Use Of Diuretic Drugs Research Articles

Spleen white pulp structural and cellular composition in experimental furosemide-­induced hypomagnesemia

Relevance. Magnesium deficiency in the blood (hypomagnesemia) is due to many reasons, among which loop diuretics (furosemide) occupy acertain place. The role of the spleen in this process has not been determined. The aim of the work was to elucidate the effect of furosemide-­induced hypomagnesemia on the immune structures of the white pulp of rat spleen. Materials and Methods. Furosemide (Lasix® Aventis Pharma Ltd, India) was injected daily intraperitoneally at adose of 30 mg/kg to the experimental group of white outbred rats for 6 days, animals of the control group received an injection of 0.9% NaCl. Investigated: blood serum for the content of magnesium, calcium, sodium and iron; serial sections of the white pulp of the spleen after staining with hematoxylin and eosin to assess the structure and azure-­II-eosin to assess the cellular composition. With amicroscope magnification of 280 times, the ratio (in%) of primary (PLNS) and secondary lymphoid nodules of the spleen (SLNS) was calculated, the following were measured (µm): the diameter of the germinal center (GC), the width of the mantle and marginal zone, the diameter of the periarteriolar lymphoid sheath (PALS). In GC, the peripheral zone of lymphoid nodules, PALS at amagnification of 1500 times per field of view (100 μm2) was counted and presented as apercentage of the number of lymphocytes; macrophages; cells, mitotic and apoptotic elements. Morphometric analysis was carried out using Image ProPlus6.0 software (Media Cybernetics, USA). Statistical processing was carried out using the Statistica 10.0 software package with the determination of the arithmetic mean (M) and its error (m). Results and Discussion. The administration of furosemide led to adecrease in magnesium in the blood serum by 1.6 times (p0.05). In the white pulp of the spleen of animals of the experimental group, the proportion of SLNS decreased by 18.14%, the number of SLNS increased by 42.5% (p0.05). The diameter of SLNS increased insignificantly, the diameter of GC and the width of the marginal zone significantly increased by 27.1 and 24.8%, respectively. The proportion of macrophages increased by 20.6% in GC SLNS, and by 17.0% in PALS. The highest increase in the proportion of cells with signs of apoptosis was found in the periarteriolar lymphoid sheath of experimental animals - 34.6% (p0.05). Conclusion. Furosemide loading causes the development of dyselementosis, with the most significant loss of magnesium (hypomagnesemia) and has apronounced effect on the immune parameters of the spleen, represented by white pulp structures. Therefore, correction of the elemental status and monitoring of the state of the spleen in hypomagnesemia caused by the use of loop diuretics is anecessary element in the prevention of complications associated with the use of diuretic drugs.

Застосування діуретиків у медицині та спорті та моніторинг їх споживання в Україні

The purpose of the work was to study the range and volume of consumption of diuretics on the pharmaceutical market of Ukraine in 2019-2021. Materials and methods. Indications for the use of diuretics in medicine and sports, as well as the results of monitoring their consumption on the pharmaceutical market of Ukraine in the period from 2019 to 2021 are given in the article. The analysis of the range of diuretic drugs on the pharmaceutical market of Ukraine was carried out according to the information and search system “Pharmstandard” of the “Morion” company. Monitoring of the volume and structure of drug consumption was carried out using the ATС/DDD methodology. Results and discussion. The results of the research showed that diuretic drugs on the pharmaceutical market of Ukraine were represented by four pharmacological subgroups of drugs: thiazide and thiazide-like diuretics, herbal drugs, loop and potassium-sparing diuretics. The number of available International Non-Proprietary Names for 2019-2021 was 11, and trade names – from 110 to 116. The correlation between foreign and domestic manufacturers was: 42-51% and 49-58%, respectively. Torasemide took the first place among the leaders on the market of Ukraine in terms of the number of trade names – from 38 to 39 trade names, because it is more effective, with a pharmacological effect that exceeds furosemide by 2-8 times. Preparations of plant origin took the second place – from 21 to 23 trade names. Indapamide was in the third place – 14 trade names. The total consumption of diuretics for 2019-2021 was 15.83 DIDs in 2019, 15.98 DIDs in 2020 and 16.36 DIDs in 2021. Conclusion. The results of the monitoring showed that the leaders in terms of consumption on the market of Ukraine were the loop diuretic furosemide (4.79-5.24 DIDs) and the potassium-sparing diuretic spironolactone (3.07-3.60 DIDs). In our opinion, the high levels of consumption of these diuretics are due to such a criterion as availability, as well as their presence in the list of drugs for the treatment of cardiovascular diseases, which are included in the Government program “Affordable Drugs” and are reimbursed at the expense of the state (partially at the expense of patients). In the future, in this direction, it is planned to investigate the safety of the use of diuretic drugs, both in patients and in athletes. It will also be necessary to monitor the adverse reactions of these drugs in order to identify serious adverse reactions that may threaten human life and to develop measures to prevent the development of undesirable consequences

