Effects of sulindac on renal function and prostaglandin synthesis in patients with moderate chronic renal insufficiency

1986 ◽  
Vol 70 (5) ◽  
pp. 501-505 ◽  
Author(s):  
C. D. Mistry ◽  
C. J. Lote ◽  
R. Gokal ◽  
W. J. C. Currie ◽  
M. Vandenburg ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Insufficiency ◽  
Creatinine Clearance ◽  
Chronic Renal Disease ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Breakdown Product ◽  
Predisposing Factor ◽  
A Minor ◽  
Therapeutic Doses

1. The renal effects of therapeutic doses of sulindac were studied in nine patients with stable renal insufficiency, mean creatinine clearance 37.0 ± 2.2 ml min−1 1.73 m−2 (range 24.7–54.6 ml min−1 1.73 m−2). 2. Nine days' treatment with sulindac produced a small, but significant, reduction in the mean creatinine clearance (37.0 ± 2.2 to 34.7 ± 2.2 ml min−1 1.73 m−2; P < 0.02) and 99mTc diethylenetriaminepenta-acetate (DTPA) clearance (35.5 ± 3.4 to 31.4 ± 3.6 ml min−1 1.73 m−2; P < 0.02) without altering body weight, effective renal plasma flow [131I]hippuran clearance), plasma renin activity (PRA), 24 h urinary volume or electrolyte excretion. 3. After discontinuation of sulindac, creatinine clearance returned to pretreatment values. 4. In five female patients, pretreatment urinary excretion of the 6-ketoprostaglandin F1α (6-keto-PGF1α), a stable breakdown product of prostacyclin (PGI2), was significantly reduced (P < 0.02) when compared with four healthy controls, whereas prostaglandin E2 (PGE2) was unchanged. Administration of sulindac did not significantly alter the excretion rate of PGE2 or 6-ketoPGF1α in this group of patients. 5. In chronic renal disease with moderate renal impairment, reduced renal prostacyclin synthesis may be an important predisposing factor to the renal toxicity associated with the use of nonsteroidal anti-inflammatory drugs (NSAID). Short term use of sulindac in therapeutic doses does not appear to influence the excretion of prostaglandins and produces only a minor reversible change in renal function; used cautiously it may have advantages over other NSAID in these patients.-

Chronic effects of oral sulindac on renal haemodynamics and hormones in subjects with chronic renal disease

1986 ◽  
Vol 70 (3) ◽  
pp. 243-247 ◽  
Author(s):  
Charles P. Swainson ◽  
Peter Griffiths ◽  
Michael L. Watson
Keyword(s):  
Renal Function ◽  
Filtration Rate ◽  
Chronic Renal Disease ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Hormonal Control ◽  
Glomerular Function ◽  
Chronic Effects ◽  
Plasma Hormones

1. The effects of oral sulindac, 600 mg daily, on renal function and plasma hormones were studied in eight subjects with chronic renal failure. 2. Renal function and plasma hormones were measured before drug administration and then after taking sulindac for 28 days. 3. Effective renal plasma flow was reduced in all subjects after 28 days but the glomerular filtration rate did not change. 4. Plasma renin activity, potassium and aldosterone concentrations and urinary sodium excretion did not change but urinary prostaglandin E2 excretion fell significantly. 5. Sulindac may be a relatively renal-sparing drug in its effects on the hormonal control of glomerular function.

Intrarenal renin inhibition increases renal function by an angiotensin II-dependent mechanism

1988 ◽  
Vol 255 (4) ◽  
pp. F749-F754 ◽  
Author(s):  
H. M. Siragy ◽  
N. E. Lamb ◽  
C. E. Rose ◽  
M. J. Peach ◽  
R. M. Carey
Keyword(s):  
Renal Function ◽  
Angiotensin Ii ◽  
Sodium Intake ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Competitive Inhibitor ◽  
Urinary Flow ◽  
Renin Substrate ◽  
Plasma Aldosterone Concentration ◽  
Renin Inhibition

