Jin-Shuen Chen

Background: Among multiple causes, diabetic nephropathy (DN) is the major underlying renal disease that leads to end‐stage renal disease (ESRD), and early diagnosis can effectively prevent or delay the progression to ESRD. Therefore, the current study aimed to develop noninvasive, accurate detection markers.Materials & Methods: For this study, 62 diabetes mellitus (DM) patients, 59 DN patients and 21 healthy controls (HCs) were recruited. All participants’ serum samples were subjected to concavanalin (Con) A affinity chromatography, which utilizes glycoproteins to discover potential markers.Results: From nano LC‐MS and Western blot analysis, apolipoprotein A‐IV (ApoA4) was selected which featured a gradual, almost twofold increase in the order of HC, DM and DN. In the Con A‐based ELISA, the DM group was 1.91‐fold higher than the HC group, while the DN group was 2.56‐fold higher than the HCs and 1.33‐fold higher than the DM group. In addition, significant positive correlations were observed between ApoA4 and blood urea nitrogen levels and between ApoA4 and creatine levels, while significant negative correlations were seen between serum protein levels and between serum albumin levels in comparisons of DM and DN samples.Conclusions: Serum Con A‐bound ApoA4 levels were higher in the DM group than in HCs, and further increased in the DN group. Levels of ApoA4 were positively correlated with blood urea nitrogen and creatine, but negatively correlated with serum protein and albumin. This evidence supports serum Con A‐bound ApoA4 as a circulating marker for predicting the progression of renal impairment in DM patients.

SuPAR biomarker generally considered a pathogenic factor in FSGS. However, studies have been published that dispute this conclusion. The current study was designed to investigate the roles of uPA and suPAR in FSGS in clinical and mouse models. Clinical subjects including those with biopsy-proven FSGS and MCD were enrolled. To verify the role of uPA in FSGS, Adriamycin was used to induce FSGS in uPA knockout (uPA−/−) and BALB/c (WT) mice. Proteinuria and suPAR, the cleaved/intact forms of the circulating suPAR, and possible proteases involving cleavage of the suPAR were also studied. FSGS clinical cases presented significantly higher serum levels of suPAR and Cr and lower serum levels of uPA. In the mice model, the uPA−/− group exhibited faster disease progression and worsening proteinuria than the WT group. In addition, the uPA−/− group had higher plasma suPAR levels, glomerular cell apoptosis, and dysregulation of the Th1/Th2 balance. In an analysis of suPAR variants in FSGS, both the intact and cleaved forms of the suPAR were higher in clinical subjects and the mouse model. However, the process of suPAR cleavage was not mediated by enzymatic activities of the uPA, elastase, or cathepsin G. A deficiency of uPA accelerated the progression of Adriamycin-induced mouse FSGS model. Decrease of serum uPA levels may be an indicator of the progression of FSGS in clinical subjects and animal models.

Growth arrest-specific protein 6 (Gas6) works synergistically with erythropoietin (EPO) to increase the proliferation and maturation of erythroblasts. However, the role of Gas 6 levels on EPO resistance in hemodialysis (HD) patients remains unclear. Therefore, the objective of this study was the first to examine the correlation between plasma Gas6 levels and EPO resistance in HD patients. We enrolled 134 HD patients and 85 healthy individuals. The HD patients were divided into 2 groups: 98 non-EPO-resistant patients and 36 EPO-resistant patients. Plasma levels of Gas6, interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and albumin were quantified. Compared with non-EPO-resistant patients, EPO-resistant patients had elevated plasma concentrations of Gas6 (15.4 ± 3.3 vs. 13.7 ± 3.2 ng/mL, P = 0.006), IL-6 (3.1 ± 3.1 vs. 2.1 ± 1.5 pg/mL, P = 0.009), and hs-CRP (12.7 ± 25.2 vs. 4.5 ± 5.5 mg/L, P = 0.002). In EPO-resistant HD patients, plasma Gas6 levels were negatively correlated with albumin levels (r = −0.388, P < 0.021). Elevated Gas6 levels are associated with EPO resistance in HD patients. Also, EPO resistance is related to inflammation and malnutrition. Thus, circulating Gas6 levels could be used as the potential marker in HD patients with EPO resistance.

Chronic kidney disease (CKD) is highly prevalent in Taiwan. More than two-thirds of end-stage renal disease is associated with diabetes mellitus (DM) or hypertension (HTN). Therefore, the formulation of a special preventative policy of CKD in these patients is essential. This study surveyed 14 traditional risk factors and identified their effects on CKD in patients with HTN/DM and compared these with their effects in the general population. This study included 5328 cases and 5135 controls in the CKD/HTN/DM outpatient and health centres of 10 hospitals from 2008 to 2010. Fourteen common effect factors were surveyed (four demographic, five disease and five lifestyle), and their effects on CKD were tested. Significance tests were adjusted by the Bonferroni method. Results of the stratified analyses in the variables were presented with significant heterogeneity between patients with different comorbidities. Male, ageing, low income, hyperuricemia and lack of exercise habits were risk factors for CKD, and their effects in people with different comorbidities were identical. Anaemia was a risk factor, and there was an additive effect between anaemia and HTN on CKD. Patients with anaemia had a higher risk when associated with HTN [odds ratio (OR) = 6.75, 95 % confidence limit (95 % CI) 4.76–9.68] but had a smaller effect in people without HTN (OR 2.83, 95 % CI 2.16–3.67). The association between hyperlipidaemia-related factors and CKD was also moderated by HTN. It was a significant risk factor in people without HTN (OR = 1.67, 95 % CI 1.38–2.01) but not in patients with HTN (OR =1.03, 95 % CI 0.89–1.19). Hepatitis B, hepatitis C, betel nut chewing, smoking, alcohol intake and groundwater use were not associated with CKD in multivariate analysis. We considered that patients with HTN and anaemia were a high CKD risk population. Physicians with anaemic patients in outpatient clinics need to recognise that patients who also have HTN might be latent CKD cases.

A 56-year-old woman has history of Type 2 diabetes mellitus and hypertension for >20 years. After a regular non-invasive blood pressure cuff was placed on his right arm above the elbow to measure blood pressure, asymptomatic skin rash on the right forearm appeared. Physical examination revealed numerous small non-blanching erythematous and violaceous macules confined from the elbow to the tips of the digits (Figure 1). The remainders of the patient’s extremities were examined, but no other areas were affected. Her laboratory results including platelet count, prothrombin time and bleeding time were all in normal range. Her petechiae resolved completely after 12 days.