Kidney and liver fat accumulation: from imaging to clinical consequences.

BACKGROUND: Recent studies indicate that accumulation of adipose tissue in various organs such as liver and kidney may contribute to the pathophysiology of metabolic syndrome. We aim to investigate the association between kidney and liver adipose tissue accumulation, assessed by the magnetic resonance imaging (MRI) proton density fat fraction technique, along with its relation to clinical and biochemical parameters. METHODS: We included 51 volunteers with phenotypical features of metabolic syndrome (mean age = 34 years, mean body-mass index = 26.4 kg/m2) in our study in which liver and kidney adipose tissue accumulation was assessed via MRI-proton density fat fraction along with multiple other clinical and biochemical parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio, serum lipid profile, liver function tests and body-mass index (BMI). RESULTS: Our results from the univariate linear regression analysis indicate that both the kidney and liver scores were positively correlated with markers such as BMI, urine albumin-to-creatinine ratio, triglycerides (p < 0.001) and negatively correlated with eGFR (p < 0.05). In multivariate analysis, urine albumin-to-creatinine ratio (p < 0.05), triglycerides (p < 0.01), eGFR (p < 0.05) and BMI (p < 0.001) were found to be independently associated with kidney and liver fat accumulation, respectively (R2 = 0.64; R2 = 0.89). There was also a positive correlation between kidney and liver fat accumulation. CONCLUSION: We have found a significant association between adipose tissue accumulation in liver and kidney and the parameters of metabolic syndrome. Moreover, the presence of a strong association between kidney and liver fat accumulation and kidney function parameters such as urine albumin-to-creatinine ratio and eGFR may be an indicator of the clinical significance of parenchymal fat accumulation.

The Mitochondrion: A Promising Target for Kidney Disease.

Mitochondrial dysfunction is important in the pathogenesis of various kidney diseases and the mitochondria potentially serve as therapeutic targets necessitating further investigation. Alterations in mitochondrial biogenesis, imbalance between fusion and fission processes leading to mitochondrial fragmentation, oxidative stress, release of cytochrome c and mitochondrial DNA resulting in apoptosis, mitophagy, and defects in energy metabolism are the key pathophysiological mechanisms underlying the role of mitochondrial dysfunction in kidney diseases. Currently, various strategies target the mitochondria to improve kidney function and kidney treatment. The agents used in these strategies can be classified as biogenesis activators, fission inhibitors, antioxidants, mPTP inhibitors, and agents which enhance mitophagy and cardiolipin-protective drugs. Several glucose-lowering drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1-RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors are also known to have influences on these mechanisms. In this review, we delineate the role of mitochondrial dysfunction in kidney disease, the current mitochondria-targeting treatment options affecting the kidneys and the future role of mitochondria in kidney pathology.

Abdominal compartment syndrome: an often overlooked cause of acute kidney injury.

Abdominal compartment syndrome (ACS) is defined as any organ dysfunction caused by intra-abdominal hypertension (IAH), referred as intra-abdominal pressure (IAP) ≥ 12 mm Hg according to the World Society of Abdominal Compartment Syndrome. Abdominal compartment syndrome develops in most cases when IAP rises above 20 mmHg. Abdominal compartment syndrome, while being a treatable and even preventable condition if detected early in the stage of intra-abdominal hypertension, is associated with high rates of morbidity and mortality if diagnosis is delayed: therefore, early detection is essential. Acute kidney injury (AKI) is a common comorbidity, affecting approximately one in every five hospitalized patients, with a higher incidence in surgical patients. AKI in response to intra-abdominal hypertension develops as a result of a decline in cardiac output and compression of the renal vasculature and renal parenchyma. In spite of the high incidence of intra-abdominal hypertension, especially in surgical patients, its potential role in the pathophysiology of AKI has been investigated in very few clinical studies and is commonly overlooked in clinical practice despite being potentially treatable and reversible. Aim of the present review is to illustrate the current evidence on the pathophysiology, diagnosis and therapy of intra-abdominal hypertension and abdominal compartment syndrome in the context of AKI.

Encapsulated peritoneal sclerosis: a single center, retrospective analysis of clinical manifestations, risk factors and prognosis.

BACKGROUND: Encapsulated peritoneal sclerosis (EPS) is a multifactorial chronic intra-abdominal inflammatory disorder affecting the peritoneum diffusely. The aim of this study was to evaluate the rates of EPS in our peritoneal dialysis (PD) population, to perform a general assessment of the clinical presentation and to determine the outcome of affected patients and risk factors. METHODS: The medical records of consecutive 384 patients who started PD therapy between January 2001 and November 2016 were evaluated. Socio-demographic characteristics, comorbidities, PD therapy details and infectious complications were recorded. Medical records were examined to make sure that the cases met the ISPD criteria for EPS diagnosis including clinical features and either radiological and/or histopathological confirmation. Patients diagnosed with EPS were identified, and the incidence, clinical presentation, treatments and recent status of the patients were reviewed. Factors that might be associated with EPS formation and mortality were investigated. RESULTS: Two hundred one of 384 patients were female, mean age was 45.9±15.6 years and mean PD follow up time were 42.6±35 months. EPS was developed in 26 patients and EPS development rate was 6.7%. PD follow-up period and duration of hypertonic solution usage were longer in patients with EPS (P<0.001 and P=0.017 respectively). Patients with and without EPS were similar in terms of modality (P=0.21) but treatment duration with APD modality was longer in patients with EPS (P<0.001). The PD follow-up period was found to be a predictor of EPS formation (P<0.001, RR:1.034 [95% CI: 1.020-1.047]). Age (P<0.001, RR:1.039 (95% CI: 1.024-1.053) and use of hypertonic dialysis solution (P=0.007, RR:0.979 (95% CI: 0.965-0.994)) were the factors affecting survival in EPS patients. CONCLUSIONS: EPS is a relatively rare but fatal complication of peritoneal dialysis and extension of PD duration is a risk for EPS formation. Younger age and usage of hypertonic dialysis solution affects mortality in patients with EPS.

