Effects of verapamil in the prevention of warm ischaemia induced acute renal failure in dogs

Acute renal failure in the immediate postoperative period remains a significant complication of renal transplantation. A major factor in the pathogenesis may be warm ischaemia (WI). Recent evidence implicates a calcium mediated mechanism as a final common pathway in certain models of acute renal failure. This study was undertaken to evaluate the effects of Verapamil, a calcium antagonist, in the prevention of warm ischaemia-induced acute renal failure following renal autotransplantation in the dog. Twenty-one mongrel dogs were randomly allocated to three groups. Group 1 (control, 8 dogs) received 20 ml normal saline before a standardized 60 min warm ischaemic insult to the left kidney. Group 2 (6 dogs) received Verapamil (0.3 mg/kg) by intravenous injection and Group 3 (7 dogs) received Verapamil (0.3 mg/kg) by intra-arterial injection into the left renal artery prior to the same ischaemic insult. The left kidney was heterotopically grafted to the right iliac fossa in the warm ischaemic period. Contralateral nephrectomy was performed. The dogs were followed up to 7 days after operation by serial creatinine estimation. Histological examination of some autografts was performed. Of the eight controls, six showed marked renal impairment (serum creatinine greater than 800, or death in renal failure). Three of the six dogs given intravenous Verapamil showed marked renal impairment. None of the seven dogs receiving intra-arterial Verapamil showed marked renal impairment (P = 0.013, chi 2 test). The mean rate of serum creatinine rise for each group was analysed by multivariate analyses of variance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amelioration of postischaemic acute renal failure in conscious dogs by human atrial natriuretic peptide

We studied the effect of human ANP (alpha-hANP)-99-126 on the course of postischaemic acute renal failure in unilaterally nephrectomised, conscious dogs subjected to 120 min of renal ischaemia. In contrast to a control group A (n = 7), the investigational group B (n = 9) received an intra-aortic bolus injection of 100 micrograms/kg alpha-hANP and an additional continuous infusion of 0.3 micrograms/kg per min x 180 min immediately after ischaemia. On days 1 and 2 after ischaemia, only the bolus injection was repeated. Administration of hANP resulted in a marked restoration of GFR (29 +/- 2 vs 18 +/- 4 ml/min, P less than or equal to 0.01), diuresis (0.8 +/- 0.1 vs 0.5 +/- 0.1 ml/min, P less than or equal to 0.05), and natriuresis (44 +/- 7 vs 25 +/- 4 mumol/min, P less than or equal to 0.05) on the first postischaemic day, which was mirrored by a reduction in nitrogen retention (Purea: 8 +/- 1 vs 12 +/- 2 mmol/l P less than or equal to 0.05, Pcrea: 137 +/- 20 vs 204 +/- 37 mumol/l). Renal perfusion, however, was only slightly improved on day 1 after ischaemia (198 +/- 20 vs 163 +/- 27 ml/min, N.S.). Our data clearly demonstrate that repeated bolus applications of hANP ameliorate postischaemic acute renal failure in conscious dogs. We assume that the observed beneficial effect on GFR might be the consequence of an increase in glomerular capillary pressure rather than an improvement of renal perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preservation of normal cortical vasculature in ischaemic renal failure in the dog.

Ischaemic renal failure in the dog was studied by clamping one renal artery for 2 hr in 18 animals. Total renal blood flow was measured for 3 hr after this and only reduced by about 30%. Fine detail renal angiography showed a normal cortical perfusion pattern. Urine flow rates and creatinine clearances from these kidneys, however, were found to be grossly impaired over this period. Seven days later the angiogram of the oliguric kidney remained normal. Two-hour unilateral renal ischaemia in the dog leads to a form of acute renal failure with a striking disparity between glomerular perfusion and clearance, arguing agains a primary circulatory defect.     

