Band 4, Heft 3 - Issue title: A special issue on kidney disease (Guest Editor: Joseph Zhou)

Chronic kidney disease (CKD), a condition that affects around 10% of the population, has become a significant public health concern. Current therapeutic strategies to slow down the progression of CKD remain limited. Thus, it is urgent to develop new strategies to manage the patients with CKD. Work within the past decade has improved our understanding of the mechanisms contributing to CKD. In particular, oxidative stress as well as inflammation appears to play a pivotal role in CKD progression. (一)-Epigallocatechin-3-gallate (EGCG), the major catechin of green tea extract, is known as a powerful antioxidant and reactive oxygen species scavenger. Various studies have shown EGCG has a potential role in chronic kidney disease models. It is suggested that EGCG modulates cellular and molecular mechanisms via inflammation-related NF-кB and Nrf2 signaling pathway, as well as apoptosis-related ER stress pathway and mitochondrial pathway. Therefore, based on these studies, this review attempts to present a recent state of our knowledge and understanding of mechanisms of its role on the process of CKD, with the aim of providing some clues for the future optimization of EGCG in renal diseases.

This article reviews the application of contrast-enhanced ultrasound (CEUS) in gauging renal microvascular perfusion in diverse renal diseases. The unique nature of the contrast agents used in CEUS provides real-time and quantitative imaging of the vasculature. In addition to the traditional use of CEUS for evaluation of kidney masses, it also emerges as a safe and effective imaging approach to assess microvascular perfusion in diffuse renal lesions, non-invasively. Although the precise CEUS parameters that may best predict disease still warrant systematic evaluation, animal models and limited clinical trials in humans raise hopes that CEUS could outcompete competing modalities as a first-line tool for assessing renal perfusion non-invasively, even in ailments such as acute kidney injury and chronic kidney disease.

There is a high risk for the survival of patients with an end-stage renal disease for kidney transplantation. To avoid rejection by strict medication adherence is of utmost importance to avoid the failure of a kidney transplant. It is imperative to develop non-invasive biomarkers to assess immunity risk, and to ultimately provide guidance for therapeutic decision-making following kidney transplantation. Urine biomarkers may represent the promising non-invasive tools that will help in predicting risk or success rates of kidney transplantations. Furthermore, composite urinary biomarkers or urinary biomarker panel array might be critical in improving the sensitivity and specificity in reflecting various risks of kidney failure during transplantation. This review primarily focuses on the role of such biomarkers in predicting chronic kidney disease (CKD) progression and/or cardiovascular disease (CVD) risk in renal allograft.

Heat Shock Proteins (HSP) belong to the family of intracellular proteins that are constitutively expressed and are upregulated by various stressors including heat, oxidative and chemical stress. HSP helps in reparative processes, including the refolding of damaged proteins and the removal of irreparably damaged proteins that would initiate cellular death or apoptosis. A growing body of evidence has expanded the role of HSP and defined their role in diseases such as neurodegenerative disorders, cancer, ischemic heart disease and kidney diseases. The protective role of HSP in ischemic renal injury has been described and HSP impairment has been noted in other forms of kidney injuries including post-transplant situation. Further research into the role of HSP in prevention of kidney injury is crucial if translation from the laboratory to patient bedside has to occur. This article aims to be a review of heat shock protein, and its relevance to kidney diseases.

