lisinopril and Hyperkalemia

Abdominal wall pain (AWP) is a common and underrecognized cause of chronic abdominal pain. The etiology of AWP varies. History and physical examination are critical to an accurate diagnosis of AWP. Trigger point injection using either a corticosteroid, a local anesthetic, or a combination of both often gives relief of pain and is of diagnostic and therapeutic value. Increased awareness of AWP as a cause of chronic, nonvisceral abdominal pain can prevent fruitless searches for intra-abdominal pathology and reduce medical costs.

Topics: Abdominal Pain; Abdominal Wall; Aged; Angiotensin-Converting Enzyme Inhibitors; Calcium Gluconate; Diagnosis, Differential; Diuretics; Furosemide; Humans; Hyperkalemia; Infusions, Intravenous; Lisinopril; Male; Potassium; Renal Insufficiency, Chronic

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the cornerstones of pharmacologic therapy in diabetic nephropathy. Mineralocorticoid receptor blockers reduce proteinuria as single agents or add-on therapy to other renin-angiotensin-aldosterone system-inhibiting drugs in these patients. The long-term benefits and ultimate role of mineralocorticoid receptor blockers in diabetic nephropathy remain unknown. A clinical trial previously showed that the kalemic effect of spironolactone is higher than losartan when added to lisinopril in patients with diabetic nephropathy. The purpose of this study was to investigate if renal potassium handling was primarily responsible for that observation.. In a blinded, randomized, three-arm placebo-controlled clinical trial, 80 participants with diabetic nephropathy taking lisinopril (80 mg) were randomized to spironolactone (25 mg daily), losartan (100 mg daily), or placebo (trial dates from July of 2003 to December of 2006). Serum potassium, aldosterone, and 24-hour urine sodium, potassium, and creatinine were measured over 48 weeks. Differences were analyzed with repeated measures mixed models.. Mean follow-up serum potassium was 5.0 mEq/L for spironolactone, 4.7 mEq/L for losartan (P=0.05 versus spironolactone), and 4.5 mEq/L for placebo (P<0.001 versus spironolactone; P=0.03 versus losartan). The difference in serum potassium was 0.23 mEq/L for losartan versus placebo (P=0.02), 0.43 mEq/L for spironolactone versus placebo (P<0.001), and 0.2 mEq/L for spironolactone versus losartan (P=0.05). Serum and urine potassium excretion and secretion rates were similar between groups throughout the study.. Spironolactone raised serum potassium more than losartan in patients with diabetic nephropathy receiving lisinopril, despite similar renal sodium and potassium excretion. This finding suggests that extrarenal potassium homeostasis contributes to hyperkalemia in these patients. A better understanding of extrarenal potassium homeostasis will provide an opportunity to use this drug more safely in patients with diabetic nephropathy as well as other patient populations.

Topics: Adult; Aldosterone; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Creatinine; Diabetic Nephropathies; Diuretics; Drug Therapy, Combination; Female; Humans; Hyperkalemia; Lisinopril; Losartan; Male; Middle Aged; Potassium; Prospective Studies; Renin-Angiotensin System; Risk Factors; Sodium; Spironolactone; Texas; Time Factors; Treatment Outcome

