scholarly journals Abnormal Expression of miR-21 in Kidney Tissue of Dogs With X-Linked Hereditary Nephropathy: A Canine Model of Chronic Kidney Disease

2018 ◽  
Vol 56 (1) ◽  
pp. 93-105 ◽  
Author(s):  
Sabrina D. Clark ◽  
Wenping Song ◽  
Rachel Cianciolo ◽  
George Lees ◽  
Mary Nabity ◽  
...  

MicroRNAs (miRNAs) are a group of small noncoding RNAs that act as regulators of posttranslational gene/protein expression and are known to play a key role in physiological and pathological processes. The objective of our study was to compare expression of miR-21 in renal tissue from dogs affected with chronic kidney disease (CKD) caused by X-linked hereditary nephropathy (XLHN), a disease equivalent to human Alport syndrome, to that from unaffected dogs. Additionally, we sought to characterize changes in relative mRNA expression of various genes associated with miR-21 function. miRNA was isolated from kidney tissue collected from both affected dogs and unaffected, age-matched littermates at defined milestones of disease progression, including end-stage renal disease (ESRD). Additionally, autopsy samples from affected dogs at ESRD and corresponding unaffected dogs were evaluated. Samples were scored based on histological changes, and relative expression of miR-21 and kidney disease-related genes was determined using quantitative real-time polymerase chain reaction. In affected dogs, significant upregulation of kidney miR-21 was first detected at the milestone corresponding with increased serum creatinine. Furthermore, miR-21 expression correlated significantly with urine protein: urine creatinine ratio, serum creatinine concentration, glomerular filtration rate, and histologic lesions (glomerular damage, tubular damage, chronic inflammation, and fibrosis). At end-stage disease, COL1A1, TGFB1 and its receptor, TGFB2, and Serpine1 were upregulated, while PPARA, PPARGC1A, ACADM, SOD1, and EGF were downregulated. In conclusion, miR-21 is abnormally upregulated in the kidneys of dogs with CKD caused by XLHN, which may play an important pathologic role in the progression of disease by dysregulating multiple pathways.

2016 ◽  
pp. 72-77
Author(s):  
Trong Ai Quoc Hoang ◽  
Tam Vo ◽  
Viet Thang Hoang

Objectives: we aimed to assess the levels of plasma ADMA in healthy people and in reserved patients with end stage renal disease (ESRD), the association between plasma ADMA with serum creatinine concentration and with eGFR. Materials and Methods: This is a controlled cross sectional study. Plasma ADMA and other variables were measured in 27 patients with ESRD and in 21 controls. Plasma ADMA levels were determined by enzyme linked immunosorbent assay (ELISA) using kits provided from immunodiagnostic AG, Germany. Data was analyzed by SPSS 19.0. Results: Mean ADMA in men- women was 0.69 ± 0.19 µmol/L and 0.61 ± 0.20 µmol/L, respectively, (p>0.05), mean ADMA in control and disease were 0.48 ± 0.17 µmol/L and 0.77± 0.12µmol/L; respectively, (p <0.001). No correlation between ADMA and age (r=-0.059, p=0.691); correlation between ADMA with serum creatinine (r=0.459, p<0.001) with eGFR r=-0.596, p<0.001). Conclusion: ADMA concentration in healthy people: 0.48 ± 0.17 µmol/L. ADMA concentration in ESRD: 0.77± 0.12 µmol/L. There is a correlation between ADMA concentration with eGFR and with serum creatinine concentration. Key words: Asymmetric dimethylarginine, end stage chronic kidney disease


Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2144
Author(s):  
Marco Giraldi ◽  
Saverio Paltrinieri ◽  
Camilla Piazza ◽  
Paola Scarpa

The endothelin-1 (ET-1) system has been implicated in the development and progression of chronic kidney disease (CKD). No information on big ET-1 in feline urine is available. The purpose of this study was to evaluate if urinary big endothelin-1 (bigET-1) is associated with feline CKD. Sixty urine samples were prospectively collected from 13 healthy cats at risk of developing CKD and 22 cats with CKD of different International Renal Interest Society (IRIS) stages (1–4). Urinary bigET-1 was measured using a commercially available ELISA. BigET-1 normalized to urine creatinine (bigET-1:UC) was compared amongst stages and substages, as proposed by IRIS, and correlated with serum creatinine concentration, proteinuria and blood pressure. BigET-1:UC at the time of inclusion was compared between cats that remained stable and cats that progressed after 12 months. BigET-1:UC was significantly higher (p = 0.002) in cats at IRIS stages 3–4 (median: 21.9; range: 1.88–55.6), compared to all other stages, and in proteinuric (n = 8, median: 11.0; range: 0.00–46.4) compared with nonproteinuric cats (n = 38 median: 0.33; range: 0.00–55.6) (p = 0.029). BigET-1:UC was not associated with CKD progression. Urinary bigET-1 increased in advanced stages of CKD and in proteinuric patients, suggesting that ET-1 may be indicative of the severity of feline CKD.


