scholarly journals “Evaluation of Anti-Inflammatory Effects of Allopurinol in Diabetic Patients with Chronic Kidney Disease (DM-CKD): A Clinical Study”

Author(s):  
Mahya Daniyali ◽  
Leila Mahmoudieh ◽  
Golnaz Afzal ◽  
Farzaneh Hematian ◽  
Omid Moradi ◽  
...  

Abstract Background: Diabetic nephropathy is the most prevalent cause of end-stage kidney disease (ESRD). Besides, factors such as; pro-fibrotic, cytokines, vascular endothelial growth factor, inflammatory factor, and uric acid may play a role in creating and progressing diabetic nephropathy. Decreasing the serum level of inflammatory factors can be useful in the treatment of diabetic nephropathy. Therefore, this study aimed to evaluate allopurinol's anti-inflammatory effects in diabetic patients with chronic kidney disease.Methods: In this clinical trial, 60 diabetic patients with chronic kidney disease and normal uric acid level were enrolled into the study with certain inclusion and exclusion criteria. Patients received allopurinol at a dose of 100 mg daily. Demographic parameters, laboratory results in blood urea nitrogen (BUN), serum creatinine (sCr), glomerular filtration rate (GFR), 24-hour urine protein (PrUrine24h), uric acid, serum albumin (Alb), systolic blood pressure (SBP), diastolic blood pressure (DBP), glycosylated hemoglobin (HbA1C) and high sensitivity C reactive protein (HSCRP), as well as adverse reactions, were recorded at baseline, ones and three months after.Results: The results showed that patients were not different in point of demographic parameters at baseline. Laboratory results such as; BUN, sCr, GFR, PrUrine24h, Alb, SBP, DBP, and HbA1C did not change significantly over study duration (P>0.05), except uric acid and HSCRP, which were significantly decreased in patients (P=0.024 and P=0.016, respectively). There was not any notable adverse reaction among patients.Conclusion: Low dose Allopurinol (100 mg/day) reduced uric acid and inflammatory biomarker (HSCRP) after three administration months. According to the present study results, Allopurinol can be considered an auxiliary, inexpensive, and low side-effect therapy in diabetic patients with chronic kidney disease.

2021 ◽  
Vol 25 (4) ◽  
pp. 11-22
Author(s):  
Ya. F. Zverev ◽  
A. Ya. Rykunova

The review is devoted to the consideration of the nephroprotective effect and its mechanisms in new hypoglycemic drugs gliflozins, identified in largescale randomized placebo-controlled trials and experimental studies. It was found that inhibition of sodium-glucose co-transporter 2 (SGLT2) in the proximal tubules of the kidneys when using these drugs not only leads to a decrease in blood glucose levels, a decrease in blood pressure, body weight, and uric acid content in blood plasma but also delays the progression of chronic kidney disease, inhibiting the development of diabetic nephropathy. This beneficial effect is multifactorial. It is caused by the diuretic and natriuretic effects, a decrease in albuminuria, a decrease in glucotoxicity in the cells of the renal tubules, a hemodynamic effect on kidney function, and a direct anti-inflammatory effect. It is discussed why the use of SGLT2 inhibitors restores tubuloglomerular feedback, which is disrupted in the initial period of diabetic nephropathy and leads to hyperfiltration in the remaining nephrons. Information is provided on the restoration of impaired mitochon drial function due to the positive effect of drugs on the ionic composition of renal tubule cells. This greatly contributes to the enhancement of autophagy, the lysosome-mediated pathway of degradation and removal of damaged organelles, and normalizes intracellular homeostasis. The probable mechanism of autophagy enhancement through increased activity of energy deprivation sensors of AMPK and SIRT1 cells is considered. Possible mechanisms of development of anti-inflammatory and antioxidant action of SGLT2 inhibitors through inhibition of inflammasome activity are discussed. The question of the possible use of gliflozins in chronic kidney disease, the pathogenesis of which is not associated with diabetes mellitus, is considered.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sebastian Cabrera ◽  
Ruben Torres ◽  
Leticia Elgueta ◽  
Erico Segovia ◽  
Maria Eugenia Sanhueza ◽  
...  

