Search Results (7)

Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-β-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB/B2M and ND2/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms. Full article

Background: Ultrasound-guided kidney biopsy is an essential diagnostics method that can increase the accuracy of the differential diagnosis between acute and chronic nephropathies. In addition, it will help clinicians perform an etiologic diagnosis, issue a prognosis, and orient therapy for the majority of parenchymal nephropathies. Due to the relative invasiveness and potential adverse effects, the use of kidney biopsies is limited among practitioners. Results: Twenty-eight dogs, of mixed breed and variable ages, of which 11 (39, 29%) were males and 17 (60, 71%) were females, were examined and underwent an ultrasound-guided kidney biopsy to establish a definitive diagnosis. The patients were presented with a variety of diffuse nephropathies, such as kidney lymphoma: 1 (3.57%), glomerulonephritis: 13 (46.43%), tubulointerstitial nephritis: 11 (39.29%), and nephrocalcinosis. A total of 3 (10.71%) of 18 (64.29%) were in acute kidney injury, and 10 (35.71%) were CKD patients. The type and the severity of the kidney lesions were correlated with changes in the urinary n-acetyl-beta-d-glucosaminidase index (iNAG. To quantify the side effects of percutaneous kidney biopsy, the magnitude of post-biopsy hematuria and changes in urinary iNAG activity were evaluated. The results indicate a significant post-biopsy increase in the urinary iNAG activity in all the patients that underwent this procedure (100.08 ± 34.45 U/g), with a pre-biopsy iNAG vs. 147.65 ± 33.26 U/g post-biopsy iNAG (p < 0.001), suggesting an intensification in the kidney tubular damage that comes consecutives to kidney puncture and sampling. Transitory macro- or microhematuria were constant findings in all the dogs that underwent ultrasound-guided kidney biopsy, but the magnitude and extent could not be associated with the platelet count (PLT 109/L), aPTT (s), and PT (s) levels in our patients, and they were also resolved after 12–24 h without therapeutic interventions. Conclusions: Ultrasound-guided renal biopsy was shown to be a minimally invasive diagnostic procedure that causes transient and limited effects on kidney structures. Although these effects were minor and resolved without intervention, we feel that the benefit of obtaining higher-quality biopsied tissue outweighs the higher risks associated with this procedure. Full article

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-β-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)—the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease. Full article

Acute and chronic kidney diseases are an evolving continuum for which reliable biomarkers of early disease are lacking. The potential use of glycosidases, enzymes involved in carbohydrate metabolism, in kidney disease detection has been under investigation since the 1960s. N-acetyl-beta-D-glucosaminidase (NAG) is a glycosidase commonly found in proximal tubule epithelial cells (PTECs). Due to its large molecular weight, plasma-soluble NAG cannot pass the glomerular filtration barrier; thus, increased urinary concentration of NAG (uNAG) may suggest injury to the proximal tubule. As the PTECs are the workhorses of the kidney that perform much of the filtration and reabsorption, they are a common starting point in acute and chronic kidney disease. NAG has previously been researched, and it is widely used as a valuable biomarker in both acute and chronic kidney disease, as well as in patients suffering from diabetes mellitus, heart failure, and other chronic diseases leading to kidney failure. Here, we present an overview of the research pertaining to uNAG’s biomarker potential across the spectrum of kidney disease, with an additional emphasis on environmental nephrotoxic substance exposure. In spite of a large body of evidence strongly suggesting connections between uNAG levels and multiple kidney pathologies, focused clinical validation tests and knowledge on underlining molecular mechanisms are largely lacking. Full article

