Iranian journal of kidney diseases最新文献

Introduction. Diabetes mellitus (DM) is one of the most common chronic diseases worldwide, and diabetic nephropathy (DN) is the most significant complication of DM, which is highly prevalent and difficult to cure. This research project aims to investigate the role and mechanism of Nucleoporin 160kDa (NUP160)-regulated autophagy in the pathogenesis of DN.

Methods: NUP160 levels in diabetic and non-diabetic kidney tissues were measured by Western blot, and the connection between NUP160 and renal function of DN patients was analyzed. The podocytes were divided into four groups, namely the standard group (culture medium: standard glucose solution), high glucose (HG) group (HG solution), HG+si-NUP160 group (HG solution+si-NUP160 transfection) and HG+si-NC group (HG solution+si-NUP 160 transfection) for the determination of apoptosis by flow cytometry and measurements of LC3B, Prostacyclin-62 (P62), Janus kinase 2 (JAK2) and Signal transducer and activator of transcription3 (STAT3) by Western blot.

Results: In DN patients, NUP160 decreased in podocytes and was inversely proportional to Blood urea nitrogen (BUN), Serum creatinine (Scr) and β2-Microglobulin (β2-MG) (P < .05). Compared with a standard group, the apoptosis rate, P62 level, and the ratios of phosphorylation-JAK2 (p-JAK2)/JAK2, phosphorylation-STAT3 (p-STAT3)/STAT3, and LC3B-Ⅱ/LC3B-Ⅰ elevated in the other three groups (P < .05). Apoptosis rate and P62 level, p-JAK2/JAK2 and p-STAT3/STAT3 ratios increased, and LC3B-Ⅱ/LC3B-Ⅰ ratio decreased in the HG+si-NUP160 group (P < .05), while those in HG+si-NC group showed no evident changes, compared with HG group (P > .05).

Conclusion: NUP160 is downregulated in DN and can affect cellular autophagy through the activation of JAK2/STAT3 signaling pathway.  DOI: 10.52547/ijkd.7884.

Introduction: Farnesoid-X-activated receptor (FXR) is considered as an upstream controller which could influence the other key regulatory genes encoding cellular antioxidant defense system.

Methods: Thirty-five male Wistar rats (240 ± 20 g) were randomly allocated into five groups: 1) control, 2) received gentamicin (100 mg/kg/d) for three days (GM-3d), 3) seven days (GM-7d), 4) 10 days (GM-10d), and 5) 14 consecutive days (GM-14d). Biochemical measurements of BUN and serum creatinine (SCr), histological assessment of renal samples as well as molecular analysis using real-time qRT-PCR were used to investigate the pattern of changes in different levels.

Results: Administration of gentamicin was associated with a significant increase in the BUN and SCr until the 10th day, which then suddenly dropped at the day 14. Meantime, the maximum histological distortion was also seen on the 10th day but in a similar pattern, 14th day was associated with clear improvement. Compared to the control value, the maximum reduction in the mRNA expression of Farnesoid X-activated receptor (FXR), nuclear factor erythroid 2-related factor 2 (Nrf2) and Glutathione cysteine ligase-modulatory subunit (GCLM), occurred at the 3rd and 7th days, respectively. Compared to the control, the mRNA expression of the mentioned genes significantly increased up to day 14. Apart from the 3rd day, the mRNA expression of alpha-glutathione S-transferase (α-GST) and superoxide dismutase (SOD) showed a similar descending and ascending pattern at 7th and 10th days, respectively.

Conclusion: The expression of FXR, as an upstream controller gene and its downstream pathways mediated by Nrf2, could play a role in gentamicin-induced nephrotoxicity but the pattern of expression was rather biphasic at the acute phase or the subacute ones.  DOI: 10.52547/ijkd.7523.

Introduction: Hypertension (HTN), also known as high blood pressure (BP), is a major global risk factor for cardiovascular and kidney diseases. Although annual BP screenings for children over three years of age are recommended, underdiagnosis of HTN in children is common. To address this issue, the American Academy of Pediatrics updated its guideline for screening and managing high BP in children in 2017, which can be cumbersome to implement in clinical practice due to the numerous cut-off points and tables. The purpose of our study is to design formulas to detect HTN in children based on the new Clinical Practice Guideline for screening and management of high BP in children and adolescents.

Methods: In this research, we analyzed forty-eight cut-off points using the 90th percentile systolic and diastolic BPs for the fifth percentile height. The final mathematical model consisted of four formulas based on different ages and sex which in turn were rounded by 0.1 and 1.0 for both systolic and diastolic BPs. The formulas were further modified to be lower than the 95th percentile systolic BPs for the fifth percentile of height to minimize false negative results.

Results: As evidenced by the tables included in this paper, except for a few exceptions, all rounded systolic and diastolic values for both sexes were equal to or lower than the 90th percentile. In a few cases where the cutoff points calculated by the formula were higher than the ones provided in the 2017 guideline, the differences were less than 2 mmHg.

Conclusion: In this study to address the complexity of the routine guidelines, we present simplified formulas for screening children aged 1 to 12 years in figures and tables and recommend their use, particularly in office and emergency settings, as an easier-to-implement first step in screening for HTN in children.  DOI: 10.52547/ijkd.7525.

