Urinary cyclic AMP and post-traumatic acute renal failure.

Consecutive daily urinary excretion of cyclic AMP has been investigated in 16 patients with severe trauma or illness, five of whom developed acute renal failure (ARF). Fluctuations in the nucleotide excretion exceeded the range found in 20 healthy volunteers (1.26-14.74, mean 7.13+/-1.18 vs. 2.04-10.10, mean 5.07+/-2.21 micronmol/24 h). This resulted in a 41% increase of cAMP excretion in the group with normal renal function (P less than 0.003) with the highest individual increase of 87%. The excretion usually reached its peak by 24 h after trauma and its lowest value by the third day, (first day vs. third day; 7.82+/-4.23 vs. 3.96+/-2.58 micronmol/24 h, P less than 0.05 for a group of 11 patients), while creatinine clearance remained normal. In four patients with severe ARF, the mean urine volume was above control value but the cAMP excretion was reduced to 3.9 to 14.4% and in one patient with a mild ARF to 60.6%. Creatinine excretion of the group was less reduced than that of cAMP (41.2% vs. 19.6%, resp.). cAMP excretion declined proportionally with diminishing creatinine clearance. In the category of 33-65 ml/min it decreased by 33.4% to 3.39 micronmol+/-1.16 micronmol/24 h. cAMP/creatinine ratio proved to be a less sensitive indicator than cAMP/24 h. Daily output of cAMP and creatinine correlated highly with diuresis in ARF patients, controls (always P less than 0.001) and less in patients with normal renal function (P less than 0.02). Urinary cAMP appears to be a very sensitive and early indicator of the onset of ARF and subsequent recovery. This warrants its further study.     

Amino acid loss in acute renal failure: comparative effects of peritoneal dialysis and haemodialysis

The concentration of free amino acids has been determined in plasma and erythrocytes of 10 patients with acute renal failure treated by peritoneal dialysis and haemodialysis, and of 10 healthy subjects as controls. The variations observed have been compared in an attempt to evaluate the effects of two different methods of dialysis on the amino acid pools. The effects of peritoneal dialysis on changes in the plasma valine, glycine, glutamic acid and taurine have been interpreted.     

Amino acids metabolism and nutritional support in acute renal failure]

It has been claimed that conventional essential amino acid (EAA) solution may give rise to adverse effects such as hyperammonemia, in acute renal failure (ARF). On the other hand the majority the ARF treated recently have been complicated by multiple organ failure (MOF). These data indicate that a new regimen in nutritional support should be applied to those patients. A new amino acid solution for renal failure, containing not only EAA but also branched chain and non-essential amino acids, has been developed. We administered this solution as total parenteral nutrition (TPN) to ARF patients complicated by MOF. Continuous hemodiafiltration is simultaneously applied to remove excess water. The nutritional status and the deranged aminogram are improved by this treatment. We believe that an ARF patient complicated by MOF should be nutritionally supported with this new regimen.     

Amino acid clearances and daily losses in patients with acute renal failure treated by continuous arteriovenous hemodialysis

OBJECTIVE: To determine daily amino acid and total protein losses in patients with acute renal failure receiving total parenteral nutrition (TPN) during treatment by continuous arteriovenous hemofiltration with hemodialysis (CAVHD). DESIGN: Prospective, nonrandomized study. SETTING: Patients in the ICU of a regional nephrology referral center. PATIENTS: Eight clearance studies of individual amino acids were performed in six patients with acute renal failure receiving TPN. Daily nitrogen intake was 9 g (one patient), 14 g (two patients), and 18 g (three patients). The clearances of individual amino acids were measured at two dialysis flow rates to calculate daily amino acid and total proten losses. RESULTS: Amino acid clearance rates ranged from 7.8 +/- 2.2 (glutamic acid) to 25.2 +/- 4.8 mL/min (3-methylhistidine) at a dialysate flow rate of 1 L/hr and from 13.6 +/- 1.7 (tryptophan) to 33.7 +/- 4.3 mL/min (3-methylhistidine) at a dialysate flow rate of 2 L/hr. These results represent daily amino acid losses of 1.5 +/- 0.4% (glutamic acid) to 111.6 +/- 16.6% (tyrosine) of the nutritional input at a dialysate flow rate of 1 L/hr and 2.1 +/- 0.6% (glutamic acid) to 145.8 +/- 17.8% (tyrosine) at a dialysate flow rate of 2 L/hr. Total losses would represent 8.9 +/- 1.2% and 12.1 +/- 2.2%, respectively, of the daily protein input. CONCLUSIONS: These studies confirm that amino acid clearances are relatively high during CAVHD and daily losses should therefore be considered.     

