Role of N-acetylcysteine on renal function in patients after orthotopic heart transplantation undergoing coronary angiography

INTRODUCTION: The aim of this study was to assess nephroprotective influence of intravenous N-acetylcysteine (NAC) on renal function after radiocontrast use in calcineurin inhibitor-treated patients after orthotopic heart transplantation (OHT). MATERIALS AND METHODS: We analyzed the results of 112 consecutive coronary angiography examinations (CAG). All patients received intravenous 500 mL multielectrolyte fluid (PWE) before catheterization. Group I of 55 randomly selected cases in addition were treated with 300 mg of NAC. The other 57 cases (group II) received only hydration. After catheterization, we administered 500 mL 0.9% saline with 20 mg furosemide. A nonionic, low-osmolality contrast agent (OPTIRAY) was used for all catheterizations. All patients underwent measurements of serum creatinine and creatinine clearance levels before and after the procedure (CREA0, CREA1, CC0, and CC1, respectively). We assessed the influence of NAC on CREA1 and the relative change of CREA1/CREA0 and CC1/CC0 ratios. RESULTS: In groups I and II we noticed decreased CC0 in 17 versus 22 cases (31% vs 39%), a relative change of CREA1/CREA0 ratio of 0% versus -3.95% and of CC1/CC0 ratio 0% versus 4, 11%, respectively. CIN was not recognized in any patient. None of the differences was significant. CONCLUSION: Intravenous NAC (300 mg) along with hydration before radiocontrast use had no impact on renal function in OHT patients undergoing CAG. It seems that there is no need for an additional preventive strategy apart from hydration and a small volume of low osmolar contrast in the majority of patients.     

Prevention of radiocontrast-media-induced nephropathy in patients with pre-existing renal insufficiency by hydration in combination with the adenosine antagonist theophylline.

BACKGROUND: Radiographic contrast media (CM) application causes a decline in renal function, especially in patients with pre-existing renal dysfunction. In addition to hydration, several vasodilating substances have been evaluated for their ability to prevent renal damage after CM application. In a prospective, double-blind, placebo-controlled study we investigated the effect of the oral administration of theophylline, an adenosine receptor antagonist, on changes in renal haemodynamics and tubular injury induced by CM in well-hydrated patients with mild-to-moderate renal insufficiency. METHODS: We studied 80 patients with pre-existing chronic renal insufficiency (creatinine > 1.5 mg/dl) who received more than 100 ml iopromide. Hydration (either oral or intravenous) started at least 24 h before and lasted until 24 h after CM application. In addition, patients were randomly assigned to receive either theophylline (810 mg daily) or placebo. Serum creatinine and creatinine clearance were measured before and for 3 days after CM application. Urine was collected to measure N-acetyl-beta-glucosaminidase (NAG) enzymuria for the same period. Sixty-four patients completed the entire study protocol (theophylline, n = 35 and placebo, n = 29). RESULTS: During the study period serum creatinine concentration and creatinine clearance did not change significantly in either group. Acute renal failure (increase of serum creatinine of at least 0.5 mg/dl) could be observed in two patients from the theophylline group (5.7%) and one from the placebo group (3.4%). The increase in NAG excretion reached statistical significance (P < 0.05) in the placebo group on days 2 and 3 after CM application. CONCLUSIONS: Our results indicate a role for adenosine in CM-induced tubulotoxicity. However, the glomerular filtration rate is preserved by hydration alone in these patients. The application of theophylline did not bring an additional benefit. The use of adenosine antagonists may be beneficial in patients where sufficient hydration may be impossible or in patients with a concomitant decrease in renal blood flow (e.g. congestive heart failure).     

Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial

The aim of the present study was to assess the possible prevention of cisplatin-induced impairment of GFR by theophylline in patients with various malignancies. The trial design was parallel, randomized, single blinded, and placebo controlled. Patients received cisplatin at a dosage of 50 mg/m(2) either combined with etoposide, ifosfamide, and epirubicin or with paclitaxel and 5-fluorouracil/folinic acid with the usual precautions, including a standard hydration scheme before application of cisplatin in both arms. In the control arm, placebo was administered; in the verum arm, patients received theophylline in a loading dose of 4 mg/kg intravenously over 30 min before cisplatin, followed by 0.4 mg/kg per min over a minimum of 6 h, and then 350 mg three times daily orally for 4 consecutive days after completion of chemotherapy. GFR of each patient was assessed by renal clearance of inulin within 3 d before and at day 5 after cisplatin chemotherapy. Despite usual precautions, patients in the placebo group had a 21% decrease (range, 11 to 31%) of inulin clearance after a single cycle of cisplatin-containing chemotherapy (92.9 +/- 3.4 versus 71.8 +/- 3.5 ml/min; P < 0.01). Patients who received theophylline had no deterioration of GFR (91.5 +/- 3.7 versus 90.0 +/- 3.8 ml/min; P > 0.05). No adverse effects have been observed during theophylline application. Conventional precautions such as hydration and osmotic diuresis cannot prevent a significant decrease of GFR after a single cycle of cisplatin-containing chemotherapy. The prophylactic application of theophylline as an intravenous loading dose and oral maintenance regimen may preserve kidney function in terms of GFR.     

A randomized trial of saline hydration to prevent contrast-induced nephropathy in patients on regular captopril or furosemide therapy undergoing percutaneous coronary intervention

Contrast-induced nephropathy (CIN) is characterized by acute deterioration of renal function that occurs after parenteral administration of contrast media in the absence of other causes. Although no definite proof has been obtained yet, the risk of diuretics or angiotensin-converting enzyme inhibitors (ACEI) to exacerbate CIN has been reported because of their effects on renal perfusion. This study was conducted to assess the protective effect of hydration alone in the prevention of CIN after percutaneous coronary intervention (PCI) in patients on diuretics or ACEI. This randomized clinical trial was conducted at the Chamran Hospital, Isfahan University of Medical Sciences, Iran, during the years 2006-2007. The study patients were divided into four groups, each group containing 60 patients. Patients in groups A and B were on regular treatment with ACEI (captopril) and patients in groups C and D were on regular diuretic (furosemide) therapy. About 36 h before PCI, captopril in group A and furosemide in group C were discontinued. The serum creatinine (Cr) levels were measured at the time of performing PCI and 24 h and 48 h after PCI in all patients. All patients received 1 mL/kg/h normal saline (0.9%) 12 h before and 24 h after PCI. The occurrence of CIN after PCI was diagnosed based on the following formula: Cr level after PCI - Cr level before PCI. If this value was greater than 0.5 mg/dL, it was coded as one and if the value was less than 0.5 mg/dL, it was coded as zero. The mean difference was analyzed and compared among the four groups by the ANOVA test. Three patients (5%) in group A, two patients (3.3%) in group B, two patients (3.3%) in group C and one patient (1.6%) in group D had a >0.5 mg/dL difference in serum Cr. The difference seen between these groups was not statistically significant (P > 0.05). This study shows that although furosemide and captopril can exacerbate CIN by impairment of renal perfusion, this can be prevented by hydration and discontinuation of furosemide and captopril may not be required.     

Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism

BACKGROUND: Endothelin is a potent vasoconstrictor that has been implicated in the pathogenesis of radiocontrast nephrotoxicity. Endothelin antagonists may reduce the renal hemodynamic abnormalities following radiocontrast administration. METHODS: One hundred fifty-eight patients with chronic renal insufficiency [mean serum creatinine +/- SD = 2.7 +/- 1.0 mg/dL (242. 3 to +/- 92.8 micromol/L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo. All patients received intravenous hydration with 0.45% saline before and after radiocontrast administration. Serum creatinine concentrations were measured at baseline, 24 hours, 48 hours, and 3 to 5 days after radiocontrast administration. The primary end point was the mean change in serum creatinine concentration from baseline at 48 hours; the secondary end point was the incidence of radiocontrast nephrotoxicity, defined as an increase in serum creatinine of > or =0.5 mg/dL (44 micromol/L) or > or = 25% from baseline within 48 hours of radiocontrast administration. RESULTS: The mean increase in serum creatinine 48 hours after angiography was higher in the SB 209670 group [0.7 +/- 0. 7 mg/dL (63.5 +/- 58.6 micromol/L)] than in the placebo group [0.4 +/- 0.6 mg/dL (33.6 +/- 55.1 micromol/L), P = 0.002]. The incidence of radiocontrast nephrotoxicity was also higher in the SB 209670 group (56%) compared with placebo (29%, P = 0.002). This negative effect of SB 209670 was apparent in both diabetic and nondiabetic patients. Adverse effects, especially hypotension or decreased blood pressure, were more common in the SB 209670 group. CONCLUSIONS: In patients with chronic renal insufficiency who were undergoing cardiac angiography, endothelin receptor antagonism with SB 209670 and intravenous hydration exacerbate radiocontrast nephrotoxicity compared with hydration alone.     

