Clinical effects of intravenous nifedipine on renal function

Nifedipine, a calcium antagonist, was administered intravenously (13.3 micrograms/min) for 45 min, and the changes in blood pressure, glomerular filtration rate (GFR), renal blood flow (RBF), total renal resistance, urinary volume, urinary sodium and potassium excretion, plasma renin activity, and plasma aldosterone concentration were studied. GFR and RBF were measured by intravenous infusion of sodium thiosulfate and sodium para-aminohippurate, respectively. The subjects included 12 cases of essential hypertension, nine of chronic glomerular nephritis with hypertension, 14 of chronic glomerular nephritis without hypertension, and 12 normotensive controls. In patients with essential hypertension, GFR and RBF increased markedly (by 45.6% and 44.8%, respectively), but in normotensive and hypertensive patients with chronic glomerular nephritis, these indices did not change significantly. The urinary volume and urinary sodium excretion increased in all groups. The natriuresis induced by nifedipine is probably due to the increase of GFR and RBF. The results of this study suggest a difference in renal vascular pathophysiology between essential hypertension and chronic glomerular nephritis. The results also suggest a functional change of the renal vascular system in essential hypertension, i.e., the increased vascular tone and the particular sensitivity of renal arterioles to nifedipine.     

Effect of race on hypertension and antihypertensive therapy

The presence of hypertension in individual patients confers significant risk in terms of coronary artery disease, myocardial infarction, stroke and congestive heart failure. However, it is also a modifiable risk factor, as risk may be decreased through either lifestyle changes or pharmacotherapy to reduce the elevated blood pressure. Over the past 3 decades, there has been strenuous debate among clinical scientists regarding the role played by racial background in both the pathogenesis and response to pharmacotherapy. A number of studies, such as the third National Health and Nutrition Examination Survey (NHANES III) have demonstrated a higher prevalence of hypertension in black populations. The Hispanic Health and Nutrition Examination Survey (HHANES) suggested that the prevalence of hypertension in Hispanics of Caribbean descent was similar to that of African Americans, while Mexican Americans had lower rates of the disease. It appears that the pathophysiological consequences of elevated blood pressure may also be more severe in black patients. Thus, these patients will have a worse prognosis than their white counterparts at any given blood pressure level. The incidence of end-stage renal disease has been reported to be as much as 17 times more common in African American patients. A number of individual factors have been postulated for these differences including increased sodium intake, differences in sodium handling, decreased potassium intake, decreased calcium intake, elevated fasting insulin levels, lower levels of plasma renin activity and urinary kallikrein excretion. These differences in prevalence and pathophysiology have resulted in recommendations for differential therapeutic approaches in the treatment of hypertension. A major trial conducted in the Veteran Affairs Medical Centers in the USA noted that African Americans are generally more responsive to diuretics and calcium channel blockers than to ACE inhibitors or beta-blockers. However, it has been reported that this resistance may be overcome by increasing the dose of these agents. It has been postulated that these differences may be related to lower plasma renin activity noted in the black population, since diuretics and calcium channel blockers appear to be better suited to this population. These differential therapeutic recommendations will be reviewed in light of our current knowledge of the disease.     

Use of renal artery infusion in dogs for evaluation of diuretics

In this paper we report on a series of experiments evaluating a model of renal artery infusion (RAI) as a screening technique for comparison of new diuretics, and test some assumptions underlying its use. The femoral artery and vein of Beagle dogs were catheterized for the infusion of solutions, measurement of arterial blood pressure and the sampling of arterial blood. The left kidney was isolated through a flank incision, and a 27 ga. needle, connected to PE10 tubing, was inserted into the renal artery for administration of test diuretics. Both ureters were catheterized for collection of urine. Effects on renal function were assessed during control, drug infusion, and recovery periods. At low doses, the loop diuretics, furosemide (FUR) and MK447, increased urinary excretion within the first 15 min of infusion. The effect of muzolimine, another loop diuretic, was delayed until about 45 min after initiation of infusion. Renal function returned to baseline after cessation of drug infusion. At high doses, excretion was increased by all the loop diuretics within the first 15 min of infusion. The response to muzolimine and MK447 was prolonged well into the recovery period, while that to furosemide returned promptly to baseline. Two distal diuretics, hydrochlorothiazide and amiloride, caused a significant increase in urinary excretion at both low and high doses. The magnitude of the response was significantly less than for the loop diuretics. Low doses of the loop diuretics had very little effect on the contralateral kidney; however, at high doses the excretion rate of the contralateral kidney was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanism of action of xipamide and its classification as a "low ceiling diuretic". Pharmacodynamic-pharmacokinetic studies in healthy volunteers and in kidney and liver patients

