Renal protective

Dopamine is a a- and P-adrenergic agent with dopaminergic activity Low doses of dopamine (1 to 5 mcg/kg per minute) maintain renal perfusion, higher doses (greater than 5 mcg/kg per minute) exhibit a- and P-adrenergic activity and are frequently utilized to support blood pressure and to improve cardiac function. Low doses of dopamine should not be used for renal protection as part of the treatment of severe sepsis.24,27-28... 

CCBs are useful add-on agents for BP control in hypertensive patients with diabetes. Limited data suggest that nondihydropyridines may have more renal protective effects than dihydropyridines. 

Rao NK. (2006) Anti-hyperglycemic and renal protective activities of Andrographis paniculata roots chloroform extract. Iran J Pharmacol Ther 5 47-50. 

Captopril (Capoten) was the original prototype product, and it was administered three times a day. A once-a-day preparation was subsequently patented and marketed. Prospective multicenter double-blind placebo-controlled clinical trials have repeatedly demonstrated an early and persistent survival benefit with ACE inhibitors in CHE patients. ACE inhibitors were found superior to hydralazine and nitrates in a direct comparison. ACE inhibitors are now clearly the agents of first choice in the pharmacological management of CHE There are also a number of additional reasons to use ACE inhibitors. The HOPE trial and other studies demonstrated additional survival and renal protective benefits of ACE inhibition in diabetic and/or hypertensive patients long before they develop CHE. 

Intravenous silymarin has been demonstrated to lower mortality from Amanita mushroom poisonings, but this formulation is available only in Europe. Animal studies have demonstrated hepatic protection against alcohol, acetaminophen, and mushroom toxins and protection against hepatic fibrosis with bile duct occlusion. There is also evidence of silybin protecting against cis-platin-induced nephrotoxicity in rats. It is not yet clear whether milk thistle extract offers any renal protection to humans. 

Potentially as effective as or more effective than ACE inhibitors, without cough no evidence for reduction in morbidity and mortality as first-line agents in hypertension yet whetherthey provide the same cardiac and renal protection also still tentative like ACE inhibitors, less effective in black patients... 

Dopamine is a major neurotransmitter which acts on multiple receptors. It can activate both a and 3 adrenoceptors in addition to acting on specific dopamine receptors. These are widely distributed throughout the CNS and are also present in the renal tubules and renal and mesentric blood vessels, and many dopaminergic drugs are used in the treatment of Parkinson s disease, psychiatric disorders, as antiemetics, and for renal protection. Neuroleptic drugs, such as haloperidol and droperidol, are dopamine receptor antagonists. 

Chander V, Chopra K. 2005. Role of nitric oxide in resveratrol-induced renal protective effects of ischemic preconditioning. J Vase Surg 42 1198-205. 

Segura J, Garcia-Donaire JA, Ruilope LM. Calcium channel blockers and renal protection insights from the latest clinical trials. J Am Soc Nephrol. 2005 16 (suppl 1) S64-S66. 

The contrast load may compound renal damage, common in HF patients, with consequent further fluid retention and worsening HF A number of adjunctive treatments are currently recommended in the renal patient but none guarantee renal protection (82). The volume of contrast medium during intervention should be minimized and hypotension should be avoided. 

Wapstra FH, Van Goor H, Navis G et al. (1996) Antiproteinuric effect predicts renal protection by angiotensin-converting enzyme inhibition in rats with established adriamycin nephrosis. Clin Sci 90 339-340... 

ARB treatment has been shown to afford significant renal protection (risk reduction 16% and 20 or 23% for primary outcome of doubling of semm creatinine, ESRD or death) in two large randomised studies of patients with type 2 diabetes and established nephropathy. 

CALCIUM CHANNEL BLOCKERS CICLOSPORIN 1. Plasma concentrations of ciclosporin are t when co-administered with diltiazem, nicardipine, verapamil and possibly amlodipine and nisoldipine. However, calcium channel blockers seem to protect renal function 2. Ciclosporin t nifedipine levels 1. Uncertain presumed to be due to impaired hepatic metabolism. Also, diltiazem and verapamil inhibit intestinal P-gp, which may t the bioavailability of ciclosporin. Uncertain mechanism of renal protection 2. Uncertain effect of ciclosporin on nifedipine 1. Monitor ciclosporin levels and i dose accordingly (possibly by up to 25-50% with nicardipine) 2. Monitor BP closely and warn patients to watch for signs of nifedipine toxicity... 