Gentamicin is an aminoglycoside antibiotic commonly used to treat Gram-negative bacterial infections that possesses considerable nephrotoxicity. Oxymatrine is a phytochemical with the ability to counter gentamicin toxicity. We investigated the effects and protective mechanism of oxymatrine in rats. The experimental groups were as follows: Control, Oxymatrine only group (100 mg/kg/d), Gentamicin only group (100 mg/kg/d), Gentamicin (100 mg/kg/d) plus Oxymatrine (100 mg/kg/d) group (n = 10). All rats were treated for seven continuous days. The results indicated that oxymatrine alleviated gentamicin-induced kidney injury, and decreased rats’ kidney indices and NAG (N-acetyl-beta-d-glucosaminidase), BUN (blood urea nitrogen) and CRE (creatine) serum levels. The oxymatrine-treated group sustained less histological damage. Oxymatrine also relived gentamicin-induced oxidative and nitrative stress, indicated by the increased SOD (superoxidase dismutase), GSH (glutathione) and CAT (catalase) activities and decreased MDA (malondialdehyde), iNOS (inducible nitric oxide synthase) and NO (nitric oxide) levels. Caspase-9 and -3 activities were also decreased in the oxymatrine-treated group. Oxymatrine exhibited a potent anti-inflammatory effect on gentamicin-induced kidney injury, down-regulated the Bcl-2ax and NF-κB mRNAs, and upregulated Bcl-2, HO-1 and Nrf2 mRNAs in the kidney tissue. Our investigation revealed the renal protective effect of oxymatrine in gentamicin-induced kidney injury for the first time. The effect was achieved through activation of the Nrf2/HO-1 pathways. The study underlines the potential clinical application of oxymatrine as a renal protectant agent for gentamicin therapy. Full article

Background: A good survival rate among patients with beta thalassemia major (beta-TM) has led to the appearance of an unrecognized renal disease. Therefore, we aimed to assess the role of serum cystatin-C as a promising marker for the detection of renal glomerular dysfunction and N-acetyl beta-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) as potential markers for the detection of renal tubular injury in beta-TM children. Methods: This case-control study was implemented on 100 beta-TM children receiving regular blood transfusions and undergoing iron chelation therapy and 100 healthy children as a control group. Detailed histories of complete physical and clinical examinations were recorded. All subjected children underwent blood and urinary investigations. Results: There was a significant increase in serum cystatin-C (p < 0.001) and a significant decrease in eGFR in patients with beta-TM compared with controls (p = 0.01). There was a significant increase in urinary NAG, KIM-1, UNAG/Cr, and UKIM-1/Cr (p < 0.001) among thalassemic children, with a significant positive correlation between serum cystatin-C, NAG and KIM-1 as regards serum ferritin, creatinine, and urea among thalassemic patients. A negative correlation between serum cystatin-C and urinary markers with eGFR was noted. Conclusion: Serum cystatin-C is a good marker for detection of glomerular dysfunction. NAG and KIM-1 may have a predictive role in the detection of kidney injury in beta-TM children. Full article

Diabetic nephropathy (DN) is presently the primary cause of chronic kidney disease and end-stage renal disease (ESRD). It has been suggested that inflammation and oxidative stress, in addition to or in concert with the metabolic changes, plays an important role in the maintenance and progression of the disease. Therefore, attenuating or blocking these mechanisms may be a therapeutic target to delay the progression of the disease. Diallyl thiosulfinate (allicin), a compound derived from garlic, inhibits free radical formation, increases glutathione synthesis and decreases the levels of proinflammatory molecules in vitro. This research aimed to assess the effect of allicin on oxidative stress and inflammation-induced diabetes. Animals were divided into control and diabetes (streptozotocin 50 mg/kg i.p.), and maintained for 30 days. After 30 days, the group of diabetic animals was subdivided into diabetes and allicin-treated diabetes (16 mg/kg/day oral gavage). The three experimental groups were maintained for another month. We analyzed the status of renal function, oxidative stress and proinflammatory cytokines. The untreated diabetic group showed hyperglycemia and increased diuresis, creatinine clearance, proteinuria, glycosuria and urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), as well as increased oxidative stress and the expression of interleukin 1β (IL-1β), IL-6, nuclear factor kappa beta (NFκβ) and transforming growth factor-β1 (TGF-β1) in plasma and kidney. In contrast, the inhibitor of NFκβ (Iκβ) is decreased in the cortex. It has been demonstrated that the allicin treatment decreases hyperglycemia, polyuria, and NAG excretion. The oxidative stress and proinflammatory cytokines were also reduced by the allicin treatment. In conclusion, allicin delays the progression of diabetic nephropathy through antioxidant and anti-inflammatory mechanisms. Full article