Atrial natriuretic peptide as a preload depressor in acute renal failure secondary to congestive heart failure

The present study was undertaken to verdy the hypothesis that infusion of atrial natriuretic peptide (ANP) might lower preload and be beneficial in the treatment of pulmonary congestion even without a diuresis in patients with acute renal failure (ARF) secondary to severe congestive heart failure (CHF). We studied 22 patients with ARF secondary to CHF. The mean age of the patients (14 men and 8 women) was 72 years (range 36 to 85 years). Seven of the patients had dilated cardiomyopathy, ten had ischemic heart disease, and five had valvular heart disease. ANP was infused intravenously and the following data before and 1 hour after the start of ANP infusion were recorded; urinary output, systemic blood pressure (SBP), pulmonary blood pressure (PBP), right atrial pressure (RAP), cardiac index (CI), heart rate (HR), and arterial blood oxygen pressure. Diastolic PBP were employed as plumonary capillary wedge pressure. Urinary output did not change. Mean SBP decreased from 92 to 85 mmHg (p < 0.05), and mean PBP decreased from 34 to 28 mmHg (p < 0.01). Mean RAP decreased from 11 to 9 mmHg (p < 0.01) and diastolic PBP decreased from 25 to 19 mmHg (p < 0.01). HR did not change significantly and CI increased 2.4 to 2.5 mi/min/m² (p < 0.05). Arterial blood oxygen partial pressure increased significantly from 71 to 82 mmHg (p < 0.05). In conclusion, ANP decreased and improved arterial blood oxygen partial prissure, though diuretic response to ANP is attenuated in ARF secondary to CHE. Infusion of ANP will be very beneficial in cases in which dyspnea and pulmonary edema due to elevation of preload are the principal clinical problems.     

Long-term infusion of atrial natriuretic peptide (ANP) improves renal blood flow and glomerular filtration rate in clinical acute renal failure

BACKGROUND: Short-term infusion of atrial natriuretic peptide (ANP) increases renal blood flow (RBF) and glomerular filtration rate (GFR) in patients with acute renal dysfunction. In the present study we evaluated the effects of long-term infusion (>48 h) of ANP on (RBF) and (GFR) in 11 postcardiac surgical patients requiring pharmacological circulatory support and with acute renal impairment. METHODS: Urinary clearance of Cr-EDTA and PAH as well as central hemodynamic measurements were performed for 2-3 consecutive 30-min periods during ANP infusion (50 ng. kg-1. min-1), one hour after abrupt discontinuation of ANP and again immediately after reinstitution of ANP infusion. RESULTS: During ANP infusion, urine flow (UF), GFR, RBF and renal vascular resistance (RVR) were 6.4+/-1.1 ml. min-1, 19.9+/-3.1 ml. min-1, 408+/-108 ml. min-1 and 0.286+/-0.054 mmHg. min. ml-1, respectively. UF, GFR and RBF decreased significantly by 28% (P<0.001), 32% (P<0.01) and 31% (P<0.05), respectively when ANP infusion was discontinued. RVR increased by 93% (P<0.05) while there was no change in filtration fraction. After reinstitution of ANP infusion, all measured renal variables returned to baseline. There was no significant correlation between the number of ANP treatment days and the percentage decrease in GFR (r=0.18) or RBF (r=0.22) during ANP withdrawal. Central hemodynamic variables were not affected by ANP withdrawal. CONCLUSIONS: ANP infusion improves RBF and GFR in patients with acute renal impairment after cardiac surgery. This renal vasodilatory effect is maintained during a long-term infusion and seems to be hemodynamically safe.     

Atrial natriuretic peptide and sodium homeostasis in chronic renal failure

In order to evaluate the possible role of vasoactive hormones in the mechanism of exaggerated sodium loss due to reduced renal mass we measured plasma concentration of atrial natriuretic peptide (ANP), aldosterone, plasma renin activity (PRA), plasma noradrenaline, and dopamine, in 12 children with advanced chronic renal failure (mean C_In17.8-2.6,x± SEM, C_PAH93.5±17 ml/min per 1.73 m², FE_Na7.0±0.95%). No patient had clinical signs of volume overload. Plasma concentrations of ANP were not significantly different from those of healthy agematched controls (29.2±7.2 vs 23.2±3.1 fmol/ml) and did not correlate with urinary sodium excretion. Plasma concentrations of aldosterone, PRA and noradrenaline, were also within the physiological range, while plasma dopamine levels were elevated (260±36 vs 98±11 pg/ml, <0.001). Our data do not support the notion that ANP or the renin-aldosterone axis play a major role in the adaptation of remaining nephrons to maintain long-term sodium balance in normotensive children with chronic renal failure.     

