Spironolactone renal function

Potassium-sparing diuretics may cause hyperkalemia, especially in patients with chronic kidney disease or diabetes, and in patients receiving concurrent treatment with an ACE inhibitor, ARB, NSAID, or potassium supplement. Eplerenone has an increased risk for hyperkalemia and is contraindicated in patients with impaired renal function or type 2 diabetes with proteinuria. Spironolactone may cause gynecomastia in up to 10% of patients, but this effect occurs rarely with eplerenone. 

Hypersensitivity to amiloride serum potassium greater than 5.5 mEq/L antikaliuretic therapy or potassium supplementation renal function impairment patients receiving spironolactone or triamaterene. 

Hyperkalemia Carefully evaluate patients for possible fluid and electrolyte balance disturbances. Hyperkalemia may occur with impaired renal function or excessive potassium intake and can cause cardiac irregularities that may be fatal. Ordinarily, do not give potassium supplements with spironolactone. 

Renal function impairment Use of spironolactone may cause a transient elevation of BUN, especially in patients with preexisting renal impairment. The drug may cause mild acidosis. 

Patients receiving spironolactone or amiloride anuria severe hepatic disease hyperkalemia hypersensitivity to triamterene severe or progressive kidney disease or dysfunction, with the possible exception of nephrosis preexisting elevated serum potassium (impaired renal function, azotemia) or patients who develop hyperkalemia while on triamterene. 

Symptomatic or prior-symptomatic fluid retention responds well to treatment with diuretics and salt restriction if LVEF is reduced. This will usually improve current HF symptoms. Especially, an aldosterone antagonist like spironolactone should be added in selected patients with advanced HF symptoms and reduced LVEF with preserved renal function. Potassium has to be normal and should be carefully monitored. Patients with renal dysfunction and with serum creatinine levels >2.5 mg/dl in men and >2.0 mg/dl in women are contraindicated for aldosterone antagonists. 

Adverse effects Renal function may deteriorate with the decreased circulating fluid volume, especially after the addition of another diuretic drug acting on the RAAS system, and careful monitoring of serum creatinine is essential. Serum potassium should be monitored within one week of initiation and at least every four weeks for the first three months and every three months thereafter. It should also be monitored at any dose change in spironolactone or if there is a change in concomitant medications that affects the potassium balance. The spironolactone dose (standard 25 mg per day) should be reduced if potassium levels are <5.4 mEq/L, and treatment should be discontinued if painful gynecomastia or serious renal dysfunction or hyperkalemia result. 

Metoclopramide should be avoided where possible, as it may cause cerebral irritation. If metoclopramide were to be used the dose should be reduced to 50% of normal, because of reduced hepatic clearance and concomitantly reduced renal clearance. The dose may also require further reduction according to renal function. As this patient is currently taking spironolactone, metoclopramide should be avoided as it may reduce the diuretic effect. 

A dosage of 20 to 40 mg xipamide per day is recommended in 1-2 (-3) single doses. For long-term therapy, it is advisable to prescribe 10 mg. Diuresis sets in after about 1 hour with a peak after 2 to 8 hours. There is no rebound effect. The excretion of sodium and chloride is increased to an almost identical degree calciuria, magnesiuresis and kaliuresis occur. For this reason, xipamide should be combined with spironolactone. Biotransformation of xipamide is clearly limited in cirrhotic patients, the half-life (7 hours) is not influenced. Xipamide passes into the ascitic fluid and reaches concentrations of 10-20% of the respective plasma level. It can even be used with restricted renal function, since it has no influence on renal haemodynamics. 

A 69-year-old man with hypertension and heart failure took losartan 25 mg/day, increasing to 50 mg/day after 2 weeks. He also took spironolactone 50 mg/day, furo-semide 40 mg/day, digoxin 0.25 mg/day, acenocou-marol, and allopurinol. Two weeks later he developed acute renal insufficiency with a plasma creatinine concentration of 725 pmol/l (previously 115 pmol/l). Within 24 hours after losartan withdrawal (it was not stated whether spironolactone was also stopped) and hemodialysis, he recovered renal function (plasma creatinine 124 mg/1). He was later found to have bilateral renal artery stenosis, which is a contraindication to angiotensin II receptor antagonists. 

