Hepatic Fibrosis Evaluated in Patients with Type 2 Diabetes with and without Chronic Kidney Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population. METHODS: Cross-sectional study including patients with type 2 diabetes with CKD stages 3-5 (N = 50) or without CKD (N = 50). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 with or without proteinuria. Three methods were used to detect significant liver fibrosis defined as either ≥8 kilopascal measured by transient elastography (FibroScan®), fibrosis-4 (FIB-4) score ≥2.67, or NAFLD fibrosis score (NFS) >0.675. RESULTS: Significant liver fibrosis was found in 38% and 28% of the patients with and without CKD, respectively, using at least one of the three methods. Both FIB-4 score and NFS were significantly higher in patients with CKD (p < 0.0009 and p < 0.0001, respectively), although insignificant after adjustments for age, sex, body mass index, and duration of diabetes. In patients without CKD, a significant association between steatosis and fibrosis was observed (p = 0.0007). CONCLUSION: Our data do not support any strong independent association between liver fibrosis and established CKD as assessed by FibroScan, FIB-4 score, and NFS, respectively.

Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is suggested as a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally in parallel to the increasing incidences of obesity and type 2 diabetes. Diabetes remains the leading cause of CKD, but the co-existence of NAFLD, CKD, and type 2 diabetes is not well elucidated. Here, we evaluated the prevalence of NAFLD in patients with type 2 diabetes with and without CKD. METHODS: This was a cross-sectional study including 50 patients with type 2 diabetes and CKD stages 3-5 (no dialysis), and 50 patients with type 2 diabetes without CKD. Liver fat content was estimated by proton magnetic resonance spectroscopy and magnetic resonance imaging proton density fat fraction. NAFLD was defined as liver fat fraction ≥5.6% according to guidelines. RESULTS: Mean age was 72 ± 4.9 years in patients with CKD and 65.9 ± 7.8 years in patients without CKD (p < 0.0001). Three out of four participants were men. BMI was 28.6 ± 3.5 kg/m2 and 27 ± 4.0 kg/m2 in patients with and without CKD, respectively (p = 0.0087). NAFLD was identified in 22 (44%) patients with CKD and 19 (38%) patients without CKD (p = 0.6845). Median (IQR) liver fat fraction was 4.7% (3.0-8.5) and 4.1% (2.9-7.7) in patients with and without CKD, respectively (difference in geometric means 5.3%, 95% CI -23; 45, p = 0.7463). CONCLUSION: These findings do not support any association between NAFLD and CKD (stages 3-5) in patients with type 2 diabetes.

Incidental finding of non-alcoholic steatohepatitis-cirrhosis.

Summary: A 72-year-old man with type 2 diabetes volunteered to participate in the control group of a clinical study. The study evaluated non-alcoholic fatty liver disease in patients with kidney disease. The patient was followed at a gastroenterology department due to Crohn's disease and post-operative bile acid malabsorption. The patient had no symptoms or biochemical findings suggesting liver disease. Surprisingly, a transient elastography (FibroScan®) suggested advanced fibrosis with a median of 16.1 kPa. A liver biopsy showed non-alcoholic steatohepatitis (NASH)-cirrhosis. The diagnosis was only made incidentally and highlights how NASH-cirrhosis may be overlooked due to the lack of symptoms. Learning points: Clinicians treating high-risk populations, including patients with type 2 diabetes and/or components of the metabolic syndrome, should be aware of the frequently occurring co-existence with non-alcoholic fatty liver disease (NAFLD) and especially non-alcoholic steatohepatitis (NASH). Liver enzymes may be in the normal range even in people with steatosis, NASH, or even cirrhosis. The diagnosis of NAFLD should include evaluation of hepatic fibrosis as this is the most important prognostic factor for liver-related complications and mortality. Guidelines about systematic screening for NAFLD in patients with type 2 diabetes are incongruent.

