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Objective:To evaluate the role of Nigella sativa in renoprotectionMaterial and Methods:This prospective, comparative study was completed in a tertiary care centre of north India in patients of Chronic Kidney Disease (CKD). Group I (Control) received conservative management of CKD and while Group II (Test) received conservative management along with Nigella sativa oil (2.5 mL, orally, once daily) for 12 weeks. Renal function tests were done at 0, 6 and 12 weeks of treatment.Results:There was more progressive improvement in biochemical values and clinical signs and symptoms in test group. There was decrement in blood urea, serum creatinine and 24-hour total urine protein (TUP). There was rise in glomerular filtration rate (GFR) and 24-hour total urine volume (TUV). Conclusion:Nigella sativa oil supplementation is effective and safe in prevention of progression of nephropathy.
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During kidney transplant, the non-specific inflammatory response induced by ischemia-reperfusion injury (IRI) will lead to decreased survival ability of transplanted kidney. However, the effect of IRI on long-term survival rate of allograft is not sure. Here we illuminated the relationship between early IRI and decreased long-term survival ability of allograft by retrospectively analyzing the clinical evidences and laboratory investigations. Previous studies showed that early IRI resulted in the graft loss through reduction of renal functional mass, vascular injury, chronic hypoxia and subsequent fibrosis. IRI was also one of the main factors to induce dysfunction of transplanted kidney and acute rejection reaction, and to decrease the allograft survival. Therefore, it's better to substitute traditional methods with novel measures during kidney transplant which may relieve the renal IRI much better.
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Both dipeptidyl peptidase-4(DPP-4)inhibitor and sodium-glucose cotransporter-2(SGLT-2) inhibitor have been approved for the treatment of type 2 diabetes mellitus(T2DM). In preclinical or clinical studies, DPP-4 inhibitor shows a potential beneficial effect on renal architecture damage,whereas SGLT-2 inhibitor has a role in renoprotection by improving renal hemodynamics. Therefore,the combination therapies with DPP-4 inhibitor and SGLT-2 inhibitor not only improve metabolic control, but also may have a synergistic or complementary effect in protecting renal structure and function in patients with T2DM. This combination therapy provides a novel option for raising the comprehensive management level in patients with T2DM.
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Objective This study was to investigate the role of trimetazidine in the prevention of contrast-induced nephropathy (CIN) in renal dysfunction patients undergoing coronary angiography. Methods A total of 151 patients with renal dysfunction who underwent coronary angiography were enrolled in our study and randomly divided into control group (n=77) and trimetazidine group (n=74). Standard hydration was administered in all the patients. In trimetazidine group, patients were administered trimetazidine orally for 48 hours before and 7 days after coronary angiography. Adverse events were observed in 12 months. Results (1) For 24 h and 48 h after the procedure:levels of SCr and CysC in the control group were significantly increased compared with baseline levels; levels of SCr and CysC in trimetazidine group were not increased, compared with baseline levels;levels of SCr and CysC were lower in trimetazidine group than the control group. (2)The incidence of CIN was reduced in trimetazidine group compared with control group (22.1%vs 9.5%,P=0.034). (3) Kaplan-Meier analysis showed that the incidence of adverse events in trimetazidine group was lower compared with the control group (P = 0.003). Conclusions Trimetazidine in combination with standard hydration is more effective than isotonic saline alone in protecting renal function in patients with renal dysfunction who undergo coronary angiography.
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Aim To investigate the ameliorative effects pseudoberberine(Y53), a berberine(BBR) analogue, on diabetic nephropathy( DN) in streptozotocin( STZ)-induced diabetic mice. Methods Diabetes mellitus ( DM) of the C57BL/6J mice was induced by intraper-itoneal injection of STZ at 120 mg·kg-1 . The diabetic animals were divided into 4 groups, which were orally treated with saline, 50 mg · kg-1 of BBR, 50 mg · kg-1 of Y53 or 5 mg · kg-1 of rosiglitazone ( ROSI ) , respectively. During and after the experiment, the u-rine, blood, serum and kidney of the animals were harvested for determination of relevant parameters by kits. Kidney tissues of the mice were subjected to pathological examination by hematoxylin & eosin( HE) staining;mRNA and protein expression levels of target genes in the kidney were determined by quantitative re-al-time reverse transcriptase-polymerase chain reaction ( qRT-PCR) and Western blot, respectively. Results Y53 greatly reduced the fasting blood glucose ( FBG ) and glycosylated hemoglobin( GHb) , improved diabet-ic symptoms such as polyphagia and polyuria in the di-abetic mice( P<0. 01 vs DM control group) . Y53 po-tently reduced the blood urea nitrogen ( BUN ) , serum creatinine( Scr) , 24 h urinary protein, kidney index, serum and kidney advanced glycation end-products ( AGEs) and nitric oxide( NO) , as well as kidney cho-lesterol( CHO ) and triglyceride ( TG ) contents ( P <0. 05 or P<0. 01 vs DM control group) . In the patho-logical examination, Y53 greatly restored kidney mor-phology and suppressed glomerular sclerosis( P<0. 001 vs DM control group). In addition, Y53 significantly reduced the renal expression of fibrosis-related genes, such as the transforming growth factor-β1 ( TGF-β1 ) and smad2(P<0. 01 vs DM control group). The reno-protective efficacies of Y53 were superior to those of BBR and ROSI in our study ( P<0. 05 or P<0. 01 ) . Conclusions The BBR analogue Y53 has potent ac-tivities in ameliorating renal injury and restoring renal function in STZ-induced diabetic mice. Y53 may be developed as a novel kind of agent for the treatment of DN in the future.