IFOSFAMIDE CISPLATIN t risk of neurotoxicity, haematotoxicity and tubular nephrotoxicity of ifosfamide due to t plasma concentrations of ifosfamide Cisplatin tends to cause renal damage, which results in impaired clearance of ifosfamide Do renal function tests before initiating therapy and during concurrent therapy, and adjust dosage based on creatinine clearance values. Advise patients to drink plenty of water -vigorous hydration - and consider mesna therapy for renal protection... 

Ramipril has a renal protective effect in non-diabetic nephropathies with nephrotic and non-nephrotic proteinuria (14). It also improves cardiovascular morbidity and all-cause mortality in patients with some cardiovascular risk (2). 

Acute renal insufficiency with severe hyponatremia has been attributed to vigorous diuretic treatment (metolazone, furosemide, spironolactone) with an ACE inhibitor (27). Because ACE inhibition impairs renal protection against reduced perfusion, the combination of an ACE inhibitor with high-dose furosemide causes a reduction in glomerular filtration rate linearly related to the change in blood pressure. 

Sodium thiosulfate protects against cisplatin-induced nephrotoxicity by reacting covalently with cisplatin in the renal tubules. Other protectors include probenecid, orgotein, fosfomycin (203), amifostine (2-[3-aminopropyl) amino] ethylphosphorothioic acid, WR-2721, ethyofos), and anthiol. Experimental study drugs that may be useful in renal protection include BNP7787 (dimesna), selenium, and silibinin (146,204-212). The beneficial role of furose-mide is uncertain. 

Leeuwenkamp OR, van der Vijgh WJ, Neijt JP, Pmedo HM. Reaction kinetics of cisplatin and its mono-aquated species with the (potential) renal protecting agents (di)mesna and thiosulfate. Estimation of the effect of protectmg agents on the plasma and peritoneal AUCs of CDDP. Cancer Chemother Pharmacol 1990 27(2) 111-14. 

Table 5. Examples of specific renal protective strategies.

One renal protective strategy that is often overlooked is the intensive control of blood glucose levels in critically ill patients [107]. Insulin therapy reduced the risk of AKI that required dialysis by 41% in one trial [107]. While the mechanism of this effect is not known, this easily implemented strategy should be considered in all at risk patients. 

Yamasowa H, Shimizu S, lnoueT,Takaoka M, Matsumura Y Endothelial nitric oxide contributes to the renal protective effects of ischemic preconditioning. Journal of Pharmacology Experimental Therapeutics 312 153-159,2005... 

Nakamura A, Flayashi K, Fujiwara K, Ozawa Y, Flonda M, SarutaT Distinct action of aranidipine and its active metabolite on renal arterioles, with special reference to renal protection. J.Cardiovasc.Pharmacol. 35 942-948, 2000... 

The demonstration of a renal protective effect of salt loading on AmB-induced nephrotoxicity in animal models has provided a rational basis to evaluate this simple intervention in patients. Clinical evidence supporting the ability of sodium loading to attenuate AmB-induced nephrotoxicity is derived from three sources case reports, retrospective studies and prospective studies. 

Two prospective, crossover, placebo controlled, double-bhnd evaluations of the nephroprotective role of misoprostol in patients with mild stable chronic renal failure, taking either ibuprofen or indomethacin have been reported [183]. The mean baseline GFR of the patients at the time of entry into the study was 53 ml/min (misoprostol)/55 ml/min (placebo), and 57 ml/min (misoprostol)/57 ml/min (placebo) in Study I (ibuprofen) and Study II (indomethacin) respectively. At this level of renal functional impairment, the use of the non-selective NSAIDs did not produce additional significant impairment of renal function, hence a renal protective role for misoprostol could not be... 

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