NAFLD as a driver of chronic kidney disease

Byrne, Christopher D.; Targher, Giovanni

doi:10.1016/j.jhep.2020.01.013

Cited by 306 publications

(320 citation statements)

References 145 publications

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“…While traditionally the hepatorenal syndrome causing AKI was the main kidney-related concern in liver disease patients, more recently a link between liver steatosis, non-alcoholic fatty liver disease (NAFLD) and CKD has been emphasized [75,76]. Since NAFLD, diabetes and CKD are complications of the metabolic syndrome, this points to the potential utility of PGC-1α-based therapeutic approaches to target the different complications of metabolic syndrome.…”

Section: Liver Diseasementioning

confidence: 99%

The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases

et al. 2020

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Chronic kidney disease (CKD) is one of the fastest growing causes of death worldwide, emphasizing the need to develop novel therapeutic approaches. CKD predisposes to acute kidney injury (AKI) and AKI favors CKD progression. Mitochondrial derangements are common features of both AKI and CKD and mitochondria-targeting therapies are under study as nephroprotective agents. PGC-1α is a master regulator of mitochondrial biogenesis and an attractive therapeutic target. Low PGC-1α levels and decreased transcription of its gene targets have been observed in both preclinical AKI (nephrotoxic, endotoxemia, and ischemia-reperfusion) and in experimental and human CKD, most notably diabetic nephropathy. In mice, PGC-1α deficiency was associated with subclinical CKD and predisposition to AKI while PGC-1α overexpression in tubular cells protected from AKI of diverse causes. Several therapeutic strategies may increase kidney PGC-1α activity and have been successfully tested in animal models. These include AMP-activated protein kinase (AMPK) activators, phosphodiesterase (PDE) inhibitors, and anti-TWEAK antibodies. In conclusion, low PGC-1α activity appears to be a common feature of AKI and CKD and recent characterization of nephroprotective approaches that increase PGC-1α activity may pave the way for nephroprotective strategies potentially effective in both AKI and CKD.

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Section: Liver Diseasementioning

confidence: 99%

The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases

et al. 2020

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“…However, most of previous studies had a much higher prevalence of diabetes in their study samples [24,25], raising the possibility of selection bias given the strong association between diabetes and CKD. Additionally, although it is reasonable to assume that NAFLD may promote renal damage, it is still uncertain if NAFLD is associated with a speci c type of kidney disease [16]. Anyhow, despite that gouty nephropathy and diabetic kidney disease (DKD) have many risk factors in common, they are actually distinct entities with differing risk pro les.…”

Section: Discussionmentioning

confidence: 99%

“…The relationship between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) has attracted much attention, since they share similar risk factors and pathogenic mechanisms, such as insulin resistance (IR), diabetes mellitus (DM), hyperlipidemia and obesity [12][13][14][15][16][17][18]. While numbers of previous studies indicated the presence and severity of NAFLD was a potential contributory risk factor for the development and progression of CKD, recent studies suggested no adverse association between NAFLD hepatic steatosis and renal function both in general populations and diabetic individuals [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

“…Some also argue that NAFLD was associated with early stages of CKD, but not the late stages of CKD [22]. In addition, although it is reasonable to assume that NAFLD may promote renal damage, it is still uncertain if NAFLD is associated with a speci c type of kidney disease [16]. Given that most of the studies were focused on patients with DM [24,25], the speci c relationship between NAFLD and gouty nephropathy has been poorly studied.…”

Section: Introductionmentioning

confidence: 99%

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The Negative Association Between Non-alcoholic Fatty Liver Disease Severity and Gouty Nephropathy in a Non-diabetic Gouty Population: A Cross-Sectional Study

Zhou¹,

Wang²,

Chi³

et al. 2020

Preprint

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Background: Nonalcoholic fatty liver (NAFLD) and chronic kidney disease (CKD) share common pathogenic mechanisms and risk factors, but the specific relationship between NAFLD and gouty nephropathy has not been well understood. We aim to evaluate the association between NAFLD and gouty nephropathy in a non-diabetic gouty population.Methods: The retrospective cross‑sectional study was performed on 1049 non-diabetic gouty participants, who were hospitalized between 2014 and 2020, across 4 districts in Shandong, China. Demographic and clinical characteristics of the study population were collected. The odds ratios (OR) and corresponding 95% confidence intervals (CI) in relation to the NAFLD severity determined by ultrasonography were obtained by multiple logistic regression analysis. Results: An unexpectedly inverse relationship was found between NAFLD severity and the risk of gout nephropathy. Multivariate logistic regression analysis demonstrated that higher degree of NAFLD severity is independently associated with lower risk of gouty nephropathy, after adjusted for age, sex, smoking, gout duration, and metabolic risk factors including obesity, hypertension, hyperglycemia, hyperuriacemia and dyslipidemia, with OR 0.392 (95 % CI 0.248–0.619, P < 0.001), 0.379 (95 % CI 0.233–0.616, P < 0.001) and 0.148 (95 % CI 0.043–0.512, P = 0.003) in participants with mild, moderate, and severe NAFLD, respectively, compared to those without NAFLD. We also observed a weakened association of serum uric acid (SUA) with metabolic risk factors and NAFLD under circumstances of gouty nephropathy (r = -0.054, P = 0.466). Conclusions: The presence and severity of NAFLD was negatively associated with the risk of gouty nephropathy in the non-diabetic gouty populations. Further investigation of NAFLD will provide insights into the pathogenesis of gouty nephropathy.Trials registration: Chinese Clinical Trials Registry ChiCTR2000035185. Registered 2 August 2020.

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“…The relationship between NAFLD and chronic kidney disease (CKD) has attracted much attention recently. NAFLD and CKD may share common pathogenic mechanisms, such as insulin resistance, type 2 diabetes mellitus, hyperlipidemia and obesity, and thus may potentially share same therapeutic targets [3][4][5]. Growing evidence suggests that patients with NAFLD have a higher risk of CKD than non-NAFLD population [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Association between NAFLD and risk of prevalent chronic kidney disease: Why there is a difference between East and West?

Zhang

Lin

Wang³

et al. 2020

Preprint

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Backgrounds: There is a discrepancy between west and east on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This study aimed to find out the possible reason for this and to clarify the association between NAFLD and CKD by analyzing two population-based datasets from the US and China. Methods: Two health examination datasets from China and the US were used. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m 2 or and/or abnormal albuminuria and/or overt proteinuria. Binary logistic regression was used to examine the association between NAFLD and CKD. Results: A total of 60965 participants were analyzed, including 11844 from the US and 51229 from China. The prevalence of NAFLD was 27.12% in the Chinese population and 36.08% in the US population (p<0.001). The proportions of CKD and late stage CKD (stages 3-5) were higher in the US population than the Chinese one. NAFLD was independently associated with an increased risk of CKD in Chinese population, whereas in the US population, the NAFLD was not an independent risk factor of CKD. In subgroup analyses which excluded late stages CKD (stages 3-5), the risks of mild renal function decline became consistent: NAFLD was associated with early stages of CKD but not the late stages of CKD in both populations. Conclusion: NAFLD increased the risk of early stages of CKD in both Chinese and the US population. The conflicting results reported by previous studies might result from the different proportion of late stages of CKD.

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NAFLD as a driver of chronic kidney disease

Cited by 306 publications

References 145 publications

The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases

The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases

The Negative Association Between Non-alcoholic Fatty Liver Disease Severity and Gouty Nephropathy in a Non-diabetic Gouty Population: A Cross-Sectional Study

Association between NAFLD and risk of prevalent chronic kidney disease: Why there is a difference between East and West?

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