Circulating Osteocalcin Fractions are Associated with Vascular Calcification and Mortality in Chronic Hemodialysis Patients.

BACKGROUND: Vascular calcification, a component of chronic kidney disease-mineral and bone disorder (CKD-MBD), is prevalent in patients with end-stage kidney disease (ESKD) and contributes to high mortality. However, the association between the blood level of total osteocalcin (OC) and vascular calcification and mortality remains inconclusive. We, therefore, investigated whether different OC fractions can serve as biomarkers of vascular calcification and mortality in the ESKD population. METHODS: This observational cohort study enrolled patients on maintenance hemodialysis. Plasma carboxylated OC (cOC), uncarboxylated OC (ucOC), and intact parathyroid hormone (PTH) were measured. The percentage of carboxylated OC (%cOC) was calculated as dividing cOC by total OC. The vascular calcification severity was defined by an aortic calcification grade. The patients were followed for three years and one month. RESULTS: A total of 184 patients were enrolled. In the multivariable logistic regression, plasma %cOC, but not cOC or ucOC, was independently associated with the severity of vascular calcification (OR 1.019, p = 0.036). A significant U-shaped correlation was found between plasma %cOC and PTH (p = 0.002). In the multivariable Cox regression, patients with higher plasma %cOC had a higher risk of mortality (quartiles Q4 versus Q1-Q3, HR 1.991 [95% CI: 1.036-3.824], p = 0.039). CONCLUSIONS: In patients undergoing chronic hemodialysis, plasma %cOC positively correlated with vascular calcification and exhibited a U-shaped correlation with PTH. Furthermore, a higher plasma %cOC was associated with increased mortality. These findings suggest that plasma %cOC may serve as a biomarker for CKD-MBD and a predictor of clinical outcomes in chronic hemodialysis patients.

Pentraxin 3 Predicts Arteriovenous Fistula Functional Patency Loss and Mortality in Chronic Hemodialysis Patients.

INTRODUCTION: Viable vascular access is the lifeline for hemodialysis patients. In the nondialysis population, emerging evidence suggests that circulating pentraxin 3 (PTX3), neutrophil gelatinase-associated lipocalin (NGAL), and chitinase-3-like protein 1 (CHI3L1) are associated with cardiovascular inflammation and endothelial injury. However, predictive values of these three biomarkers on arteriovenous fistula (AVF) outcomes are unknown. METHODS: This prospective observational cohort study enrolled 135 hemodialysis patients using AVF and then followed them for 3 years. Plasma levels of PTX3, NGAL, and CHI3L1 were measured. Patients were followed up prospectively for two clinical outcomes, including AVF functional patency loss and death. Cox proportional hazards regression models were used to analyze hazard ratios for the commencement of AVF functional patency loss and mortality. RESULTS: Among 135 patients, the mean age was 66.0 ± 15.7 years old and 48.1% were male. The plasma level of PTX3, NGAL, and CHI3L1 was 2.8 ± 2.3 ng/mL, 349.2 ± 111.4 ng/mL, and 185.5 ± 66.8 ng/mL, respectively. During a 3-year follow-up period, the plasma level of PTX3 was an independent predictor for AVF functional patency loss (per 1 ng/mL increase, HR 1.112 [95% CI: 1.001-1.235], p = 0.048). Besides, patients with higher plasma levels of PTX3 were more likely to suffer from cardiovascular mortality (per 1 ng/mL increase, HR 1.320 [95% CI: 1.023-1.703], p = 0.033), infectious mortality (per 1 ng/mL increase, HR 1.394 [95% CI: 1.099-1.769], p = 0.006), and all-cause mortality (per 1 ng/mL increase, HR 1.233 [95% CI: 1.031-1.476], p = 0.022). CONCLUSIONS: The plasma level of PTX3, not NGAL or CHI3L1, was associated with higher risks of AVF functional patency loss in chronic hemodialysis patients, showing its value in reflecting AVF endothelial dysfunction. Furthermore, PTX3 also predicts mortality in chronic hemodialysis patients.

Timing of kidney biopsy in type 2 diabetic patients: a stepwise approach.

BACKGROUND: Diabetic nephropathy (DN) is the most prevalent cause of renal disease in type 2 diabetic patients and is usually diagnosed clinically. A kidney biopsy is considered when non-diabetic renal disease (NDRD) is suspected, such as rapid progression in renal function impairment and severe proteinuria. Still, there is yet no consensus on the timing of kidney biopsy in type 2 diabetic patients. This study aims to identify markers that can help differentiate between DN and NDRD and guide the decision of kidney biopsy. METHODS: We retrospectively reviewed patients with type 2 diabetes who received kidney biopsy from 2008 to 2017 at Taipei Veterans General Hospital. Ophthalmologist consultation and outpatient records, diagnosis of kidney biopsy, laboratory data, and clinical characteristics were collected. RESULTS: This study enrolled 160 type 2 diabetic patients, among which 120 (75%) had isolated DN and 40 (25%) had NDRD ± DN (26 had isolated NDRD, and 14 had NDRD superimposed on DN). In multivariate logistic regression analysis, DM duration (odds ratio [OR]: 0.907; 95% confidence interval [CI]: 0.842-0.977; P = 0.01), diabetic retinopathy (OR: 0.196; 95% CI: 0.061-0.627; P = 0.006), and urinary RBC (OR: 1.068; 95% CI: 1.024-1.115; P = 0.002) were independent predictors of NDRD. In patients with diabetic retinopathy (n = 112, 70%), the presence of proliferative diabetic retinopathy, pan-retinal photocoagulation, and hematuria were factors predicting NDRD; and in patients without diabetic retinopathy (n = 48, 30%), short DM duration and hematuria were factors predicting NDRD. CONCLUSIONS: Using diabetic retinopathy, DM duration, and hematuria, we developed a 3-step approach to stratify patients into three categories with the different likelihoods of having NDRD. Then different strategies could be taken accordingly. Our stepwise approach is easy to follow and may serve as an appropriate and useful tool to help clinicians in making decisions of kidney biopsy in type 2 DM patients presenting with kidney diseases.

Key pathological features characterize minimal change disease-like IgA nephropathy.

AIMS: A subset of IgA nephropathy (IgAN) patients exhibiting minimal change disease (MCD) like features present with nephrotic-range proteinuria and warrants immunosuppressive therapy (IST). However, the diagnosis of MCD-like IgAN varied by reports. We aimed to identify the key pathological features of MCD-like IgAN. METHODS: In this cohort, 228 patients had biopsy-proven IgAN from 2009 to 2021, of which 44 without segmental sclerosis were enrolled. Patients were classified into segmental (< 50% glomerular capillary loop involvement) or global (> 50%) foot process effacement (FPE) groups. We further stratified them according to the usage of immunosuppressant therapy after biopsy. Clinical manifestations, treatment response, and renal outcome were compared. RESULTS: 26 cases (59.1%) were classified as segmental FPE group and 18 cases (40.9%) as global FPE group. The global FPE group had more severe proteinuria (11.48 [2.60, 15.29] vs. 0.97 [0.14, 1.67] g/g, p = 0.001) and had a higher proportion of complete remission (81.8% vs. 20%, p = 0.018). In the global FPE group, patients without IST experienced more rapid downward eGFR change than the IST-treated population (-0.38 [-1.24, 0.06] vs. 1.26 [-0.17, 3.20]mL/min/1.73 m2/month, p = 0.004). CONCLUSIONS: The absence of segmental sclerosis and the presence of global FPE are valuable pathological features that assist in identifying MCD-like IgAN.