Severe tricuspid regurgitation worsens prognosis outcome after edge-to-edge mitral valve repair

Abstract Introduction MitraClip has been well established for treatment of severe mitral regurgitation (MR). MR and tricuspid regurgitation (TR) often occur simultaneously and symptoms of biventricular heart failure can overlap. While it has been shown that TR grade regression can be achieved through repair of MR1, presence of moderate to severe TR can increase all-cause mortality after MitraClip2. There is currently no consensus on the management of combined MR and TR. We evaluated the impact of TR on echocardiographic and functional outcome after MitraClip. Methods 370 patients underwent MitraClip for moderate to severe MR at our center from 2010 to 2018. Patients were dichotomized into low grade TR (grade <I - I (trace - mild)) and high grade TR (grade III - V (severe - torrential)). Moderate TR (grade II) was excluded. After MitraClip for MR, patients were followed up for 12 months and their echocardiographic and functional outcome was evaluated. Use of diuretic drugs throughout 12 month follow-up was registered. Results Low grade TR (<I - I) occurred in 225 patients (67.0%), high grade TR (III - V) was present in 111 patients (33.0%). 34 patients (9.2%) with moderate TR (II) were excluded. Patients with high grade TR had an increased morbidity (higher age, worse renal function, higher prevalence of atrial fibrillation, higher levels of natriuretic peptides, increased left atrial and right heart diameters, higher TR gradient). These patients also received significantly higher doses of torasemid (33.5±36.7 mg vs. 21.6±20.9 mg, p=0.003) and furosemid (163.4±155.5 mg vs. 75.8±72.3 mg, p=0.01). Average grade of MR at baseline was similar in both groups (2.9±0.46 vs. 2.8±0.5, p=0.66). Procedural success of MR repair was achieved similarly in both groups (96.4% vs. 96.9%, p=0.82) and residual MR grade immediately after device implantation was comparable (p=0.61). However, recurrent MR in the high grade TR group increased during follow up, while MR further decreased in the low grade TR group (3 months: 1.24±0.7 vs. 1.16±0.7, p=0.5; 12 months: 1.46±0.93 vs. 1.12±0.61, p=0.04). Accordingly, use of diuretic drugs after 12 months rose in the high grade TR group while it did not change or even decreased in the low grade TR group (torasemid: 40.2±48.4 mg vs. 24.1±30.0 mg, p=0.04; furosemid: 197.5±251.0 mg vs. 67.1±81.8 mg, p=0.22). Kaplan-Meier-Analysis showed significantly higher mortality (24.9 vs. 14.1%, p=0.01), higher risk for heart failure induced rehospitalisation (25,4 vs. 12,5%, p=0.005) and for major adverse cardiac and cerebrovascular events (MACCE: 42.3 vs. 29.1%, p=0.008) in the high grade TR group after 12 months. Conclusion MitraClip patients for MR with concomitant high grade TR (≥ III) had an increased morbidity at baseline compared to low grade TR patients. By MitraClip comparable reduction of MR was achieved. However, during 12 month follow-up in the high grade TR group recurrent MR occurred more often while use of diuretics increased. Funding Acknowledgement Type of funding sources: None.