Xipamide (CAS 14293-44-8) shows structural features comparable with the thiazide- as well as the class of loop diuretics. According to earlier findings this diuretic, in contrast to the thiazides, should not decrease the glomerular filtration rate (GFR) and be effective even in patients with advanced renal failure. Therefore recently the question, which class of diuretics xipamide should be related to, has been increasingly discussed. In order to solve this issue, the diuretic effect of xipamide was assessed in healthy volunteers once without and once under strict water and salt restriction. Additionally, changes in GFR were monitored by means of measurement of the creatinine clearance. Kinetic parameters were determined in plasma and urine; further, in patients with liver cirrhosis, renal elimination kinetics of the diuretic were correlated with the concentration of direct plasma bilirubin, as a marker of cholestasis, at the beginning of a treatment with xipamide, 40 mg qd. The investigations proved that xipamide, like a typical thiazide diuretic, gives rise to a temporary decrease in GFR of about 30 %, provided the renin-angiotensin-aldosterone system of the volunteer is activated by previous salt and water restriction. Xipamide leads to an increase of K+ and Mg2+ excretion, but to a decrease of Ca2+ excretion in urine, a charactaristical feature of the thiazide-like diuretics. The correlation between Na+ excretion and drug excreted in urine over time showed a functional graph that is characteristic for a "low ceiling" thiazide diuretic. In patients with renal failure FE(Na) was increased when related to the GFR-adjusted drug excretion rate, whereas it was diminished in conditions with decreased effective circulating volume like in liver cirrhosis with ascites. It could be shown that the elimination kinetics of xipamide are determined by renal drug clearance, which proportionally decreases with GFR. In patients with liver failure, a decrease of non-renal drug clearance went along with an increase in urinary drug excretion. The amount of drug excreted in urine (Ae) proportionally increased with the concentration of the patients' direct plasma bilirubin. Thus, from a pharmacological as well as clinical point of view xipamide acts like a thiazide diuretic. As could be shown for other thiazides some time ago, xipamide is effective not only in patients with cardiovascular diseases, but also in those with advanced renal failure.     

Calcium Channel Blockade and Renal Function

Abstract: Since calcium channel blocking agents were introduced into the treatment of hypertension their influence on renal function has become an important issue. In animal experiments calcium channel blocking agents have been shown to increase renal blood flow and glomerular filtration rate and to augment urine flow and electrolyte excretion. In human acute studies the administration of calcium channel blocking agents have elicited similar renal hemodynamic and diuretic effects. Clinical studies on the renal effects of long-term treatment are however still lacking. Studies on the effect on renin release have given divergent results. In acute experiments renin release is increased by calcium channel blocking agents. En long-term treatment, however, no change in peripheral plasma levels of renin has been demonstrated. The influence of decreased renal function on the pharmacokinetics of calcium channel blocking agents has been studied in patients with renal disease. For verapamil the volume of distribution is smaller in uremic patients than in normals and both metabolic and renal clearances are decreased. For nifedipine, on the other hand, similar plasma levels, plasma half life and total plasma clearance are found in uremic patients and normal subjects.     

Endogenous cardiac glycoside-like substances in newborns, adults, pregnant women and patients with hypertension or renal insufficiency

In an attempt to confirm the presence of endogenous substances with cardiac glycoside-like activity, the biological and immunological cardiac glycoside-like activity was measured by a sensitive solid-phase radioimmunological assay (RIA), two radioreceptor assays (RRA), and a 86Rb uptake method in normal subjects and in some pathophysiological conditions characterized by sodium retention and volume expansion. Significant concentrations of digoxin-like immunoreactive substances (DLIS) were measured in plasma (or serum) of normal subjects while significantly higher levels were found in pregnant women, newborns and in patients with renal impairment, and in some with essential hypertension. Concentrations in urine of normal adults or newborns were several times higher than in plasma. The results obtained by RIA correlated with those obtained by RRA and 86Rb uptake methods. In 88 normal subjects, DLIS excretion rates (overnight urine collection) in men were significantly higher than in women (68.6 +/- 23.6 pg/min vs 50.9 +/- 21.0 pg/min, p less than 0.01). The DLIS excretion rates correlated with creatinine, Na and K urinary excretion rates, and also with the subjects' body weight, height, body mass index, and systolic blood pressure. These findings confirm the presence of endogenous substances with immunological and biological activity similar to cardiac glycosides in human body fluids and also confirm the hypothesis that these endogenous factors may be involved in fluid and electrolyte regulation in man. In addition, the present data indicate that urinary excretion of DLIS is dependent on body mass and renal glomerular filtration.     