ACRIP is a competitive inhibitor of renin in which an analogue of statine, (3R,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of porcine renin substrate. ACRIP inhibits the enzymatic activity of renin, thus blocking the initiation of the angiotensin cascade. We studied the intrarenal action of ACRIP in small quantities without measurable systemic effects on renal function. In the first experiment, ACRIP was administered intrarenally at 0.02, 0.2, and 2 micrograms.kg-1.min-1 to uninephrectomized conscious dogs (n = 6) in metabolic balance at sodium intake of 10 meq/day. ACRIP, in doses of 0.02 and 0.2 micrograms.kg-1.min-1, markedly increased urine sodium excretion (UNaV) from 5.8 +/- 1.4 to 15.1 +/- 5.1 and 19.9 +/- 3.2 mu eq/min, respectively. Urinary flow rate (UV) underwent a similar increase and glomerular filtration rate (GFR) increased from 25.7 +/- 2.5 to 35.6 +/- 2.5 at 0.02 micrograms.kg-1.min-1 of ACRIP. Renal plasma flow (RPF), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were not affected. At 2 micrograms.kg-1.min-1, ACRIP traversed the kidney in quantities large enough to produce a reduction in systemic PRA and mean arterial pressure and caused natriuresis, diuresis, and increased GFR. In a second experiment, ACRIP was administered intrarenally at 0.2 micrograms.kg-1.min-1 in a separate group (n = 4) under identical conditions. ACRIP-induced increases in UV and UNaV were completely blocked by concurrent intrarenal administration of angiotensin II. The results indicate that intrarenal angiotensin II acts as a physiological regulator of renal sodium and fluid homeostasis.

Low-flow Sevoflurane Compared with Low-flow Isoflurane Anesthesia in Patients with Stable Renal Insufficiency

2002 ◽  
Vol 97 (3) ◽  
pp. 578-584 ◽  
Author(s):  
Peter F. Conzen ◽  
Evan D. Kharasch ◽  
Stephan F. A. Czerner ◽  
Alan A. Artru ◽  
Florian M. Reichle ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Insufficiency ◽  
Serum Creatinine ◽  
Creatinine Clearance ◽  
Blood Urea Nitrogen ◽  
Gas Flow ◽  
Minimum Alveolar Concentration ◽  
Low Flow ◽  
Sevoflurane Anesthesia ◽  
Urine Protein

Background Sevoflurane is degraded to compound A (CpA) by carbon dioxide absorbents containing strong base. CpA is nephrotoxic in rats. Patient exposure to CpA is increased with low fresh gas flow rates, use of Baralyme, and high sevoflurane concentrations. CpA formation during low-flow and closed circuit sevoflurane anesthesia had no significant renal effects in surgical patients with normal renal function. Preexisting renal insufficiency is a risk factor for postoperative renal dysfunction. Although preexisting renal insufficiency is not affected by high-flow sevoflurane, the effect of low-flow sevoflurane in patients with renal insufficiency is unknown. Methods After obtaining institutional review board approval, 116 patients with a stable preoperative serum creatinine concentration 1.5 mg/dl or greater were assessable. Patients were randomized to receive either sevoflurane (n = 59, 0.8-2.5 vol%) or isoflurane (n = 57, 0.5-1.4 vol%) at a fresh gas flow rate of 1 l/min or less. Use of opioids was restricted to a minimum, and Baralyme was used to increase CpA exposure. Inspiratory and expiratory CpA concentrations were measured during anesthesia. Renal function (serum creatinine and blood urea nitrogen, urine protein and glucose, creatinine clearance) was measured preoperatively and 24 and 72 h after induction. Results Demographic patient data did not differ between groups. Patients received 3.1 +/- 2.4 minimum alveolar concentration-hours sevoflurane or 3.8 +/- 2.6 minimum alveolar concentration-hours isoflurane (mean +/- SD). Durations of low flow were 201.3 +/- 98.0 and 213.6 +/- 83.4 min, respectively. Maximum inspiratory CpA with sevoflurane was 18.9 +/- 7.6 ppm (mean +/- SD), resulting in an average total CpA exposure of 44.0 +/- 30.6 ppm/h. There were no statistically significant changes from baseline to 24- and 72-h values for serum creatinine or blood urea nitrogen, creatinine clearance, urine protein, and glucose, nor were there significant differences between both anesthetics. Conclusion There were no statistically significant differences in measured parameters of renal function after low-flow sevoflurane anesthesia compared with isoflurane. These results suggest that low-flow sevoflurane anesthesia is as safe as low-flow isoflurane and does not alter kidney function in patients with preexisting renal disease.