Fractional Excretion of Uric Acid as a Predictor for Saline Responsiveness in Long-Term Kidney Transplant Patients

Background/Aims: Subclinical hypovolemia may contribute to allograft dysfunction in long-term kidney transplant (KT) patients. In order to predict responsiveness to saline hydration, indices for tubular transport were investigated. Methods: Fifty-four clinically euvolemic long-term KT patients with recently aggravated azotemia were given intravenous hydration as follows: 0.9% saline 5 ml/kg over 1 h, followed by 0.9% saline 1 ml/kg/h over 12 h and 1 liter of 0.45% saline over the next 24 h. Serum and urine data were collected and analyzed to assess responses. Results: In all patients, saline hydration relieved azotemia, as shown by blood urea nitrogen (46.9 ± 17.2 vs. 39.3 ± 15.4 mg/dl; p < 0.01) and serum creatinine levels (2.9 ± 1.1 vs. 2.5 ± 1.1 mg/dl; p < 0.01) on day 0 versus day 2. In 38 patients, serum creatinine did not increase in the following month (70% responders). Compared with the nonresponders, the responders had a higher urine-to-plasma creatinine ratio and lower fractional excretion of sodium, uric acid and urea at admission. Multivariate logistic regression analysis revealed that responsiveness to saline hydration was independently associated with lower fractional excretion of uric acid. Conclusion: Subclinical hypovolemia should be considered in long-term KT patients with azotemia of unexplainable causes. Fractional excretion of uric acid may predict responsiveness to saline hydration.     

Synergism of dopamine plus furosemide in preventing acute renal failure in the dog

The protective effects of a combination of dopamine and furosemide were studied in dogs during the initial phase of acute renal failure (ARF) induced by intravenous uranyl nitrate (10 mg/kg). Fifteen minutes after injection of the nephrotoxin, and infusion of dopamine (3 micrograms/kg/min), furosemide (1 mg/kg/bolus followed by 1 mg/kg/hr), or both drugs simultaneously were given for 6 hours. Exogenous creatinine clearance was measured for 6 hours, and the intrarenal blood flow was measured with radioactive microspheres before and 3 hours after the induction of ARF. Treatment with both dopamine and furosemide produced renal vasodilatation, high urine flow rate, and attenuation of the fall in GRF seen in untreated animals. In contrast, single use of dopamine or furosemide was totally ineffective in producing renal vasodilation, a diuresis, or the maintenance of the GFR. These data indicate that dopamine plus furosemide have a synergistic effect in preventing the early pathophysiologic changes associated with ARF in this animal model. Maintenance of a high GFR correlated best with the enhancement of solute excretion and urine flow rate. Potential protective effects of dopamine plus furosemide in other models of ARF deserve careful investigation.     

Preoperative intravenous hydration confers renoprotection in patients with chronic kidney disease undergoing cardiac surgery

Patients with chronic kidney disease (CKD) are at risk to develop acute renal failure (ARF) after open heart surgery. This complication is associated with high morbidity, mortality, and cost. Because the ability to concentrate urine is lost early in the progression of CKD, renal patients kept on fluid restriction prior to surgery may develop severe dehydration, a situation consistently found to be one of the most critical risk factors for postoperative ARF. Our goal was to investigate whether intravenous hydration for 12 h prior to cardiac surgery could prevent acute renal injury in patients with CKD. This is a prospective study in a tertiary cardiac surgery center. Forty-five patients admitted for elective open heart surgery with moderate-to-severe CKD, as evidenced by a quantified glomerular filtration rate less than 45 mL/min, were assigned using a 2/1 randomization process, to either receive an intravenous infusion of half-isotonic saline (1 mL/kg/h) for 12 h before the operation (hydration group, n = 30, 29 men, 64 + 1.7 years old), or to be simply kept on fluid restriction (control group, n = 15, 14 men, 64.2 + 2.8 years old). Groups were not different in clinical and intraoperative variables associated with postoperative renal injury. ARF developed in 8 of 15 (53%) patients in the control group, but in only 9 of the 30 (30%) patients in the hydration group. Four patients in the control group (27%), but no one in the hydration group, required dialysis after the operation (P < 0.01). Peak creatinine and blood urea nitrogen values were two to three times higher in the control group than in the hydration group. Preoperative intravenous hydration may ameliorate renal damage in patients with moderate-to-severe renal insufficiency undergoing cardiac surgery.     