Blood pressure lowering for the prevention and treatment of diabetic kidney disease

The current pandemic of diabetes mellitus will inevitably be followed by an epidemic of chronic kidney disease. It is anticipated that 25-40% of patients with type 1 diabetes and 5-40% of patients with type 2 diabetes will ultimately develop diabetic kidney disease. The control of blood pressure represents a key component for the prevention and management of diabetic nephropathy. There is a strong epidemiological connection between hypertension in diabetes and adverse outcomes in diabetes. Hypertension is closely linked to insulin resistance as part of the 'metabolic syndrome'. Diabetic nephropathy may lead to hypertension through direct actions on renal sodium handling, vascular compliance and vasomotor function. Recent clinical trials also support the utility of blood pressure reduction in the prevention of diabetic kidney disease. In patients with normoalbuminuria, transition to microalbuminuria can be prevented by blood pressure reduction. This action appears to be significant regardless of whether patients have elevated blood pressure or not. The efficacy of ACE inhibition appears to be greater than that achieved by other agents with a similar degree of blood pressure reduction; although large observational studies suggest the risk of microalbuminuria may be reduced by blood pressure reduction, regardless of modality. In patients with established microalbuminuria, ACE inhibitors and angiotensin receptor antagonists (angiotensin receptor blockers [ARBs]) consistently reduce the risk of progression from microalbuminuria to macroalbuminuria, over and above their antihypertensive actions. The clinical utility of combining these strategies remains to be established. In patients with overt nephropathy, blood pressure reduction is associated with reduced urinary albumin excretion and, subsequently, a reduced risk of renal impairment or end stage renal disease. In addition to actions on systemic blood pressure, it is now clear that ACE inhibitors and ARBs also reduce proteinuria in patients with diabetes. This anti-proteinuric activity is distinct from other antihypertensive agents and diuretics. Although there is a clear physiological rationale for blockade of the renin angiotensin system, which is strongly supported by clinical studies, to achieve the optimal lowering of blood pressure, particularly in the setting of established diabetic renal disease, a number of different antihypertensive agents will always be needed. In the end, the choice of agents should be individualised to achieve the maximal tolerated reduction in blood pressure and albuminuria. Ultimately, no matter how it is achieved, so long as it is achieved, renal risk can be reduced by agents that lower blood pressure and albuminuria.     

Antihypertensive and hypouricaemic effects of nitrendipine in chronic renal failure

Summary To evaluate the potential therapeutic value of calcium antagonists in hypertension associated with impaired renal function, blood pressure (BP), certain regulatory factors, and metabolic correlates of cardiovascular risk have been assessed in 15 patients with mild to marked chronic renal failure before and after 6 weeks of therapy with nitrendipine.Compared to placebo, nitrendipine (mean final dose 55 mg/day) decreased supine BP from 173/102 to 146/81 mm Hg and upright BP from 170/105 to 145/86 mm Hg. Heart rate, body weight (+0.8 kg) and exchangeable sodium (+176 mmol, not significant) were minimally increased, and plasma and whole blood volume, plasma angiotensin II and creatinine concentrations, and urinary electrolyte and creatinine excretion were not significantly changed.Nitrendipine increased uric acid excretion and lowered plasma uric acid by 24%; glucose, insulin, serum total lipids, and lipoprotein fractions were unchanged.     

Acute effect of indapamide on urine calcium excretion in nephrolithiasis and human essential hypertension

The effects of indapamide (2.5 mg once a day) on urinary composition are reported in 20 patients (10 with recurrent calcium nephrolithiasis and 10 with essential hypertension) compared with 20 controls. Indapamide was well absorbed in every patient (mean plasma level at the steady state was 111 +/- 41 ng/ml) and its antihypertensive action was more pronounced in hypertensive than in normotensive patients. It lowered calcium excretion in 18/20 patients (mean fall on the 7th day of treatment: 53%) and raised the Mg/Ca ratio in 20/20 patients (mean increase on the 7th day: 167%). The effect on Ca2+ and Mg2+ excretion was not associated with a strong diuretic effect. During intravenous calcium loading (0.375 mmol/kg body weight) 6 normal subjects after a single oral dose of indapamide excreted less calcium, suggesting a direct renal hypocalciuric action by the drug. Indapamide could represent an alternative drug to thiazide diuretics in diseases with dangerous renal calcium losses, but long-term studies are needed.     