Use of Therapeutic Dose Low Molecular Weight Heparin in Patients with Renal Insufficiency: Analysis of Anti-Xa Levels and Creatinine Clearance.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 884-884
Author(s):  
Wendy Lim ◽  
Manasa Sridhara ◽  
Luqi Wang ◽  
Krystyna Kinnon ◽  
James Douketis ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Creatinine Clearance ◽  
Therapeutic Dose ◽  
Low Molecular Weight Heparin ◽  
Dose Adjustment ◽  
Low Molecular Weight ◽  
Recurrent Vte ◽  
Dependent Patient

Abstract Low molecular weight heparin (LMWH) is predominantly eliminated by the kidneys. In patients with severe renal impairment, use of therapeutic dose LMWH may be associated with accumulation and a resultant bleeding risk. Tinzaparin may be less dependent on renal clearance due to its higher molecular mass and greater negative charge compared to other LMWHs. The objective of this prospective cohort study was to serially measure the anti-Xa anticoagulant effect of therapeutic dose tinzaparin over 5–7 days, used for the initial treatment of venous thromboembolism (VTE) in patients with varying degrees of renal insufficiency. We present the anti-Xa results from the first 78 patients enrolled in the study, correlated with renal function. In this study, consecutive in- and outpatients with objectively confirmed VTE requiring anticoagulation were enrolled and stratified into 4 groups based on the calculated Cockcroft-Gault creatinine clearance (CrCl): &gt; 60 mL/min, 30–60 mL/min, ≤ 30 mL/min and hemodialysis-dependent. Tinzaparin 175 IU/kg was administered subcutaneously once daily for 5–7 days or until the INR ≥ 2.0 with warfarin therapy. Trough anti-Xa levels were measured prior to the 3rd, 5th and/or 7th tinzaparin doses. Patients with anti-Xa level &gt; 0.5 IU/mL received tinzaparin dose adjustment using a standardized nomogram. Bleeding and recurrent VTE events were recorded. The relationship between anti-Xa levels and CrCl is shown in Figure 1. Based on our predefined anti-Xa threshold of 0.5 IU/mL, 5 of 78 patients (6.4%) required dose adjustment; 1 hemodialysis dependent patient, 2 patients with CrCl &lt; 30 mL/min, 1 patient each with CrCl 30–60 and &gt; 60 mL/min, respectively. None of these patients developed bleeding or recurrent VTE. Among all 78 patients, 1 hemodialysis-dependent patient developed a hematoma following a traumatic line insertion, and no patients developed recurrent VTE. In conclusion, in a cohort of 78 patients with differing degrees of renal function including patients requiring hemodialysis, use of therapeutic-dose tinzaparin for the initial treatment of VTE resulted in accumulation (defined by trough anti-Xa &gt; 0.5 IU/mL) in 6% of patients. There appears to be a weak inverse relationship between renal function and trough anti-Xa levels, but does not result in clinically significant accumulation when tinzaparin is used for up to 7 days. Further evaluation of tinzaparin in patients with severe renal insufficiency is required. Figure Figure

The Use of Frusemide and Propranolol in the Treatment of the Hypertension of Chronic Renal Disease

1974 ◽  
Vol 19 (1_suppl) ◽  
pp. 25-32 ◽  
Author(s):  
R. Wilkinson ◽  
Mary Pickering ◽  
Valerie Robson ◽  
R. W. Elliott ◽  
D. N. S. Kerr
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Renal Disease ◽  
Serum Creatinine ◽  
Marked Reduction ◽  
Chronic Renal Disease ◽  
Plasma Renin ◽  
Sodium Retention ◽  
Exchangeable Sodium ◽  
Standing Blood Pressure

Nine patients with renal disease, hypertension and impairment of renal function of varying degree have been studied before and during treatment with frusemide. In three patients observations were repeated following the addition of propranolol. In most cases frusemide resulted in a reduction of both lying and standing blood pressure but for the group the fall was not significant (P>0.05). In all patients a reduction in exchangeable sodium was achieved and the fall was significant for the group (P<0.05); this was accompanied by a significant increase in serum creatinine (P < 0.05). Plasma renin activity was increased in all patients during treatment with frusemide and the change for the group was significant (P<0.05). The addition of propranolol resulted in a marked reduction in renin in the three patients treated but in two blood pressure actually rose; in these two sodium retention had occurred following the introduction of propranolol.

Systemic hemodynamics and renal function during long-term pathophysiological increases in circulating endothelin

1995 ◽  
Vol 268 (2) ◽  
pp. R375-R381 ◽  
Author(s):  
F. C. Wilkins ◽  
A. Alberola ◽  
H. L. Mizelle ◽  
T. J. Opgenorth ◽  
J. P. Granger
Keyword(s):  
Renal Function ◽  
Renal Plasma Flow ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Chronic Hypertension ◽  
Systemic Hemodynamic ◽  
Endothelin 1 ◽  
Control Value ◽  
Renal Vascular

