Relationship between non-alcoholic fatty liver disease and kidney function: A communication between two organs that needs further exploration

Abstract

Non-alcoholic fatty liver disease (NAFLD) is now regarded as hepatic component of the metabolic syndrome. In addition, NAFLD has emerged as a growing public health problem worldwide and an important challenge for health authorities. NAFLD is associated with insulin resistance and hyperlipidaemia and this appears as the potential pathogenic role of NAFLD in the development and progression of chronic kidney disease (CKD). Interestingly, NAFLD and CKD may share common pathogenic mechanisms like obesity, abdominal obesity, insulin resistance, hyperlipidaemia, hypertension and inflammation. Importantly, the association between NAFLD and CKD is also being shown to be independent of obesity, hypertension, and other potentially confounding features of the metabolic syndrome, and it occurs both in patients without diabetes and in those with diabetes. How the liver communicates with kidney in individuals with NAFLD is not well known and indeed an urgent research is needed to further elucidate the complex and intertwined mechanisms that link NAFLD and CKD. One potential pathway for future exploration may be inflammatory mediators in NAFLD that may lead to deterioration in renal function. In addition, large clinical studies are needed to study the impact of NAFLD on the progression of CKD and in particular during dialysis and transplant and importantly how treatment of NAFLD and weight loss will have reversible potential benefit in improving renal function.

Introduction

The prevalence of chronic kidney disease worldwide is estimated to increase significantly by year 2015. Over 1.1 million patients are estimated to have End Stage Renal Disease (ESRD) worldwide, with an addition of 7% annually [1]. Therefore, the search for causes of CKD has attracted more research. The possible link between non-alcoholic fatty liver disease (NAFLD) and kidney disease is subject for considerable research interest.

NAFLD is emerging as an important public health problem across the globe with an estimated prevalence of 20–30% in Western communities and 90% in morbidly obese [2], [3]. Nonalcoholic steatohepatitis (NASH), the more severe form of NAFLD is much less common at 2–3% prevalence [4]. NAFLD refers to a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. NAFLD is strongly associated with insulin resistance and is defined by accumulation of liver fat >5% per liver weight, in the presence of <10 g of daily alcohol consumption [5]. The characteristic histology of NAFLD resembles that of alcohol-induced liver injury, but occurs in people who consume minimal amounts of alcohol. NAFLD is regarded as the most common cause of increased liver enzymes and is associated with metabolic syndrome, obesity, type 2 diabetes and hyperlipidaemia [6]. The increase in prevalence of obesity is also associated with an increase in prevalence of NAFLD and type 2 diabetes. The most common causes of fatty liver disease are attributable to alcohol excess; however, as obesity and type 2 diabetes are increasing in prevalence it is likely that there will be a marked increase in numbers of individuals with NAFLD [6]. The importance of early diagnosis of NAFLD is the risk that it may progress silently to cirrhosis, portal hypertension, and liver-related death in early adulthood, in the absence of successful orthotopic/living donor liver transplant. In addition, NAFLD is also associated with an increased risk of all-cause mortality and predicts future CVD events [7]. Hence, there is an urgent need for sensitive and specific biochemical markers for NAFLD as serial measurements of alanine aminotransferase (ALT) can be misleading and cannot accurately predict the severity or outcome [8]. Interestingly, different studies have shown that NAFLD is associated with an increase in incidence of CVD [9], [10] and considerable numbers of studies show an increase in the incidence of CVD with CKD [11].

The subsequent discussion will focus on the association of NAFLD with CKD, insulin resistance and hyperlipidaemia and how ultimately this may lead to deterioration in renal function.