Effect of U-74500A,A 21-Aminosteroid on Renal Ischemia-Reperfusion Injury in Rats

Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antioxidant U-74500A, a 21-aminosteroid in a rat model of renal ischemia-reperfusion injury. Renal ischemia-reperfusion was induced by clamping unilateral renal artery for 45 min followed by 24 h of reperfusion. Two doses of U-74500A (4.0 mg/kg, i.v.) were administered 45 min prior to renal artery occlusion and then 15 min prior to reperfusion. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) in kidney homogenates. Renal function was assessed by estimating serum creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin stained sections of the kidneys. Ischemia-reperfusion produced elevated levels of TBARS and deteriorated the renal function as assessed by increased serum creatinine, BUN and decreased creatinine and urea clearance as compared to sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. U-74500A markedly attenuated elevated levels of TBARS as well as morphological changes, but did not improve renal dysfunction in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect of U-74500A, a 21-aminosteroid in attenuating renal ischemia-reperfusion injury.     

Carvedilol, an antihypertensive drug with antioxidant properties, protects against glycerol-induced acute renal failure

BACKGROUND/AIMS: The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves, among other causes, ischaemia, vascular congestion and reactive oxygen metabolites. The aim of this study was to investigate the role of carvedilol, an antihypertensive drug with antioxidative potential, in glycerol-induced acute renal failure in rats. METHODS: Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (8 ml/kg, i.m.) and group 3 was given glycerol plus carvedilol (3 mg/kg, i.p.). Renal injury was assessed by measuring plasma creatinine, blood urea nitrogen, creatinine and urea clearance. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and enzymatic activity of catalase, glutathione reductase and superoxide dismutase. RESULTS: Glycerol treatment resulted in marked renal oxidative stress and significantly deranged renal functions. Both of these factors were significantly improved by carvedilol treatment. Carvedilol, by its interaction with Fenton reaction chemistry and radical scavenging activity, protected the kidney against the oxidative stress and resultant renal dysfunction produced by glycerol. CONCLUSION: Based on these results, this study indicates the protective effect of carvedilol in this rhabdomyolysis-mimicking model.     

Aortic clamping during elective operations for infrarenal disease: The influence of clamping time on renal function

OBJECTIVE: Aortic clamping proximal to the renal arteries is sometimes necessitated during infrarenal and juxtarenal aortic surgery and may be associated with an increased risk of renal ischemia and its consequences. The aim of the study was to estimate this risk and possibly identify a "safe" duration of renal ischemia. METHODS: Medical records were retrospectively reviewed for 60 consecutive patients (from 1987 to 1994) with abdominal aortic aneurysm (n = 43) and occlusive disease (n = 17) confined to the infrarenal or juxtarenal aorta who underwent infrarenal aortic reconstruction with temporary suprarenal clamping. The data obtained included risk factors, preoperative and postoperative serum creatinine level, blood urea nitrogen (BUN) value, proteinuria before surgery, and suprarenal clamping times. RESULTS: The mean age of the patients was 64.4 years (+/- 11.4 years), and 74% were men. Concomitant cardiac disease was present in 41% of the patients, and 9% had diabetes. The preoperative creatinine level was 1.21 mg/dL (+/- 0.54 mg/dL), and the BUN value was 16.6 mg/dL (+/- 7.8 mg/dL). During surgery, blood flow to the renal arteries was interrupted for 32.0 minutes (+/- 17 minutes). None of the surviving patients needed dialysis or had signs of acute renal failure after the operations, but transient azotemia (rise in creatinine level) occurred in 23% of the patients. Risk factors for this condition were high preoperative creatinine values and hypotension during surgery, but the main determinant was total renal ischemia time. Odds ratios for such transient renal dysfunction showed as much as a 10-fold risk when suprarenal aortic clamping was greater than 50 minutes as compared with 30 minutes or less. CONCLUSION: Postoperative renal function impairment is rare in this group of patients. If suprarenal clamp duration (renal ischemia time) is brief, patients with normal preoperative creatinine levels exhibit no increase or a marginal increase in BUN or creatinine levels after surgery. Accordingly, suprarenal aortic clamping less than 50 minutes in this patient group appears safe and well tolerated.     