Concerns exist that diuretic-induced changes in serum potassium may have adverse effects in hypertensive patients. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a large practice-based clinical trial, made it possible to examine consequences of observed changes in potassium during care in conventional practice settings. Normokalemic participants randomized to chlorthalidone (C) versus amlodipine or lisinopril as a first-step drug were stratified by year-1 potassium. Postyear-1 outcomes among hypokalemics (potassium, <3.5 mmol/L) and hyperkalemics (potassium, >5.4 mmol/L) were compared with normokalemics (potassium, 3.5-5.4 mmol/L). Year-1 hypokalemia incidence was 6.8%; incidence in C (12.9%) differed from amlodipine (2.1%; P<0.001) and lisinopril (1.0%; P<0.01). Hyperkalemia incidence (2.0%) was greater in lisinopril (3.6%) than in C (1.2%; P<0.01) or amlodipine (1.9%; P<0.01). Coronary heart disease occurred in 8.1% with hypokalemia, 8.0% with normokalemia, and 11.1% with hyperkalemia. Overall, mortality was higher in hypokalemics than in normokalemics (Cox hazard ratio, 1.21 [95% CI, 1.02-1.44]) with statistically significant (interaction, P<0.01) disparity in hazard ratios for the 3 treatment arms (hazard ratios, C=1.21, amlodipine=1.60, lisinopril=3.82). Hyperkalemia was associated with increased risk of combined cardiovascular disease (hazard ratio, 1.58 [95% CI, 1.15-2.18]) without significant treatment interactions. In conventional practice settings, the uncommon appearance of hyperkalemia was associated with increased cardiovascular disease risk. Hypokalemia was associated with increased mortality; however, the statistically significant heterogeneity in hazard ratios across treatment groups strongly suggests that the observed increase in mortality is unrelated to the specific effects of C. Thus, for most patients, concerns about potassium levels should not influence the clinician's decision about initiating hypertension treatment with low-moderate doses of thiazide diuretics (12.5-25.0 mg of C).

Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Chemical Analysis; Cardiovascular Diseases; Chlorthalidone; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hyperkalemia; Hypertension; Hypokalemia; Incidence; Kaplan-Meier Estimate; Lisinopril; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Risk Assessment; Survival Rate; Treatment Outcome

Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can slow the progression of diabetic nephropathy. Even with ACEI or ARB treatment, the proportion of patients who progress to end-stage renal disease (ESRD) remains high. Interventions that achieve more complete blockade of the renin-angiotensin system, such as combination ACEI and ARB, might be beneficial. This approach may decrease progression of nondiabetic kidney disease. In diabetic nephropathy, combination therapy decreases proteinuria, but its effect in slowing progression is unknown. In addition, the potential for hyperkalemia may limit the utility of combined therapy in this population. VA NEPHRON-D is a randomized, double-blind, multicenter clinical trial to assess the effect of combination losartan and lisinopril, compared with losartan alone, on the progression of kidney disease in 1850 patients with diabetes and overt proteinuria. The primary endpoints are time to (1) reduction in estimated GFR (eGFR) of > 50% (if baseline < 60 ml/min/1.73 m(2)); (2) reduction in eGFR of 30 ml/min/1.73 m(2) (if baseline > or = 60 ml/min/1.73 m(2)); (3) progression to ESRD (need for dialysis, renal transplant, or eGFR < 15 ml/min/1.73 m(2)); or (4) death. The secondary endpoint is time to change in eGFR or ESRD. Tertiary endpoints are cardiovascular events, slope of change in eGFR, and change in albuminuria at 1 yr. Specific safety endpoints are serious hyperkalemia (potassium > 6 mEq/L, requiring admission, emergency room visit, or dialysis), all-cause mortality, and other serious adverse events. This paper discusses the design and key methodological issues that arose during the planning of the study.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Glomerular Filtration Rate; Humans; Hyperkalemia; Kidney Failure, Chronic; Kidney Transplantation; Lisinopril; Losartan; Prospective Studies; Proteinuria; Renal Dialysis; Research Design; Time Factors; Treatment Outcome; United States; United States Department of Veterans Affairs

Hyperkalemia is a known side effect during treatment with Angiotensin Converting Enzyme Inhibitors (ACEIs). The purpose of this study was to compare the effect of an ACEI (Lisinopril) to an Angiotensin II Receptor Blocker (Losartan) on serum potassium (K) level in patients with known history of high normal serum K (mean = 4.8) while on treatment with ACEIs or Angiotensin II Receptor Blockers (ARBs).