The effect of α-human atrial natriuretic peptide on the incidence of acute renal failure in cadaveric kidney transplantation

Abstract. In previous studies in humans, mannito (20%, 250 ml) has been shown to reduce the in cidence of acute renal failure (ARF) after transplan tation from 54% to 19%. In rats, atrial natriuretic peptide appears to prevent ischemia-induced ARF We therefore decided to evaluate the effects of α-human atrial natriuretic peptide (α-h-ANP) both alone and combined with mannitol during transplantation in humans. First, we demonstrated thai systemic α-h-ANP infusion during kidney transplantation was safe in dosages up to 0. 08 μg/kg pei minute. In these patients the calculated metabolic clearance rate of α-h-ANP was relatively low ranging from 0. 68 to 1. 801/min. In a second study of 11 renal graft recipients, no mannitol was used and α-h-ANP (0. 05 μg/kg per minute) was infused into the donor kidney artery during transplantation for 46 ± 2min, followed by IV administration for 71 ± 2 min. Our aim was to reduce the incidence of ARF. Nevertheless, ARF occurred immediately after surgery in four of the patients (36%) in this group and, as a result, mannitol was reintroduced. A third group of nine renal graft recipients received α-h-ANP (total dose 400 μg) as five IV injections within 90 min after transplantation. ARF occurred in four of these patients (44%). We conclude that α-h-ANP, administered according to the aforementioned protocols in such small groups of patients, does not seem to be of value in the prevention of ARF after transplantation.     

The effect of α-human atrial natriuretic peptide on the incidence of acute renal failure in cadaveric kidney transplantation

In previous studies in humans, mannitol (20%, 250 ml) has been shown to reduce the incidence of acute renal failure (ARF) after transplantation from 54% to 19%. In rats, atrial natriuretic peptide appears to prevent ischemia-induced ARF. We therefore decided to evaluate the effects of α-human atrial natriuretic peptide (α-h-ANP) both alone and combined with mannitol during transplantation in humans. First, we demonstrated that systemic α-h-ANP infusion during kidney transplantation was safe in dosages up to 0.08 μg/kg per minute. In these patients the calculated metabolic clearance rate of α-h-ANP was relatively low ranging from 0.68 to 1.80 l/min. In a second study of 11 renal graft recipients, no mannitol was used and α-h-ANP (0.05 μg/kg per minute) was infused into the donor kidney artery during transplantation for 46±2 min, followed by IV administration for 71±2 min. Our aim was to reduce the incidence of ARF. Nevertheless, ARF occurred immediately after surgery in four of the patients (36%) in this group and, as a result, mannitol was reintroduced. A third group of nine renal graft recipients received α-h-ANP (total dose 400 μg) as five IV injections within 90 min after transplantation. ARF occurred in four of these patients (44%). We conclude that α-h-ANP, administered according to the aforementioned protocols in such small groups of patients, does not seem to be of value in the prevention of ARF after transplantation.     

Atrial natriuretic peptide in renal development

Although discovered little more than a decade ago, atrial natriuretic peptide (ANP) has been shown to play a significant role in the maintenance of sodium homeostasis. Immediately after birth, plasma ANP concentration is very high concurrent with right atrial dilatation and a high urinary excretion of cyclic GMP (cGMP), the second messenger for ANP. Following postnatal diuresis and natriuresis, atrial volume, plasma ANP concentration, and urinary cGMP excretion decrease to baseline levels. In the ensuling suckling period, the diuretic and natriuretic response to acute saline volume expansion are attenuated, an effect which is offset by the lower hematocrit at this age. Increase in hematocrit by isovolemic exchange transfusion results in a greater rise of plasma ANP concentration following volume expansion, but a reduced excretion of cGMP. Intravenous infusion of ANP results in greater plasma ANP concentration, and greater urinary excretion of cGMP and sodium, in adult than in young rats. This increased metabolic clearance of ANP during early development is due at least in part to increased activity of clearance receptors. In addition, neutral endopeptidase contributes to removal of circulating ANP in maturing as well as adult rats. Infusion of ANP in neonatal or adult rats results in accumulation of cGMP in glomerular podocytes, with a higher threshold for activation in immature animals. Despite the similar response of intracellular generation of cGMP following exposure to ANP in neonatal and adult rats, egression of ANP out of glomeruli is low in neonates, an effect that is due to immaturity of an organic acid transporter. It is possible that these maturational differences in the processing of cGMP account for the developmental changes in renal response to ANP or to acute volume expansion.     

