Nephrology

Correction to: Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome The original article can be found online

Focus on POCUS: it is time for the kidney doctors to upgrade their physical examination

Negative impact of proteinuria on circulating myeloid dendritic cells Abstract Background A decrease in absolute numbers (abs.) of circulating dendritic cells (DCs) and recruitment into target organs has been reported, but whether the level of proteinuria associates with circulating DC abs. has not been clarified. Methods We conducted a cross-sectional study of 210 patients with kidney disease aged 21–96 years who were admitted to our hospital for kidney biopsy in 2007–2010. For accuracy, the level of proteinuria was thoroughly measured by 24-h urine collection from patients in their admitted condition. The abs. of total DCs (tDCs), myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) was measured by three-color fluorescence-activated cell sorting (FACS). Patients were divided into four groups based upon the quartile of each DC abs. and one-way ANOVA, and multivariable-adjusted regression analyses were performed. Results Quantile analysis showed that the level of daily proteinuria decreased with increasing blood mDC abs., with mean proteinuria levels (g/day) of 2.45, 1.68, 1.68, 1.10 for those in mDC abs. quartiles ≤ 445, < 686, < 907, ≥ 907 cells/102 µL (p = 0.0277), respectively. Multivariate-adjusted regression analysis revealed that the mDC abs. was negatively associated with proteinuria (95% CI − 57.0 to − 8.5) and positively associated with male gender (95% CI 66.2–250.5). Independent associations were also shown between pDCs abs. and estimated glomerular filtration rate (eGFR) (95% CI 0.14–2.67) and C-reactive protein (95% CI − 49.4 to − 9.9) and between tDCs abs. and male gender (95% CI 54.5–253.6) and C-reactive protein (95% CI − 80.5 to − 13.4). Conclusion We first reported that circulating mDC abs. has a negative association with the level of proteinuria.

A simple risk score model for predicting contrast-induced nephropathy after coronary angiography in patients with diabetes Abstract Background Contrast-induced nephropathy (CIN) is a common complication in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) and associated with poor outcome. Some previous studies have already set up models to predict CIN, but there is no model for patients with diabetes mellitus (DM) especially. Therefore, we aim to develop and validate a simple risk score for predicting the risk of CIN in patients with DM undergoing CAG/PCI. Methods A total of 1157 consecutive patients with DM undergoing CAG/PCI were randomly assigned to a development cohort (n = 771) and a validation cohort (n = 386). The primary endpoint was CIN, which was defined as an absolute increase in serum creatinine (SCr) by 0.5 mg/dL from the baseline within 48–72 h after contrast exposure. The independent predictors for CIN were identified by multivariate logistic regression, and the discrimination and calibration of the risk score were assessed by ROC curve and Hosmer–Lemeshow test, respectively. Results The overall incidence of CIN was 45 (3.9%). The new simple risk score (Chen score), which included four independent variables (age > 75 years, acute myocardial infarction, SCr > 1.5 mg/dL, the use of intra-aortic balloon pump), exhibited a similar discrimination and predictive ability on CIN (AUC 0.813, 0.843, 0.796, P > 0.05, respectively), mortality (AUC 0.735, 0.771, 0.826, respectively) and MACEs when being compared with the classical Mehran or ACEF risk score. Conclusion Our data suggest that the new simple risk score might be a good tool for predicting CIN in patients with DM undergoing CAG/PCI.

Effects of lactulose on renal function and gut microbiota in adenine-induced chronic kidney disease rats Abstract Background Constipation is frequently observed in patients with chronic kidney disease (CKD). Lactulose is expected to improve the intestinal environment by stimulating bowel movements as a disaccharide laxative and prebiotic. We studied the effect of lactulose on renal function in adenine-induced CKD rats and monitored uremic toxins and gut microbiota. Methods Wistar/ST male rats (10-week-old) were fed 0.75% adenine-containing diet for 3 weeks to induce CKD. Then, they were divided into three groups and fed as follows: control, normal diet; and 3.0- and 7.5-Lac, 3.0% and 7.5% lactulose-containing diets, respectively, for 4 weeks. Normal diet group was fed normal diet for 7 weeks. The rats were observed for parameters including renal function, uremic toxins, and gut microbiota. Results The control group showed significantly higher serum creatinine (sCr) and blood urea nitrogen (BUN) 3 weeks after adenine feeding than at baseline, with a 8.5-fold increase in serum indoxyl sulfate (IS). After switching to 4 weeks of normal diet following adenine feeding, the sCr and BUN in control group remained high with a further increase in serum IS. In addition, tubulointerstitial fibrosis area was increased in control group. On the other hand, 3.0- and 7.5-Lac groups improved sCr and BUN levels, and suppressed tubulointerstitial fibrosis, suggesting preventing of CKD progression by lactulose. Lac groups also lowered level of serum IS and proportions of gut microbiota producing IS precursor. Conclusion Lactulose modifies gut microbiota and ameliorates CKD progression by suppressing uremic toxin production.