Renal effects of the new calcium channel blocking drug isradipine

Summary The acute effect of a single oral dose of isradipine 5 mg on blood pressure, renal haemodynamics, electrolyte excretion and plasma renin activity was studied in 10 healthy males.Isradipine did not produce a significant change in systolic or diastolic blood pressure, and glomerular filtration rate, renal plasma flow, renal vascular resistance, and urinary albumin excretion remained constant. There was a marked natriuretic and diuretic effect about 1–3 h after isradipine. Plasma renin activity showed a slight, insignificant increase 1 h after dosing. Uric acid clearance and 2-microglobulin excretion showed no significant changes, despite an increase in sodium clearance, suggesting an additional mechanism of action other than the proximal tubular natriuretic effect of isradipine in normotensive volunteers.     

临床药师参与 1例大剂量甲氨蝶呤排泄延迟的案例分析

目的 通过临床药师参与救治大剂量甲氨蝶呤(HD-MTX)排泄延迟病人,促进临床HD-MTX的安全、合理使用.方法 安徽省肿瘤医院临床药师对2018年10月收治的1例HD-MTX排泄延迟病人实施全程化药学监护,积极分析甲氨蝶呤排泄延迟发生原因及血药浓度波动原因,提出合理性药学服务建议,协助医师制定个体化用药方案.结果 病人HD-MTX化疗后出现早期排泄延迟,临床药师分析认为其原因可能与尿pH值过低、药物相互作用、肾功能损伤、第三空间存在、低蛋白血症等因素相关;之后,病人甲氨蝶呤血药浓度出现波动现象,临床药师分析可能与利尿药的使用、肾功能进一步恶化及第三空间的存在相关.通过以上分析,临床药师及时建议充分碱化尿液促进甲氨蝶呤排泄;停用可能导致甲氨蝶呤排泄延迟的药物泮托拉唑,改用雷尼替丁继续治疗;避免使用磺胺类药物以免排泄延迟及肾功能损伤进一步加重等.在药师的积极参与下,病人成功救治,顺利出院.结论 HD-MTX排泄延迟的发生及血药浓度变化受多种因素影响,临床药师参与临床药物治疗,有助于促进临床合理用药,保障病人用药安全.     

Pharmacodynamics and pharmacokinetics of xipamide in patients with normal and impaired kidney function

Summary The effect of a single oral dose of 40 mg xipamide on urinary excretion of Na⁺, K⁺, Cl^–, Ca²⁺ and Mg²⁺ in healthy subjects and in patients with varying degrees of renal impairment was compared with various conventional diuretics. Xipamide caused marked excretion of Na⁺ and Cl^–, whereas the diuretic produced only moderate kaliuresis; urinary excretion of Ca²⁺ was increased in proportion to Na⁺, like the loop diuretics. Xipamide affected electrolyte excretion even in patients with a creatinine clearance below 30 ml/min, as do the loop diuretics, too. Therefore, the pharmacodynamic characteristics of xipamide are more like those of a loop diuretic than of a thiazide. Xipamide was good bioavailable, its t_1/2 was 7 h and urinary recovery of the undegraded drug was 40% of the given dose. In renal insufficiency, t_1/2 increased from 7 to only 9 h, yielding a moderate increase in the AUC. Urinary recovery of the drug was reduced in proportion to the reduction in the creatinine clearance of the patient. Therefore, significant extrarenal elimination of the diuretic must be postulated, which suffices to prevent significant drug accumulation in renal failure.     

Effect of inflammation on kidney function and pharmacokinetics of COX-2 selective nonsteroidal anti-inflammatory drugs rofecoxib and meloxicam