Predictors of worsening renal function in adult patients with congestive heart failure receiving recombinant human B-type brain natriuretic peptide (nesiritide).

BACKGROUND: A recent meta-analysis suggested that the use of nesiritide (NES), a new agent for the treatment of congestive heart failure (CHF), is associated with an increased risk of acute renal failure (ARF). METHODS: We examined this issue among 219 consecutive CHF patients, and determined the risk factors for development of ARF [defined as a rise in serum creatinine (SCr) >0.3 mg/dl]. The sole primary outcome was the development of ARF. RESULTS: Seventy one of 219 patients received NES. There was no difference in ARF between patients receiving vs not receiving NES (29 vs 20%, P = 0.17). Evaluation of the entire cohort employing forward stepwise regression analysis revealed the following independent predictors of ARF: admission blood urea nitrogen (BUN) [P = 0.0004, odds ratio (OR) = 1.026], and admission brain natiuretic peptide (P = 0.04, OR = 1.0003). We repeated the same analysis for the subgroups of patients receiving or not receiving NES. For patients not receiving NES (n = 148), ARF developed in 30 (20%), with lower estimated glomerular filtration rate and older age being independent predictors. For patients receiving NES (n = 71), ARF developed in 21 (29%), with hypertension, elevated BUN/SCr ratio, and lack of use of angiotensin inhibitors being independent predictors. CONCLUSION: Among all patients with CHF, the use of NES was not an independent risk factor for the development of ARF. However, risk factors for developing ARF differed among patients receiving vs not receiving NES. Comparison of these differing factors suggests that administering NES in the setting of diminished renal perfusion and/or altered renal autoregulation may confer an increased risk of ARF.     

Prevention of acute cyclosporin nephrotoxicity by verapamil and atrial natriuretic factor in the rat

Nephrotexicity is the most common and important side-effectof cyclosporin (CsA) therapy. CsA alters renal haemodynamicswith a reduction in renal blood flow (RBF) and glomerular filtrationrate (GFR) and a significant increase in renal vascular resistances(RVR). The present experimental study investigates whether verapamilor atrial natriuretic factor (ANF) are able to prevent the nephrotoxicityof CsA. All studies were conducted in an in-situ autoperfused rat kidneymodel which allows continuous measurement of renal blood flowwithout dissection of the renal artery. CsA as a 40 mg/kg bolus dose significantly decreased RBF (from2.15±0.1 and 2.19±0.1 before CsA, to 1.29±0.16ml/min/100 g BW, 60 mm after CsA administration) (P<0.05),and GFR (from 0.14±0.1 and 0.13±0.01 before CsA,to 0.08±0.01 ml/min/100 g BW, 60 min after CsA administration)(P<0.05). CsA significantly increased RVR (from 9.5±0.73and 9.8±0.78 before CsA, to 16.7±2.9 mmHgxmin/ml60 min after CsA administration) (P<0.05). Verapamil pretreatment(as continuous intrarenal infusion at the rate of 1.25 µg/kg/min)attenuated the fall in GFR (from 0.16±0.01 and 0.19±0.03ml/min/100 g before CsA to 0.20±0.05 ml/min/100 g BW,60 mm after CsA administration) (NS) and in RBF (from 2.42±0.2and 2.6±0.22 ml/min/100 g before CsA to 1.79±0.17ml/min/100 g BW, 60 min after CsA administration (P<0.05).Pretreatment with ANF (as continuous intrarenal infusion atthe rate of 2.5 µg/kg/min) protected GFR (from 0.11±0.02and 0.18±0.03 ml/min/100 g before CsA, to 0.11±0.03ml/min/100 g BW, 60 min after CsA administration) (NS) and RVR(from 9.53±0.6 and 8.95±0.74 mmHgxmin/ml beforeCsA to 11.93±1.19 minHgxmin/ml, 60 min after CsA administration)(NS)and attenuated the fall in RBF (from 2.17±0.11 and 2.2±0.14ml/min/100g before CsA to 1.56±0.25 ml/min/100 g BW 60mm after CsA administiation)(P<0.05) when compared with initialvalues. These studies suggest that verapamil and ANF can prevent CsA-inducedrenal toxicity. Further studies should evaluate their usefulnessin clinical practice.     