Nocturia as an Unrecognized Symptom of Uncontrolled Hypertension in Black Men Aged 35 to 49Years.

BackgroundHypertension is assumed to be asymptomatic. Yet, clinically significant nocturia (≥2 nightly voids) constitutes a putative symptom of uncontrolled hypertension. Black men with hypertension may be prone to nocturia because of blunted nocturnal blood pressure (BP) dipping, diuretic drug use for hypertension, and comorbidity that predisposes to nocturia. Here, we test the hypothesis that nocturia is a common and potentially reversible symptom of uncontrolled hypertension in black men.Methods and ResultsWe determined the strength of association between nocturia (≥2 nightly voids) and high BP (≥135/85 mm Hg) by conducting in‐person health interviews and measuring BP with an automated monitor in a large community‐based sample of black men in their barbershops. Because nocturia is prevalent and steeply age‐dependent after age 50 years, we studied men aged 35 to 49 years. Among 1673 black men (mean age, 43±4 years [SD]), those with hypertension were 56% more likely than men with normotension to have nocturia after adjustment for diabetes mellitus and sleep apnea (adjusted odds ratio, 1.56; 95% CI, 1.25–1.94 [P<0.0001]). Nocturia prevalence varied by hypertension status, ranging from 24% in men with normotension to 49% in men whose hypertension was medically treated but uncontrolled. Men with untreated hypertension were 39% more likely than men with normotension to report nocturia (P=0.02), whereas men whose hypertension was treated and controlled were no more likely than men with normotension to report nocturia (P=0.69).ConclusionsUncontrolled hypertension was an independent determinant of clinically important nocturia in a large cross‐sectional community‐based study of non‐Hispanic black men aged 35 to 49 years.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unqiue identifier: NCT 02321618.

Pharmacological Properties of Loop Diuretics and Their Clinical Effects

Edematous states caused by an excessesive extracellular fluid retention are major components of cardiovascular and renal disorders including chronic kidney disease, nephrotic syndrome, and heart failure. The use of diuretic drugs from various groups including loop duiretics are important means of pharmacological correction of these clinical conditions. Moreover, diuretics used to lower bood pressure as a part of antihypertensive treatment, reduce cardiovascular events. The response of patients to the dose of a diuretic is reflected by a sigmoid dose-response curve which can be affected by changes of sodium content in the body. Loop diuretics may fail to control salt and water retention despite the use of appropriate doses. The main reasons for loop diuretic resistance may be determined by further reduction of glomerular filtration rate and reduced peak concentration of loop diuretics in primary urine. Chronic treatment with loop diuretics can cause compensatory hyperthrophy of epithelial cells along the ascending limb of the loop of Henle and thus decrease of its diuretic effect. The principles of avoiding this phenomenon are the restriction of sodium intake, correction of doses, timing and frequency of drug administration, and use of combination diuretic therapy. Loop diuretic - related adverse events that involve uricaemia and ototoxicity also should be taken into consideration.

Incident diuretic drug use and adverse respiratory events among older adults with chronic obstructive pulmonary disease.

Diuretic drugs may theoretically improve respiratory health outcomes in chronic obstructive pulmonary disease (COPD) through several possible mechanisms, but they might also lead to respiratory harm. We evaluated the association of incident oral diuretic drug use with respiratory-related morbidity and mortality among older adults with COPD. This was a population-based, retrospective cohort study using health administrative data from Ontario, Canada, for the period 2008-2013. We identified adults aged 66years and older with nonpalliative COPD using a validated algorithm. Respiratory-related morbidity and mortality were evaluated within 30days of incident oral diuretic drug use compared to nonuse using Cox proportional hazard regression and applying inverse probability of treatment weighting using the propensity score to minimize confounding. Out of 99 766 individuals aged 66years and older with COPD identified, incident diuretic receipt occurred in 51.7%. Relative to controls, incident diuretic users had significantly increased rates for hospitalization for COPD or pneumonia [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.07-1.40], as well as more emergency room visits for COPD or pneumonia (HR 1.35, 95% CI 1.18-1.56), COPD or pneumonia-related mortality (HR 1.41; 95% CI 1.04-1.92) and all-cause mortality (HR 1.20, 95% CI 1.06-1.35). The increased respiratory-related morbidity and mortality observed were specifically as a result of loop diuretic use. Incident diuretic drugs, and more specifically loop diuretics, were associated with increased rates of respiratory-related morbidity and mortality among older adults with nonpalliative COPD. Further studies are needed to determine if this association is causative or due to unresolved confounding.

