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PubMed2001

Estimation of absorption rate of alpha-human atrial natriuretic peptide from the plasma profile and diuretic effect after intranasal administration to rats.

The absorption rate of alpha-human atrial natriuretic peptide (alpha-hANP) after intranasal (i.n.) administration to rats was estimated from the plasma profile and pharmacological effect (diuretic effect) using a pharmacokinetic (PK) model and a PK-pharmacodynamic (PD) model involving data obtained after intravenous (i.v.) bolus injection. The plasma concentrations of alpha-hANP after i.v. administration at different doses were fitted to a two-compartment PK model with zero-order excretion and input of endogenous alpha-rat atrial natriuretic peptide (alpha-rANP) and two elimination processes represented by Michaelis-Menten and first-order kinetics. However, the saturable process was ignored at low doses. The plasma concentrations after low doses via the i.n. route could also be expressed by this model, but with first-order absorption, so that an absorption rate constant was calculated using a deconvolution method. In addition, the diuretic effect plotted against the i.v. dose was represented by the Hill equation and showed an anti-clockwise hysteresis loop versus the plasma concentration. These results suggest that the diuretic effect could be estimated by a PK-PD model having an 'effect' compartment or a homeostatic system. Such a PK-PD model accurately expressed the diuretic effect of alpha-hANP at all doses after i.v. and i.n. administrations. The resulting absorption rate constant calculated using the PK-PD model agreed closely with that obtained by the PK model alone. The absorption rate and simulated diuretic effect suggest that, for i.n. administration of alpha-hANP, a higher absorption rate constant causes a more potent diuretic effect (a dramatic effect over the early period), whereas greater bioavailability is associated with a better hypotensive effect (sustained effect).

Absorption↗
PubMedDate not supplied

Pharmacology, therapeutic efficacy, and adverse effects of bumetanide, a new "loop" diuretic.

Bumetanide is a recently developed natriuretic and diuretic agent, belonging to the "loop" class of diuretics. Since it is rapidly and almost completely absorbed after oral administration, oral and parenteral formulations have a similar pharmacokinetic profile. Peak plasma levels are achieved approximately 30 min after oral administration. The apparent half-life is 1.2-1.5 hr, and the volume of distribution is about 25 liters. Plasma clearance is 228-255 ml/min. Bumetanide is promptly and almost completely eliminated by metabolism of the butyl side chain and urinary excretion of the parent drug and its metabolites. The principle renal site of action is the ascending limb of the loop of Henle, with a minor effect on the proximal tubule. The drug causes decreases in both free water clearance (during water diuresis) and solute free water reabsorption (during hydropenia), increased fractional delivery of sodium chloride to the distal tubule and a natriuresis approaching 20% of the filtered load of sodium, calciuria, phosphaturia, and minimal bicarbonaturia. Extensive clinical studies have been conducted with both oral and parenteral bumetanide in patients with a variety of edematous conditions. The agent has been clearly demonstrated to be an effective diuretic in the treatment of edema due to cardiac disease (congestive heart failure) and edema, with or without ascites, due to hepatic disease. Bumetanide has also been shown effective in treating edema due to renal disease, even when modest to severe renal insufficiency is present, and it may be useful in the treatment of edema refractory to other loop diuretics. As would be predicted for any potent diuretic, bumetanide administration has been associated with hypokalemia, hypochloremia, metabolic aklalosis, hyperuricemia, and prerenal azotemia. Alterations in glucose metabolism are an inconsistent finding. Transient thrombocytopenia and granulocytopenia have been noted, but no consistent or important alterations in biochemical parameters have been observed. In some patients, especially those with renal failure receiving high doses, myalgias and muscle tenderness have been described. To date only a very limited potential for ototoxicity has been observed. Bumetanide has been administered without difficulty to patients having side effects from other loop diuretics.

Animals↗
PubMed1996

The interaction between short-term exercise training and a diuretic-induced hypovolemic stimulus.