Atrial natriuretic peptide, sodium retention, and proteinuria in nephrotic syndrome

BACKGROUND.: Oedema formation in the nephrotic syndrome is primarily dueto tubular sodium retention. The pathogenetic role of alphaatrial natriuretic peptide (ANP), a hormonal promoter of natriuresisis unknown. METHODS.: In 31 patients (aged 35±11 years) with nephrotic syndromeand histopathological evidence of primary glomerulonephritis,we investigated plasma ANP concentration and its influence onrenal haemodynamics, natriuresis, and proteinuria (total protein,albumin, IgG excretion). Patients with a compensated treatedform of nephrotic syndrome due to primary glomerulonephritiswere included in the study. Serum creatinine levels were 1.4mg/dl. Diuretic medication was discontinued at least 24 h beforethe investigation was started. Patients were randomly assignedto ANP infusion (0.005 µg/kg*min; group II, n=15) or receivedplacebo (group III, n=16). Ten healthy subjects (group I) servedas normal controls. RESULTS.: In normal subjects (group I), ANP caused an increase in natriuresisfrom 14.5±4.2mmol/h to 26.4±11.1 mmol/h (P<0.01).In patients with nephrotic syndrome (group II), baseline sodiumexcretion of 10.5±6.0 mmol/h was increased to 19.6±14.8mmol/h with ANP infusion (P<0.01). No changes were seen inthe placebo group III. The absolute increase in ANP inducednatriuresis was not significantly different between group Iand II. However, plasma ANP levels were significantly higherin patients with nephrotic syndrome (166±87 pg/ml vs.74±21 pg/ml, P<0.05) and also reached higher levelsafter ANP infusion (P<0.01). Therefore, natriuresis was significantlyreduced when circulating ANP levels were taken into account(P<0.05). ANP administration resulted in an increase of totalprotein excretion in patients with the nephrotic syndrome (groupII, from 219±277 mg/h to 264±268 mg/h). Albuminelimination rose from 128±151 mg/h to 167±170mg/h (P<0.05) and IgG excretion from 4.91±6.67mg/hto 9.27±10.78mg/h (P<0.05). Healthy subjects alsoshowed a small but significant increase in albuminuria (48±38%,P<0.05). Low-dose ANP infusion did not, however, induce anysignificant alteration in GFR, ERPF and blood pressure. CONCLUSION.: ANP plasma concentrations in the steady state are elevated inpatients with the nephrotic syndrome. The natriuretic effectof ANP is reduced when referring to circulating ANP plasma levels.Elevated ANP levels enhance urinary protein excretion in thenephrotic syndrome. This is not due to modulation of GFR orFF, but is most probably attributable to increased glomerularpermeability.     

慢性肾衰竭患者血浆NT-proBNP水平的研究

目的探讨慢性肾衰竭患者血浆脑钠肽前体N末端片段（N—terminal-pro—brain natriuretic prptide,NT-proBNP）水平与慢性肾功能不全之间的关系。方法选择临床诊断慢性肾衰竭患者59例,根据肾小球滤过率将患者分为氮质血症期25例、肾衰竭期20例、尿毒症期14例,对照组20例。检测血浆NT—proBNP水平、测量超声心动图并收集患者临床资料。对比不同肾功能状态患者的血浆NT—proBNP水平差异及其与肾功能损害等临床指标及心脏结构功能改变之间的相关性。结果慢性肾衰竭各期患者血浆NT-proBNP水平明显升高,且与左心室后壁厚度、血磷水平正相关,与左室射血分数呈负相关。结论慢性肾衰竭患者血浆NT-proBNP水平升高,其浓度与患者心脏结构和功能的改变以及肾功能下降有关。血浆NT-proBNP水平可作为慢性肾衰竭患者心血管疾病的生化指标。     

The efficacy and safety of B-type natriuretic peptide (nesiritide) in patients with renal insufficiency and acutely decompensated congestive heart failure.