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Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i.p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a signifi cant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i.p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats.
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Animals , Rats , Body Weight , Creatinine , Diabetes Mellitus , Diabetes Mellitus, Experimental , Diabetic Nephropathies , Glucose , Kidney , Lipoproteins, HDL , Lisinopril , Streptozocin , Triglycerides , Urea , Vascular ResistanceABSTRACT
Background: Accumulating evidences during the past decade suggest that erythropoietin (EPO) may have many beneficial actions other than on erythropoiesis because many non-hematopoietic cells, including kidney cells, also express EPO receptors. Objective: To summarize evidences of the renoprotective effects of EPO and review the possible mechanisms of renoprotection provided by EPO. Results: Experimental studies have demonstrated the renoprotective effects of EPO in acute as well as chronic renal injury models. These renoprotective actions are likely to be mediated by several mechanisms, either directly or indirectly. However, EPO therapy is also associated with adverse effects. Conclusion: EPO is potentially a novel renoprotective drug. Clinical use of EPO for renoprotection could not be beneficial if adverse side effects of EPO have been overcome.
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Objective To investigate the effects of valsartan on the expression of receptors for advanced glycation end-products(RAGE) in kidneys of diabetic rats,and to explore its renoprotection mechanisms. Methods Thirty rats were divided into normal control group,diabetes control group and diabetes with valsartan group(n=10).Blood glucose,blood lipid,HbA1c,kidney to body weight ratio and 24 h urinary protein excretion were measured after 12 weeks.RAGE mRNA level was detected by real-time quantitative PCR. Results Compared with normal control group,kidney to body weight ratio,24 h urinary protein excretion and RAGE mRNA were significantly increased in diabetes control group.Compared with diabetes control group,kidney to body weight ratio,24 h urinary protein excretion and RAGE mRNA were significantly decreased in diabetes with valsartan group. Conclusion Valsartan can inhibit renal hypertrophy and decrease urinary protein excretion in diabetic rats.The renoprotective effects may be related to its inhibition on RAGE expression.
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BACKGROUND: We compared the renoprotective effect of angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) between early treatment and delayed treatment in chronic uremic rats. METHODS: Male Sprague-Dawley rats underwent 5/6 nephrectomy or sham operation (sham) and received no treatment (UC), enalapril (E) 100 mg/L, candesartan cilexetil (C) 10 mg/L or combination of E and C in drinking water. Some rats began to be treated from the next day of 5/6 nephrectomy (early group) and the others began from 12 weeks of 5/6 nephrectomy (delayed group). Blood pressure, renal function, proteinuria, histological changes and renal cortical TGFbeta1 expression were observed for 24 weeks. RESULTS: Blood pressure was significantly lower in E, C or E+C of both early and delayed group than in UC. Particularly blood pressure in E+C of early group was lower than in E or C. In E, C or E+C of both early and delayed group, BUN was lower and creatinine clearance was higher compared with UC. Proteinuria was also significantly lower in E, C or E+C of both early and delayed group compared with UC. In addition, remnant kidney weight in E, C or E+C of early and delayed group was significantly lower compared with UC, representing less renal hypertrophy. On the histological examination, glomerulosclerosis score, interstitial fibrosis score and the number of infiltrated glomerular macrophage were significantly lower in E, C or E+C of both early and delayed group compared with UC. Furthermore, renal cortical TGF-beta1 expression was also lower in E, C or E+C of both early and delayed group compared with UC. CONCLUSION: ACEi and ARB have renoprotective effect biochemically and histologically even though the treatment was delayed until moderate chronic renal failure had occurred.