Nine healthy untrained males [mean (SEM) age, 20.2 (1) years; peak oxygen uptake (VO2max, 48.2 (2) ml.kg-1.min-1] took part in a study to examine whether short-term exercise training (cycle exercise 2 h.day-1 for 3 days at 60% VO2max), which normally results in an expansion of plasma volume (PV), can counteract a diuretic-induced hypovolemic stimulus (100 mg triamterene + 50 mg hydrochlorothiazide.day-1 for 5 days concurrent with exercise training) and restore PV to control levels. Resting and exercise responses (90 min, 60% VO2max) in the diuretic plus exercise training condition (D+E) were compared to a control (C) and a diuretic (D) condition in which no exercise was performed. Following the short-term training, PV was still decreased (P < 0.05) below C by -8.3 (3)% in D+E and was similar (P > 0.05) to the reduction in D [-12.4 (2)%]. The reduced PV in response to the diuretic was associated with similar (P > 0.05) elevations in resting aldosterone (ALDO) and norepinephrine (NOREPI) levels (ng.100 ml-1) in D [101 (12), 61 (4)] and D+E [85 (16), 60 (10)] above (P < 0.05) C [22 (5), 37 (4)]. During exercise, ALDO levels were increased (P < 0.05) by 66 (5) and 70 (10) ng.100 ml-1 in D and D+E, respectively, and the increase was greater (P < 0.05) than C [44 (8) ng.100 ml-1]. The rise in NOREPI during exercise was lower (P < 0.05) in D+E [164 (44) ng.100 ml-1] than in D [244 (24) ng.100 ml-1] with levels similar to C [176 (25) ng.100 ml-1]. Thus, the ALDO response to the diuretic was heightened at rest and during exercise but was not additionally affected by the short-term training session. Results suggest that 3 days of exercise training are unable to counteract the hypovolemic effects of a diuretic and restore PV to control levels despite chronic elevations in NOREPI and ALDO.

Adult↗
PubMed1987

[Unexplained edema in females--diuretic-induced or idiopathic?].

Both women with diuretic induced edema and with idiopathic edema present a typical history leading to the diagnosis in most cases. These women are almost exclusively in the reproductive age and they tend to have some other characteristics in common additionally. There is controversy whether idiopathic edema exists as a syndrome with multifactorial pathogenesis or if fluid retention in these women is due to diuretic abuse. In either case the use of diuretics is not indicated as they can increase and perpetuate the edema and moreover may bring about impairment of renal function. Abstinence of diuretic intake is the only way out of the vicious circle of fluid retention induced by intermittent diuretic intake resulting in intermittent edema and prostrained use of diuretics. Therapy of idiopathic edema is difficult; it includes physical therapy, psychotherapy and pharmacotherapy with aldosterone antagonists or ACE-inhibitors in some severe cases.

Diuretics↗
PubMed1992

Comparison of withdrawing antihypertensive therapy between diuretics and angiotensin converting enzyme inhibitors in essential hypertensives.

One hundred thirteen patients with essential hypertension receiving single or multiple antihypertensive agents were enrolled in the study. All had had mild to severe hypertension before treatment, but their diastolic blood pressure (DBP) at study entry was lower than 90 mm Hg for all measurements. In half of the subjects, non-thiazide diuretics (n = 35) or angiotensin-converting enzyme inhibitors (ACEI, n = 37) were discontinued, and their remaining drugs were maintained throughout the study. The other patients (n = 41) continued all their medications. Forty-one percent of subjects remained normotensive for 12 months after withdrawal of diuretics, and 37% of patients with ACEI discontinuation remained normotensive, although the recurrence of hypertension after withdrawal of ACEI tended to be earlier than its recurrence after withdrawal of diuretics. Serum uric acid and creatinine concentration decreased after diuretic withdrawal, but not after ACEI withdrawal. Diuretic withdrawal resulted in an increase in serum potassium, but ACEI withdrawal induced a decrease in serum potassium. Withdrawal of diuretics or ACEI both significantly reduced plasma renin activity. The present study may be indicative of the ability to withdraw some medications in many patients being treated with multiple antihypertensive agents.

Adult↗
PubMed1986

Diuretic use in critical care.