High levels of stromal cell-derived factor-1α predict short-term progression of renal dysfunction in patients with coronary artery disease Abstract Background Stromal cell-derived factor-1α (SDF-1α) is an inflammatory chemokine that plays a critical role in cardiovascular disease. Although persistent inflammation causes renal dysfunction, it remains unclear whether SDF-1α is related to progression of chronic kidney disease. This study examined whether high levels of SDF-1α are associated with future declines in renal function in patients with coronary artery disease (CAD). Methods Plasma levels of SDF-1α in the peripheral blood were measured by enzyme-linked immunosorbent assay in 344 patients with CAD. All patients were followed for 24 months or until the occurrence of renal dysfunction, defined as ≥ 25% decrease in estimated glomerular filtration rate (eGFR) from baseline. Results During the follow-up period, 36 patients developed renal dysfunction. Multivariate logistic regression analysis showed that high plasma levels of SDF-1α were significantly associated with progression of renal dysfunction (odds ratio 1.65; 95% confidence intervals 1.07–2.35, p = 0.03). In addition, high plasma levels of SDF-1α had a significant incremental effect on the predictive value of known risk factors for renal dysfunction in analyses using net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.58 [0.07–1.02], p < 0.01; and IDI 0.030 [0.001–0.085], p = 0.02). Conclusion High plasma levels of SDF-1α were associated with the short-term decline of eGFR in patients with CAD. Thus, SDF-1α may be useful for predicting the progression of renal dysfunction in patients with CAD.

Role of the putative PKC phosphorylation sites of the type IIc sodium-dependent phosphate transporter in parathyroid hormone regulation Abstract Background Injection of parathyroid hormone (PTH) rapidly stimulates renal Pi excretion, in part by downregulating NaPi-IIa (Npt2a/SLC34A1) and NaPi-IIc (Npt2c/SLC34A3) transporters. The mechanisms underlying the effects of PTH on NaPi-IIc are not fully elucidated. Methods We analyzed the effect of PTH on inorganic phosphate (Pi) reabsorption in Npt2a−/− mice to eliminate the influence of Npt2a on renal Pi reabsorption. In opossum kidney (OK) cells and Xenopus oocytes, we investigated the effect of NaPi-IIc transporter phosphorylation. Studies of mice with mutations of NaPi-IIc protein in which serine and threonine were replaced with either alanine (A), which prevents phosphorylation, or aspartic acid (D), which mimics the charged state of phosphorylated NaPi-IIc, were also performed to evaluate the involvement of phosphorylation in the regulation of transport function. Results The Npt2a−/− experiments showed that PTH administration rapidly inactivated NaPi-IIc function in the apical membrane of proximal tubular cells. Analysis of mutant proteins (S71, S138, T151, S174, T583) at putative protein kinase C sites, revealed that S138 markedly suppressed the function and cellular expression of mouse NaPi-IIc in Xenopus oocytes and OK cells. In addition, 138D had a short half-life compared with wild-type protein. Conclusions The present study suggests that acute regulation of NaPi-IIc protein by PTH is involved in the inactivation of Na+-dependent Pi cotransporter activity and that phosphorylation of the transporter is involved in the rapid modification.