Effect of U-74500A,a 21-aminosteroid on renal ischemia-reperfusion injury in rats

Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antioxidant U-74500A, a 21-aminosteroid in a rat model of renal ischemia-reperfusion injury. Renal ischemia-reperfusion was induced by clamping unilateral renal artery for 45 min followed by 24 h of reperfusion. Two doses of U-74500A (4.0 mg/kg, i.v.) were administered 45 min prior to renal artery occlusion and then 15 min prior to reperfusion. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) in kidney homogenates. Renal function was assessed by estimating serum creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin stained sections of the kidneys. Ischemia-reperfusion produced elevated levels of TBARS and deteriorated the renal function as assessed by increased serum creatinine, BUN and decreased creatinine and urea clearance as compared to sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. U-74500A markedly attenuated elevated levels of TBARS as well as morphological changes, but did not improve renal dysfunction in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect of U-74500A, a 21-aminosteroid in attenuating renal ischemia-reperfusion injury.     

Results of supraceliac aortic clamping in the difficult elective resection of infrarenal abdominal aortic aneurysm

We have used clamping of the aorta above the celiac axis (SC) in 30 of 431 elective resections of infrainguinal abdominal aortic aneurysms (AAA) during the past five years as an alternative to a difficult aortic cuff dissection. The results of SC clamping in these 30 patients are compared with the results of 379 routine aneurysm resections with infrarenal (IR) clamping and 22 additional aneurysm resections where the clamp was placed immediately above the renal arteries. These difficult cuff dissections occurred in 12 patients with inflammatory AAA, in 11 patients with juxtarenal AAA, and in seven patients with recurrent or noninfected false AAA of the proximal cuff. Patients with ruptured or suprarenal aneurysms and those undergoing combined operation for a visceral ischemic syndrome and an aneurysm were excluded from this study. Patients with SC clamping had similar operative mortality rates, comparable renal function, and frequency of cardiac events as patients with IR clamping. Blood loss was slightly higher in the SC group (p = 0.07) and serum aspartate amino transferase (AST) levels were three times higher than in the IR group; however, this was of no clinical significance. In contrast, those 22 patients whose aortas were clamped immediately above the renal arteries (AR) had higher perioperative mortality rates (2% IR, 3% SC vs 32% AR) and a higher incidence of kidney failure requiring dialysis (1% IR, 3% SC vs 23% AR). The mean values of serum creatinine and blood urea nitrogen were also significantly higher in the AR group when compared with both the IR and the SC groups (IR: 25 and 1.5 mg/dl, respectively; SC: 27 and 1.8 mg/dl; AR: 41 and 3.5 mg/dl). The single most important risk factor accounting for the differences between clamping above the celiac artery and clamping above the renal arteries was the presence of atherosclerotic debris in the nonaneurysmal, juxtarenal aortic segment. Clamping the aorta with juxtarenal atherosclerosis caused either atheroembolization to kidneys, legs, and intestine or injury to the aorta, renal arteries, or both; it was the cause of morbidity in all five cases of kidney failure requiring dialysis and accounted for all seven of the deaths in the AR group. SC clamping does not add risk to the patient undergoing resection of an infrarenal AAA and is the preferred method of achieving proximal control of the infrarenal aorta when a a hazardous cuff dissection is likely.(ABSTRACT TRUNCATED AT 400 WORDS)     

The impact of warm ischaemia on renal function after laparoscopic partial nephrectomy