Prevention of contrast-induced nephropathy in vascular surgery patients

Presently, only hydration and N-acetylcysteine have been shown to be effective in decreasing the incidence of radiographic contrast-induced nephropathy. We investigated the role of N-acetylcysteine and various hydration protocols in vascular surgery patients undergoing angiography. A single-center, randomized, placebo-controlled trial was conducted in patients with stable, preexisting renal dysfunction undergoing elective, outpatient angiography. Patients were randomized to outpatient oral hydration and N-acetylcysteine, inpatient hydration plus N-acetylcysteine, or our standard therapy of inpatient intravenous hydration alone. Two of twenty-eight (7%) patients who received outpatient oral hydration and N-acetylcysteine developed contrast-induced nephropathy, while two of 25 (8%) who recieved inpatient hydration plus N-acetylcysteine developed contrast-induced nephropathy and two of 25 (8%) who received standard therapy of inpatient intravenous hydration alone developed contrast-induced nephropathy. There was no statistical difference in incidence of contrast-induced nephropathy between the groups. No statistically significant independent risk factors were identified among the patients who developed contrast-induced nephropathy. N-Acetylcysteine did not confer additional benefit to patients treated with inpatient intravenous hydration. Outpatient oral hydration plus N-acetylcysteine was as effective at preventing contrast-induced nephropathy as inpatient therapies and avoided costly hospital admission.     

The role of theophylline in contrast-induced nephropathy: a case-control study.

BACKGROUND: Various strategies for the prevention of contrast-induced nephropathy (CN) have been studied, with conflicting results. Adenosine may play an important role in the pathogenesis of CN. This study prospectively assessed the role of oral theophylline in the prevention of CN. METHODS: We randomized into two groups 70 patients with diabetes mellitus who were undergoing coronary angiography (CAG) with high-osmolar contrast media. Group I (n=35) underwent routine CAG, and group II (n=35) received oral theophylline 200 mg b.d. 24 h before and for 48 h after CAG. Serum Na(+), K(+), blood urea nitrogen (BUN), creatinine, osmolality, glomerular filtration rate (GFR) and urinalysis were performed before and after CAG. The (99m)Tc-DTPA-clearance method was used to assess GFR. RESULTS: Following angiography, patients in the control group showed a significant rise in serum creatinine (1.19+/-0.23 vs 1.44+/-0.32 mg/dl, P=0.003) and BUN (13.95+/-2.61 vs 17.55+/-3.9 mg/dl, P=0.01) along with a fall in GFR (85.4+/-14.7 vs 66.85+/-14.8 ml/min, P=0.008). The mean percentage fall in GFR was 35.8%. There was no significant change in serum creatinine (1.16+/-0.18 vs 1.24+/-0.21 mg/dl), BUN (12.8+/-3.36 vs 14.8+/-2.5 mg/dl) and GFR (86.8+/-15.8 vs 80.3+/-16.0 ml/min) in those receiving theophylline. No patient in the theophylline group had a >25% rise in serum creatinine, compared with 7/35 in the control group (P=0.017). In the control group, 11/35 (31%) developed CN, as demonstrated by a >/=25% fall in GFR, while only one patient in the theophylline group had a fall in GFR (P=0.004). None of the pre-angiographic variables could predict the development of CN. CONCLUSIONS: Following the use of high-osmolar contrast media for routine CAG, CN may develop in 31% of diabetic patients. Patients who received prophylactic oral theophylline had a significantly lower risk of CN than those who did not.     

Lack of renoprotective effect of theophylline during aortocoronary bypass surgery.

