Altered kidney function in fatty liver disease: confronting the “MAFLD-renal syndrome” DOI Creative Commons

Suleiman Al Ashi,

Ali A. Rizvi, Manfredi Rizzo

et al.

Frontiers in Clinical Diabetes and Healthcare, Journal Year: 2025, Volume and Issue: 5

Published: Jan. 8, 2025

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes chronic globally. In 2020, a new terminology, namely "metabolic dysfunction-associated disease" (MAFLD), was proposed (1). Cardiometabolic criteria have been added in updated definition to highlight elevated cardiovascular risk these patients. The revised better emphasizes central role metabolic dysfunction development and progression this highly prevalent condition. From morbidity standpoint, both definitions are associated with an increased developing diabetes, disease, renal dysfunction. study 6873 individuals 4.6-year follow-up, associations MAFLD NAFLD kidney (CKD), (CVD) were similar (2). Epidemiological evidence indicates that not only liver-related complications, but also increases possibility several extra-hepatic diseases, including new-onset type 2 diabetes (T2DM) as well adverse outcomes (3). Metabolic disorders, overweight/obesity, T2DM, hypertension, dyslipidemia often systemic organ dysfunction, thereby suggesting could occur (Figure 1). novel understanding underscores bidirectional relationship between hepatic steatosis continuum.The association intriguing has highlighted recent years. be independently CKD (4). Parvanova colleagues investigated prevalence prediabetes, visceral obesity, preserved function, explored whether hyperfiltration, early sign damage (5). Renal hyperfiltration generally defined estimated glomerular filtration rate (eGFR) standard deviations above age- sex-specific mean, i.e.: >98th percentile. They analyzed data from more than 6000 Spanish civil servants, aged 18-65 years, fasting plasma glucose ≥ 100 ≤ 125 mg/dL (prediabetes). Approximately 4000 patients (62.9%) had MAFLD, 330 (4.9%) hyperfiltration. frequent without (86.4% vs 61.7%, P < 0.001). More half subjects 60 ml/min presented Interestingly, pathophysiologic basis altered function still fully unraveled. A finding dysregulation (6). It regarded by some manifestation syndrome (MetS), Heightened heightened inflammation, hemodynamics, proinflammatory markers, endothelial may all playing part (7). setting oxidative stress chronically abnormal adipokine profile, low-grade, subclinical inflammation promotes lipid accumulation atherogenic ("lipotoxicity"). regard, roles two key adipocytokines worth mentioning. Increased leptin secretion steatohepatitis, concomitant reduction adiponectin, which anti-inflammatory anti-atherogenic properties (8). fat deposition enhances release tumor necrosis factor-a (TNF-a) interleukin-6 (IL-6)(9). aforementioned factors shown contribute likelihood involvement (10). share factors, insulin resistance (IR), impaired tolerance, dyslipidemia, hypertension. Abbate et al. found dysglycemia (11). reported averaged 19.3%, progressively 14.7% 33.2% 48.9% normoglycemia, prediabetes respectively. Chen aimed clarify incident end-stage (ESRD) prospectively cohort 337,783 UK Biobank participants over median duration 12.8 years (12). Participants twice likely develop ESRD, ESRD remained significant non-CKD participants. Since IR accompaniment it surprising T2DM shows epidemiologic overlap latter. Worldwide, 18%-33% while up 66%-83% those varying degrees (13,14). Clinical improvements can favorably impact (15).Studies coexistence predicts ischemic heart (IHD) or alone (16). addition, combination abdominal obesity of, mortality from, CKD. retrospective 9161 National Health Nutrition Examination Surveys III (NHANES III) 1988 1994, abdominally obese group highest all-cause disease-specific during 30-year follow-up period (17). Abdominal therefore serve mediator CKD.Ascertaining fibrosis obvious clinical importance. respect, exhibited greater incidence compared (75.6% vs. 24.4%) (18). Liver assessed transient elastography albuminuria (19). noteworthy predictor (20). Having CKD, we would like recommend aggressive measures order natural history "MAFLD-Renal Syndrome". main interventions listed Table 1. Firstly, primary importance identification reversible stages, population increasing rates cannot over-emphasized. This requires high index suspicion involves screening asymptomatic high-risk for condition using approved tools. diagnosis presence its should promptly followed evaluation Such strategy justified based on showing epidemiologic, pathophysiologic, conditions. reasonable employ sensitive measurements damage, such microalbuminuria, emerging biomarkers nystatin C. Lifestyle dietary modifications, weight loss, physical activity beneficial amelioration obesity-metabolic form therapeutic cornerstone management (21). Pharmacologic at loss helpful kidneys, although detailed review beyond scope paper. There preliminary supporting use nutraceutical approaches certain MiRNAs mitigating deleterious milieu modifying gene expression steatohepatitis (22,23). thyroid hormone receptor activator resmetirom drug reduce treat noncirrhotic hepatitis moderate-to-advanced (24); however, unknown. evident preventive aspects intervention reducing burden MAFLD. Future efforts need directed investigating targeting unique hepatorenal pathways operate evolving relationship. context areas research therapeutics include following: 1) potential renin-angiotensin system genesis (25); 2) immune mechanisms antigen-activated CD8+ T cells, immune-modulating agents, pathogenesis MAFLD-associated (26), 3) applicability promising biomarkers, injury molecule-1 (KIM-1) liver-type acid binding protein (L-FABP), detection surveillance (27).