Outcome in post-traumatic acute renal failure when continuous renal replacement therapy is applied early vs. late

Objective: To determine whether the timing of initiation of continuous renal replacement therapy (CRRT) affects outcome in patients with post-traumatic acute renal failure (ARF). Design: The medical records of patients treated with CRRT for post-traumatic ARF were retrospectively reviewed. Chi-square testing was used to test frequencies between groups, and Student's t -test was used to compare means. Setting: A Level I trauma center. Patients: 100 Adult trauma patients treated with CRRT for ARF from 1989 to 1997. Patients were characterized as “early” or “late” starters, based upon whether the blood urea nitrogen (BUN) was less than or greater than 60 mg/dl, prior to CRRT initiation. Results: The mean BUN of the early and late starters was 42.6 and 94.5 mg/dl, respectively (p < 0.0001). CRRT was initiated earlier in the hospital course of early starters compared to late starters (hospital day 10.5 vs 19.4, p < 0.0001). Creatinine clearance prior to CRRT did not differ statistically between the two groups. No significant difference was found between early and late starters with respect to Injury Severity Score, admission Glasgow Coma Scale, presence of shock at admission, age, gender distribution, or trauma type. Admission laboratory values including BUN, serum creatinine, lactate, and bilirubin as well as fluid and blood requirements in the first 24 h were statistically the same for the two groups, suggesting a similar risk of developing renal failure. Survival rate was significantly increased among early starters compared to late starters (39.0 vs 20.0 %, respectively, p = 0.041). Conclusions: This retrospective review indicates that an earlier initiation of CRRT, based on pre-CRRT BUN, may improve the rate of survival of trauma patients who develop ARF. Received: 23 October 1998 Final revision received: 12 May 1999 Accepted: 20 May 1999     

Micropuncture studies of the recovery phase of myohemoglobinuric acute renal failure in the rat

Micropuncture studies of the recovery phase of glycerol-induced myohemoglobinuric acute renal failure were performed in rats whose blood urea nitrogen (BUN) had fallen at least 20% below its peak value. The glomerular filtration rate (GFR) of individual nephrons in a single kidney in the recovery period generally either was in the normal range or minimal. Each animal's BUN concentration at the time of the study was inversely related to the proportion of functioning surface nephrons, but did not correlate with individual nephron GFR values. Proximal tubule fractional water absorption was significantly depressed as manifested by both depressed inulin (TF/P) values and supernormal volumes of collections, a finding which, in the absence of a urea-induced osmotic diuresis, suggests impaired sodium transport by the damaged nephron. The mean proximal tubule hydrostatic pressure in recovery was normal and there was little variation in pressure among functioning nephrons. It is concluded that recovery from this model of acute renal failure reflects the progressive recruitment of increasing numbers of functioning nephrons. The recovery of individual nephron glomerular filtration, once begun, was rapid and complete. No evidence could be adduced that the gradual return of renal function towards normal reflects a slow release of tubular obstruction or repair of disrupted tubular epithelium. Rather, recovery appeared to be directly attributable to the return of an adequate effective glomerular filtration pressure. Significant limitation in proximal tubule water absorption persisted after individual nephron GFR had returned to normal or supernormal values in this model of experimental acute renal failure in the rat, a finding which readily accounts for the diuresis associated with the recovery phase of this syndrome.     

高胆固醇血症环境下注射造影剂诱发急性肾功能衰竭

目的：探讨高胆固醇血症是否是造影剂肾损害的促进因素。方法：24只雄性Wistar大鼠随机分成两组，分别给予正常饮食(N组)和高胆固醇饮食（H组，4％胆固醇和1％胆酸钠）8周。8周末从N组和H组中各取半数大鼠（6只）尾静脉注射60％泛影葡胺（6ml/kg，NC组和HC组），另半数大鼠尾静脉注射等量生理盐水。注射造影剂后的第二天测定血清总胆固醇、甘油三酯、血肌酐、内生肌酐清除率、肾皮质一氧化氮的含量；彩色多普勒和频谙式多普勒测定肾血流；光镜观察肾组织学改变。结果：HC组和H组血清总胆固醇及肾血管阻力指数显著性增加，而内生肌酐清除率、肾皮质一氧化氮含量显著性降低。HC组的内生肌酐清除率显著低于H组，HC组的血清肌酐、钠钾排泄分数显著高于其它三组。组织病理也显示HC组大鼠肾小管上皮细胞发生严重变性和坏死，而NC组和H组大鼠仅见肾小管变性。结论：高胆固醇血症是造影剂肾损害的促进因素；肾皮质一氧化氮含量的减少可介导了高胆固醇血症环境下造影剂诱导的急性肾功能衰竭。     

