Nonalcoholic fatty liver disease (NAFLD)--is it a new marker of hyporesponsiveness to recombinant human erythropoietin in patients that are on chronic hemodialysis?

Anemia is a major consequence of chronic kidney disease (CKD) that develops early in the course of illness and affects most patients who exhibit some degree of reduced renal function. Erythropoietin (EPO) deficiency is considered the most important cause of anemia in CKD. Renal anemia has serious clinical consequence. In addition to reducing patient physical capacity and quality of life, anemia induces adaptive cardiovascular mechanisms that increase the risk of cardiovascular disease and death. Thus, treatment of anemia in CKD is very important. While EPO is effective in correcting anemia in most cases, up to 10% of patients however, have an inadequate response to therapy. The two most common and important reasons why patients become relatively unresponsive to EPO therapy are the development of true iron deficiency and the onset of an inflammatory state that impairs the response to EPO. Indeed, the role of inflammation and pro-inflammatory cytokines in resistance to EPO therapy is gaining increasing recognition. On the other hand, the main organ for C-reactive protein (CRP) synthesis is the liver and it is well known that the synthesis of an acute-phase proteins by the liver is up regulated by inflammation. The main consequence of nonalcoholic fatty liver disease (NAFLD) is sub-chronic liver inflammation that leads and contributes to dyslipidemia, inflammation, enhanced oxidative stress and endothelial dysfunction. Considering the recent data about high prevalence of NAFLD in CKD patients, probably due to shared metabolic risk factors, we hypothesized that end-stage renal disease (ESRD) patients with NAFLD will need a much higher dose of EPO to achieve the target hemoglobin levels in comparison with ESRD patients without NAFLD. The possible underlying mechanism is sub-chronic liver inflammation in NAFLD patients that leads and contributes to poor response to EPO. Therefore, we believe that NAFLD could be a new clinical marker of poor response to EPO therapy in ESRD patients. Optimizing response to EPO therapy is important for both patient outcomes and the cost of treatment, and require consideration of a growing number of factors. Detection of NAFLD by some of non-invasive methods in ESRD patients could identify responsiveness and resistance to EPO therapy. Furthermore, we propose that all the patients who undergo dialysis treatment should be screened for NAFLD in order to identify the patients that will have a poor response to EPO therapy. The work could help to determine whether we have a new marker of poor EPO response in ESRD patients.

Transient elastography: a new noninvasive diagnostic tool for assessment of chronic allograft nephropathy.

PURPOSE: Chronic allograft nephropathy (CAN) is the most common cause of kidney allograft failure. Protocol biopsies remain the "gold standard" in CAN recognition. However, renal allograft biopsies have numerous limitations. It is an invasive procedure connected with risk of complications, patient discomfort, and sampling errors. The aim of our study was to investigate the usefulness of transient elastography (TE) for the assessment of kidney allograft fibrosis in renal transplant recipients (RTRs). METHODS: In this cross-sectional study, we involved 52 RTRs. Renal allograft stiffness was used to assess its fibrosis by using transient elastography (Fibroscan, Echosense, Paris, France). In 23 patients with a deterioration of graft function, percutaneous renal allograft biopsy was performed closely around the time of TE. RESULTS: We have found that the renal allograft stiffness was highly negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.640; p < 0.0001). However, renal allograft stiffness showed a statistically significant difference between patients who had an eGFR > 50 ml/min per 1.73 m(2) and patients with eGFR < 50 ml/min per 1.73 m(2) (28 ± 2.7 vs. 33.9 ± 5.5 kPa; p = 0.0003). Also, there was a highly positive correlation between renal allograft stiffness and extent of interstitial fibrosis on renal biopsy (r = 0.727; p = 0.0001). CONCLUSION: According to our results, parenchymal stiffness obtained by TE reflects interstitial fibrosis. Therefore, TE provides the opportunity for noninvasive screening of CAN.

Nonalcoholic Fatty liver disease in renal transplant recipients proven by transient elastography.

BACKGROUND: The increasing recognition of the importance of nonalcoholic fatty liver disease (NAFLD) and its strong association with the metabolic syndrome has stimulated interest in the putative role of NAFLD in the development and progression of cardiovascular disease. Furthermore, recent studies investigated the association of NAFLD and chronic kidney disease. We analyzed the incidence of NAFLD diagnosed by transient elastography (TE) in renal transplant recipients (RTRs). We also assessed whether TE-defined NAFLD is associated with decreased graft function in RTRs. METHODS: Our study included 73 RTRs with a functioning graft for more than 1 year. Liver stiffness was used to assess liver fibrosis and the controlled attenuation parameter (CAP) was used to detect and quantify liver steatosis by using TE (Fibroscan, Echosense, Paris, France). Therefore, with CAP being implemented on TE, both steatosis and fibrosis could be evaluated simultaneously. According to this evaluation, NAFLD was defined by the presence of steatosis with CAP values ≥ 238 dB.m(-1) regardless of presence or absence of any stage of fibrosis. RESULTS: According to the TE findings, NAFLD was present in 57.5% of RTRs. We have found that the severity of liver steatosis was positively correlated with serum creatinine levels (r = 0.664; P < .0001) and negatively correlated with estimated glomerular filtration rate (eGFR; r = -0.692; P < .0001) levels. The severity of liver fibrosis was positively correlated with the serum creatinine, serum iron, and C-reactive protein levels indicating a more severe form of NAFLD in those patients. None of the investigated liver tests showed any differences between those RTR patients who had NAFLD compared to those without NAFLD. CONCLUSION: Our results showed that RTRs have high prevalence of TE-defined NAFLD which possibly contributes to graft dysfunction. Measuring aminotransferase levels would not be a useful tool for NAFLD detection in RTRs. Our study showed the value of TE as an effective, noninvasive screening method for the diagnosis of NAFLD in RTRs.

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

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.

Nonalcoholic fatty liver disease (NAFLD): a new risk factor for adverse cardiovascular events in dialysis patients.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. Today it is believed that NAFLD is a hepatic manifestation of metabolic syndrome, and thus it is closely related to the cardiovascular morbidity and mortality. Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in patients with end-stage-renal disease (ESRD). NAFLD and ESRD share some important cardiometabolic risk factors and possible common pathophyisiological mechanisms, and are linked to an increased risk of incident CVD events. We hypothesize that the coexistence of these two conditions could lead to much faster progress of the aterogenic process. Furthermore, patients with ESRD who suffer from NAFLD have a much higher risk for the development of adverse CVD events. Given the high prevalence of NAFLD, and its tight association with other manifestations of the metabolic syndrome and thus cardiovascular complications, it is important to recognize and aggressively treat this condition in ESRD patients. To evaluate this hypothesis, we propose the use of non-invasive methods such as transient elastography (TE) (Fibroscan-CAP) for the detection and quantification of liver steatosis and fibrosis, as well as an abdominal ultrasound for detecting liver steatosis. We focus on their correlation with carotid intima-media thickness (IMT) and plaque as surrogate measures of increased cardiovascular risk in HD patients in order to investigate the association of NAFLD and increase risk of adverse CVD events. This evaluation will prove useful in assessing the risk in HD patients with NAFLD for increase CVD mortality.