BACKGROUND: The incidence of acute renal failure (ARF) after cardiac surgery remains high, despite improvements in surgical techniques and perioperative care, and is associated with an unacceptably high mortality. The adenosine receptor antagonist theophylline has been shown to confer some benefit in experimental and clinical ARF due to ischaemia, contrast media and various nephrotoxic agents. METHODS: In a double-blind, randomized, placebo-controlled trial, the effectiveness of theophylline for prevention of renal impairment after elective coronary artery bypass grafting (CABG) was evaluated. Fifty-six patients with normal renal function received a bolus of 4 mg/kg and a subsequent continuous infusion of 0.25 mg/kg/h theophylline (n=28) or isotonic saline (n=28) for up to 96 h. Serum creatinine concentrations were measured preoperatively and daily until day 5 after surgery, and the glomerular filtration rate (GFR) ([(51)Cr]EDTA-clearance) was determined preoperatively, and at days 1, 3 and 5 after surgery. RESULTS: Serum creatinine and GFR were the same in both groups. The number of patients with increases of serum creatinine > or =0.4 mg/dl were five in the theophylline group and four in the placebo group. Volumes of infused fluid and urine volumes were not different between groups, both ranging from approximately 7.5 to 8 l during the first 24 h after surgery. The number of patients with termination of study medication due to presumed side effects was not different between placebo and theophylline groups. CONCLUSIONS: Theophylline administration for renal protection after CABG appears to be ineffective in a pilot study in well-hydrated patients. However, the statistical power of our study was not sufficient to exclude a possible protective effect of theophylline. The present study demonstrated the feasability of a larger trial with theophylline or one of the new specific adenosine A1 receptor antagonists in the setting of ARF after cardiac surgery.     

High doses of furosemide in children with acute renal failure

The diuretic effect of high doses of furosemide alone and furosemide plus maniitol was analysed retrospectively in 30 children with acute renal failure. In 10 children (Group 1) renal failure developed mainly during glomerulonephritis, and in 20 children (Group 2) the cause was gastroenteritis. The diuretic effects of furosemide and furosemide plus mannitol were evaluated measuring the 24-hour urine volume at the time of anuria, oliguria or normal diuresis. The highest mean single intravenous doses of furosemide were 6.5 and 14 mg/kg in Groups 1 and 2, respectively; the highest average daily doses were 10.1 and 25.5 mg/kg, respectively. A broad relationship was observed between single i.v. dose and diuretic response following administration of furosemide (1.2 to 30.8 mg/kg). In both groups of patients a statistically significant negative linear correlation was found between the daily intravenous dose of furosemide and the 24-hour urine volume. Calculations based on the obtained regression equations showed that the expected 24-hour urine volumes corresponding to daily diuresis normal for age could be obtained after administration of daily 2.8 to 1.4 mg/kg furosemide in Group 1 and 9.3 to 2.3 in Group 2. It is therefore suggested that the total daily dose of furosemide should not exceed 100 mg in children with acute renal failure. Administration of furosemide plus mannitol did not result in higher daily diuresis as compared to 24-hour urine volume obtained when furosemide was given alone. Furosemide was well tolerated. Electrolyte disturbances, especially in Group 2, were the most frequent side effects due to high doses of furosemide. This work was presented in part at the 19th International Congress of Paediatrics, July 23–28, 1989, Paris, France (Abstracts Book, p. 377).     

The potential role of statins in contrast nephropathy

BACKGROUND: Administration of contrast agents may result in an acute reduction in renal function and occasionally end-stage renal disease. Risk factors for contrast-induced nephropathy (CN) are preexisting renal dysfunction, diabetes and reduced effective arterial volume. Hydration and use of nonionic contrast agents have been reported to ameliorate CN. Reactive oxygen species may have a role in the pathogenesis of CN. Statins decrease free oxygen radicals in animals. We retrospectively tested the hypothesis that administering statins prior to cardiac catheterization decreases the incidence of CN. METHODS: A total of 1,002 patients were studied. Patients with a stable baseline serum creatinine (SCr) > or = 1.5 mg/dl who had cardiac catheterization between July 1997 and June 2002, were included in the study. None of the patients were taking statins before admission. 250 patients were started on a statin before the procedure and 752 patients were not. The SCr was followed for 7 days after the procedure looking for an acute decrement in renal function, dialysis requirement and survival. RESULTS: The baseline characteristics, SCr, GFR, amount of intravenous fluids and contrast were similar in both groups. The post cath SCr (2.26 vs 3.1 mg/dl, p = 0.001) was significantly better in the statin group. Length of stay (2.72 vs 3.32 days, p = 0.01) and number of patients with acute renal failure (43 (17.2%) vs 168 (22.3%) patients, p = 0.028) were significantly lower in the statin group. Dialysis requirement within 7 days and 28-day survival were similar in both groups. CONCLUSION: Prophylactic administration of statins along with hydration may be associated with less CN induced by a nonionic, low-osmolality contrast.     