Diuretics have found wide application in critical care medicine. The use of mannitol and loop diuretics in a variety of life-threatening disorders is reviewed. The combined venodilatory and natriuretic effects of bumetanide, furosemide and ethacrynic acid relieve congestive symptoms in pulmonary edema. Although commonly administered to prevent development of acute tubular necrosis or in varying stages of evolving disease, few data are available to demonstrate the efficacy of mannitol or loop diuretics. An approach to the oliguric patient with acute tubular necrosis is described. The dangers of hyponatremia are reviewed, and the rational use of loop diuretics and hypertonic saline is outlined. The 3 loop-active agents inhibit calcium reabsorption in the thick ascending limb of Henle's loop and therefore have proved useful in treating hypercalcemia. A practical approach to the diuretic-saline treatment of severe hypercalcemia is outlined. The kaliuretic effect of loop diuretics can be used to advantage in patients with acute or chronic hyperkalemia. A guide to such therapy is described.

Biological Transport↗
PubMed1995

Cellular colocalization of diuretic peptides in locusts: a potent control mechanism.

Locust abdominal ganglia are shown to colocalize Locusta-diuretic peptide-, leucokinin I-, and lysine vasopressin-like immunoreactivity in posterior lateral neurosecretory cells. Extracts of abdominal ganglia were partially purified by RP-HPLC then dot immunoassay screened with the same antisera used for immunocytochemistry. Locusta-diuretic peptide-like immunoreactive material coeluted with synthetic Locusta-diuretic peptide, and leucokinin-like immunoreactive material coeluted with locustakinin. Lysine vasopressin-like material eluted in fractions that also showed Locusta-diuretic peptide and leucokinin I immunoreactivity. The diuretic activity of synthetic Locusta-diuretic peptide and locustakinin is demonstrated, and they are shown to act at least additively to promote Malpighian tubule fluid secretion. The immunoreactive neurosecretory cells are assumed to express at least these two peptides, and a model for promoting fluid secretion is proposed.

Abdomen↗
PubMed2005

Is population-wide diuretic use directly associated with the incidence of end-stage renal disease in the United States? A hypothesis.

BACKGROUND: We introduce the hypothesis that population-wide use of diuretics might be associated with acceleration of the incidence of end-stage renal disease (ESRD). METHODS: Based on the technique of data fusion, pooled-data trends in disease incidence and antihypertensive medication use were examined to determine whether changes in drug use patterns are predictive of disease emergence in the United States. National databases for all-cause cardiovascular disease (CVD) mortality and stroke mortality from the National Vital Statistics Registry, renal failure data obtained from the United States Renal Data Service, and drug information obtained from IMS Health (Fairfield, CT) were examined. RESULTS: A statistically significant inverse relationship was observed between all-cause CVD mortality rates and ESRD incidence rates for the period 1980 to 1998 (r = -0.98948; P < .0001). A statistically significant direct time-lagged relationship was found between both annual changes in diuretic distribution and total diuretic expenditure to annual changes in the ESRD growth rate (r = 0.754, P = .03, r(2) = 0.568, 95% CI for slope = 0.08975 to 1.3010). CONCLUSIONS: Increasing annual diuretic distribution in the US is directly associated with accelerated time-lagged growth rates of ESRD incidence. One potential explanation is that diuretic therapy could promote ESRD expression. A large-scale, randomized, controlled trial to investigate acceleration of ESRD by diuretics would be justifiable. The data invites the hypothesis that reliance on nondiuretic antihypertensive therapies such as calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers might attenuate the epidemic rise of ESRD that is prevalent in the United States.

Cardiovascular Diseases↗
PubMed2004

Diuretic activity of Spilanthes acmella flowers in rats.

In the Sri Lankan traditional medicine, Spilanthes acmella Murr. (Family: Compositae) flowers are claimed to possess powerful diuretic activity. However, as yet, the diuretic potential of these flowers is not investigated by scientifically controlled studies. The aim of this study was to evaluate the diuretic potential of Spilanthes acmellaflowers in rats using a cold-water extract (CWE). Different concentrations of CWE (500, 1000, 1500 mg/kg) or vehicle or furosemide (13 mg/kg) were orally administered (N = 6 per each treatment group) to hydrated rats and their urine output was monitored at several intervals of time (1-5 h). The highest dose of CWE significantly (P < 0.05) and markedly increased the urine output. The onset of this diuretic action was extremely prompt (within 1 h) and lasted throughout the studied period (up to 5 h). The peak effect was evident between 1 and 2 h. Further, the intensity of diuresis induced by the CWE in the first hour was almost similar to that of furosemide. Spilanthes acmella CWE also caused marked increase in urinary Na(+) and K(+) levels and a reduction in the osmolarity of urine suggesting that it is mainly acting as a loop diuretic. It may also inhibit ADH release and/or action. It is concluded that the Spilanthes acmella CWE has strong diuretic action as is claimed.