Serum uric acid as a marker of all-cause mortality in an elderly patient cohort.

There is growing evidence of the role of serum uric acid (SUA) as a risk factor for cardiovascular and renal disease. We analysed the association between baseline SUA and overall mortality in a cohort of elderly patients followed prospectively for 5 years. Eighty clinically stable patients, median age 83 years (range 69-97), 31.3% men, 35% diabetics, 83% hypertensives were randomly recruited at Geriatrics and Nephrology visits between January and April 2006 and followed for 5 years. We measured baseline SUA and serum creatinine and estimated glomerular filtration rate (GFR) with MDRD abbreviated. In Nephrology Department patients, we measured proteinuria in 24-hour urine and in Geriatrics department patients we measured proteinuria (mg/dl)/creatinine (mg/dl) in urine (first morning urine). Predictive variables were: baseline SUA and plasma creatinine; estimated GFR (abbreviated MDRD formula); and we recorded age, gender, baseline comorbidity (Charlson index), individualised cardiovascular treatment and mortality. SPSS15.0. baseline SUA was normally distributed and its median was 5.85 mg/dl. We found no significant differences in levels of SUA by gender, history of diabetes mellitus, hypertension, diuretic drug use, heart disease, peripheral arterial disease or stroke. Patients with a history of heart failure had significantly higher SUA (7.00 ± 1.74 vs 5.90 ± 1.71, P=.031). Some 41 deaths occurred during follow-up (15 men and 26 women): 15 due to general deterioration, 8 due to infections, 4 due to stroke, 4 due to tumours, 3 due to cardiovascular disease, 2 due to complications of fractures and 5 due to unknown causes. Patients with SUA higher than the median had significantly lower GFR and higher mortality at 5 years. In the Cox analysis for overall mortality [independent variables: age, gender, Charlson Index, history of heart failure, SUA, creatinine, proteinuria and GFR (MDRD)] only SUA levels (HR: 1.35; 1.17-1.56 P=.000) were independently associated with mortality. In our study, levels of SUA are an independent risk factor for mortality in elderly patients.

The Relation of Coffee Consumption to Serum Uric Acid in Japanese Men and Women Aged 49–76 Years

Objective. Few studies have suggested an inverse relation between coffee intake and serum concentrations of uric acid (UA), but none has addressed the relation in men and women separately. We examined the relation between coffee intake and serum UA levels in free-living middle-aged and elderly men and women in Fukuoka, Japan. Methods. Study subjects were derived from the baseline survey of a cohort study on lifestyle-related diseases, and included 11.662 men and women aged 49–76 years; excluded were those with medication for gout and hyperuricemia, use of diuretic drugs, and medical care for cancer or chronic kidney disease. Statistical adjustment was made for body mass index, alcohol use, hypertension, diabetes mellitus, and other factors. Results. There were inverse associations of coffee consumption with serum UA concentrations and hyperuricemia in men regardless of adjustment for covariates. Women showed a statistically significant, but weaker, inverse association between coffee and serum UA levels after allowance for the confounding factors. Conclusion. The findings add to evidence for a protective association between coffee intake and hyperuricemia.