Contrast-induced nephrotoxicity in renal allograft recipients

BACKGROUND: Intravenous administration of radiographic contrast agents is an important cause of acute renal failure, accounting for one third of the cases of hospital-acquired acute renal failure in patients with native kidneys. The safety of intravenous contrast has not been studied in renal allograft recipients since the availability of cyclosporine as a maintenance immunosuppressive therapy. As patients with renal transplantation may be at a higher risk of contrast-induced nephrotoxicity (CIN) due to concomitant use of cyclosporine and higher prevalence of diabetes and renal insufficiency, we retrospectively studied development of CIN in these patients. PATIENTS AND METHODS: We identified 44 patients (1988 1997) with functioning renal allograft who underwent different intravenous or intraarterial contrast studies (ICS). Pre- and post-ICS renal function tests were done in 35 of these patients. The following were the various ICS done in these patients: coronary angiogram (6), CT scan with intravenous contrast ( 11), angiogram for evaluation of peripheral vascular disease (11), allograft angiogram with angioplasty (5), pulmonary angiogram (1) and intravenous pyelogram (1). The mean age of the patients was 42 +/- 2.1 years and the mean serum creatinine was 2.3 +/- 0.25 mg/dl (mean +/- SEM). Fourty percent of patients (14 of 35) had diabetes, and 25.7% (9 of 35) had chronic rejection. Ninety four percent (33 of 35) of the patients were taking cyclosporine at the time of ICS. RESULTS: Nine patients had > or = 25% increase in serum creatinine from baseline after ICS. Two of these patients were excluded from the analysis as renal functions in these patients had deteriorated prior to ICS and renal failure was attributed to sepsis. Of the remaining 7 patients, 5 had diabetes and 2 had chronic rejection. Only 4 of these 7 patients with CIN received prophylaxis (I/V hydration) prior to ICS. The baseline serum creatinines were not different in patients who had no change in renal function to those who developed CIN (1.97 +/- 0.20 vs 1.54 +/- 0.17 mg/dl, p = 1.5, mean +/- SEM). More than 50% increase in baseline serum creatinine was seen in only 3 of these 7 patients, 2 of these patients had diabetes and third had chronic rejection and congestive heart failure. None of these patients received prophylaxis for CIN. Dialysis was not required in any patient. Three patients also had a > 25% decrease in baseline serum creatinine after ICS, and all of them had allograft angiography with angioplasty for renal artery stenosis. CONCLUSION: In our retrospective study, the incidence of CIN in renal allograft recipients applying a broader classification of > or = 25% increase in baseline serum creatinine was 21.2% (7 of 33 patients). The incidence of CIN was lower 15.3% (4 of 26) in patients who received intravenous hydration compared to 42.8% (3 of 7) in patients who received no prophylaxis prior to ICS.     

Does furosemide prevent renal dysfunction in high-risk cardiac surgical patients? Results of a double-blinded prospective randomised trial.