The major limitation to the use of spironolactone is its liability to cause (sometimes lethal) hyperkalemia, particularly in the elderly, in patients with reduced renal function, and in patients who simultaneously take potassium supplements or ACE inhibitors. As with other diuretics, hyponatremia and dehydration can occur. Other less frequent adverse effects are gastrointestinal intolerance, neurological symptoms, and skin rashes. Hypersensitivity rashes and a lupus-Uke syndrome have been reported rarely. A few cases of mammary carcinoma have been reported and potential human metabolic products of spironolactone are carcinogenic in rodents. Second-generation effects have not been reported. 

Short-term pirfenidone and spironolactone treatment was recently found to reverse cardiac and renal fibrosis and to attenuate increased diastolic stiffness without normalizing cardiac contractility or renal function in STZ-diabetic rats [402]. 

Van den Meiracker AH, Baggen RGA, Pauli S, Lindemans A,Vulto AG, Polermans D, Boomsma F. Spironolactone in type 2 diabetic nephropathy effects on proteinuria, blood pressure and renal function. J Hypertension 2006 24 2285-2292. 

Svensson M, Gustafsson F, Galatius S, et al. Hyperkalaemia and impaired renal function in patients taking spironolactone for congestive heart failure Retrospective smdy. Br Med J 2003 327 1141-1142. 

The potassium-sparing diuretics should not be used concurrently with potassium supplanents, as this combination is likely to produce hyperkalemia. Poor renal function also heightens the risk of hyperkalemia G1 disturbances, rash, drowsiness, or dizziness are aU associated with their use. Spironolactone can cause the blood urea nitrogen level to uiCTease and lead to menstrual irregularities (see also Table 25). 

A study in 4 healthy subjects found that indometacin 150 mg daily given with triamterene 200 mg daily over a 3-day period reduced the creatinine clearance in 2 subjects by 62% and 72%, respectively. Renal function returned to normal after a month. Indometacin alone caused an average 10% fall in creatinine clearance, but triamterene alone caused no consistent change in renal function. No adverse reactions were seen in 18 other subjects treated in the same way with indometacin and furosemide, hydrochlorothiazide or spironolactone. Five patients are reported to have rapidly developed acute renal failure after receiving indometacin and triamterene, either concurrently or sequentially. " ... 

In healthy subjects with normal renal function, acidosis does not usually occur, as the kidneys correct it by increasing the excretion of chloride and production of bicarbonate. " However, in patients with renal impairment, volume depletion (e.g. secondary to diuretics) or concurrent conditions that predispose to acidosis, this interaction may be significant. It has been suggested that electrolytes should be closely monitored when patients who are at risk of an interaction are taking colestyramine and spironolactone, although note that the interaction appears to be rare. 

Electrolyte balance When 175 patients with resistant hypertension took spironolactone 25-100 mg/day adverse effects that were attributed to the drug included an acute reduction in renal function in two patients and asymptomatic hyperkalemia (serum potassium concentration over 5.5 mmol/1) in two patients spironolactone was withdrawn in these patients and in one patient, hyperkalemia resolved following a reduction in spironolactone dosage [25 ]. 

Renal disease Spironolactone is more likely to cause hyperkalemia in patients with chronic renal disease. In a retrospective cohort study, 88 patients (34 patients with chronic kidney disease, GFR bellow 45 ml/ minute) were given spironolactone 12.5-25 mg/day for hypertension [29 ]. There was a non-significant mean increase in the plasma potassium concentration of 0.5 mmol/1 in those with chronic kidney disease compared with 0.3 mmol/1 in those with normal renal function. Three patients with chronic kidney disease changed therapy because of hyperkalemia spironolactone was withdrawn in two patients, but continued in the third because another medication was withdrawn instead. The mean rise in the potassium concentration from baseline in these three patients was 0.9 mmol/1. No patient required hospitalization for hyperkalemia. Multivariate analysis showed that a GFR below 45 ml/minute was a significant predictor of a significant (greater than 0.5 mmol/1) rise in potassium (OR=7.9). 

Electrolyte balance Hypernatremia has been reported in a 44-year-old woman with normal renal function who was given too much sodium polystyrene sulfonate she was also taking furosemide, spironolactone, and lisinopril [39 ]. The authors attributed this to net intestinal water loss because of profuse osmotic diarrhea. 

Fourkiotis V, Vonend O, EHederich S, Fischer E, Lang K, Endres S, et al. Effectiveness of eplerenone or spironolactone treatment in preserving renal function in primary aldosteronism. Eur J Endocrinol/Eur Fed Endocr Soc 2013 168(1) 75-81. 

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