Serum VEGF-C levels as a candidate biomarker of hypervolemia in chronic kidney disease.

Attaining and maintaining optimal "dry weight" is one of the principal goals during maintenance hemodialysis (MHD). Recent studies have shown a close relationship between Na load and serum vascular endothelial growth factor-C (VEGF-C) levels; thus, we aimed to investigate the role of VEGF-C as a candidate biomarker of hypervolemia. Physical examination, basic laboratory tests, N-terminal pro b-type natriuretic peptide (NT-ProBNP), echocardiography, and bioimpedance spectroscopy data of 3 groups of study subjects (euvolemic MHD patients, healthy controls, and hypervolemic chronic kidney disease [CKD] patients) were analyzed. Research data for MHD patients were obtained both before the first and after the last hemodialysis (HD) sessions of the week. Data of 10 subjects from each study groups were included in the analysis. Serum VEGF-C levels were significantly higher in hypervolemic CKD versus in MHD patients both before the first and after the last HD sessions (P = .004 and P = .000, respectively). Healthy controls had serum VEGF-C levels similar to and higher than MHD patients before the first and after the last HD sessions of the week (P = .327 and P = .021, respectively). VEGF-C levels were correlated with bioimpedance spectroscopy results (r 0.659, P = .000) and edema (r 0.494, P =0.006), but not with ejection fraction (EF) (r -0.251, P = .134), blood pressures (systolic r 0.037, P = 0.824, diastolic r -0.067, P = .691), and NT-ProBNP (r -0.047, P = .773). These findings suggest that serum VEGF-C levels could be a potential new biomarker of hypervolemia. The lack of correlation between VEGF-C and EF may hold a promise to eliminate this common confounder. Further studies are needed to define the clinical utility of VEGF-C in volume management.

Prognostic significance of NGAL in early stage chronic kidney disease.

BACKGROUND: Neutrophilgelatinase-associated lipocalin (NGAL) has been proven to be a useful biomarker for early detection of acute kidney injury, but it is not known whether adding NGAL measurements to conventional risk factors will improve the risk assessment in the setting of chronic kidney disease (CKD). The aim of the present study was to examine the correlation of NGAL with early stage renal impairment in CKD and to evaluate its prognostic value in these subjects. METHODS: This is a prospective observational cohort study of 54 patients with early stage (stage 1-2) CKD. Patients aged between 18 and 65 years with stable disease were enrolled in this study. Patients with a history of primary glomerulonephritis, diabetes mellitus, acute kidney injury, systemic diseases and stage 3-4-5 CKD were excluded from the study group. Estimated glomerular filtration (eGFR) rate was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. The patients were followed for two years to determine the ability of baseline NGAL for prediction of renal outcome. In our study disease progression was defined as changes in eGFR (ΔeGFR) and proteinuria (Δproteinuria). Patients divided into two groups according to NGAL cut-off value as group 1 (N.=23, NGAL ≤98.71 ng/mL) and group 2 (N.=31, NGAL >98.71 ng/mL). RESULTS: Out of 54 patients (mean age: 45.6±7.6 years, 64.8% female, baseline eGFR: 84.6±16.8 mL/min/1.73 m2, baseline NGAL level: 157.47±121.52 ng/mL); 18 patients were stage 1 and 36 patients were stage 2 CKD. In the ROC analysis, we found that the optimal cut-off value of NGAL for predicting stage 2 CKD was 98.71ng/mL (P=0.005) with the 72.2% sensitivity and 72.2% specificity. In correlation analysis, we evaluated significantly positive correlations between NGAL and CKD stage (r=0.389, P=0.004), baseline/last serum creatinine level (r=0.530, P<0.001 and r=0.439, P=0.003; respectively), last proteinuria level (r=0.359, P=0.043). There were significantly negative correlation between NGAL and baseline/last eGFR (r=-0.498, P<0.001 and r=-0.462, P=0.002; respectively). Compared to the group 1, we determined that group 2 patients had further deterioration in renal functions regarding ΔeGFR (-1.12±12.6 mL/min vs. -1.46±12.4 mL/min: respectively, P=0.930) and Δproteinuria (98.1±569.3 mg/day vs. 339±701.6 mg/day; respectively, P=0.305); however these differences were not statistically significant at the end of the two years follow-up period. CONCLUSIONS: Altough NGAL has a positive correlation with disease severity, it does not seem to be a marker of disease progression in patients with early stage CKD. But further studies stated in different patient groups may also explain the usability of NGAL in clinical practice.