An overall incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are expected as we see the prevalence of obesity and diabetes increase throughout the world. We now know, risk factors associated with NAFLD are also associated with the development of chronic kidney disease (CKD). Research has found, patients with NAFLD are at a higher risk of developing CKD than those in the general population, the shared comorbidities and direct pathogenic mechanisms linking NAFLD and CKD can further explain this finding.
So, let’s start by explaining what NFALD is.
NAFLD is an umbrella term for a whole range of conditions that impact the liver. It is the most common form of liver disease in the United States, affecting approximately one-quarter of the population. NAFLD is a condition where excess fat builds up on the liver, this excess fat is not due to the consumption of alcohol. In comparison, when heavy alcohol use causes fat to build up in the liver, the condition is called alcohol-associated liver disease.
There are two types of NAFLD:
- Non-alcoholic fatty liver disease (NAFL)- this is a form of NAFLD where there is fat on the liver, however, there is little or no inflammation or damage to the liver. NAFL can cause pain from the liver enlarging, however, it does not typically progress or cause liver damage or other complications.
- Non-alcoholic steatohepatitis (NASH)- NASH is a form of NAFLD where there is inflammation of the liver and there is liver damage as well as fat in the liver. Fibrosis and scarring can be the result of NASH. It may lead to cirrhosis, which is where the liver is scarred and permanently damaged, and this can lead to liver cancer.
Symptoms of NAFLD
NAFLD doesn’t usually cause any signs and symptoms, when it does, it includes-
- Pain or discomfort in the upper right quadrant
Possible signs & Symptoms of NASH & Cirrhosis
- Ascites (abdominal swelling)
- Enlarged spleen
- Red palms
- Enlarged blood vessels just below the skin’s surface
Research has found, you are more at risk of NAFLD or NASH if you;
- Are overweight or obese
- Have Type 2 diabetes or prediabetes
- Have metabolic syndrome ( a combination of symptoms that occur together increasing the risk of heart disease, type 2 diabetes and stroke)
NASH is more likely to occur in individuals that;
- Are older in age (although children can also get it)
- Have type 2 diabetes
- High blood pressure
- Have obstructive sleep apnoea
- If you are Hispanic or Asian
- Obesity with fat concentrated around the waist
There are fewer common reasons individuals may get NAFLD or NASH, these include;
- Exposure to certain toxins
- Certain infections, such as Hep C
- Polycystic ovarian syndrome
- Certain medications can be implicated, such as Glucocorticoids, synthetic estrogens, amiodarone (Cordarone, Pacerone), methotrexate (Rheumatrex, Trexall), tamoxifen (Nolvadex, Soltamox)
- Rapid, excessive weight loss
The Connection between NAFLD & Kidney Disease
It has been shown that NAFLD and NASH are hepatic manifestations due to metabolic syndrome. We know metabolic syndrome encompasses a multitude of comorbidities such as insulin resistance, CKD, cardiovascular disease, obstructive sleep apnoea and an increased risk of malignancy. As NAFLD is linked to underlying insulin resistance, growing evidence suggests NAFLD is a risk factor for CKD due to their shared metabolic risk factors. Studies have now shown an association between the severity of NASH and CKD.
Approximately one-third of patients with NAFLD experience impaired renal function. Research has found the development of NAFLD in patients with diabetes predisposes these individuals to a higher risk of developing CKD. A recent study published in the World Journal of Gastroenterology has also concluded, patients with type 2 diabetes Mellitus or type 1 diabetes Mellitus and NAFLD are at a higher risk of developing CKD compared to diabetics that did not have NAFLD present.
Insulin resistance (IR) has been established as a mediator for NAFLD. In turn, IR is further exacerbated by the progression of NAFLD, as shown in animal models, this leads to atherogenic dyslipidaemia and the release of inflammatory cytokines resulting in CKD. Studies have found IR leads to the increased production of very-low-density-lipoprotein and endoplasmic reticulum stress; causing podocyte damage in the glomeruli which has been linked to proteinuria and the hastening of CKD.