Administration, Oral↗
PubMed1984

The role of diuretics in the treatment of hypertension.

An oral diuretic has been the most popular step-one drug for the treatment of hypertension in the United States for more than 15 years. Diuretics have many of the attributes of the ideal step-one drug: they are inexpensive, easy to titrate, effective in a large percentage of patients with mild to moderate hypertension, well tolerated, and they enhance the effectiveness of other antihypertensive drugs. Recently, concerns about the safety of diuretics have been raised. All of the placebo-controlled trials that have demonstrated a reduction in cardiovascular morbidity and mortality have used an oral diuretic as step one. Diuretics have more desirable attributes for step-one antihypertensive therapy than any of the alternatives. In the absence of a specific indication for another antihypertensive drug, diuretics in low dosage should continue to be the step-one drug of choice for treating most hypertensive patients.

Adrenergic beta-Antagonists↗
PubMed1996

Tolerability, safety, and quality of life and hypertensive therapy: the case for low-dose diuretics.

The safety and tolerability of antihypertensive therapies are an important clinical concern, because the demonstrated benefits of successful blood pressure-lowering depend on long-term compliance with pharmacologic treatments. Thiazide diuretics and beta blockers have been specifically recommended as preferred initial drug therapy by the Fifth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V), unless their use is contraindicated by concomitant disease, there is intolerance to these agents, or there is a specific indication for another drug class. These recommendations are a result of the lengthy clinical experience with these drugs and the results of long-term clinical trials that have demonstrated significant reductions in cardiovascular morbidity and mortality. However, data from these same clinical studies have also shown that diuretics (and beta blockers) can cause abnormalities in carbohydrate, electrolyte, and lipid metabolism and also may influence quality of life. The safety of diuretics was evaluated with regard to effects on carbohydrate, electrolyte, and lipid metabolism by seeking references from a MEDLINE search of documents published from 1966 to 1994 based on the search terms "hypertension," "human," and "hydrochlorothiazide" (HCTZ) dosed in a range of 12.5-25 mg daily. Two long-term clinical trials using low-dose (12.5-15 mg/day) chlorthalidone-the Systolic Hypertension in the Elderly Program (SHEP) and the Treatment of Mild Hypertension Study (TOMHS)-were also included. During the course of treatment with HCTZ in these studies, serum potassium was reduced and uric acid was increased in a dose-dependent manner. Although low doses of HCTZ elevated serum glucose, cholesterol, and triglycerides, the magnitude of effect was small in most cases and was probably of no clinical significance. Other laboratory parameters were not adversely affected, and subjective reporting of clinical adverse events was generally lower with low-dose HCTZ than with placebo or standard HCTZ dosing. The literature on the effects of low-dose diuretic therapy on quality of life is not large, although the results from the SHEP and TOMHS studies support the concept that diuretics either do not interfere with, or may actually improve, quality of life in hypertensive patients. Low-dose thiazide treatment is a well-tolerated, excellent first-line choice for hypertensive patients, especially older patients. However, diuretics should probably be avoided, whenever possible, in patients with preexisting diabetes, gout, and in men with erectile dysfunction.

Antihypertensive Agents↗
PubMed2003

Only weak vasorelaxant properties of loop diuretics in isolated resistance arteries from man, rat and guinea pig.

