Studying Of Pharmacotherapy In Acute Renal Failure

Acute tubular necrosis(ATN) is a common and clinically severe form of acuterenal failure. Although the advancement in dialytic technology has protective effect on the outcome of ATN, the cost of dialysis inflicts a tremendous financial burden on patients and dialysis maybe cause many complications. So it is important to find economical and practical pharmacotherapy for ATN. Ischemia is the most common cause of ATN. Recent studies suggested that cytokines played important roles in ischemia/reperfusion(I/R) injury. Modulating their production and reconstructing renal recovery mechanism maybe bring a new approach to the therapy of ATN. Muscular amino acids and peptides and nucleosides injection (A&P&N) has been demonstrated to be a certain protective effect to the heart, cerebral I/R injury. Based on the use of some drug, we applied A&P&N to the patients with ATN and the curative effect is satisfactory. But its mechanism is still unknown. In the study 59 critically ill patients with ATN were enrolled and 162 rats with renal I/R injury were used. We hypothesized that multiple drug treatment may decrease the need for dialysis in patients with ATN and A&P&N may have the effect of alleviation the renal I/R injury by modulation the production of cytokines.Part I Clinical studyObjective: To study and observe the clinical effect and value of pharmacotherapy in acute tubular necrosis (ATM) patients.Methods: 59 ATN patients had been cured and observed. The drug which were used comprised dopamine, furosemide, A&P&N (containing atrial natriuretic peptide(ANP), Calcitonin gene-related peptide (CGRP), adenosine, variety of amino acids and so on), Dexamethasone and so on. Patients were divided in two groups, Group A&P&N and Group regular treatment according to whether A&P&N was used. Plasma BUN, Cr, urine volume and renal size were observed .Results: Compared with Group regular treatment, creatinine and urine volume came to normal more quickly in Group A&P&N (P<0.05-P<0.001). Among 59 patients, 18 would eventually needed dialysis. The pathogeny may be the main reason which influenced the effect of treatment.Part II Animal experimentObjective: To investigate the effect of muscular amino acids and peptides and nucleosides injection (A&P&N) and the change and role of plasma interleukin-4 (IL-4) and interleukin-6(IL-6) in acute renal ischemia/reperfusion(I/R) injury.Methods: Rat renal I/R model was performed by placing the atraumatic vascular clamp in renal pedical for 60 minutes. A&P&N was used on the rat models. Plasma BUN, Cr, IL-4, IL-6, urine volume and renal weight were observed at various intervals.Results : 1.Plasma levels of BUN, Cr decreased in rats treated with A&P&N, as compared to the control. 2. IL-6 began to increase from 3h post-reperfusion , reached the peak at 6h post-reperfusion, went on to 24h post-reperfusion and came back to normal at 48h post-reperfusion. But there was not obvious variation for IL-4 during rat renal I/R injury. 3. The urine volume increased at 3d post-reperfusion and came back to normal at 14d post-reperfusion in rats treated with A&P&N. These changes were faster than that of the control. The change of renal weight in A&P&Ngroup was also slighter than that of the controlConclusion1. To some ATN patients, multiple drug treatment could bring their renal function back, instead of dialysis.2. A&P&N has the effect of alleviation the renal I/R injury by modulation the production of IL-6.3. The levels of IL-6 increased with time of rat renal I/R injury. But there was not obvious variation for IL-4.