Now, this is a term we hear a lot of! We know how important our microbiome is and there is always new and exciting research in this area of health. Research supports, changes in the gut microbiome play a role in the development of NAFLD and CKD. The low-grade inflammation responsible for NAFLD and CKD can be due to the increased consumption of fructose. A vitamin D deficiency has also been shown to cause dysbiosis. The combination of dysbiosis and bacterial fermentation leads to the production of uremic toxins indoxyl sulphate and p-cresyl sulphate, this has been found to directly correlate to the progression of CKD.
Authors have also found the short-chain fatty acids butyrate, acetate and propionate diffuse through the gut mucosa disturbing the integrity of the intestinal barrier. Once in the bloodstream, these short-chain fatty acids can cause systemic inflammation which is the common pathogenic link between CKD and NAFLD.
Gut- Liver-Kidney Axis
Over the last decade, there has been an increased interest in understanding the liver-kidney axis and its role in both health and disease. A 2002 article published in Pharmacological Research states that gut microbiota has been demonstrated to modulate the severity of chronic illness found in the liver and kidneys and evidence suggests NAFLD and NASH are both independent risk factors for rapid CKD progression. The main mechanisms that have been focused on are low-grade inflammation, dyslipidaemia and the alteration in of gut microbiome.
As a result, targeting the gut-liver-kidney axis may be a therapeutic strategy for patients with CKD associated with fatty liver.
Managing NAFLD and CKD
For patients with diabetes and NAFLD, it is suggested they undergo frequent checkups for any underlying kidney dysfunction, this is suggested more so than for patients with diabetes only.
Waist to hip Ratio
A recent study has shown, non-obese patients with NAFLD are at high risk of adverse kidney outcomes, however, what they found was a decrease in WHR, more than an average of 5%, was associated with a risk reduction of CKD development in those with NAFLD, even if not obese. Based on this outcome, authors speculated reducing abdominal fat, may in fact, be a useful strategy to help reduce the increased risk of adverse kidney outcomes in those with NAFLD.
Coenzyme CoQ10 (CoQ10)
CoQ10 is known for its antioxidant and anti-inflammatory actions. It plays a key role in cellular metabolism and cellular energy generation. It has been reported, patients with NAFLD, CKD AND/OR CVD have a CQ10 deficiency. As CoQ10 is also produced in the liver, those with NAFLD have diminished CoQ10 production. A 2019 study found supplementation with COQ10 improves glycaemic control, and vascular dysfunction in type 2 diabetes, improves renal function in those with CKD and reduces liver inflammation in patients with NAFLD. CoQ10 may be a supplement worth considering in these cases.
Evidence suggests vitamin D may play a role in the development of NAFLD. Numerous publications support the idea that low vitamin D contributes to the development of insulin resistance and also metabolic syndrome. Animal studies show vitamin D plays a pivotal role in regulating oxidative stress, hepatocyte apoptosis and even liver fibrosis, it also holds immune-modulating and anti-inflammatory properties. As vitamin D requires hydroxylation by the liver and kidneys, it makes sense there is vitamin D resistance in the presence of CKD and NAFLD. Studies suggest vitamin D is linked to the pathogenesis and severity of NAFLD and CKD.
Although it seems more research has to be done in this area, vitamin D supplementation is worth considering and discussing.
Now, this is a huge topic!
The gut and liver communicate through the gut-liver axis. We know the major contributors in the pathogenesis of NAFLD are oxidative stress, insulin resistance and inflammation, it’s here the gut microbiota plays a crucial role. The job of gut microbiota is to maintain homeostasis via supporting nutrient digestion, immune modulation, metabolism and barrier protection. Research supports the fact dysbiosis leads to the overgrowth of detrimental bacteria, it increases gut permeability and impacts the flow of metabolites to the liver initiating and aggravating NAFLD. Research is now showing, supporting and manipulating gut microbiota could become a therapeutic strategy in the treatment of NFLAD. Research has also demonstrated that CKD is associated with dysbiotic gut bacteria. This topic is huge, and requires a stand-alone article!
As there are shared risk factors in both NAFLD and CKD, early surveillance is important. Research supports the implementation of treatment directed specifically towards NASH, which will hopefully slow the progression of renal dysfunction in individuals affected. Research continues to grow in this area of health which is great to see.
There is still so much to write on this topic!
Maybe I’ll follow up with another article?
Please remember as with any dietary/ supplemental change in those with a chronic health concern, to make sure you consult your health professional first.
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