Abstract Background and Aims Diabetic nephropathy is one of the main causes of chronic kidney disease (CKD) in the world. In the past years new studies using SGLT-2 inhibitors in diabetic patients have shown benefit in both mortality and progression of CKD. However, these works show heterogeneity between studies regarding the severity of CKD of patients included. All above complicates the interpretation of the benefits of SGLT-2 inhibitors. Method We did a systematic search of the literature in PUBMED, EMBASE, Cochrane CENTRAL trials database and in references of the selected studies. Terms used for the search were Canaglifozin, Dapaglifozin, Ertuglifozin, Empaglifozin, diabetes, mortality and CKD. Search included studies in all languages. We selected only randomized and controlled studies that reported mortality and relevant renal outcomes (doubling serum creatinine or decrease in eGFR> 40%, need for renal replacement or renal death). We included studies until September 30, 2019. For the meta-analysis, a Mantel-Haenszel model of random effects was used. The software Review Manager, Version 5.3 The Cochrane Collaboration, 2014 was used. Results We obtained results from 142 studies, fifteen studies met the selected criteria, but only four reported mortality and renal outcomes (EMPA-REG, CANVAS, CREDENCE AND DECLARE-TIMI 58). A total of 38,721 patients (SGTL2 inhibitors n = 21,264 and control n = 17,457) were included for the analysis. The EMPA-REG study used Empaglifozin, the CANVAS and CREDENCE studies used Canaglifozin and the DECLARE-TIMI 58 used Dapaglifozin. All studies were funded by pharmaceutical laboratories.The average age range of the studies was between 62 to 67 years. The percentage of patients with eGFR <60ml/min were 26%, 20%, 60% and 7% for the EMPA-REG, CANVAS, CREDENCE and DECLARE-TIMI 58 studies respectively.Mortality was lower in patients who used SGTL2 inhibitors OR 0.86 (CI 0.80-0.94) Figure 1. Renal outcomes were also lower in patients who used SGTL-2 inhibitors OR 0.69 (CI 0.60-0.78) Figure 2. We assessed whether the effect was related to the severity of the CKD taking out the work with patients with more severe CKD (CREDENCE study), the effect on mortality did not change OR 0.87 (CI 0.80-0.95) as well as renal outcome OR 0.66 (CI 0.52- 0.83). Conclusion The SGTL-2 inhibitors decrease mortality and improve renal outcomes in patients with diabetic nephropathy. These benefits remain in patients with less severe CKD.


2017 ◽  
Vol 19 (11) ◽  
pp. 1570-1578 ◽  
Author(s):  
Antonio Ceriello ◽  
Salvatore De Cosmo ◽  
Maria Chiara Rossi ◽  
Giuseppe Lucisano ◽  
Stefano Genovese ◽  
...  

2009 ◽  
Vol 32 (5) ◽  
pp. 364-368 ◽  
Author(s):  
Daisaku Andoh ◽  
Mayumi Kobayashi ◽  
Gen Yasuda ◽  
Nobuhito Hirawa ◽  
Sanae Saka ◽  
...  

2021 ◽  
Author(s):  
Lu Xu ◽  
Hang Sun ◽  
Lili Liu ◽  
Siyan Zhan ◽  
Shengfeng Wang ◽  
...  

Abstract Background: To explore whether dyslipidemia, hyperglycemia or hypertension has mediating effect on the association between serum uric acid (SUA) and the development of chronic kidney disease (CKD).Methods: We conducted a mediation analysis to explore the potential mediating effects of systolic blood pressure (SBP), diastolic blood pressure (DBP), blood glucose, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) on the association between SUA and estimated glomerular filtration rate (eGFR). The data were obtained from China Health and Retirement Longitudinal Study (CHARLS), covering 5 762 individuals. Results: SUA had a negative dose-response total effect on eGFR (β -3.11, 95% CI -3.40 to -2.82, P-value<0.001). The linear regression between SUA and seven potential mediators indicated that blood glucose (β 0.80, 95% CI 0.18 to 1.42, P-value=0.012), TG (β 10.01, 95% CI 8.22 to 11.79, P-value<0.001), TC (β 2.64, 95% CI 1.83 to 3.45, P-value<0.001), HDL-C (β -0.27, 95% CI -0.52 to -0.02, P-value=0.034) and LDL-C (β 1.15, 95% CI 0.49 to 1.80, P-value=0.001) all had significant dose-response association with SUA, but SBP and DBP showed no significant association with SUA. In terms of the association between potential mediators and eGFR, only TG did not have significant linear association with eGFR (β 0.00, 95% CI 0.00 to 0.01, P-value=0.117). The linear regression showed that SUA was directly associated with eGFR (P-value<0.001).Conclusions: This study supported that the association between SUA and the risk of CKD was not mediated by hypertension, hyperglycemia or dyslipidemia.