OBJECTIVE: Renal dysfunction following cardiac surgery is more apparent in high-risk patients with pre-existing renal dysfunction, diabetes and impaired left-ventricular function, and following complicated procedures involving prolonged cardiopulmonary bypass (CPB). The aim of this prospectively randomised double-blinded placebo-controlled study was to evaluate reno-protective effect of low-dose furosemide infusion in this high-risk group. METHODS: Patients with preoperative serum creatinine >130 micromol/l (1.4 mg/dl), left-ventricular ejection fraction <50%, congestive heart failure, diabetes, or procedures involving prolonged CPB were randomised to receive either saline at 2 ml/h (n=21), or furosemide at 4 mg/h (n=21). Infusion was commenced after induction of anaesthesia and continued for 12h postoperatively. Renal dysfunction was defined as >50% increase in serum creatinine postoperatively, or >130 micromol/l (1.4 mg/dl), or requirement for haemodialysis, or all of these. In patients with preoperative serum creatinine >130 micromol/l, >50% increase over preoperative levels was used to define postoperative renal dysfunction. RESULTS: Following cardiac surgery, patients receiving furosemide had a higher urine output (3.4+/-1.2 ml/kg/h in furosemide group and 1.2+/-0.5 ml/kg/h in placebo group; p<0.001), higher postoperative fluid requirement (4631+/-1359 ml in furosemide group and 3714+/-807 ml in placebo group, p=0.011), and lower urinary-creatinine (2+/-1.3 micromol/l in furosemide group and 5.9+/-2.5 micromol/l in placebo group p<0.001). Both groups had significant increase in retinol binding protein/creatinine ratio (7.2+/-6 to 3152+/-1411 in furosemide group; 4.9+/-2.1 to 2809+/-1125 in placebo group; p<0.001) and peak serum creatinine (98+/-33 to 177+/-123 micromol/l in furosemide group; 96+/-20 to 143+/-87 micromol/l in placebo group; p<0.001), and a significant decrease in peak creatinine-clearance (64.3+/-29.4 to 39.1+/-16.6 ml/min in furosemide group; 65.5+/-38.6 to 41.8+/-17.8 ml/min in placebo group; p<0.001) following cardiac surgery, implying significant renal injury following cardiac surgery. Peak creatinine levels (177+/-123 micromol/l in furosemide group and 143+/-87 micromol/l in placebo group; p=0.35) and peak creatinine-clearance (39.1+/-16.6 ml/min in furosemide group and 41.8+/-17.8 ml/min in placebo group; p=0.61) were similar in the two groups. Importantly, there was no difference in incidence of renal dysfunction between the furosemide group (9/21) and the control group (8/21) (relative risk 1.1, 95% confidence interval 0.6-2.2; p=0.99). CONCLUSIONS: Our randomised trial did not demonstrate any benefit of furosemide-infusion postoperatively in high-risk cardiac surgical patients. Although urinary output increased with furosemide, there was no decrease in renal injury, and no decrease in incidence of renal dysfunction.     

Sodium Bicarbonate versus Normal Saline for Protection against Contrast Nephropathy

Contrast-induced nephropathy (CIN) is a form of acute kidney injury and a significant source of morbidity and mortality. We defined CIN as an increase in serum creatinine (SCr) of 25%?or more within 48 hours of receiving contrast. We retrospectively compared sodium bicarbonate with normal saline for prevention of CIN. One hundred and eighty-seven patients exposed to contrast during cardiac angiography, treated prophylactically either with sodium bicarbonate (n?=?89) or with normal saline (n?=?98), were studied. Baseline characteristics of both groups were similar in terms of age, amount of contrast, presence of diabetes mellitus, and use of furosemide and angiotensin-converting enzyme inhibitor. Patients in bicarbonate group had more severe renal disease with higher baseline SCr (1.58?±?0.5 mg/dL vs. 1.28?±?0.3 mg/dL, p?=?0.001) and lower estimated glomerular filtration rate (eGFR, 51.06?±?14.0 mL/min vs. 62.3±13.5 mL/min, p?=?0.001) compared to the normal saline group. After the contrast exposure, there was significant drop in eGFR (6.4%) and increase in SCr (11.3%) in the normal saline group and no significant change in the bicarbonate group. Three patients (3.4%) in the bicarbonate group as opposed to 14 patients (14.3%) in the normal saline group developed CIN (p?=?0.011). Two patients in the normal saline group and none in the bicarbonate group needed dialysis. There was no significant difference in serum creatinine at three-month follow-up in either group. The above findings suggest that hydration with intravenous sodium bicarbonate is more effective than normal saline in preventing contrast-induced nephropathy.     

Familial hypokalemia-hypomagnesemia or Gitelman's syndrome: a further case.