The Clinical Significance of New-Onset Diabetes Mellitus in Hypertension

Several intervention trials found that some antihypertensive drugs, mostly ACE inhibitors, calcium-channel blockers and angiotensin II receptor blockers, are associated to a lesser risk of developing diabetes mellitus in comparison with other drug classes, including diuretics and β-blockers. This finding is clinically relevant because it has been demonstrated that patients who develop new-onset diabetes during therapy rapidly become a high-risk population, not dissimilar from patients with prior diagnosis of diabetes. In a recent analysis of the PIUMA (Progetto Ipertensione Umbria Monitoraggio Ambulatoriale) study, pre-treatment glucose levels and use of diuretic drugs were independent predictors of new-onset diabetes. Although there is some controversy on this topic, prevention of new-onset diabetes could contribute to explain at least part of the benefit attributed to ACE inhibitors, calcium-channel blockers and angiotensin II receptor blockers in some intervention trials. In clinical practice, when faced with subjects at high risk of diabetes, it is important to implement nonpharmacological strategies whenever appropriate (diet, physical activity, weight loss). In these subjects, ACE inhibitors, calcium-channel blockers and angiotensin II receptor blockers could be considered first-line drugs.

Serum Uric Acid Is a Determinant of Metabolic Syndrome in a Population-Based Study

Determination of serum uric acid concentrations and role in risk of metabolic syndrome (MS) were investigated in 1877 participants in a cross-sectional population-based study including a brief follow-up. The MS was identified by modified criteria of the Adult Treatment Panel III, and coronary heart disease (CHD) by clinical findings and Minnesota coding of resting electrocardiograms. Uric acid concentrations were measured by the uricase method. Metabolic syndrome was present in 39.1% of the cohort. Linear regression analysis of uric acid levels in a model comprising 13 variables identified gender, waist girth, total cholesterol (TC), alcohol usage, triglycerides, log C-reactive protein (CRP), and log gamma-glutamyl transferase (GGT), and in women diuretic use and elevated blood pressure (BP), as significant independent covariates whereby the largest contribution (1.6 mg/dL) was generated by waist girth. Logistic regression analysis of serum uric acid for MS disclosed for the top versus the bottom tertile an odds ratio (OR) of 1.89 (95% confidence interval [CI]: 1.45-2.46) in men and women combined, after adjustment for sex, age, TC, log CRP, log GGT, alcohol, and diuretic drug use, presence of diabetes/impaired fasting glucose, elevated BP, and smoking status. This corresponded to an increase by 35% in MS likelihood for each 1 SD uric acid increment. This rate declined to a significant 15% by inclusion of waist girth into the model. The OR of uric acid concentrations for prevalent and incident CHD, adjusted for age, MS, smoking, and diuretic use, was not significant among women and only tended toward significance in men. Abdominal obesity is the main determinant of uric acid variance. An increment of 1 SD in serum uric acid levels are associated in both sexes with a 35% higher MS likelihood, independent of 10 risk factors related to MS. After adjustment for waist girth, a more modest but significant likelihood persists, which suggests that serum uric acid is a determinant of MS.

Normal Values and Determinants of Circadian Urine Production in Older Men: A Population Based Study

We evaluated circadian urine production and its determinants in a large population based sample of older men. We collected data on 1,688 men 50 to 78 years old, without radical prostatectomy, prostate or bladder cancer, neurogenic bladder disease or negative advice from their general practitioner, recruited from the population of Krimpen, the Netherlands. Measurements consisted of self-administered questionnaires, including the International Prostate Symptom Score, a 3-day frequency-volume chart, transrectal prostatic ultrasound, uroflowmetry and post-void residual volume. Hourly urine production was determined and urine production day-to-night ratio was calculated from the frequency-volume chart. Men younger than 65 years showed a clear circadian urine production pattern, whereas in older men this pattern was less clear. Smoking, use of diuretic drugs, post-void residual and 24-hour polyuria reinforced the circadian pattern, in favor of daytime urine production. The urine production day-to-night ratio was not associated with prostate enlargement, reduced urinary flow rate, body weight, hypertension, cardiac symptoms, diabetes mellitus, use of antidepressants, cardiac or hypnotic drugs. Urine production in men younger than 65 years showed a clear circadian pattern in contrast to men older than 65 years. These data can be used as a reference when describing urine production patterns in select populations. In daily practice frequency-volume charts can be used to determine urine production. This method is inexpensive, easy to use and provides valid information on urine production in a natural environment.