Language: Английский

Altered kidney function in fatty liver disease: confronting the “MAFLD-renal syndrome” DOI Creative Commons

Suleiman Al Ashi,

Ali A. Rizvi, Manfredi Rizzo

et al.

Frontiers in Clinical Diabetes and Healthcare, Journal Year: 2025, Volume and Issue: 5

Published: Jan. 8, 2025

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes chronic globally. In 2020, a new terminology, namely "metabolic dysfunction-associated disease" (MAFLD), was proposed (1). Cardiometabolic criteria have been added in updated definition to highlight elevated cardiovascular risk these patients. The revised better emphasizes central role metabolic dysfunction development and progression this highly prevalent condition. From morbidity standpoint, both definitions are associated with an increased developing diabetes, disease, renal dysfunction. study 6873 individuals 4.6-year follow-up, associations MAFLD NAFLD kidney (CKD), (CVD) were similar (2). Epidemiological evidence indicates that not only liver-related complications, but also increases possibility several extra-hepatic diseases, including new-onset type 2 diabetes (T2DM) as well adverse outcomes (3). Metabolic disorders, overweight/obesity, T2DM, hypertension, dyslipidemia often systemic organ dysfunction, thereby suggesting could occur (Figure 1). novel understanding underscores bidirectional relationship between hepatic steatosis continuum.The association intriguing has highlighted recent years. be independently CKD (4). Parvanova colleagues investigated prevalence prediabetes, visceral obesity, preserved function, explored whether hyperfiltration, early sign damage (5). Renal hyperfiltration generally defined estimated glomerular filtration rate (eGFR) standard deviations above age- sex-specific mean, i.e.: >98th percentile. They analyzed data from more than 6000 Spanish civil servants, aged 18-65 years, fasting plasma glucose ≥ 100 ≤ 125 mg/dL (prediabetes). Approximately 4000 patients (62.9%) had MAFLD, 330 (4.9%) hyperfiltration. frequent without (86.4% vs 61.7%, P < 0.001). More half subjects 60 ml/min presented Interestingly, pathophysiologic basis altered function still fully unraveled. A finding dysregulation (6). It regarded by some manifestation syndrome (MetS), Heightened heightened inflammation, hemodynamics, proinflammatory markers, endothelial may all playing part (7). setting oxidative stress chronically abnormal adipokine profile, low-grade, subclinical inflammation promotes lipid accumulation atherogenic ("lipotoxicity"). regard, roles two key adipocytokines worth mentioning. Increased leptin secretion steatohepatitis, concomitant reduction adiponectin, which anti-inflammatory anti-atherogenic properties (8). fat deposition enhances release tumor necrosis factor-a (TNF-a) interleukin-6 (IL-6)(9). aforementioned factors shown contribute likelihood involvement (10). share factors, insulin resistance (IR), impaired tolerance, dyslipidemia, hypertension. Abbate et al. found dysglycemia (11). reported averaged 19.3%, progressively 14.7% 33.2% 48.9% normoglycemia, prediabetes respectively. Chen aimed clarify incident end-stage (ESRD) prospectively cohort 337,783 UK Biobank participants over median duration 12.8 years (12). Participants twice likely develop ESRD, ESRD remained significant non-CKD participants. Since IR accompaniment it surprising T2DM shows epidemiologic overlap latter. Worldwide, 18%-33% while up 66%-83% those varying degrees (13,14). Clinical improvements can favorably impact (15).Studies coexistence predicts ischemic heart (IHD) or alone (16). addition, combination abdominal obesity of, mortality from, CKD. retrospective 9161 National Health Nutrition Examination Surveys III (NHANES III) 1988 1994, abdominally obese group highest all-cause disease-specific during 30-year follow-up period (17). Abdominal therefore serve mediator CKD.Ascertaining fibrosis obvious clinical importance. respect, exhibited greater incidence compared (75.6% vs. 24.4%) (18). Liver assessed transient elastography albuminuria (19). noteworthy predictor (20). Having CKD, we would like recommend aggressive measures order natural history "MAFLD-Renal Syndrome". main interventions listed Table 1. Firstly, primary importance identification reversible stages, population increasing rates cannot over-emphasized. This requires high index suspicion involves screening asymptomatic high-risk for condition using approved tools. diagnosis presence its should promptly followed evaluation Such strategy justified based on showing epidemiologic, pathophysiologic, conditions. reasonable employ sensitive measurements damage, such microalbuminuria, emerging biomarkers nystatin C. Lifestyle dietary modifications, weight loss, physical activity beneficial amelioration obesity-metabolic form therapeutic cornerstone management (21). Pharmacologic at loss helpful kidneys, although detailed review beyond scope paper. There preliminary supporting use nutraceutical approaches certain MiRNAs mitigating deleterious milieu modifying gene expression steatohepatitis (22,23). thyroid hormone receptor activator resmetirom drug reduce treat noncirrhotic hepatitis moderate-to-advanced (24); however, unknown. evident preventive aspects intervention reducing burden MAFLD. Future efforts need directed investigating targeting unique hepatorenal pathways operate evolving relationship. context areas research therapeutics include following: 1) potential renin-angiotensin system genesis (25); 2) immune mechanisms antigen-activated CD8+ T cells, immune-modulating agents, pathogenesis MAFLD-associated (26), 3) applicability promising biomarkers, injury molecule-1 (KIM-1) liver-type acid binding protein (L-FABP), detection surveillance (27).

Language: Английский

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