Introduction: This study utilized serum proteomics with tandem mass tags (TMT) to investigate potential biomarkers associated with femoral central venous catheter (CVC) thrombosis in endstage kidney disease (ESKD) patients. TMT proteomics analysis on serum samples was conducted to identify proteins with distinct expression levels that may be linked to thrombosis. The findings have important implications for enhancing anticoagulant procedures, catheter closure techniques, and determining optimal intervention timing for post-catheterization dialysis.

Methods: Thirty ESKD patients with CVC receiving hemodialysis between May 2021 and October 2022 at the First Affiliated Hospital of Chengdu Medical College were included in the study, and grouped according to vascular color Doppler ultrasound results, including 23 patients in the thrombo-positive group and 7 patients in the thrombo-negative group. Selection criteria were: 1) Patients with ESKD candidate for hemodialysis initiation; 2) no dialysis access has been placed previously, and CVC needs to be inserted as a temporary access; 3) patients volunteered to participate in this clinical study. Clinical data, blood tests, coagulation function, and biochemical parameters were collected and analyzed on the 14th day after catheterization. Color ultrasonography was conducted on the same day to categorize patients into two groups: those with thrombus-positive results and those with thrombus-negative results.

Results: TMT proteomics analysis identified twenty-eight differently expressed proteins, including 16 upregulated and 12 downregulated proteins. Enrichment analysis demonstrated nine proteins that were significantly enriched in four pathways within the thrombus-positive group after CVC insertion. Enzyme-linked immunosorbent assay (ELISA) test confirmed the TMT proteomics findings, specifically highlighting significant differences in human plasma kallikrein B1 (KLKB1) and angiopoietin-like protein 3 (ANGPTL3) levels on the 14th day after CVC insertion. Additionally, KLKB1, fibrinogen (FIB), D-dimer, and fibrinogen degradation products (FDP) levels were significantly elevated, while ANGPTL3 levels were decreased on the 14th day after CVC insertion in the thrombus-positive ESKD patient group.

Conclusion: Monitoring coagulation status post-CVC catheterization and evaluating potential biomarkers like KLKB1 and ANGPTL3 can contribute to the development of personalized treatment plans, improving the quality of hemodialysis and the overall quality of life for ESKD patients.  DOI: 10.52547/ijkd.7671.

Introduction: The pathophysiology of diabetic nephropathy (DN) is fundamentally dependent on glomerular endothelial cells (GECs), which are a crucial portion of the glomerular filtration barrier. This study aimed to identify biomarker candidates associated with GECs dysfunction in DN by combining microarray and single-cell sequencing dataset analysis.

Methods: Microarray dataset GSE30528 was downloaded from the Gene expression omnibus (GEO) database. Key gene sets for diabetic kidney disease (DKD) were selected by using weighted gene co-expression network analysis (WGCNA). Biomarker candidates were then identified using least absolute shrinkage and selection operator (LASSO) logistic regression. The single-cell sequencing data (GSE131882) was used to explore the biological functional differences in glomerular endothelium between the control and DKD groups. The diagnostic efficiency of the selected biomarker was tested in the Receiver operating characteristic (ROC) curve. Moreover, we used the single-sample gene set enrichment analysis (ssGSEA) to compare immune cell infiltration between DKD and control groups. RT-PCR was used to validate the selected gene expression in cultured glomerular endothelial cells under high glucose stimulation.

Results: Phosphatase and actin regulator 4 (PHACTR4) was ultimately selected as the key GEC-related biomarker in DKD. Significantly downregulated PHACTR4 mRNA expression was further validated in human glomerular endothelial cells (HGECs) under high glucose stimulation by using RT-PCR. The decreased PHACTR4 was found to be associated with abnormal endothelial proliferation and neo-angiogenesis. Additionally, immune infiltration analysis revealed that PHACTR4 was negatively associated with inflammatory infiltration, especially pro-inflammatory cells including activated CD4 and CD8 T cells, B cells, and Mast cells, indicating PHACTR4 downregulation may exacerbate inflammatory reaction.

Conclusion: PHACTR4 is a potential diagnostic marker for DKD and plays an essential role in aberrant glomerular endothelial proliferation and inflammation in DKD.  DOI: 10.52547/ijkd.7858.

Fabry disease (FD) is a multi-organ disorder caused by a deficiency of alpha-galactosidase (α-GLA) or reduced activity of the enzyme due to mutations in the GLA gene on the X chromosome, making it an X-linked hereditary disease. A 37-year-old man previously diagnosed with sudden deafness and cardiac hypertrophy was referred to our department after an abnormal urine finding during a public health checkup. A renal biopsy revealed characteristic findings, and he was diagnosed with FD with a novel GLA abnormality (c.714dupT (p.I239Yfs*11)). We are currently administering enzyme replacement therapy (ERT) with agalsidase α. This case shows that a novel genetic abnormality in FD can be overlooked for 37 years, even in the presence of typical symptoms. The significance of a renal biopsy in diagnosing FD is emphasized, highlighting the crucial role of nephrologists.  DOI: 10.52547/ijkd.7595.