Effect of smoking cessation and tobacco type on the risk of cancers of the upper aero-digestive tract in Brazil.

Tobacco smoking has long been identified as the most important risk factor for upper aero-digestive tract cancers. To investigate the effect of different tobacco types and the benefit of smoking cessation, we analyzed data from a case-control study of 784 cases of mouth, pharynx, and larynx cancers and 1,578 non-cancer controls in three metropolitan hospital areas in Brazil. Subjects were interviewed as to their smoking and drinking habits, demographics, environmental exposures, occupational history, health characteristics, and diet. Controlling for total tobacco and alcohol consumption, risks for ex-smokers compared with current smokers decreased substantially with time since cessation of the habit. Compared with never smokers, ex-smokers of >20 years had a relative risk (RR) of 1.98 [95% confidence interval (CI) = 1.0-3.8] for all upper aerodigestive tract cancers. RRs for long-term (>20 years) ex-smokers tended to be lower for mouth (RR = 1.61) and pharynx (RR = 1.52) than for larynx (RR = 3.63) cancers. The benefit of quitting was strongest for commercial cigarettes (RR = 1.45, 95% CI = 0.7-3.0) for ex-smokers of >10 years, as compared with smoking of black tobacco (RR = 2.57, 95% CI = 1.4-4.6), cigars (RR = 2.59, 95% CI = 0.6-11.6), and pipe tobacco (RR = 3.40, 95% CI = 1.3-8.8).

Addition of a Thiazide: An Effective Remedy for Furosemide Resistance After Cardiac Operations

Background. The frequent use of diuretic drugs in cardiac surgical practice contrasts with the lack of documentation regarding diuretic treatment in this setting. The aims of this study were to delineate the need for diuretic drugs in adult cardiac surgical practice and to evaluate the impact of adding a combination of 50 mg hydrochlorothiazide and 5 mg amiloride orally to patients responding poorly to furosemide.Methods. Two hundred ten consecutive patients, 159 undergoing coronary artery bypass grafting procedures and 51 having valve operations, were studied.Results. Seventy-seven patients received large doses of furosemide (≥80 mg/24 h) at some time during the postoperative course, and of these 20 responded poorly to furosemide (weight loss 0.3 ± 0.2 kg) despite considerable fluid retention. The addition of hydrochlorothiazide and amiloride provided a prompt and effective remedy to relative furosemide resistance. Average weight loss was 2.3 ± 0.2 kg (p < 0.01 compared with response to furosemide) and average diuresis was 2,949 ± 156 mL in the following 24 hours.Conclusions. Relative furosemide resistance is common after cardiac operations. Thiazides, although they are mild diuretic agents, may serve as useful adjuncts in this setting.(Ann Thorac Surg 1997;63:993–7)

Activation of neurohumoral systems in postinfarction left ventricular dysfunction

Objectives. This study was conducted to evaluate the degree of neurohumoral activation around the time of hospital discharge after myocardial infarction.Background. Because pharmacologic interventions that block the effects of neurohumoral activation improve the prognosis after infarction, we hypothesized that widespread neurohumoral activation persists in some patients until at least the time of hospital discharge and that the determinants of activation vary from one system to another.Methods. Five hundred nineteen patients in the Survival and Ventricular Enlargement Study (SAVE) had plasma neurohormones measured before randomization at a mean of 12 days after infarction. All patients had left ventricular dysfunction (left ventricular ejection fraction ≤40%) but no overt heart failure.Results. Although all neurohormones except epinephrine were increased compared with values in age-matched control subjects, plasma norepinephrine (301 ± 193 vs. 222 ± 87 pg/ml, p < 0.001), renin activity (3.0 ± 3.7 vs. 1.2 ± 1.2 ng/ml per h, p < 0.001), arginine vasopressin (1.9 ± 6.9 vs. 0.7 ± 0.3 pg/ml, p < 0.001) and atrial natriuretic peptide (75 ± 75 vs. 21 ± 9 pg/ml, p < 0.001) values ranged from normal to very high, indicating a wide spectrum of neurohumoral activation. Activation of one system did not correlate with activation of another. The clinical and laboratory variables most closely associated with neurohumoral activation were Killip class, left ventricular ejection fraction, age and use of diuretic drugs. The association between neurohumoral activation and clinical and laboratory variables varied from one neurohormone to another.Conclusions. Neurohumoral activation occurs in a significant proportion of patients at the time of hospital discharge after infarction. Which neurohormone is activated and which clinical and laboratory variables determine this activation vary from one neurohormone to another.