2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Mao ◽  
Nizhi Yang ◽  
Lei Zhang ◽  
Chuang Li ◽  
Yifan Wu ◽  
...  

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: −2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: −4.03,−0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects.Clinical Trial Registration:http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.


2021 ◽  
pp. 23-25
Author(s):  
Brahmarshi Das ◽  
Narendranath Hait ◽  
Titol Biswas ◽  
Debarshi Jana

INTRODUCTION: Chronic Kidney Disease (CKD) is dened as a disease characterized by alterations in either kidney structure or function or both for a minimum of 3 months duration. According to the National Kidney Foundation criteria, 1 CKD has been classied into ve stages with stage 1 being the earliest or mildest CKD state and stage 5 being the most severe CKD stage. To stage CKD, it is necessary to estimate the GFR rather than relying on serum creatinine concentration. Glomerular ltration rate (GFR), either directly measured by computing urinary clearance of ltration marker such as inulin or estimated by calculating from different equations using serum creatinine. is the most commonly used parameter to assess kidney function. AIM AND OBJECTIVES: a) Establish relationship between serum CKD and eGFR MATERIAL AND METHOD: A Cross-sectional study on 100 cases of newly diagnosed Chronic Kidney Disease patients and matched control subjects is undertaken to study.100 Patients who are newly diagnosed as CKD are selected after proper initial screening. RESULT AND ANALYSIS: In case, the mean eGFR (mean± s.d.) of patients was 25.1500 ± 11.8929. In control, the mean eGFR (mean± s.d.) of patients was 87.2200 ± 17.8295. Difference of mean eGFR in two groups was statistically signicant (p<0.0001). In case, the mean creatinine (mean± s.d.) of patients was 3.6350 ± 2.4419 mg/dl. In control, the mean creatinine (mean± s.d.) of patients was .9435 ± .1317 mg/dl. Difference of mean creatinine in two groups was statistically signicant (p<0.0001). CONCLUSION: eGFR was strongly associated with CKD that also statistically signicant. The positive correlation was found in eGFR.


2018 ◽  
Vol 8 (2) ◽  
pp. 107-111 ◽  
Author(s):  
Yasuhiko Tomino ◽  
Atsuko Hisada-Urita ◽  
Takuto Seki ◽  
Tomonari Watanabe ◽  
Reo Kanda ◽  
...  

We report herein an adult case of chronic kidney disease (CKD) associated with diabetes. The patient had been treated with insulin injection for diabetes 10 years ago. At the time of his first visit to our division for further examinations, we diagnosed him as CKD: cause (C) diabetes; glomerular filtration rate (GFR) (G) G5 (estimated [e] GFR, 10.2 mL/min/1.73 m2; serum creatinine of 4.90 mg/dL); and albuminuria (A) A3 (2.62 g/gCr) by the Japanese Society of Nephrology (JSN) CGA classification. Because he had complained of severe constipation and kidney function, i.e., eGFR was not improved by previous medications, we added on a minimal dosage (2 g/day) of AST-120 (Kremezin®; ordinary dose 6 g/day). After 3 months of AST-120 therapy, eGFR was increased to 17.8 mL/min/1.73 m2 (serum creatinine of 2.90–2.72 mg/dL). Although the patient used some laxative products, he could not continue to take Kremezin and completely stopped 8 months after starting this drug. Kidney function then abruptly declined and progressed to end-stage kidney disease (ESKD). In June 2017, he was introduced to hemodialysis. It appears that the adherence of Kremezin is very important for inhibiting the progression to ESKD for patients with CKD with diabetes.