Effect of theophylline on the initiation phase of postischemic acute renal failure in rats

These experiments were designed to test, pharmacologically, the hypothesis that adenosine mediates the reduction in glomerular filtration rate (GFR) observed during the initiation phase of postischemic acute renal failure (ARF). Six groups of pentobarbital-anesthetized rats were studied; in all groups, the left renal arteries were completely occluded for either 30 or 45 minutes, and 30 minutes after relieving the occlusion, two consecutive 40-minute clearances were begun. Two control groups received no pretreatment; two experimental groups were pretreated with intravenous theophylline (24 mumol/kg prime followed by 0.28 mumol/min/kg infusion); two further experimental groups were pretreated with a higher dose of theophylline (111 mumol/kg prime followed by 1.1 mumol/min/kg infusion). As assessed by reduction in inulin clearance, the impairment of GFR was directly related to the duration of ischemia. The lower dose of theophylline had no significant effects on inulin clearances of right or left kidneys in either group (previously ischemic for 30 or 45 minutes). The higher dose of theophylline also had no significant effects on right kidney inulin clearances, but it significantly increased the inulin clearances of left kidneys previously ischemic for 30 to 45 minutes. This theophylline-induced increase in inulin clearance after 30 minutes of ischemia was accompanied by an increase in renal plasma flow. Because theophylline is a competitive antagonist at adenosine receptors, these results are consistent with the hypothesis that endogenous adenosine mediates, at least in part, the hemodynamic changes in postischemic ARF in rats.     

Nutrition in acute renal failure

Nutrition is an integral part of supportive therapy of acute renal failure. Since ARF usually develops as a consequence of severe illness or injury, the metabolic changes due to failing kidney function are superimposed, often indistinguishably, on the metabolic effects of the primary disease. The majority of patients are hypercatabolic and may therefore become rapidly nutritionally depleted. The general principles of treatment are early dialysis, strict monitoring of vital functions, vigorous treatment of observed disorders, and metabolic monitoring and therapy. Use of enteral nutrition is rarely feasible and hence nutrition is given as TPN. The volume of fluid is not limiting for the application of TPN if adequate dialysis or continuous filtration methods are available. The TPN program of an average adult should contain daily approximately 35 to 40 kcal/kg of energy, given as both fat and glucose, and 1 g/kg of amino acids, given as both essential and nonessential amino acids, though the true requirements in ARF are unknown. The actual intakes of nutrients may have to be frequently adjusted according to the response of the patient.     

Nutrition in acute renal failure

The nutritional value of regimes enriched with branched chain amino acids has been evaluated in 22 adult patients suffering from acute post-traumatic renal failure. The study was carried out for 12 days. The following data were recorded and compared daily: nitrogen balance, daily blood urea nitrogen (BUN), BUN/creatinine ratio, and plasma albumin levels. Also after 6 days of dialysis and nutritional support, the plasma medium molecular weight compounds (uremic toxins) were studied. It was concluded that: (a) the combined use of parenteral and oral nutrition appears most adequate in this type of patient; (b) the nitrogen intake should provide an essential amino acid/total nitrogen ratio of greater than or equal to 4 and a branched chain essential amino acid ratio of greater than or equal to 0.5; and (c) caution is still necessary in interpreting analyses of middle molecular weight compounds in this type of patient.     

Radiocontrast-induced acute renal failure

The intravascular administration of iodinated radiocontrast media can lead to acute renal dysfunction. Even small changes in renal function have been associated with increased morbidity and mortality, making the prevention of radiocontrast nephropathy of paramount importance. This review summarizes the principal risk factors for radiocontrast nephropathy and evidence-based preventive strategies that should be used to limit its occurrence. Risk factors for radiocontrast nephropathy include preexistent kidney disease, diabetes mellitus, dose of radiocontrast used, advanced congestive heart failure, and intravascular volume depletion. Proven preventive measures include volume expansion with intravenous saline or sodium bicarbonate and the use of low-osmolar or iso-osmolar radiocontrast media. Studies evaluating N-acetylcysteine have been conflicting, with meta-analyses suggesting a small beneficial effect. Studies of other pharmacologic agents have not demonstrated clinical benefit.