Background and Objectives The studies were designed to test the efficacy of two peroxisome proliferator-activated receptor γ (PPARγ) agonists in two rodent models of polycystic kidney disease (PKD). Materials and Methods The PCK rat is a slowly progressing cystic model while the Wpk -/- rat is a rapidly progressing model. PCK rats were fed with a pharmacological (0.4 mg/kg body weight [BW]) and a sub-pharmacological (0.04 mg/kg BW) dose of rosiglitazone (week 4–28). Wpk -/- rats were fed with pharmacological (2.0 mg/kg BW) and sub-pharmacologic (0.2 mg/kg BW) doses of pioglitazone from day 5 to 18. At termination, kidney weights of treated versus untreated cystic animals were used to determine efficacy. The current studies were also compared with previous studies containing higher doses of PPARγ agonists. The concentrations used in the animals were calculated with reference to equivalent human doses for both drugs. Results The current studies demonstrate: 1) that low, pharmacologically relevant, doses of the PPARγ agonists effectively inhibit cyst growth; 2) there is a class action of the drugs with both commercially available PPARγ agonists, rosiglitazone, and pioglitazone, inhibiting cyst growth; 3) the drugs showed efficacy in two different preclinical cystic models. In the PCK rat, animals fed with a sub-pharmacological dose of rosiglitazone for 24 weeks had significantly lower kidney weights than untreated animals (3.68 ± 0.13 g vs . 4.17 ± 0. 11 g, respectively, P < 0.01) while treatment with a pharmacologic dose had no significant effect on kidney weight. The rapidly progressing Wpk -/- rats were fed with pharmacological and sub-pharmacologic doses of pioglitazone from day 5 to 18 and the kidneys were compared with non-treated, cystic animals. Kidney weights on the pharmacologic dose were not statistically lower than the untreated animals while rats fed a sub-pharmacologic dose showed a significant decrease compared with untreated animals (3.35 ± 0.15 g vs. 4.55 ± 0.46 g, respectively, P = 0.045). Conclusion Concentrations of PPARγ agonists below the human equivalent diabetic doses are effective in slowing cyst growth in two rodent models of PKD.

Objective To examine the frequency of insulin resistance (IR) and its relation with anthropometric measurements in patients with autosomal dominant polycystic kidney disease (ADPKD). Material and Methods Nonobese 82 patients with ADPKD and 58 age matched healthy controls were enrolled into the study. None of participants were diabetic or receiving renal replacement therapies (RRT). IR was determined by homeostasis model assessment of insulin resistance (HOMA-IR) formula. Tanita body composition analyzer was used for anthropometric measurements. Creatinine clearance of participant were assessed by the modification of diet in renal diseases (MDRD). Results Patients with ADPKD had significantly higher level of urea and creatinine, microalbuminuria, and lower level of MDRD. Body fat distribution and HOMA-IR in both the groups were similar. Systolic and diastolic blood pressure of patients were higher than those of controls. Conclusion We failed to determine a higher frequency of IR among patients with ADPKD.

Objectives To determine the association of fibroblast growth factor 23 (FGF23) with left ventricular hypertrophy (LVH) through the assessment of left ventricular (LV) mass and left ventricular mass index (LVMI) in patients on hemodialysis, this study was done. Methods All patients on hemodialysis who are older than 18 years and in whom hemodialysis vintage was at least 6 months were enrolled. All patients were on hemodialysis thrice a week for 4 h using low-flux dialysis filters, polysulfone membranes, reverse osmosis purified water, and bicarbonate-base hemodialysis solution. The exclusion criteria were any respiratory illness or pulmonary infection, cigarette smoking, and the presence of pericarditis or pericardial effusion. Additionally, patients with a known coronary artery disease, any form of cardiac arrhythmias, any cardiomyopathy or severe valvular heart disease diagnosed by echocardiography, acute congestive heart failure (CHF), and acute myocardial infarction were not included. Echocardiography was conducted by an experienced operator for all the enrolled patients using the ACUSON SC2000™ ultrasound system transducer (Siemens), with a frequency bandwidth of: 1.5–3.5 MHz. Patients were considered to have LVH if the LVMI was greater than 134 g/m 2 for men and greater than 110 g/m 2 for women. Results A total of 61 patients (19 female and 42 male) were enrolled to the study. Mean (± SD) age of the patients was 59.6 ± 13.1 years. The median duration of hemodialysis was 23 (range: 6–120) months. The median predialysis level of FGF23 was 1,977 pg/mL (range: 155–8,870). LVH was seen in 73.8% of the patients (n = 45) and of them 66.7% were male. There was a statistically significant direct correlation between FGF23 and left ventricle diameter in end systole (LVDs) (r = 0.29, P = 0.027). However, the association of FGF23 with LV mass, LVMI, and left ventricular ejection fraction (LVEF) was not significant. Conclusion This study does not show the correlation between FGF23 and LV mass in stable hemodialysis patients.