Authors from Cleveland assessed the impact of warm ischaemia on renal function, using their large database of laparoscopic partial nephrectomies for tumour. While agreeing that renal hilar clamping is essential for precise excision of the tumour, and other elements of the operation, the authors indicate that warm ischaemia may potentially damage the kidney. However, they found that there were virtually no clinical sequelae from warm ischaemic of up to 30 min. They also found that advancing age and pre-existing renal damage increased the risk of postoperative renal damage. OBJECTIVE: To assess the effect of warm ischaemia on renal function after laparoscopic partial nephrectomy (LPN) for tumour, and to evaluate the influence of various risk factors on renal function. PATIENTS AND METHODS: Data were analysed from 179 patients undergoing LPN for renal tumour under warm ischaemic conditions, with clamping of the renal artery and vein. Renal function was primarily evaluated in two groups of patients: 15 with tumour in a solitary kidney, who were evaluated by serial serum creatinine measurements; and 12 with two functioning kidneys undergoing unilateral LPN, and evaluated by renal scintigraphy before and 1 month after LPN to quantify differential renal function. Also, in all 179 patients, mean serum creatinine data at baseline, 1 day after LPN, at hospital discharge, and at the last follow-up were provided as supportive evidence. Logistic regression analyses were used to assess the effect of various risk factors on renal function after LPN, i.e. patient age, baseline serum creatinine, tumour size, solitary kidney status, duration of warm ischaemia, pelvicalyceal suture repair, urine output and intravenous fluids during LPN. RESULTS: In the group of patients with a solitary kidney the mean warm ischaemia time was 29 min, kidney parenchyma excised 29%, and serum creatinine at baseline, discharge, the peak after LPN and at the last follow-up (mean 4.8 months) 1.3, 2.3, 2.8, and 1.8 mg/dL, respectively. One patient (6.6%) required temporary dialysis. In the second group, assessed by renal scintigraphy, the function of the operated kidney was reduced by a mean of 29%, commensurate with the amount of parenchyma excised. For all 179 patients, a combination of age > or = 70 years and a serum creatinine level after LPN of > or = 1.5 mg/dL correlated with a higher serum creatinine after LPN. On logistic regression, baseline serum creatinine and solitary kidney status were the only variables significant for serum creatinine status after LPN. CONCLUSIONS: The bloodless field provided by renal hilar clamping is important for precise tumour excision, pelvicalyceal suture repair and securing parenchymal haemostasis during LPN. However, renal hilar clamping causes warm ischaemia. These data indicate that the clinical sequelae of warm ischaemic renal injury of approximately 30 min are minimal. Advancing age and pre-existing azotaemia increase the risk of renal dysfunction after LPN, especially when the warm ischaemia exceeds 30 min.     

前列地尔联合持续性血液净化对急性肾功能衰竭的疗效影响

目的 探讨前列地尔联合连续性血液净化对急性肾功能衰竭患者肾功能的影响.方法 急性肾功能衰竭患者60例,按随机数字表法分为前列地尔组(30例)和对照组(30例),两组均予以连续性血液净化治疗7d,前列地尔组在此基础上联合前列地尔治疗.记录治疗3、7d后患者的血肌酐、血尿素氮,血尿酸、肌酐清除率、尿量、APACHEⅡ评分....     

Supraceliac aortic occlusion: A safe approach to pararenal aortic aneurysms

Twenty-four patients who underwent surgery for pararenal aortic aneurysms between January 1992 and April 1997 are reviewed. Eighteen patients had primary atherosclerotic aneurysms, three patients had symptomatic infected aneurysms, two patients had an aneurysm proximal to a prior aortic repair, and one patient had a pseudoaneurysm of a proximal aortic graft anastomosis. Thirteen patients underwent elective operation, five had an urgent operation, and six patients underwent an emergency procedure. Five patients had the proximal aortic clamp placed between the renal arteries (Group I), three patients had it placed between the superior mesenteric and the renal arteries (Group II), and 16 patients had it placed in a supraceliac location (Group III). Aneurysm size, age, sex, preoperative blood chemistries (including hemoglobin, hematocrit, liver function studies, and coagulation studies) were similar in all groups. Two patients in Group III were on hemodialysis preoperatively. Preoperative renal function (blood urea nitrogen and creatinine) was the same in all groups. Visceral ischémic time was 43.4 ± 9.37 min to the distal kidney in Group I, 26.6 ± 7.63 min in Group II, and 24.5 ± 6.22 min in Group III. Mean transfusion requirements were similar in all groups. Two patients in Group I required postoperative hemodialysis. No patient in either Group II or III developed renal insufficiency. Mortality was the same in each group but was related to the urgency of operation (elective 7.6%, urgent 40%, emergent 50%). Intrarenal clamping (Group I) was associated with more renal and gastrointestinal complications than either suprarenal or supraceliac clamping. Although suprarenal and supraceliac clamping had similar results, our preference is supraceliac clamping because it is technically easy to achieve and is associated with few end-organ complications.     

Effect of diet on creatinine clearance and excretion in young and elderly healthy subjects and in patients with renal disease.