Besides their diuretic action, loop diuretics may induce a rapid vasodilator effect that contribute to their short-term therapeutic properties. We examined the effects of furosemide (10(-6)-10(-3) mol l(-1)) in comparison with bumetanide (10(-6)-10(-4) mol l(-1)) on isolated resistance arteries from rat and guinea pig mesentery and human subcutaneous fat, and investigated the mechanism of the acute direct vasorelaxant action on an isometric microvascular myograph. Both loop diuretics induced concentration-dependent relaxation of resistance vessels irrespective of membrane potential. The maximal effect of furosemide was greatest in rat and least in human arteries. Both diuretics caused a rightward shift in the concentration-response curve to extracellular Ca(2+). Incubation with indomethacin (2 x 10(-5) mol l(-1)) or mechanical removal of the endothelium did not inhibit the loop diuretic-induced relaxation. At high concentrations (10(-4)-10(-3) mol l(-1)) loop diuretics exert only weak direct relaxant effects on isolated human subcutaneous resistance arteries compared to the vasorelaxant effects in rat and guinea pig mesenteric vessels.

Animals↗
PubMed2000

Use of a three-factor interpretive optimisation strategy in the development of an isocratic chromatographic procedure for the screening of diuretics in urine samples using micellar mobile phases.

Screening of diuretics in urine is feasible through direct injection of the samples into the chromatographic system and isocratic reversed-phase liquid chromatography (RPLC) with micellar-organic mobile phases of sodium dodecyl sulfate (SDS) and 1-propanol. The surfactant coverage of the chromatographic column makes the addition of organic competing amines less necessary than in conventional aqueous-organic RPLC to achieve well-shaped peaks. Also, the range of elution strengths of micellar mobile phases required to elute mixtures of hydrophobic and hydrophilic diuretics is smaller. This allows the isocratic separation of the diuretics within adequate analysis times. An interpretive methodology is applied to optimise the resolution of a mixture of 15 diuretics of diverse polarity and acid-base behaviour (althiazide, amiloride, bendroflumethiazide, benzthiazide, bumetanide, canrenoic acid, chlorthalidone, ethacrynic acid, furosemide, piretanide, probenecid, torasemide, triamterene, trichloromethiazide and xipamide), using pH and concentrations of surfactant and organic modifier in the mobile phase as separation factors. Twelve diuretics were resolved in 25 min using 0.055 M SDS-6.0% 1-propanol at pH 3.0. The mixture of 15 diuretics was also resolved with two mobile phases showing complementary behaviour: 0.05 M SDS-5.6% 1-propanol at pH 5.4 and 0.11 M SDS-5.4% 1-propanol at pH 4.2. The results were applied to the analysis of urine samples with limits of detection similar to those usually reported for aqueous-organic RPLC, taking into account that the samples were injected without any previous treatment to separate or preconcentrate the analytes.

Calibration↗
PubMed1988

Diuretic radionuclide assessment of obstruction in the infant: guidelines for successful interpretation.

Diuretic renography frequently is used to assess obstruction in hydronephrosis of infancy but it is invalidated by poor renal function, which occurs frequently in this age group. In an attempt to establish a guideline to determine when renal function is too poor in infancy to rely on diuretic renography for an accurate diagnosis we analyzed the slope of the diuretic renographic washout curve of the normal, nonaffected kidney in 33 infants with unilateral hydronephrosis. When the T 1/2 time in the normal, nonaffected kidney was greater than 9 minutes, as occurred in 68 per cent of the infants less than 1 month old, it defined a significant renal functional impairment in both kidneys that interfered with diuretic renographic test interpretation. With time renal function improved and after 4 months of age the T 1/2 time in all nonaffected kidneys became normal and the diuretic renographic diagnosis of obstruction became accurate. Our study indicates that nonaffected kidney T 1/2 time provides a qualitative assessment of global renal function in infancy and defines a level of renal functional maturity that must be achieved to ensure diuretic renographic test accuracy.

Diuretics↗
PubMed1997

Edema and principles of diuretic use.

Diuretics have changed the approach to many disease and have turned once fatal conditions into tolerable ones. Treatment of salt and water overload and edema can be quite satisfying for the clinician as long as the patient is closely watched for side effects. Thiazide diuretics have their greatest use in hypertension, loop diuretics in edema and congestive heart failure, CA inhibitors in glaucoma and altitude sickness, potassium-sparing diuretics in hypokalemia induced by other diuretics and ascites, and osmotic diuretics in acute renal failure and dialysis. They are among the most widely prescribed medications in the world today and rightly have a prominent place in the armamentarium against disease.