1970 ◽  
Vol 28 (6) ◽  
Author(s):  
Shewaneh Damtie ◽  
Belete Biadgo ◽  
Habtamu Wondifraw Baynes ◽  
Sintayehu Ambachew ◽  
Tadele Melak ◽  
...  

BACKGROUND: The prevalence of chronic kidney disease, particularly in diabetic patients, is increasing rapidly throughout the world. Nowadays, many individuals in developing nations are suffering from diabetes which is one of the primary risk factors of chronic kidney disease.METHODS: Institution based cross-sectional study was conducted at the University of Gondar Hospital from February to April 2016. A total of 229 study participants were selected using systematic random sampling technique. Urine sample was collected for albumin determination by dipstick. The Simplified Modification of Diet in Renal Disease study equation was used to estimate glomerular filtration rate. Binary logistic regression model was used to identify risk factors.RESULTS: Of the total 229 study participants, 50.2% were females and the mean age was 47±15.7 years. Among study participants, the prevalence of chronic kidney disease (CKD) was found to be 21.8% (95% CI: 16% - 27%). Of all study participants, 9(3.9%) had renal impairment (eGFR < 60 ml/min/ 1.73 m2) and 46 (20.1%) had albuminuria. Older age (AOR: 5.239, 95% CI: 2.255-12.175), systolic blood pressure ≥140mmHg (AOR: 3.633, 95% CI: 1.597-8.265), type 2 diabetes mellitus (AOR: 3.751, 95% CI: 1.507-9.336) and longer duration of diabetes (AOR: 3.380, 95% CI: 1.393-8.197) were independent risk factors of CKD.CONCLUSIONS: The study identified high prevalence (21.8%) of CKD among diabetic adults. CKD was significantly associated with older age, systolic blood pressure, type 2 DM and longer duration of DM. Thus, DM patients should be diagnosed for chronic kidney disease and then managed accordingly. 


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Oliva Mejía-Rodríguez ◽  
Jorge E. Herrera-Abarca ◽  
Guillermo Ceballos-Reyes ◽  
Marcela Avila-Diaz ◽  
Carmen Prado-Uribe ◽  
...  

Objective. The objective of this study was to investigate the effect of bromocriptine (BEC) on left ventricular mass index (LVMI) and residual renal function (RRF) in chronic kidney disease (CKD) patients with type 2 diabetes (T2D).Research Design and Methods. A 6-month double-blind randomized controlled trial was conducted in 28 patients with T2D and stage 4 CKD with increased LVMI. Fourteen patients received BEC (2.5 mg, initially 1 tablet with subsequent increase to three times a day) and 14 received a placebo (PBO; initially 1 tablet with subsequent increase to three times a day). Cardiovascular changes were assessed by monitoring 24 h ambulatory blood pressure, two-dimensional-guided M-mode echocardiography, and N-terminal brain natriuretic peptide (NT-proBNP) plasma levels. RRF was evaluated by creatinine clearance and cystatin-C plasma levels.Results. Both BEC and PBO groups decreased blood pressure—but the effect was more pronounced in the BEC group. Average 24 h, diurnal and nocturnal blood pressures, and circadian profile showed improved values compared to the PBO group; LVMI decreased by 14% in BEC and increased by 8% in PBO group. NT-proBNP decreased in BEC (0.54±0.15to0.32±0.17 pg/mL) and increased in PBO (0.37±0.15to0.64±0.17 pg/mL). Creatinine clearance did not change in the BEC group and decreased in the PBO group.Conclusions. BEC resulted in a decrease on blood pressure and LVMI. BEC also prevented the progression of CKD while maintaining the creatinine clearance unchanged.


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