Pediatric organ transplantation, specifically kidney transplant, has improved considerably in recent decades in Iran. Since infections are the most common cause of morbidity and mortality among transplanted children, pre-transplant vaccination is an effective preventive tool in this regard. In addition, administration of some vaccines is contraindicated in post- transplant period and the efficacy and immunogenicity of authorized vaccines may also be suboptimal in comparison to normal population. Therefore, pre-transplant period offers an outstanding chance to boost the immunization of this population. With regard to this population, it is imperative to establish a localized vaccination guideline, which can be used by nephrologists and other clinicians who are part of the transplant team, in Iran. Currently, such a local guideline for Iranian pediatric kidney transplant candidates is not available. The aim of this study is to provide a comprehensive overview of the existing vaccines recommended for these cases regarding the Expanded Program on Immunization (EPI) and available vaccines in Iran. In addition, general principles of vaccination, the use of specific vaccines as well as accelerated vaccination in this population are discussed in this article. This review could be a preliminary guide for preparing a comprehensive guideline for vaccination of this population in Iran.  DOI: 10.52547/ijkd.7660.

Introduction: Membranous nephropathy (MN) has variable clinical outcomes, ranging from spontaneous remission to slow progression to kidney failure. Since the clinical outcomes of MN have not been studied in a large sample size in Iran, this study was designed to evaluate the outcome of patients diagnosed with MN at Hasheminejad Kidney Center (HKC), Tehran.

Methods: In this retrospective cohort study, 1086 patients with a diagnosis of MN who were biopsied between 1998 and 2018 in HKC were evaluated through a review of medical records for baseline clinical and laboratory characteristics at the time of biopsy and through a review of follow-up charts and phone calls for the evaluation of clinical outcomes. Of these patients, 551 could be followed for clinical outcomes. The composite outcome included kidney loss (hemodialysis, transplantation, or death). The effect of demographic, clinical, laboratory, and pathological variables on kidney survival was determined by the Cox-regression model using SPSS-16 software at a significance level of .05.

Results: Sex (P < .05), higher weight (P < .05), older age (P < .001), hypertension (P < .001), higher baseline proteinuria and lower glomerular filtration rate (GFR) at the onset of the disease were associated with kidney failure (P < .001). A higher percentage of interstitial fibrosis, tubular atrophy, global sclerosis, and a higher pathological class of membranous nephropathy were significantly associated with disease outcome in the univariate Cox-regression analysis (P < .001). Kidney survival rates at 5, 10, and 15 years were 86%, 74%, and 56%; respectively.

Conclusion: Our study suggests that baseline demographic, clinical and laboratory factors affect kidney outcomes. Patients who are considered high-risk based on the criteria listed above may need to be candidates for more aggressive therapy.  DOI: 10.52547/ijkd.7373.

Chronic kidney disease leads to significant functional limitations and severe disability, which requires the application of an appropriate physical rehabilitation strategy that helps patients achieve social well-being and significant health benefits. Data sources MEDLINE, PubMed, Google Scholar and Web of Science were electronically searched, by using search terms: physical exercise, hemodialysis, barriers, risks of exercise, expected benefits. The contraindications for exercise are recent myocardial infarction, uncontrolled arrhythmia and hypertension, unstable angina pectoris, unregulated diabetes mellitus, the presence of neurological and muscular dysfunctions, malignancies, and pregnancy. The implementation of the physical exercise program for hemodialysis patients confirmed all the expected benefits: improvement of cardiovascular functions, stabilization of blood pressure, increased muscle strength, improvement of nutritional status and quality of dialysis, reduction of negative emotions, anxiety and depression, as well as social interaction of patients and their families. Despite the fact that a large number of studies have proven the beneficial effects of exercise during hemodialysis, a physical rehabilitation program as a standard form of treatment has not yet been introduced. Although there is no doubt that the effects of physical activity on the survival and the quality of life of patients on hemodialysis are positive, rehabilitation program still falls under the routine practice program in a small number of dialysis centers. One of the biggest obstacles to the implementation of the physical therapy program in hemodialysis patients is the lack of a clearly defined program that defines all the needs of dialysis patients.  DOI: 10.52547/ijkd.7570.

Following allogenic hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD) may develop which may affect several organs. Although the presence of nephrotic syndrome after HSCT is rare, sometimes it occurs in the setting of GVHD. The most common histological finding on kidney biopsy of patients with proteinuria owing to GVHD is membranous glomerulonephritis (MGN). However, reports of immune complex deposition in the tubular basement membrane (TBM) and glomerular basement membrane (GBM) are extremely rare. Herein we present a 65-year-old female with a history of HSCT at six years ago who was referred to Dr.Shariati Hospital in Tehran with nephrotic syndrome. Secondary serologic laboratory tests were all normal. The histopathologic study indicated diffuse GBM and TBM thickening, spike formation, infiltration of inflammatory mononuclear cells in tubulointerstitial area and acute tubular injury in light microscopy. Immunofluorescence staining showed immune complex deposits in GBM, mesangial cells, and TBM.  DOI: 10.52547/ijkd.7550.