BACKGROUND: Nesiritide (B-type natriuretic peptide) reduces preload and afterload, and causes natriuresis, diuresis and suppression of norepinephrine, endothelin-1 and aldosterone. In this study, we sought to explore the safety and efficacy of nesiritide in patients with acute congestive heart failure (CHF) and renal insufficiency (RI). METHODS: We studied the effects of nesiritide in patients with RI in the VMAC trial database, a multi-centre, randomized controlled trial (n = 489) of patients with acute decompensated CHF. RESULTS: The mean serum creatinine (SCr) in nesiritide-treated patients with RI (SCr > or = 2.0 mg/dl, n = 60, range 2.0-11.1 mg/dl) and without RI (SCr < 2.0 mg/dl, n = 209) was 3.0+/-1.51 and 1.2+/-0.34 mg/dl, respectively. Pulmonary capillary wedge pressure (PCWP) was reduced significantly and similarly in both RI and no RI groups starting at 15 min into nesiritide infusion from a baseline of 29.9+/-8.1 and 26.6+/-6.0 mmHg, respectively. Addition of placebo to standard therapies yielded no further improvement in PCWP in patients with RI; in contrast, nesiritide significantly reduced PCWP at every time point during 24 h. The effects of nitroglycerin were less robust than those of nesiritide, and PCWP was not significantly reduced by nitroglycerin at the 3 h primary end-point. At 24 h, 83% of the RI patients and 91% of patients without RI treated with nesiritide reported improvements in dyspnoea. Nesiritide was well tolerated in patients with RI and no RI, and renal function was preserved in both groups. CONCLUSIONS: In patients with RI, nesiritide was safe and improved haemodynamics and dyspnoea.     

Predictors of mortality in adult patients with congestive heart failure receiving nesiritide--retrospective analysis showing a potential adverse interaction between nesiritide and acute renal dysfunction.

BACKGROUND: A recent meta-analysis has suggested that nesiritide (NES), a new agent for the treatment of congestive heart failure (CHF), is associated with an increased risk of short-term mortality. METHODS: We retrospectively examined this issue among 1407 consecutive elderly CHF patients by Pearson's chi-squared test, and determined independent risk factors for 60-day mortality by multivariate analysis in a cohort of 682 patients for whom we had sufficient clinical and laboratory data. RESULTS: Univariate analysis revealed that NES usage was associated with increased mortality (n=1407, 10 vs 6%, P=0.011; n=682, 19 vs 12.5%, P=0.046). However, by forward stepwise regression analysis, NES usage did not survive as an independent predictor of mortality. The following variables were independent predictors of mortality: development of acute renal failure (ARF) defined as an increase of serum creatinine (SCr) >or= 0.5 mg/dl; lack of beta-adrenergic blockade; increased admission blood urea nitrogen; digoxin use; and increased admission brain natriuretic peptide. When patients were stratified according to NES usage, ARF emerged as an independent risk factor for mortality only among patients who received NES. Strikingly, among CHF patients who developed ARF (n=102), NES usage emerged as the only independent predictor of mortality (P=0.006, OR=3.73, 95% CI 1.45-9.56). CONCLUSION: We conclude that, while NES per se is not independently associated with an increased risk for mortality, the development of ARF in association with NES use may confer an increased risk of mortality.     

Atrial natriuretic peptide and dopamine in established acute renal failure in the rat.