Topics: Adult; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cross-Over Studies; Female; Humans; Hyperkalemia; Kidney Failure, Chronic; Lisinopril; Losartan; Male; Middle Aged

Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF.. The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction.. Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol/L [> or =1.5 mg/dL]; age, > or =70 years; and patients with diabetes) generally tolerated the high-dose strategy.. These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Double-Blind Method; Drug Administration Schedule; Female; Heart Failure; Humans; Hyperkalemia; Hypotension; Kidney Diseases; Lisinopril; Male

Both angiotensin-converting enzyme (ACE) inhibitors like lisinopril and nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin have been shown to lower urinary protein excretion in renal disease. If this effect is caused by different mechanisms of action, the combination of these agents could have an additive antiproteinuric effect. We studied the effects of lisinopril and indomethacin separately and in combination in 10 patients with the nephrotic syndrome. Proteinuria was lowered from 10.5 +/- 1.8 g/24 h in the control period to 4.5 +/- 1.1 g/24 h on indomethacin, 4.3 +/- 1.0 g/24 h on lisinopril and to 2.4 +/- 0.8 g/24 h on the combination. Glomerular filtration rate (GFR) fell on either monotherapy, but particularly on the combination of drugs. The renal hemodynamic changes suggested a preglomerular vasoconstriction by indomethacin and a postglomerular vasodilation by lisinopril. Severe hyperkalemia occurred in 3 patients on the combination therapy. We conclude that the combination of indomethacin and lisinopril has an additive antiproteinuric effect. This, as well as the more pronounced fall in GFR on the combination, may suggest that both drugs lower proteinuria by decreasing intraglomerular capillary pressure but via different mechanisms. Combining these drugs may be useful in the symptomatic treatment of nephrotic syndrome, but renal function and serum potassium should be monitored carefully.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Drug Therapy, Combination; Enalapril; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Indomethacin; Lisinopril; Male; Middle Aged; Nephrotic Syndrome

Topics: Antihypertensive Agents; Arrhythmias, Cardiac; Humans; Hyperkalemia; Lisinopril; Potassium

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiac Catheterization; Coronary Angiography; Diagnosis, Differential; Electrocardiography; Feeding Behavior; Heart Conduction System; Humans; Hyperkalemia; Lisinopril; Male; Musa; Myocardial Infarction; Potassium; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Angiotensin-converting enzyme (ACE) inhibitors are recommended for patients with chronic kidney disease (CKD) because they slow disease progression. But physicians' concerns about the risk of hyperkalemia (elevated serum potassium level), a potentially fatal adverse effect, may limit optimal management with ACE-inhibitors. We synthesized known predictors of hyperkalemia into a prognostic risk score to predict the risk of hyperkalemia.. We assembled a retrospective cohort of adult patients with possible CKD (at least one estimated glomerular filtration rate (eGFR) value less than 60 ml/min/1.73 m(2)) who started an ACE-inhibitor (i.e., incident users) between 1998 and 2006 at a health maintenance organization. We followed patients for hyperkalemia: (1) potassium value >5.5 mmol/L; or (2) diagnosis code for hyperkalemia. Cox regression synthesized a priori predictors recorded in the electronic medical record into a risk score.. We followed 5171 patients and 145 experienced hyperkalemia, a 90-day risk of 2.8%. Predictors included: age, eGFR, diabetes, heart failure, potassium supplements, potassium-sparing diuretics, and a high dose for the ACE-inhibitor (lisinopril). The risk score separated high-risk patients (top quintile, observed risk of 6.9%) from low-risk patients (bottom quintile, observed risk of 0.7%). Predicted and observed risks agreed within 1% for each quintile. The risk increased gradually in relation to declining eGFR with no apparent threshold for contraindicating ACE-inhibitors.. The risk score separated high-risk patients (who may need more intensive laboratory monitoring) from low-risk patients. The risk score should be validated in other populations before it is ready for use in clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Cohort Studies; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hyperkalemia; Kidney Diseases; Lisinopril; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Risk; Risk Factors