Thirty-seven young healthy subjects with normal renal function were studied to assess the quantitative effect of protein intake on creatinine clearance. A standard 24-h urine collection and blood sample at the end of the collection were obtained for creatinine and urea concentrations. Correlations between creatinine clearance and urinary urea nitrogen excretion (r = 0.8; P less than 0.0001) and calculated protein intake (r = 0.8; P less than 0.0001) were observed. A significant relationship between creatinine clearance and urea nitrogen excretion was also demonstrated in 28 elderly healthy subjects and 33 patients with renal disease. To demonstrate a cause and effect between urea nitrogen excretion and creatinine clearance in healthy subjects, 18 of the 37 healthy subjects repeated the 24-h urine collection and blood sample after ingesting 5 g of urea in addition to their usual diet. Mean urinary urea nitrogen excretion increased from a mean value of 9.8 +/- 4.0 to 11.8 +/- 4.0 g/day. There was a strong correlation between the changes in urea nitrogen excretion and the changes in creatinine clearance. In acute studies with oral protein loading, there was a significant correlation between creatinine clearance and urinary urea nitrogen excretion. It was concluded that protein intake has a direct and quantitative effect on creatinine clearance in healthy subjects. In normal humans, it is likely that GFR is not a fixed function. Thus, a low creatinine clearance is not a categorical sign of renal disease. A low creatinine clearance adjusted for urea nitrogen excretion may be a useful clinical tool to assess renal function.     

An experimental model for unilateral ischaemic acute renal failure in dog

We determined the recovery of unilateral ischaemic acute renal failure in both ischaemic and non-ischaemic canine kidneys. Split renal clearance studies were repeated for seven weeks after 90 minutes of left renal artery clamping. Clearance of inulin and para-aminohippuric acid in the ischaemic kidneys dropped significantly for 3 weeks. Significant increase of the fractional excretion of sodium in those kidneys was observed at only 1 week after ischaemia. In the contralateral non-ischaemic kidneys, these indices did not change significantly throughout the experiments. This animal model of acute renal failure would be helpful in testing possible preventive measures and therapy for human acute renal failure.     

Acute renal failure after extracorporeal circulation with aortic counterpulsation in surgically treated patients

In a series of 604 adults operated on for cardiac surgery with cardiopulmonary bypass (CPB), 21 (3.5%) underwent circulatory assistance by intra-aortic balloon pump (IABP); in 5 of them (24%), acute renal failure (ARF) was observed. ARF occurred in only 26 (4.4%) of the other patients who did not require IABP. Evolution of ARF and its factors were therefore investigated in those patients having received IABP. ARF was defined as serum blood urea nitrogen (BUN) greater than or equal to 16 mmol X 1(-1), urinary urea/BUN less than 10, creatinine clearance less than 40 ml X min-1 X 1.73 m-2. Some perioperative features were compared between patients with postoperative ARF and those without ARF. ARF occurred in the 5 patients with IABP during, or immediately after, weaning from IABP. ARF was more frequent in patients operated on for mechanical complications of myocardial infarction with a significant more severe haemodynamic status. They had significantly longer CPB and aortic clamping times. The prognosis depended on the cardiac failure and not on the ARF. In patients with mechanical complications of infarction, early IABP seemed to be the predominant preventive measure. Other therapeutic implications are suggested, particularly the use of dopamine (1 to 3 micrograms X kg-1 X min-1) because of its renal vasodilating action which can contribute to the maintenance of urinary flow.     