A woman aged 33 years presented hypokalemia and hypomagnesemia associated with renal potassium and magnesium wasting. Her mean 24-hour urinary calcium excretion was strikingly low despite normocalcemia, normal creatinine clearance, normal serum PTH and calcitriol. Normal distal fractional chloride reabsorption [CH2O/(CH2O + CCl)] was noted during water load but was reduced during hypotonic saline infusion. In response to intravenous furosemide (1 mg/kg), the patient showed significant increments in sodium, chloride and magnesium excretion as well as abolition of hypocalciuria. The association of renal calcium transport from magnesium transport together with exaggerated natriuresis after furosemide suggests the presence of a defect in the distal tubule rather than in the loop of Henle. We propose that our patient is affected by the syndrome of primary renotubular hypomagnesemia-hypokalemia with hypocalciuria, known as Gitelman's syndrome.     

Leptospiral Acute Renal Failure: Effects of Dopamine and Furosemide

From unpublished experience of clinicians in the rural tropics, the combination of furosemide and dopamine is beneficial in the management of mild acute renal failure in tropical disease. We studied two groups of patients with leptospirosis and mild acute renal failure whose serum creatinine ranged from 2.4 to 5 mg/dL and fractional excretion of sodium varied from 1.21 to 2.08%. Group 1, consisting of 9 patients with the serum creatinine ranging from 2.4 to 5 mg/dL, served as the control. They received only penicillin G sodium and supportive treatment. Group 2, consisting of 8 patients with the serum creatinine ranging from 2.8 to 5 mg/dL, received, in addition to penicillin, dopamine (renal dose) and furosemide along with fluid and electrolyte replacement. The control group ran the usual clinical course of acute renal failure, and 3 patients required dialysis. There was profuse diuresis, and the recovery of renal function was faster in group 2 patients. Dopamine and furosemide are therefore useful in mild acute renal failure in leptospirosis. It is felt that this combination could be beneficial in the management of mild acute ischemic renal failure due to a clean single insult.     

贝那普利联合丹参多酚酸盐对糖尿病肾病大鼠的肾脏保护作用

目的:评价贝那普利联合丹参多酚酸盐对链脲佐菌素(STZ)致大鼠糖尿病肾病的肾脏保护作用。方法:SD大鼠32只,分为正常组(A组)、糖尿病模型组(B组)、贝那普利组(C组)、贝那普利联合丹参多酚酸盐组(D组)。B组及C组、D组大鼠单次腹腔注射STZ,制备大鼠糖尿病模型;A组注射等量生理盐水。血糖稳定1周后C组给予贝那普利(10 mg/kg,ig),D组给予贝那普利(10 mg/kg,ig)联合丹参多酚酸盐(18 mg/kg,静脉注射)。给药3个月后处理。结果:比较大鼠血肌酐、肌酐清除率、肾组织乳酸脱氢酶、超氧化物歧化酶等生化指标,各组间差异均有统计学意义(P<0.05)。光镜下观察肾脏病理形态的改变,联合治疗比单用贝那普利效果更好。结论:贝那普利联合丹参多酚酸盐组对糖尿病肾病大鼠肾脏具有更好的保护作用。     

Leptospiral acute renal failure: effects of dopamine and furosemide

From unpublished experience of clinicians in the rural tropics, the combination of furosemide and dopamine is beneficial in the management of mild acute renal failure in tropical disease. We studied two groups of patients with leptospirosis and mild acute renal failure whose serum creatinine ranged from 2.4 to 5 mg/dL and fractional excretion of sodium varied from 1.21 to 2.08%. Group 1, consisting of 9 patients with the serum creatinine ranging from 2.4 to 5 mg/dL, served as the control. They received only penicillin G sodium and supportive treatment. Group 2, consisting of 8 patients with the serum creatinine ranging from 2.8 to 5 mg/dL, received, in addition to penicillin, dopamine (renal dose) and furosemide along with fluid and electrolyte replacement. The control group ran the usual clinical course of acute renal failure, and 3 patients required dialysis. There was profuse diuresis, and the recovery of renal function was faster in group 2 patients. Dopamine and furosemide are therefore useful in mild acute renal failure in leptospirosis. It is felt that this combination could be beneficial in the management of mild acute ischemic renal failure due to a clean single insult.