<i>CCL2</i>/<i>MCP</i>-1 and <i>NFκB</i>Gene Transcription in Remnant Kidneys after Physical Activity and Renoprotection

Chronic kidney disease (CKD) is a progressive disease and affects approximately 10% of the population. The major late pathologic feature of CKD is interstitial fibrosis in the kidney characterized by extracellular matrix deposition but in early stage, several profibrotic and proinflammatory cytokines as well as growth factors are expressed. The renin-angiotensin and ET systems both play an important role in the pathogenesis of CKD and the blockade of these systems has been shown to suppress proinflammatory cytokines and to arrest the progression of CKD. We have demonstrated earlier also the renoprotective effect of physical activity on the experimental CKD progression (Pechter et al., 2003). Aim of the study was to investigate the effects of non-drug treatment, physical activity, to the extent of gene expression in experimental CKD and to compare with endothelin receptor blocker (ERB, sitaxentan) and standard nephroprotective drug, angiotensin receptor blocker (ARB, losartan) treatments. Expression of mRNA was assessed by real-time reverse transcription-polymerase chain reaction. CCL2/MCP-1 and nuclear factor-κB (NFκB) gene expression was measured in whole kidneys. Results revealed that CCL2/MCP-1 gene expression (data presented in poster presentation ASN Renal Week 2010, Pechter et al.) was increased in the 5/6 NPX rat kidneys, and the increase was lessened significantly after physical activity and losartan therapy. ERB treatment appeared less effective. Combined ARB and ERB treatment as well as drugs alone or physical therapy prevented the increase in systemic blood pressure, albuminuria and CCL2/MCP-1 as well as NFκB gene expression. We conclude that non-drug and drug treatments both were effective regarding the rate of the progression of experimental CKD measured by physiological and molecular biomarkers of chronic inflammation in kidney tissue.

Renoprotective strategies

Kidney disease remains a condition with an increasing incidence,high morbidity and mortality associated with cardiovascular events.The incidence of end-stage renal disease is expected to increase.Despite of the technical improvement,dialysis never achieved a full clearance of the blood dialysis.Therefore,the demand for new renoprotective measures has never been greater.Here,we report new strategies for preventing renal damage.

Evaluation of renoprotective effect of Chinese chive extracts on adenine-induced chronic renal failure

The renoprotective effects of Chinese chive water and ethanol extracts(CCWE and CCEE)on adenineinduced chronic renal failure(CRF)mice were evaluated in this study.Results showed that the renal pathological damages and the enhancement of serum creatinine and blood urea nitrogen of CRF mice could be significantly alleviated by the treatment of CCWE,but not CCEE.When the concentration of CCWE reached 200 mg/kg/day,the area of renal pathological damage was decreased to the 48.1%of model group,and the levels of serum creatinine and blood urea nitrogen were decreased to the 87.7%and 83.9%of model group,respectively.Meanwhile,it could be found that renal oxidative stress and inflammation of CRF mice were remarkably inhibited by CCWE.These results indicated CCWE could improve the kidney function of CRF mice via enhancing antioxidant ability and inhibiting inflammation,and was the main renoprotective fraction of Chinese chive.

Chances and risks of sodium-glucose cotransporter 2 inhibitors in solid organ transplantation:A review of literatures

Solid organ transplantation offers life-saving treatment for patients with endorgan dysfunction.Patient survival and quality of life have improved over the past few decades as a result of pharmacological development,expansion of the donor pool,technological advances and standardization of practices related to transplantation.Still,transplantation is associated with cardiovascular complications,of which post-transplant diabetes mellitus(PTDM)is one of the most important.PTDM increases mortality,which is best documented in patients who have received kidney and heart transplants.PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus,but also from specific posttransplant risk factors such as metabolic side effects of immunosuppressive drugs,post-transplant viral infections and hypomagnesemia.Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients.However,the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited.The favourable risk/benefit ratio,which is suggested by large-scale and long-term studies on new glucoselowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors,makes studies warranted to assess the potential role of these agents in the management of PTDM.

Renoprotective Effect of the Combination of Renin-angiotensin System Inhibitor and Calcium Channel Blocker in Patients with Hypertension and Chronic Kidney Disease

Background：Renin-angiotensin system inhibitor and calcium channel blocker （CCB） are widely used in controlling blood pressure （BP） in patients with chronic kidney disease （CKD）.We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） and CCB （i.e.,ACEI/ARB ＋ CCB） with ACEI/ ARB monotherapy in patients with hypertension and CKD.Methods：Publications were identified from PubMed,Embase,Medline,and Cochrane databases.Only randomized controlled trials （RCTs） of BP lowering treatment for patients with hypertension and CKD were considered.The outcomes of end-stage renal disease （ESRD）,cardiovascular events,BP,urinary protein measures,estimated glomerular filtration rate （GFR）,and adverse events were extracted.Results：Based on seven RCTs with 628 patients,ACEI/ARB ＋ CCB did not show additional benefit for the incidence of ESRD （risk ratio [RR] =0.84;95% confidence interval [CI]：0.52-1.33） and cardiovascular events （RR =0.58;95% CI：0.21-1.63） significantly,compared with ACEI/ARB monotherapy.There were no significant differences in change from baseline to the end points in diastolic BP （weighted mean difference [WMD] =-1.28 mmHg;95% CI：-3.18 to-0.62）,proteinuria （standard mean difference =-0.55;95% CI：-1.41 to-0.30）,GFR （WMD =-0.32 ml/min;95% CI：-1.53 to-0.89）,and occurrence of adverse events （RR =1.05;95% CI：0.72-1.53）.However,ACEI/ARB ＋ CCB showed a greater reduction in systolic BP （WMD =-4.46 mmHg;95% CI：-6.95 to-1.97）,compared with ACEI/ARB monotherapy.Conclusion：ACEI/ARB ＋ CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.

Herbal Medicines for Acute Kidney Injury: Evidence, Gaps and Frontiers

Acute kidney injury(AKI) is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI, promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to chronic kidney disease(CKD). Altogether, 16 herbal formulae and a few extracts derived from individual herbs were reported to prevent or mitigate AKI in animal models induced by renal ischemia/reperfusion, cisplastin,gentamicin, glycerol, adenine, sepsis or physical exhaustion. Four formulae and six individual herbs were reported to accelerate recovery and/or to prevent CKD in established AKI animal models. Intrarectal herbal medicines, with or without simultaneous oral administration, were reported in six clinical trials and in an animal model to increase extrarenal clearance of uremic toxins. Additional 13 clinical trials reported oral or intravenous herbal interventions in AKI of different etiologies. Despite recurring problems, notably poor compliance with good practice guidelines for clinical trials and for authentication, naming and quality control of herbal materials, accumulating experimental data on the preventive effects of herbal medicines in AKI look encouraging and urge for better, definitive trials to guide clinical practice. Herbal enemas promoting extrarenal clearance of uremic toxins seem cost-effective, but better clinical evidence is certainly needed before any affirmative recommendation be made for AKI patients without access to dialysis. New frontiers, however, lie in those herbal remedies that promote repair/regeneration and prevent chronicity after AKI. Recent experimental data suggest that this may be possible.