Failure of verapamil to protect from ischaemic renal damage

To reassess the reported protective effects of verapamil in renal ischaemia, we perfused the left kidney of uninephrectomized female Wistar rats with verapamil (0.1 and 1.0 mg/kg) immediately prior to clamping the renal artery for 60 min. When compared to controls, both doses of verapamil failed to afford protection with respect to urine flow, plasma creatinine, creatinine clearance or histology 24 and 48 h after ischaemia, whereas the purine nucleotide inosine (200 mg/kg) was partially protective: mean plasma creatinine 48 h after ischaemia (+/- SEM) was 547 +/- 54 mumol/l in controls, 686 +/- 38 mumol/l with 0.1 mg/kg verapamil, 491 +/- 68 mumol/l with 1.0 mg/kg verapamil and 374 +/- 45 mumol/l with inosine (p less than 0.05 vs. controls). Using the same model, the effect of verapamil 1.0 mg/kg on renal blood flow, creatinine clearance, urine flow and arterial pressure was studied in the first 2 h after ischaemia. Although significant amounts of verapamil were present in the kidney during ischaemia as evidenced by decreases in systemic blood pressure and in renal vascular resistance after unclamping the renal artery, the early course of renal failure was not altered when compared to controls. In conclusion, we have been unable to confirm earlier reports of a protective effect of verapamil in this rat model of ischaemic renal failure. If there is such an effect, its demonstration appears to depend on very specific experimental circumstances. Based on the results of this and other studies, verapamil is unlikely to afford an impressive overall benefit in the clinical setting of ischaemic renal failure.     

Effect of Nifedipine in the Protection of Renal Function During In Situ Preservation

In an experimental study on six healthy dogs both kidneys wereexposed and subjected to 1 h of ischaemia by clamping both renalvessels. To the left renal artery, 300 ml of cold (4°C)Euro-Collins solution in which nifedipine (Bay a 1040—20µg/kg per min) was diluted, was infused for 15 min. Simultaneously300ml of cold Euro-Collins solution plus 20 µg/kg permin of placebo (Bay a 1040—placebo) was infused in theright renal artery. The 1 h of ischaemia was divided in a 15-minperiod of cold ischaemia and 45 min of warm ischaemia, at theend of which both clamps were removed. During the 2 h (4x30min) following the removal of the clamps, urine volume, ureaand creatinine clearances, urine sodium concentration, sodiumfractional excretion (%) and urine/plasma osmolality ratio measurementswere made and results compared to the pre-ischaemia values.Both kidneys were then removed for histological study. The nifedipine group restored diuresis of 0.43±0.23 ml/minwithin 30 min, while this degree of diuresis (0.64±0.16ml/min) was achieved by the placebo group at 120 min. Urinevolume as well as creatinine and urea clearances of the nifedipinegroup were significantly higher in all studied periods comparedto the placebo group (P<0.01 or P<0.025). Urine sodiumand FE_Na (%) were not different between the two groups, andurine/plasma osmolality ratio was above 1.1 in all studied periodsfor both groups. The microscopic study did not show any significantdifferences between the two groups. We conclude that nifedipineis effective in the protection of renal function when it isadministered during experimental in situ preservation.     

A trial of the prostaglandin E1 analogue, enisoprost, to reverse chronic cyclosporine-associated renal dysfunction.

Cyclosporine (CYA) reduces the renal synthesis of prostaglandins of the E series (PGE). Analogue of PGE1 have been shown to mitigate the vasoconstriction and abnormal renal function of experimental acute CYA nephrotoxicity. We examined the hypothesis that the orally bioavailable PGE analogue enisoprost (EP) would improve renal function in renal transplant recipients chronically exposed to CYA. In a randomized double-blind study, 40 patients at two centers who were being monitored for 3 to 30 months after renal transplantation, were allocated to receive either EP 100 micrograms orally four times daily or placebo (P) for 2 weeks. CYA dosing was fixed at existing levels. There could be no evidence of concurrent acute renal injury, including that of acute rejection. Glomerular filtration rate (GFR) was measured by the clearance of radiolabeled DTPA, while effective renal plasma flow (ERPF) was measured as the clearance of p-aminohippuric acid (PAH). The acute effects of EP were examined twice, by comparing immediate postdose to predose values for GFR and ERPF on day 1 and again on day 14. Chronic effects were examined by comparing baseline (predose) values only for GFR and ERPF between days 1 and 14 and by an examination of creatinine clearances (CCR) on days 0, 14, and 21. At enrollment, patients were well matched for renal function (CCR:EP 47 +/- 5 v P 49 +/- 4 mL/min/1.73 m2; P = NS). Baseline demographics were similar, although patients treated with EP were older (46 +/- 2 v 36 +/- 3 years, mean +/- SEM, P = 0.003). CYA doses and blood levels did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preoperative inhibition of angiotensin-converting enzyme improves systemic and renal haemodynamic changes during aortic abdominal surgery