Human MiR-4660 regulates the expression of alanine–glyoxylate aminotransferase and may be a biomarker for idiopathic oxalosis Abstract Background Dysfunction of oxalate synthesis can cause calcium oxalate stone disease and inherited primary hyperoxaluria (PH) disorders. PH type I (PH1) is one of the most severe hyperoxaluria disorders, which results in urolithiasis, nephrocalcinosis, and end-stage renal disease. Here, we sought to determine the role of microRNAs in regulating AGXT to contribute to the pathogenesis of mutation-negative idiopathic oxalosis. Methods We conducted bioinformatics to search for microRNAs binding to AGXT, and examined the expression of the highest hit (miR-4660) in serum samples of patients with oxalosis, liver tissue samples, and determined the correlation and regulation between the microRNA and AGXT in vitro. Results MiR-4660 expression was downregulated in patients with oxalosis compared with healthy controls (84.03 copies/µL vs 33.02 copies/µL, P < 0.0001). Moreover, miR-4660 epigenetically decreased the expression of AGT in human liver tissues (Rho = − 0543, P = 0.037). Overexpression of miR-4660 in HepG2 and L02 cell lines led to dysregulation of AGXT at both the mRNA (by 71% and 81%, respectively; P < 0.001) and protein (by 49% and 42%, respectively; P < 0.0001) levels. We confirmed the direct target site of miR-4660 binding to the 3′UTR of AGXT by a luciferase assay. Conclusion MiR-4660 is probably a new biomarker for mutation-negative idiopathic oxalosis by regulating the post-transcription of AGXT, providing a potential treatment target of mutation-negative idiopathic oxalosis.

Analysis of 2897 hospitalization events for patients with chronic kidney disease: results from CKD-JAC study Abstract Background Chronic kidney disease is a known risk factor for end-stage renal and cardiovascular diseases. However, data are limited on the causes of hospitalization in patients with chronic kidney disease of maintenance period. This study aimed to aggregate hospitalization data of CKD patients and to determine the high-risk population. In addition, we compared CKD population to general population. Methods We conducted a post hoc analysis of the chronic kidney disease-Japan cohort study, a multicenter prospective cohort study of 2966 patients with chronic kidney disease with a median 3.9 years of follow-up. We examined the hospitalization reasons and analyzed the risk factors. Results We found 2897 all-cause hospitalization events (252.3 events/1000 person-years), a hospitalization incidence 17.1-fold higher than that in an age- and sex-matched cohort from the general Japanese population. Kidney, eye and adnexa, and heart-related hospital admissions were the most common. All-cause hospitalization increased with chronic kidney disease stage and with the presence of diabetes. Patients with diabetes at enrollment had 345.7 hospitalization events/1000 person-years, which is considerably higher than 196.8 events/1000 person-years for those without diabetes. Survival analysis, using hospitalization as an event, showed earlier all-cause hospitalization with the progression of chronic kidney disease stage and diabetes. Cardiovascular disease hospitalizations were more strongly influenced by diabetes than chronic kidney disease stage. Conclusions Patients with chronic kidney disease and diabetes are highly vulnerable to hospitalization for a variety of diseases. These descriptive data can be valuable in predicting the prognosis of patients with chronic kidney disease.

Assessment of treatment efficacy using surface-enhanced Raman spectroscopy analysis of urine in rats with kidney transplantation or kidney disease Abstract Background Individuals who have kidney disease or kidney transplants need routine assessment of their kidney damage and function, which are largely measured based on histological examination of kidney biopsies, blood test, and urinalysis. These methods are practically difficult or inconvenient, and expensive. The objective of this study was to develop a model to estimate the kidney damage and function by surface-enhanced Raman spectroscopy (SERS). Methods Urine samples were collected from two previous studies: renal allograft recipient Lewis rats receiving anti-TGF-β antibody or control antibody treatment and obese diabetic ZSF1 rats with kidney disease fed with whole grape powder-containing chow or control chow. Silver nanoparticle-based SERS spectra of urine were measured. SERS spectra were analyzed using principal component analysis (PCA) combined with linear discriminant analysis (LDA) and partial least squires (PLS) analysis. Results PCA/LDA separated anti-TGF-β antibody-treated group from control group with 90% sensitivity and 70% specificity in kidney transplants, and grape-fed group from controls with 72.7% sensitivity and 60% specificity in diabetic kidneys. The receiver operating characteristic curves showed that the integration area under the curve was 0.850 ± 0.095 (p = 0.008) in kidney transplant groups and 0.800 ± 0.097 (p = 0.02) in diabetic kidney groups. PLS predicted the biochemical parameters of kidney function using the SERS spectra, resulting in R2 = 0.8246 (p < 0.001,urine protein), R2 = 0.8438 (p < 0.001, urine creatinine), R2 = 0.9265 (p < 0.001, urea), R2 = 0.8719 (p < 0.001, serum creatinine), and R2 = 0.6014 (p < 0.001, urine protein to creatinine ratio). Conclusion Urine SERS spectral analysis suggesting that it may become a convenient method for rapid assessment of renal impairment.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com