2015 ◽  
pp. 114-119
Author(s):  
Hoang Thanh Van Nguyen ◽  
Tam Vo

Background: Osteoporosis is a common complication in chronic kidney disease, with dangerous consequences such as fracture which make the disease more severe. For early detecting osteoporosis, it is important to measure bone mineral density and to assay bone turnover markers. The aims of this study were to determine the percentage of osteoporosis and osteopenia and to find an association between level of serum creatinine, level of beta-crosslaps and bone mineral density. Methods: A cross-sectional study. Measurement of BMD in patients with end-stage chronic renal disease in the department of nephrology and rheumatology, Hue central hospital from Oct 2010 to May 2011. Results: The prevalence of osteoporosis and osteopenia in end-stage chronic renal disease patients without hemodialysis is 47.37%. There is a significiantly relationship between concentration of serum creatinine, serum beta crosslaps and bone mineral density. Conclusion: The prevalence of osteoporosis and osteopenia in patients with end-stage chronic renal disease is high. There is a significantly relationship between level of serum beta-crosslaps, serum creatinine and bone mineral density. Keyword: bone mineral density, chronic kidney disease, bone turnover, osteoporosis, bone marker, beta-crosslaps.


2019 ◽  
Vol 22 (8) ◽  
pp. 729-735 ◽  
Author(s):  
Kellyi K Benson ◽  
Jessica M Quimby ◽  
Kristy L Dowers ◽  
Liberty G Sieberg ◽  
Joshua B Daniels ◽  
...  

Objectives The aims of this study were to determine the side effect frequency and serum and urine drug concentrations of amoxicillin–clavulanic acid in cats with and without azotemic chronic kidney disease (azCKD). Methods Owners whose cats had been prescribed amoxicillin–clavulanic acid completed a survey regarding the occurrence and type of side effects, and whether treatment was altered as a result. Cats were defined as azCKD (serum creatinine concentration >2.0 mg/dl, urine specific gravity [USG] <1.035 with a clinical diagnosis of chronic kidney disease) and without azCKD (serum creatinine concentration <2.0 mg/dl). Data were assessed with Fisher’s exact test. Serum and urine samples were obtained from client-owned cats with azCKD (n = 6) and without azCKD (n = 6, serum creatinine concentration <1.8 mg/dl, USG >1.035) that were receiving amoxicillin–clavulanic acid. Amoxicillin and clavulanic acid were measured with liquid chromatography coupled to tandem mass spectrometry and compared between groups with a Mann–Whitney test. Correlation between serum creatinine and drug concentrations in urine and serum was determined using Spearman’s rank test. Results Sixty-one surveys were returned (11 azCKD cats and 50 without azCKD cats). No significant difference in the presence of side effects or type of side effects was seen between groups; however, significantly more azCKD cats had more than one side effect ( P = 0.02). More owners of azCKD cats reported that an alteration in treatment plan was necessitated by side effects (55% vs 12%; P = 0.008). Urine amoxicillin was significantly lower in cats with azCKD ( P = 0.01) and serum amoxicillin trended toward significance ( P = 0.07). Serum amoxicillin concentration was positively correlated with serum creatinine ( P = 0.02; r = 0.62) and urine amoxicillin concentration was negatively correlated with serum creatinine ( P = 0.01; r = –0.65). Conclusions and relevance The data suggest that cats with azCKD have altered pharmacokinetics of amoxicillin, which may contribute to an increased incidence of multiple side effects.


2019 ◽  
Vol 16 (2) ◽  
pp. 7-18
Author(s):  
Mădălina-Gabriela Stăncescu ◽  
Mircea Penescu

AbstractRenal pathology is a pluralism of acute or chronic conditions in which the main victim is the nephron. Regardless of the nature of the injury, the primary lesion will always lead - in absence of efficient treatment - to end-stage kidney disease and renal replacement therapy. Although we are in the 21st century and amazing advances have been recorded in the medical field, the diagnosis of chronic kidney disease is performed - most frequently - based on the estimation of the glomerular filtration rate, based on serum creatinine. Unfortunately the serum creatinine level increases only when > 50% of the nephrons are already irremediably destroyed. In the last 20 years, an intensive research is performed in order to discover new plasma or urinary biomarkers for an earlier diagnosis of the renal pathology. Neutrophil gelatinase-associated lipocalin (NGAL) has a central place in this research, and its diagnostic and prognostic utility is proven particularly in acute kidney injury, but also in glomerulonephrites, diabetic nephropathy, and chronic kidney disease.


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