Prevalence of non-alcoholic fatty liver disease in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and represents a wide spectrum ranging from mild steatosis to non-alcoholic steatohepatitis with or without fibrosis to overt cirrhosis. Patients with NAFLD have a high risk of developing cardiovascular disease and chronic kidney disease (CKD). So far there has been scarce evidence of the prevalence of NAFLD among patients with CKD. We investigated the prevalence of moderate-severe hepatic steatosis graded according to the definition of NAFLD in a cohort of patients with CKD. METHODS: Hepatic liver fat content was evaluated by computed tomography (CT) scan in 291 patients from the Copenhagen CKD Cohort Study and in 866 age- and sex-matched individuals with normal kidney function from the Copenhagen General Population Study. Liver attenuation density <48 HU was used as a cut-off value for moderate-severe hepatic steatosis. RESULTS: The prevalence of moderate-severe hepatic steatosis was 7.9 and 10.7% (P = 0.177) among patients with CKD and controls, respectively. No association between liver fat content and CKD stage was found. In the pooled dataset from both cohorts, adjusted odds ratios for moderate-severe hepatic steatosis among persons with diabetes, overweight and obesity were 3.1 [95% confidence interval (CI) 1.6-5.9], 14.8 (95% CI 4.6-47.9) and 42.0 (95% CI 12.9-136.6), respectively. CONCLUSIONS: In a cohort of 291 patients with CKD, kidney function was not associated with the prevalence of moderate-severe hepatic steatosis as assessed by CT scan.

The Use of HbA1c, Glycated Albumin and Continuous Glucose Monitoring to Assess Glucose Control in the Chronic Kidney Disease Population Including Dialysis.

BACKGROUND: Glycated haemoglobin A1c (HbA1c) has limitations as a glycemic marker for patients with diabetes and CKD and for those receiving dialysis. Glycated albumin is an alternative glycemic marker, and some studies have found that glycated albumin more accurately reflects glycemic control than HbA1c in these groups. However, several factors are known to influence the value of glycated albumin including proteinuria. Continuous glucose monitoring (CGM) is another alternative to HbA1c. CGM allows one to assess mean glucose, glucose variability, and the time spent in hypo-, normo-, and hyperglycemia. Currently, several different CGM models are approved for use in patients receiving dialysis; CKD (not on dialysis) is not a contraindication in any of these models. Some devices are for blind recording, while others provide real-time data to patients. Small studies suggest that CGM could improve glycemic control in hemodialysis patients, but this has not been studied for individual CKD stages. SUMMARY: Glycated albumin and CGM avoid the pitfalls of HbA1c in CKD and dialysis populations. However, the value of glycated albumin may be affected by several factors. CGM provides a precise estimation of the mean glucose. Here, we discuss the strengths and limitations for using HbA1c, glycated albumin, or CGM in CKD and dialysis population. Key Messages: Glycated albumin is an alternative glycemic marker but is affected by proteinuria. CGM provides a precise estimation of mean glucose and glucose variability. It remains unclear if CGM improves glycemic control in the CKD and dialysis populations.

[Continuous glucose monitoring of patients with type 1- and type 2 diabetes on haemodialysis].

Studies indicate, that the glycated haemoglobin (HbA1c) level underestimates the mean blood glucose level in patients with Type 1- and Type 2 diabetes on haemodialysis. In patients receiving peritoneal dialysis the validity of HbA1c level is undetermined. Continuous glucose monitoring (CGM) could be an option for patients with diabetes receiving dialysis to assess the mean blood glucose level independently of the HbA1c level. In addition, CGM makes it possible to investigate periodic hypo- and hyperglycaemia and glucose variability. The evidence for the use of CGM in the dialysis population is limited but could represent an improved approach to glycaemic control.

Mannose-binding lectin genotypes and outcome in end-stage renal disease: a prospective cohort study.

Background: Patients with end-stage renal disease (ESRD) have high morbidity and mortality rates, with cardiovascular diseases and infections being the major causes of death. Mannose-binding lectin (MBL) has been suggested to play a protective role in this regard. The aim of this study was to investigate a possible clinical association of MBL genotypes (MBL2) with outcome among patients on dialysis or with a functioning graft. Methods: A total of 98 patients with ESRD accepted for living-donor renal transplantation or on the waiting list for transplantation were included and prospectively followed for an average of 9 years (range 7.5-9.9). Medical records were evaluated regarding transplantation status, diabetes mellitus, vascular parameters and infections for all the patients. Cox regression models and logistic regression analysis were used for statistical analyses. The cohort was divided into two groups according to the MBL2 genotype (normal A/A versus variant A/O or O/O). Results: We found no evidence for an association between the MBL2 genotype and all-cause mortality, cardiovascular events or bacterial infections (pneumonia, urinary tract infection, fistula infection or other infections). Conclusion: In this cohort, the MBL2 genotype did not seem to be associated with any long-term clinical effects in ESRD patients on dialysis or with a functioning graft.