Recent studies have shown that atrial natriuretic peptide (ANP) alone or combined with dopamine (D) markedly improved renal function when given immediately after an ischemic insult. However, the potential beneficial effect of ANP or ANP-D in the established phase of acute renal failure (ARF) and the duration of this effect have not been examined. In the present study atriopeptin III (APIII) and D, sufficient to maintain mean arterial pressure between 100 and 110 mm Hg, or normal saline were given i.v. for four hours to awake Munich-Wistar rats (N = 6 each group) two days after ARF induction with intrarenal norepinephrine (NE). Renal function and morphology were then examined two days after treatment (Day 4). Serum creatinine (SCr) was similarly increased in both groups at the time of APIII-D or saline infusion (Day 2). By Day 4 SCr had decreased to the pre-ARF induction level in APIII-D-treated rats (P less than 0.005), but continued to rise in saline-treated animals (P less than 0.025). Day 4 renal blood flow and glomerular filtration rate (GFR) were higher in APIII-D-compared to the saline-treated group (9.13 +/- 1.14 vs. 4.41 +/- 2.25 ml/min and 0.787 +/- 0.066 vs. 0.370 +/- 0.185 ml/min, respectively, both P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic peptide and N-terminal atrial natriuretic peptide in plasma reflect right ventricular volumes following coronary artery surgery

Background: Atrial natriuretic peptide (ANP) and the more stable N-terminal fragment (N-ANP) of prohormone are peptides, released in equimolar amounts from cardiac myocytes in response to atrial stretch or ventricular overload and myocardial ischaemia. Protection of the right ventricular (RV) myocardium during ischaemia in cardiac surgery is difficult, especially in patients with severe right coronary artery (RCA) disease. This prospective study was designed to ascertain a possible relationship between changes in plasma ANP/N-ANP concentration and RV function in RCA-diseased patients.
Methods: Plasma ANP and N-ANP concentrations and RV function, measured by fast-response thermodilution, were determined serially in 15 patients with total RCA stenosis and in another 15 with no significant RCA disease (controls) before, during and after coronary artery surgery.
Results: The RV ejection fraction was lower and the RV end-systolic volume index higher in the RCA-diseased patients than in the controls ( P < 0.05) on the second postoperative day, and both ANP and N-ANP were higher in the RCA patients ( P < 0.05) from 6 h after cardiopulmonary bypass till the second postoperative day. At the same time the changes in N-ANP concentrations from the levels before induction of anaesthesia correlated with RV ejection fraction and RV volume indexes, but not with heart rate or parameters indirectly reflecting left-sided loading. Right atrial pressure did not differ between the groups nor did it increase significantly during the study.
Conclusions: The relationships found between N-ANP and RV volume indexes and RV ejection fraction suggest ventricular expression of ANP: ANP release may be stimulated by RV distension, the more so the poorer the RV function.     

Diagnostic potential of circulating natriuretic peptides in chronic kidney disease.

BACKGROUND: Measurement of natriuretic peptides, particularly brain natriuretic peptide (BNP) is an established method for the diagnosis of cardiovascular disorders, chiefly left ventricular (LV) dysfunction. The influence of renal function on the diagnostic utility of natriuretic peptides is unclear. METHODS: We performed a cross-sectional study of 296 patients with renal disease but no history of cardiac disease using echocardiography to assess LV mass and function. Circulating levels of atrial natriuretic peptide (ANP) and BNP were also measured. RESULTS: The incidence of LV hypertrophy increased with progressive renal dysfunction; from 39% in patients with near-normal renal function, to 80% in renal transplant patients. There was a negative correlation between both ANP and BNP, and glomerular filtration rate (GFR) (ANP: r = -0.28, P<0.001; BNP: r = -0.40, P<0.001). Serum ANP and BNP had sensitivity and specificity for LV hypertrophy of 39.9%, 87.4% (ANP) and 61.4%, 67.6% (BNP) respectively. Sensitivity and specificity for LV dysfunction was 77.2%, 32.4% (ANP) and 71.8%, 40.0% (BNP). Significant confounders in determining serum ANP were haemoglobin, beta blockade and albumin, while serum BNP levels were significantly confounded by GFR, albumin, haemoglobin, beta blockade and age. CONCLUSIONS: Across a spectrum of renal dysfunction, GFR is a more important determinant of serum BNP than ventricular function, and several factors are predictors of natriuretic peptide levels. In chronic kidney disease, the use of natriuretic peptides to diagnose LV hypertrophy must be interpreted in light of these other factors. The use of these peptides in renal dysfunction to diagnose LV dysfunction may be of limited value.     

