Elsevier

Medical Hypotheses

Volume 82, Issue 1, January 2014, Pages 36-39
Medical Hypotheses

Non-alcoholic fatty liver disease; a part of the metabolic syndrome in the renal transplant recipient and possible cause of an allograft dysfunction

https://doi.org/10.1016/j.mehy.2013.10.030Get rights and content

Abstract

Despite all improvements in transplant medicine, renal transplant recipients have a high risk for cardiovascular mortality. A high prevalence of cardiovascular complications in renal transplant recipients (RTR) is explained by cardiovascular risk factors present before transplantation, in addition to the development of new risk factors as well as worsening of preexisting risk factors after transplantation. A majority ot these patients develop metabolic syndrome within a year after the transplantation. The metabolic syndrome (MS) is associated with impaired renal allograft function and increased insulin resistance. Non alcoholic fatty liver disease (NAFLD) represents a liver manifestation of metabolic syndrome and it development is strongly associated with all components of MS in general population. The current importance of NAFLD and its link to the MS has encouraged an interest in its possible role in the development of atherosclerosis in recent years. Considering the fact that all components of MS are more common among renal transplant recipients compared to general population, it would be expected that RTR may have a much higher incidence of NAFLD compared to general population. We propose that the presence of NAFLD in RTR could be a strong predictor in cardiovascular morbidity and mortality. Also, according to the recent investigations about the possible link between NAFLD and chronic kidney disease, we hypothesis that NAFLD may be associated with deteriorating graft function, causing a chronic allograft nephropathy and graft loss. Common factors underlying the pathogenesis of NAFLD and chronic allograft dysfunction may be insulin resistance, oxidative stress, activation of rennin–angiotensin system, and inappropriate secretion of inflammatory cytokines by steatotic and inflamed liver.

Introduction

Renal transplantation has significantly improved the survival of patients with end-stage renal disease (ESRD). Despite major advancements in immunosuppressive treatment of renal transplant recipients (RTR) that significantly increased graft and patient short-term survival and lowered the incidence of rejection crises, long-term prognosis is still poor. Efforts to increase long-term patient and graft survival are directed to the prevention and treatment of cardiovascular diseases (CVD), as they are the leading cause of mortality in these patients. Traditional risk factors for the development of CVD (e.g. arterial hypertension, new onset diabetes after transplant – NODAT, and metabolic lipid disorder) are up to fifty times more often among renal transplant recipients than in the general population. Namely, 50–60% of post-transplant deaths are directly attributable to cardiovascular deaths [1], [2], [3], [4]. Approximately one-third of non-diabetic kidney transplant recipients develop persistently impaired glucose metabolism within six months after transplantation [5]. About 70–90% of renal transplant recipients have either arterial hypertension or require antihypertensive therapy [6], [7]. Furthermore, according to one study that used data from the United Network for Organ Sharing, among 27,372 renal transplant recipients, 20% were obese (BMI 30–35) or morbidly obese (BMI ⩾35), and additional 30% were classified as overweight (BMI 25–29) [8]. Dyslipidemia remains a significant problem in transplant population. The pathogenesis of above mentioned disorders is multifactorial in most cases, but it is mainly related to immunosuppressive drugs. Namely, immunosuppressive drugs increase incidence and severity of traditional cardiovascular risk factors and thus have expected effects on components of the metabolic syndrome (MS) after kidney transplantation. All of these conditions are strong risk factors for ischemic heart disease, congestive heart failure, coronary heart disease, and stroke. Also, they can be harmful for the long-term kidney graft outcome, causing deteriorating of graft function and graft loss [1], [2], [3], [4], [5], [6], [7], [8], [9].

All components of metabolic syndrome have been shown to correlate with liver fat in the general population. Non-alcoholic fatty liver disease (NAFLD) has reached epidemic proportions and represents the most common cause of chronic liver disease in the community. It encompasses a spectrum of conditions with lipid deposition in hepatocytes and occurs in people who drink little or no alcohol. It ranges from simple steatosis to non-alcoholic steatohepatitis (NASH – fatty liver with inflammation and hepatocellular injury with or without fibrosis), to advanced fibrosis and cirrhosis, in which hepatocellular carcinoma can develop. Today, it is believed that NAFLD represent a liver manifestation of metabolic syndrome, considering its strong association with arterial hypertension, diabetes mellitus type 2, insulin resistance, obesity and lipid metabolism disorders. Cardiovascular diseases followed by liver-related mortality are the most common causes of death in NAFLD patients. It is believed that NAFLD is not merely a marker of CVD, but is also involved in its pathogenesis due to the release of various pro-atherogenic factors from the liver that contribute to enhanced oxidative stress, and account for the pro-atherogenic effect of NAFLD. Thus, NAFLD is emerging as a new significant health problem in many countries. In recent years, the possible link between NAFLD and chronic kidney disease (CKD) has also attracted research interest. Namely, several studies have shown that NAFLD is associated with a significant decrease in glomerular filtration rate and an increase in albuminuria and the incidence of CKD [10], [11], [12], [13], [14], [15], [16]. Furthermore, in the study conducted by Yasui et al. [15] patients with biopsy proven NASH had significantly higher prevalence of CKD than non-NASH patients. Similar results were observed by some other authors.

Section snippets

Hypothesis

The component of metabolic syndrome (obesity, arterial hypertension, lipid metabolism disorders, insulin resistance and diabetes mellitus type 2) are highly present after kidney transplantation, mainly due to use of immunosuppressive therapy. Considering the fact that those disorders are strongly associated with NAFLD development in general population, we hypothesis that renal transplant recipients will have higher incidence of NAFLD than general population. Furthermore, renal transplant

Discussion

Transplant recipients have a high rate of cardiovascular deaths which is partly due to the large number of diabetic patients in the end-stage renal disease (ESRD) population. On the other hand, the cardiovascular risk among transplant recipients who do not have ESRD related to diabetic nephropathy is still high compared to general population. This is mainly a consequence of an exacerbation of traditional risk factors (diabetes mellitus, obesity, arterial hypertension and lipid metabolism

Conclusion

Despite major advancements in immunosuppressive treatment of renal transplant recipients that significantly increased graft and patient short-term survival and significantly lowered the incidence of rejection crises, long-term prognosis is still poor. Cardiovascular diseases are the leading cause of morbidity and mortality in renal transplant recipients. Metabolic syndrome is highly present in those patients regarding it negative effect on graft function and increasing the incidence of CVD.

Conflict of interest

None.

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