Although recent studies have reported endogenous plasma endothelin levels to be elevated two- to fivefold in chronic pathophysiological states, whether such an increase in circulating endothelin levels alone can lead to significant long-term alterations in cardiovascular and renal function is not known. The purpose of this study was to examine the long-term systemic hemodynamic and renal effects of a pathophysiological increase in plasma endothelin concentration in chronically instrumented, conscious dogs (n = 7). Infusion of endothelin-1 (2.5 ng.kg-1.min-1) for 8 days increased plasma concentration of immunoreactive endothelin approximately two- to threefold from 6.7 +/- 0.4 to 16.0 +/- 2.2 pg/ml. Mean arterial pressure increased 21% from a control value of 86.7 +/- 2.1 to 105.0 +/- 2.5 mmHg during the endothelin infusion period. Cardiac output averaged 2,200 +/- 205 ml/min during control and fell by 33% on day 4 of endothelin infusion (1,484 +/- 146 ml/min) and was still 14% below control after day 8 of endothelin infusion (1,885 +/- 154 ml/min). Endothelin increased total peripheral resistance from 42.0 +/- 3.1 to 80.3 +/- 9.1 mmHg.l-1.min. Increasing plasma endothelin two- to threefold was associated with an increase in renal vascular resistance and decreases in glomerular filtration rate and renal plasma flow. Endothelin-1 had no long-term effect on plasma renin activity or aldosterone concentration. These data indicate the importance of pathophysiological levels of endothelin in controlling renal and cardiovascular function in chronic conditions. Furthermore, the results indicate that endothelin may play a role as a mediator of chronic hypertension in pathophysiological states associated with endothelial dysfunction.

Renal Function in Obstructive Nephropathy: Long-Term Effect of Reconstructive Surgery

PEDIATRICS ◽  
1975 ◽  
Vol 56 (5) ◽  
pp. 740-747
Author(s):  
Georges Mayor ◽  
Noël Genton ◽  
Antonio Torrado ◽  
Jean-Pierre Guignard
Keyword(s):  
Renal Function ◽  
Renal Insufficiency ◽  
Reconstructive Surgery ◽  
Renal Plasma Flow ◽  
Solitary Kidney ◽  
Obstructive Nephropathy ◽  
First Year ◽  
Long Term Effect ◽  
One Year ◽  
First Year Of Life

Renal function was studied in 24 children with chronic hydronephrosis and renal insufficiency. The follow-up period after reconstructive surgery was 1 to 12 years. Glomerular filtration rate (GFR) was assessed by the clearance of endogenous creatinine or inulin. Effective renal plasma flow was assessed by the clearance of PAH. Reconstructive surgery was performed during the first year of life in 12 out of 24 patients, between one and two years of life in 6 patients, and after two years of life in 6 patients. Three different patterns of evolution could be observed after relief of obstruction: (1) An improvement or a normalization of renal function only occurred in patients operated upon before one year of life. (2) A stabilization of renal function without normalization was observed in patients operated upon between one and two years of life. (3) A pro-gressive deterioration of renal function towards terminal renal failure was observed in five out of six patients operated upon after two years of age. This deterioration could not be explained by recurrence of detectable urinary tract infection or urinary stasis. The changes in GRF in four patients with a solitary kidney followed the same pattern. We conclude that it is essential to correct severe chronic hydronephrosis associated with renal insufficiency before one year of age if a lasting improvement of renal function is to be expected.

Renal Effects of Angiotensin I-Receptor Blockade and Angiotensin Convertase Inhibition in Man

1996 ◽  
Vol 90 (3) ◽  
pp. 205-213 ◽  
Author(s):  
Francois Schmitt ◽  
Svetlozar Natov ◽  
Frank Martinez ◽  
Bernard Lacour ◽  
Thierry P. Hannedouche
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Plasma Renin Activity ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Renin Activity ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibition

1. The objective was to compare two means of inhibition of the renin—angiotensin system [angiotensin-converting enzyme inhibition and selective antagonism of angiotensin II subtype 1 (AT1) receptor] on renal function in 10 healthy normotensive volunteers on a normal sodium diet. Since mechanisms of action may differ between both drugs, a synergistic action was further studied by combining the two drugs. 2. The design was a double-blind randomized acute administration of either placebo or a single oral dose of enalapril, 20 mg, followed in each case by administration of the AT1 selective antagonist losartan potassium, 50 mg orally. 3. The methods included measurements of hormones (plasma renin activity, plasma aldosterone), blood pressure and renal function from 45 to 135 min after administration of placebo or enalapril, and from 45 to 135 min after losartan and placebo or losartan and enalapril. Renal function was studied using clearance of sodium, lithium, uric acid, inulin and para-aminohippuric acid. To examine further the determinants of glomerular filtration at the microcirculation level, fractional clearance of neutral dextran was determined and sieving curves were applied on a hydrodynamic model of ultrafiltration. 4. Losartan did not change plasma renin activity, blood pressure or glomerular filtration rate, but increased significantly renal plasma flow and urinary excretion of sodium and uric acid. Enalapril increased plasma renin activity and renal plasma flow, and decreased blood pressure without natriuretic, lithiuretic or uricosuric effects. The renal vasodilatation was potentiated when losartan and enalapril were combined, despite a further rise in plasma renin. In contrast to enalapril, losartan either alone or in combination with enalapril significantly depressed fractional clearances of dextran of small radii (34–42 Å). These changes in fractional clearances of dextran were presumably related to the rise in glomerular plasma flow since the other major determinants of filtration, i.e. transcapillary glomerular pressure gradient, ultrafiltration coefficient and membrane property, were computed as unchanged by either losartan, enalapril or a combination of both. 5. In conclusion, these findings suggest that in normal sodium-repleted man the renal, hormonal and blood pressure effects of AT1 antagonism and angiotensin-converting enzyme inhibition are not strictly similar and could be synergistic.