Chronic arthritis adversely affects glomerular function and nonsteroidal anti-inflammatory drugs (NSAIDs) reduce electrolyte urinary excretion. In addition, both acute and chronic inflammations may alter clearance of drugs. We studied (a) the effects of inflammation on the renal function and pharmacokinetics of rofecoxib and meloxicam; (b) whether inflammation could exacerbate reduced electrolytes excretion changes observed with NSAIDs; and (c) the influence of inflammation on distribution of these drugs into the kidney. Single oral doses of rofecoxib (10 mg kg(-1)), meloxicam (3 mg kg(-1)) or placebo were administered to normal or pre-adjuvant arthritic rats. Blood and urine samples were collected for the measurement of plasma nitrite, BUN and creatinine. The urinary excretion of sodium and potassium was also determined. Nitrite, BUN and plasma creatinine were increased starting on day 9 in the groups with inflammation. Sodium and potassium excretion rates were not affected by inflammation. Meloxicam did not alter the electrolyte excretion in any of the groups. Rofecoxib significantly decreased sodium and potassium excretion in normal rats and potassium excretion in inflamed rats. Inflammation significantly increased plasma concentrations of rofecoxib, but not meloxicam. The ratios of the kidney:plasma concentrations were not significantly altered by inflammation following either drug. Inflammation altered kidney function, demonstrated by increases in BUN and plasma creatinine. However, it did not influence the urinary electrolytes excretion. Since we have observed similar patterns of the effect of NSAIDs on kidney under healthy and inflammatory conditions, one may conclude that inflammation does not exacerbate the adverse effect.     

Indapamide. A review of its pharmacodynamic properties and therapeutic efficacy in hypertension

Indapamide is an orally active sulphonamide diuretic agent. Although some evidence appears to indicate that the antihypertensive action of indapamide is primarily a result of its diuretic activity, only a limited diuresis occurs with the usual antihypertensive doses of 2.5 mg daily, and in vitro and in vivo data suggest that it may also reduce blood pressure by decreasing vascular reactivity and peripheral vascular resistance. In mild to moderate hypertension it is as effective as thiazide diuretics and beta-adrenergic blocking agents in lowering blood pressure when used as the sole treatment. Indapamide has been successfully combined with beta-adrenergic blocking agents, methyldopa, and other anti-hypertensive agents. While such findings need confirmation, it appears that indapamide shares the potential with other diuretic agents to induce electrolyte and other metabolic abnormalities, although it may do so with less frequency or severity. Thus, indapamide appears to offer a suitable alternative to more established drugs as a 'first-line' treatment in patients with mild to moderate hypertension. Whether it differs significantly from other diuretics when used as antihypertensive therapy, either in its mode of action or its side effect profile, needs further clarification.     

Time-dependent change in renal clearance of bethanidine in humans.

Blood levels and urinary excretion rates of bethanidine were determined in three normal human subjects following oral administration of a single dose of the drug. The postabsorptive decline of blood concentration with time was noticeably slower than the corresponding decline in the urinary excretion rate. The discrepancy can be attributed to a continual decrease in the renal clearance of bethanidine throughout the study. Therefore, pharmacokinetic modeling of urinary excretion data alone would lead to erroneous conclusions concerning the persistence of drug in the blood.     

Effect of metoprolol on 24-hour urinary excretion of adrenal steroids and kallikrein in patients with essential hypertension.

Treatment of fifteen patients with essential hypertension over four weeks using the beta 1-adrenoceptor blocking agent, metoprolol, resulted in a decrease in 24 h urinary excretion of kallikrein and aldosterone along with a decrease in plasma renin activity. There was no significant change in 24 h excretion rates of the free adrenal steroids deoxycorticosterone, 18-OH-deoxycorticosterone, corticosterone, cortisol or 18-OH-corticosterone during treatment, which were not significantly different from excretion rates of normal males, thus excluding inhibitory effects of adrenal steroids on urinary kallikrein activity. A positive correlation was found between plasma renin activity and urinary excretion of kallikrein during the control period and after 2 weeks on metoprolol, supporting the assumption of a preserved link between the renin-angiotensin-aldosterone system and the renal excretion of kallikrein in these patients. The decrease in kallikrein excretion during beta 1-adrenoceptor blockade in patients with essential hypertension may be explained by a reduction in sympathetic tone and by reduced activity of the renin-aldosterone system.     

Clinical pharmacokinetics of calcium antagonists. An update.

The calcium antagonists are valuable and widely used agents in the management of essential hypertension and angina. There is an increasing number of new agents to add to the 3 prototype substances nifedipine, diltiazem and verapamil. These new agents are dihydropyridines structurally related to nifedipine. However, they tend to have longer elimination half-lives (t 1/2 beta) and may be suitable for twice-daily administration. Amlodipine is an exception with a t 1/2 beta in excess of 30h. Apart from elimination rates, however, the pharmacokinetic characteristics of the newer agents have a notable tendency to resemble those of the established agents. They are highly cleared drugs, are relatively highly protein bound. As they are subject to significant first-pass metabolism, old age and hepatic impairment will increase their plasma concentrations due to a reduced first-pass effect. Renal impairment does little to their pharmacokinetics since the fraction eliminated unchanged by the kidney is small. For most agents, plasma concentration-response relationships have been described. Interesting areas for further research include chronopharmacokinetics, stereoselective pharmacokinetics and lipid solubility. Drugs affecting hepatic blood flow and drug metabolising capacity have predictable interaction potential. Some of the newer calcium antagonists will, like verapamil, increase plasma digoxin concentrations. Verapamil and diltiazem decrease phenazone (antipyrine) metabolism and therefore tend to decrease the metabolism of other drugs.     