We studied 22 patients undergoing aortic surgery, allocated randomly to receive, before induction of anaesthesia, a single i.v. dose of enalapril 50 micrograms kg-1 or saline. During infrarenal aortic cross- clamping, we observed similar reductions in oxygen uptake in the two groups, despite greater systemic oxygen delivery in enalapril-treated patients; angiotensin-converting enzyme inhibition prevented the reduction in cardiac output and attenuated the decrease in glomerular filtration. Changes in glomerular filtration secondary to aortic clamping were related positively to changes in renal plasma flow (r = 0.83 (saline group) and r = 0.65 (enalapril group)). Creatinine clearance on the first day after operation was significantly higher in the enalapril compared with the saline group. We conclude that enalapril pretreatment is effective in improving systemic oxygen delivery, renal plasma flow and glomerular filtration during aortic abdominal surgery.      

Naloxone in renal ischemia: a functional and microanatomical study

Naloxone HCl (Nx) improves cardiopulmonary performance, reverses cellular hypoxia, and stabilizes lysosomal membranes in shock states. However, no detailed study has yet explored its potential role in renal ischemia, which is inevitable in transplantation and surgical and nonsurgical conditions associated with hypotension and shock. This functional and microanatomical study was carried out on dogs subjected to renal warm ischemia with contralateral nephrectomy. Group I (control; N = 4) had bilateral renal dissection and right nephrectomy. Groups II-IV had their kidney pedicles cross-clamped for 60 min and then reperfused. Group II (N = 9) ischemic kidneys received no treatment. Group III (N = 6) kidneys were flushed with pure Nx HCl (2 mg/kg) during ischemia. Group IV (N = 6) dogs received one iv Nx bolus (2 mg/kg) before clamping and another dose before declamping. Biopsies for adenine nucleotides, histology, and ultrastructure were obtained before ischemia, before reflow, and 15 min and 7 days after reflow. Serum creatinine and blood urea nitrogen were measured daily. Ischemia induced significant renal dysfunction, which was reversed by systemic Nx. Nx offered a remarkable protection against postischemic structural damage. Seventy percent of Group II cortical sections showed grade 4 acute tubular necrosis (ATN), and severe residual damage after a week. Eighty-three percent of Group IV sections showed grade 1 ATN and no residual damage after a week. One week survival was 33% in Group II and 100% in Group IV. Nx can be useful in prevention of acute renal failure in clinical situations with arterial hypotension and shock.     

Decreased fractional excretion of urate as an indicator of prerenal azotemia

Although the fractional excretion of uric acid (FEUA) is known to reflect extracellular fluid volume changes, the diagnostic significance of decreased FEUA in dehydration has not been previously reported. We studied the possible association between low FEUA and acute prerenal azotemia, and its diagnostic value, compared with other traditional indices, in discriminating prerenal azotemia from renal parenchymal causes of acute renal failure. In 65 chronic renal disease patients, 174 FEUA measurements were obtained from 24-hour urine collections. FEUA levels increased as reciprocal serum creatinine levels decreased. All 8 patients with prerenal azotemia showed significantly decreased FEUA values compared with chronic renal disease patients with a comparable degree of serum creatinine elevation, whereas all 7 patients with acute renal failure had FEUA values higher than those of chronic renal disease patients with comparable creatinine levels. FEUA values in prerenal azotemia were distinctly lower than those in acute renal failure (p less than 0.001). Patients with prerenal azotemia showed a lower fractional excretion of sodium, a lower fractional excretion of chloride and renal failure index, and a higher urine-to-plasma creatinine ratio than those with acute renal failure (p less than 0.05). However, these traditional indices were not useful in discriminating between the two conditions. The urine-to-plasma urea nitrogen ratio and the ratio of plasma urea nitrogen to creatinine showed no statistical difference between prerenal azotemia and acute renal failure. We conclude that, in acute azotemia, a decreased FEUA value may represent a reliable indicator of prerenal azotemia in the differential diagnosis of acute renal failure.