Evidence that dopamine-2 mechanisms control renal function

1990 ◽  
Vol 259 (5) ◽  
pp. F793-F800 ◽  
Author(s):  
H. M. Siragy ◽  
R. A. Felder ◽  
N. L. Howell ◽  
R. L. Chevalier ◽  
M. J. Peach ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Urinary Flow ◽  
Plasma Aldosterone Concentration ◽  
Arterial Blood ◽  
Ly 171555 ◽  
Renal Vascular ◽  
Dose Dependent

Dopamine is synthesized by the kidney, and dopamine-2 (DA2) receptors are present in the renal glomerulus. However, no role for DA2 receptors in the kidney has been defined. We investigated the possible role of DA2 receptors in control of renal function by intrarenal infusion of a highly specific DA2 antagonist YM-09151 (YM), in conscious uninephrectomized dogs (n = 5) in metabolic balance at Na intake 40 meq/day. YM infused at 0.01 pmol.kg-1.min-1 did not cause any changes in urinary flow rate or Na excretion. Administration of YM (infusions from 0.1 to 10.0 pmol.kg-1.min-1) caused a significant dose-dependent diuresis (F = 20.3; P less than 0.001) and natriuresis (F = 35.2; P less than 0.0001) and an increase in glomerular filtration rate (F = 45.4; P less than 0.0001), renal plasma flow (F = 209.3; P less than 0.0001), and filtration fraction (F = 11.2; P less than 0.0001). No significant changes in plasma renin activity, plasma aldosterone concentration, or mean arterial blood pressure occurred with any of the doses of YM infused into the renal artery. Coinfusion of LY-171555, a specific DA2 agonist, at a dose that itself did not affect renal function, completely abrogated the renal hemodynamic and excretory changes induced by YM. The data suggest that dopamine produced intrarenally may act at renal vascular and/or glomerular DA2 receptors to control renal function.

scholarly journals Glurenorm in diabetic nephropathy: effects on renal function and vascular endothelium

1996 ◽  
Vol 42 (2) ◽  
Author(s):  
M. V. Shestakova ◽  
M. Sh. Shamkhalova ◽  
T. T. Ukhanova ◽  
M. G. Ryndina ◽  
I. I. Dedov
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Renal Insufficiency ◽  
Vascular Endothelium ◽  
Chronic Renal Insufficiency ◽  
Renal Involvement ◽  
Dependent Diabetes Mellitus ◽  
Antiproteinuric Effect ◽  
Initial Stage ◽  
Therapeutic Doses

Study of the effects of glurenorm, an oral sugar- reducing drug, on renal function and vascular endothelium in patients with noninsulin-dependent diabetes mellitus at different stages of diabetic involvement of the kidneys, including those with chronic renal insufficiency, revealed that glurenorm in therapeutic doses had no nephrotoxic effect; moreover, it maintained the filtration function of the kidneys even in patients with the initial stage of chronic renal insufficiency (with blood serum creatinine of up to 200 mmol/liter. Therapy with glurenorm for 3 and 6 months caused a reliable reduction of the production of thromboxane A, a vasoconstrictor, this probably improving the intrarenal hemodynamics, and exerting an antiproteinuric effect in patients with manifest diabetic nephropathy. At the same time, glurenorm therapy did not appreciably influence the production of factors released by vascular endothelium (prostacyclin and endothelin-1). Hence, a detailed study of renal function and vascular endothelium in patients with type II diabetes demonstrated that administration of glurenorm to patients with manifest renal involvement was not only safe, but even favorably affected the intrarenal hemodynamics and had an antiproteinuric effect.

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