Effects of a beta 1-adrenoceptor agonist, prenalterol, on renal function and renin secretion rate in anesthetized dogs

Experiments were conducted to examine the effects of prenalterol on renal function and renin secretion in anesthetized dogs. Specifically, we tested whether prenalterol alters renal function directly, or only indirectly as a consequence of a systemic action of the drug. Accordingly, prenalterol was infused into one renal artery for five consecutive 15-min periods, at incremental rates of 0.1, 0.3, 0.9, 2.7, and 8.1 micrograms X kg-1 X min-1. Heart rate and mean arterial blood pressure were recorded, and renal functions and renin secretion rates were measured bilaterally. Direct intrarenal prenalterol infusion caused a 60 bpm increase in heart rate and resulted in marked increases in renin secretion rates from both kidneys. Intrarenal prenalterol infusion also reduced urinary sodium and potassium excretions bilaterally and equally. There were no consistent changes in mean arterial blood pressure, or in glomerular filtration rate or renal blood flow, during prenalterol infusion. We conclude that although prenalterol increases renin secretion rate markedly and may alter renal electrolyte excretion, these effects are not mediated by a direct intrarenal action of the drug.     

The impact of antihypertensive drug groups on urinary albumin excretion in a non-diabetic population

AIMS: Microalbuminuria (30-300 mg 24 h-1) is recognized to be independently associated with renal and cardiovascular risk. Antihypertensives may lower microalbuminuria. We questioned whether the use of different antihypertensive drug classes in general practice influences microalbuminuria as related to blood pressure in nondiabetic subjects. METHODS: To study this, we used the data from 6836 subjects of an on-going population based study, focused on the meaning of microalbuminuria (PREVEND). Odds ratios, adjusted for age, sex, blood pressure, cholesterol level, smoking and the use of other antihypertensive or cardiovascular drugs, were calculated to determine the association of drug groups with microalbuminuria. Influence of antihypertensives on the relation between blood pressure and (log) urinary albumin excretion was determined by comparing linear regression lines. RESULTS: Microalbuminuria was significantly associated with the use of dihydropyridine calcium channel blockers (odds ratio: 1.76 [1.22-2.54]), but not with other antihypertensive drug groups. The linear regression line of the relation between blood pressure and (log) urinary albumin excretion was significantly steeper (P = 0.0047) for users of calcium channel blockers, but not for other antihypertensives, compared with subjects using no antihypertensive. Users of a combination of renin-angiotensin system inhibitors and diuretics however, had a less steep regression line (P = 0.037). CONCLUSIONS: This study suggests a disadvantageous effect of dihydropyridine calcium channel blockers on microalbuminuria compared with other antihypertensive drug groups. Thus, if microalbuminuria is causally related to an increased risk for cardiovascular morbidity and mortality, dihydropyridines do not seem to be agents of choice to lower blood pressure. Furthermore, the combination of renin-angiotensin system inhibition and diuretics seems to act synergistically.     

替诺福韦的肾脏-骨骼毒性及其防治

替诺福韦是一种新型核苷酸类逆转录酶抑制剂,用于治疗HIV感染和慢性乙型肝炎。替诺福韦的潜在肾毒性与药物在肾脏排泄有关,病理改变表现为肾小管损害,临床表现为血磷降低和血清肌酸升高,还可导致Fanconi综合征、间质性肾炎和急性肾衰竭。替诺福韦的骨毒性是肾毒性的继发表现,临床表现为肌无力、骨痛和骨折。替诺福韦对肾脏-骨骼损害与基础疾病、基因多态性、血药浓度和药物相互作用有关。服用替诺福韦的患者应定期监测肾功能、电解质,低磷血症患者给予补磷治疗。肌酐清除率﹤50 ml/min的患者应调整替诺福韦的给药剂量。大部分患者在停用替诺福韦后肾功能会明显改善,部分患者可发展为慢性肾病。