B型脑钠肽在围术期心力衰竭的应用

背景 严重心力衰竭时,可能存在内源性脑钠肽相对不足和/或脑钠肽的抵抗.B型脑钠肽(B-type natriuretic peptide,BNP)因在心力衰竭的诊断、治疗及预后判断的特殊价值而备受关注.奈西立肽是重组人脑钠肽,已成为治疗心力衰竭的一种新药.目的 了解BNP与围术期心力衰竭的关系及其重组体--奈西立肽临床应...     

Atrial natriuretic peptide and dopamine in a rat model of ischemic acute renal failure

Atrial natriuretic peptide (ANP) has been shown to reverse experimental models of ischemic acute renal failure (ARF). However, infusion of ANP has been associated with systemic hypotension making its use in clinical ARF impractical. Therefore, in this investigation, dopamine (D) was combined with intravenous (i.v.) atriopeptin III (AP III) to determine if this regimen was effective in reversing ARF while preventing systemic hypotension and maintaining renal blood flow (RBF). Four groups of Munich-Wistar rats were studied. Group 1, sham-ARF; Group 2, renal artery (RA) clamp (55 min) followed by i.v. saline; Group 3, RA clamp followed by i.v. AP III-D; and Group 4, RA clamp followed by i.v. D only. All infusions were begun after RA clamp release and continued for four hour. Mean arterial pressure in Group 3 rats given AP III-D were similar to that in Group 2, slightly less than that in Groups 1 and 4 (P less than 0.05), but consistently greater than 100 mm Hg during the four hour infusion. RBF in Group 3 was elevated above the level in Group 1 at P less than 0.05. Glomerular filtration rate (GFR), depressed by 52% in Group 2, was corrected to control (sham-ARF) levels in Group 3. In Group 4 there was a small but significant increase in GFR compared to Group 2 (P less than 0.05), but it remained less than that in sham-ARF or AP III-D treated ARF rats (P less than 0.01). Urine flow rate and urine sodium excretion rate were more than sixfold higher in Group 3 than any other group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal osteopontin protein and mRNA upregulation during acute nephrotoxicity in the rat.

BACKGROUND: The effect of segment-specific proximal tubular injury on spatio-temporal osteopontin (OPN) distribution was determined in two different nephrotoxic rat models to evaluate its conceivability with a possible role for OPN in acute renal failure (ARF). OPN gene expression was further determined in proximal and distal tubular cells to investigate the origin of increased renal OPN. METHODS: Renal OPN protein and mRNA expression were compared in the rat during mercuric-chloride- vs gentamicin-induced ARF using immunohistochemistry and in situ hybridization. RESULTS: Mercuric chloride primarily induced tubular injury and subsequent cell proliferation in proximal straight tubules (PST), whereas gentamicin predominantly injured proximal convoluted tubules (PCT). In both models, the distribution of OPN protein was associated with increased OPN mRNA levels in proximal as well as distal tubular cells. However, upregulation was delayed in the proximal tubular segment suffering most from injury, i.e. PCT in gentamicin ARF vs PST in mercuric-chloride ARF. OPN immunostaining at the apical cell membrane from distal tubules was in contrast to perinuclear vesicular staining in proximal tubular cells. CONCLUSIONS: OPN gene and protein expression is induced in both proximal and distal tubular cells during rat toxic ARF. The distinct subcellular localization in proximal vs distal tubular cells indicates differences in OPN processing and/or handling. The spatio-temporal distribution is consistent with a possible role in renal injury and regeneration.     

Acyclovir-induced acute renal failure

SUMMARY: Acyclovir is an effective antiviral agent in the treatment of herpes simplex and varicella-zoster viral infections. the best known side-effects of this drug are significant nephrotoxicity and neurotoxicity. We report on a diabetic patient with acute retinal necrosis who developed non-oliguric acute renal failure during the administration of high doses of intravenous acyclovir (500 mg/m² intravenous infusion every 8h). No obvious uremic symptoms or signs were noted. No obvious haematuria, proteinuria or crystalluria were noted in the urine. After discontinuing the acyclovir administration, renal function partially recovered. In this paper, we also review the mechanism of acyclovir-induced acute renal failure, and the precipitating factor of acyclovir-induced acute renal failure. Finally, we must once again emphasize the importance of hydration and routine check ups for renal function in preventing acyclovir-induced acute renal failure.