Diuretics↗
PubMed2000

Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study.

BACKGROUND: Calcium antagonists are a first-line treatment for hypertension. The effectiveness of diltiazem, a non-dihydropyridine calcium antagonist, in reducing cardiovascular morbidity or mortality is unclear. We compared the effects of diltiazem with that of diuretics, beta-blockers, or both on cardiovascular morbidity and mortality in hypertensive patients. METHODS: In a prospective, randomised, open, blinded endpoint study, we enrolled 10,881 patients, aged 50-74 years, at health centres in Norway and Sweden, who had diastolic blood pressure of 100 mm Hg or more. We randomly assigned patients diltiazem, or diuretics, beta-blockers, or both. The combined primary endpoint was fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death. Analysis was done by intention to treat. FINDINGS: Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups (reduction 20.3/18.7 vs 23.3/18.7 mm Hg; difference in systolic reduction p<0.001). A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group (16.6 vs 16.2 events per 1000 patient-years; relative risk 1.00 [95% CI 0.87-1.15], p=0.97). Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group (6.4 vs 7.9 events per 1000 patient-years; 0.80 [0.65-0.99], p=0.04) and fatal and non-fatal myocardial infarction in 183 and 157 patients (7.4 vs 6.3 events per 1000 patient-years; 1.16 [0.94-1.44], p=0.17). INTERPRETATION: Diltiazem was as effective as treatment based on diuretics, beta-blockers, or both in preventing the combined primary endpoint of all stroke, myocardial infarction, and other cardiovascular death.

Adrenergic beta-Antagonists↗
PubMed1994

Total paracentesis with dextran 40 vs diuretics in the treatment of ascites in cirrhosis: a randomized controlled study.

The aim of the current study was to compare total paracentesis associated with dextran-40 infusion with diuretics in the treatment of tense ascites in patients with cirrhosis. Eighty patients were randomly allocated to two groups: 40 patients were treated with paracentesis plus dextran-40 infusion (8 g per liter of ascitic fluid removed), and 40 patients with diuretics. After treatment patients were discharged with diuretics, and patients developing tense ascites during follow up (54 +/- 4 weeks) were treated according to their initial schedule. Paracentesis was more effective than diuretics in mobilizing the ascitic fluid. The incidence of complications was significantly higher (p < 0.05) in the diuretic group (38%) than in the paracentesis group (15%). This difference was mainly due to a higher incidence of hepatic encephalopathy in the former group (30% vs. 2.5%). A significantly higher incidence of hepatic encephalopathy was also observed in the diuretic group during the follow-up readmissions for ascites recurrence. There were no significant differences between the two treatment groups in the probability of survival after inclusion. Plasma renin activity and plasma aldosterone concentration measured before and 2 and 6 days after paracentesis in 20 randomly selected patients increased significantly (p < 0.05) (baseline values: 5.3 +/- 1.4 ng.ml-1.h-1 and 63 +/- 21 ng/dl; 48 h after paracentesis: 11.7 +/- 3.9 ng.ml-1.h-1 and 99 +/- 31 ng/dl; 6 days after paracentesis: 10.9 +/- 3 ng.ml-1.h-1 and 110 +/- 27 ng/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

The effect of diuretics on systemic and renal hemodynamics in patients with renal insufficiency.

Diuretics have been used in acute renal failure in an attempt to increase urine flow and ameliorate the reduction in glomerular filtrate rate. A beneficial response occurs in some experimental models of acute renal failure when diuretics are administered prophylactically or very early in the course of renal failure and may require a renal vascular bed capable of responding partially, at least, to vasodilating stimuli. In chronic renal insufficiency the most important indications for diuretic use are for the treatment of systemic hypertension and for the correction of the congested state. However, the precise effect of diuretic therapy under these conditions is unpredictable and dependent on the functional state of the renal vessels. Diuretic administration may at times prove detrimental, resulting in a deterioration of glomerular filtration rate. In hemodynamically unstable conditions the slow removal of extracellular fluid by continuous arteriovenous hemofiltration may prove preferable to diuretic administration or standard forms of dialysis.

Acute Kidney Injury↗