phenotype control in DN and highlight the potential factors contributing to phenotype change and injury or repair in DN.

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New Pharmacologic Agents That Target Inflammation and Fibrosis in Nonalcoholic Steatohepatitis–Related Kidney Disease

Cited by 29 publications

References 123 publications

Chronic kidney disease is independently associated with increased mortality in patients with nonalcoholic fatty liver disease

Chronic kidney disease is independently associated with increased mortality in patients with nonalcoholic fatty liver disease

NAFLD as a driver of chronic kidney disease

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

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