Hypokalemia and cardiovascular disease

A growing body of experimental, epidemiologic and physiologic evidence testifies to the hazards of hypokalemia and other electrolyte disorders that can complicate the chronic use of diuretic drugs in patients with cardiovascular disease. This study reviews the complex renal and extrarenal mechanisms that regulate potassium balance in normal persons with special attention to the role of stressrelated hormones. Disturbances of potassium balance are common in patients taking diuretics; indeed, the potential number of people in this country at risk of diuretic-related hypokalemia approaches 9 million. The magnitude of this problem is of particular concern, because of the compelling data that link hypokalemia in such patients to electrical instability of the heart and to a fatal outcome after an acute cardiac injury. Therefore, aggressive correction of hypokalemia is warranted in patients with cardiovascular disorders.

Sulfinpyrazone: Risk for Renal Insufficiency

To the Editor. —In the JuneArchivesBlackshear et al1observed that renal insufficiency induced by nonsteroidal anti-inflammatory drugs is more frequent in patients with the following risk factors: advanced age, atherosclerotic cardiovascular disease, and use of diuretic drugs. We would like to add sulfinpyrazone to the list of these nonsteroidal anti-inflammatory drugs, which can lead to renal dysfunction in these clinical settings. Although devoid of anti-inflammatory activity, sulfinpyrazone inhibits prostaglandin synthesis not only in the platelets, but also in the kidney.2-4We recently reviewed the reports of acute renal failure during sulfinpyrazone therapy. Eighteen patients who received this drug after myocardial infarction showed an average serum creatinine rising from 1.3 to 6.3 mg/dL. Their mean age was 60 years and eight of them had concomitant diuretic therapy.5Sulfinpyrazone therapy has also been advocated early after coronary bypass surgery. It was considered safe, but renal function was

Identification of Risk for Renal Insufficiency From Nonsteroidal Anti-inflammatory Drugs

Risk for renal insufficiency (RI) resulting from nonsteroidal anti-inflammatory drugs (NSAID) exists in cirrhosis with ascites, nephrotic syndrome, decompensated congestive heart failure, and chronic renal disease. We saw seven cases of NSAID RI that demonstrate important additional clinical risk factors. These include advanced age (mean, 76 years), use of diuretic drugs (6/7 patients), and evidence of renal vascular disease as suggested by long-standing hypertension, diabetes, or atherosclerotic cardiovascular disease (7/7 patients). Analysis of past case reports of NSAID RI also showed these features. Treatment of acute gouty arthritis was the most common precipitating event. Evolving NSAID RI was suggested by rising serum urea nitrogen, serum creatinine, and serum potassium levels, and body weight gain associated with low fractional excretion of sodium. We conclude that since NSAID RI is preventable and reversible, it is important to recognize and monitor the conditions of those patients at risk.

How to avoid complications of potent diuretics

EFFECTIVE use of diuretic drugs requires an understanding of the principles involved in their action. I have found that posing the following questions often will in turn clarify questions and problems raised by physicians consulting me. 1. What is the goal of treating a patient with a diuretic drug? Clearly, the practical goal is improved health of your patient, but the drug itself cannot guarantee this goal. The drugs included in the term diuretic—as the term is ordinarily used today—directly accomplish one thing only, a decrease in the amount of sodium in the body. This decrease in total-body sodium will usually lead to decrease in the amount of water associated with sodium throughout the body and thus in loss of accumulations of extracellular fluids such as edema, ascites, and pleural effusion. The obvious corollary of this statement is that if you do not want to reduce the total body sodium