Hyperkalemia is an electrolyte abnormality that can lead to severe consequences. Paralysis induced by hyperkalemia has been described in only a few reports. We describe a 60-year-old man who experienced paralysis presumably due to hyperkalemia. He presented to the emergency department with severe weakness in all extremities. The patient's serum potassium concentration was greater than 8 mEq/L and his serum creatinine concentration was 7 mg/dl. Findings on electrocardiography were abnormal. Of note, his drug therapy included lisinopril and naproxen. After treatment for hyperkalemia, the patient's symptoms resolved; however, he was admitted for further workup for renal failure. The patient was discharged after approximately 1 week with a diagnosis of end-stage renal disease. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's paralysis and hyperkalemia. Although hyperkalemia as a cause of paralysis is extremely rare, clinicians should be aware of this potentially life-threatening, noncardiac toxicity.

Topics: Creatinine; Humans; Hyperkalemia; Kidney Failure, Chronic; Lisinopril; Male; Middle Aged; Naproxen; Paralysis

Four patients presented to the emergency room with life-threatening hyperkalemia and concomitant watery diarrhea. Hypovolemia, acidosis, and renal insufficiency were present in all 4 cases. In 2 patients, hyperkalemia followed initiation of angiotensin-converting enzyme (ACE) inhibitor therapy, whereas 1 patient experienced hyperkalemia after a dose increase of an ACE inhibitor, and the fourth patient was on continuous ACE-inhibitor therapy at the time of the hyperkalemia episode. Two of the 3 patients with functioning kidneys required hemodialysis to correct the hyperkalemia, whereas the other patient was on long-term hemodialysis therapy. In the 2 patients in whom transtubular potassium (K+) gradients were available, their values ranged far below normal, indicating tubular failure to secrete K+. This abnormality was attributed to decreased distal delivery of sodium and water and to renin/angiotensin II/aldosterone blockade. It has been proposed that aldosterone blockade impairs the capacity of the colonic epithelial cells to secrete K+. In all 4 patients the watery diarrhea ceased in parallel with the correction of serum K+ to normal values. It is suggested that hyperkalemia, most likely by stimulating intestinal motility, induced the watery diarrhea in all 4 patients. The watery diarrhea, however, failed to compensate for the renal tubular failure to secrete K+.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Diarrhea; Humans; Hyperkalemia; Lisinopril; Male; Renal Dialysis

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Beverages; Diabetes Mellitus, Type 1; Humans; Hyperkalemia; Kidney Failure, Chronic; Lisinopril; Male; Rosales

Topics: Acute Kidney Injury; Aged; Angiotensin-Converting Enzyme Inhibitors; Diabetes Complications; Humans; Hyperkalemia; Hypertension; Lisinopril; Male; Potassium; Water Softening

The antihypertensive and renal effects of the angiotensin-converting enzyme inhibitor lisinopril were studied in a group of patients with moderate-to-severe hypertension and impaired renal function. After 12 weeks of treatment, most patients had good blood pressure response to lisinopril monotherapy. During this period, correlations between antihypertensive effect, drug dose, and serum drug level were observed. These correlations were no longer evident after prolonged treatment. During a 1-year follow-up period, the drug dose was lowered gradually without losing antihypertensive effect. Hyperkalemia occurred in one third of the patients. During the 1-year follow-up, the glomerular filtration rate (GFR) decreased in two thirds of the patients and remained stable in the other third. In this latter group, the pretreatment GFR was higher, and the effective renal plasma flow had increased, whereas in the patients with a decreased GFR no renal vasodilation had occurred during lisinopril therapy. Thus, lisinopril is an effective antihypertensive drug for patients with impaired renal function. The dose should be adjusted to the pretreatment GFR, and a decrease in dosage should be considered with prolonged treatment.

Topics: Blood Pressure; Enalapril; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Hypertension; Kidney Diseases; Lisinopril; Male; Time Factors

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diet, Reducing; Enalapril; Female; Humans; Hyperkalemia; Lisinopril; Middle Aged

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Hyperkalemia; Lisinopril; Male; Middle Aged