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Prescribed medications, over-the-counter drugs, and nutritional supplements are used by many patients. Although most of these products are well tolerated, drug-induced hyperkalemia may develop in patients with underlying renal impairment or other abnormalities in potassium handling. Drug-induced hyperkalemia most often occurs from impaired renal potassium excretion. However, disturbed cellular uptake of a potassium load as well as excessive ingestion or infusion of potassium-containing substances may also occur. Physicians must be aware of medications that can precipitate hyperkalemia, how these drugs induce alterations in potassium homeostasis, and the patient characteristics that increase the risk of hyperkalemia. [ABSTRACT FROM AUTHOR]

Several medications--notably acyclovir, sulfonamides, methotrexate, indinavir, and triamterene--are associated with the production of crystals that are insoluble in human urine. Intratubular precipitation of these crystals can lead to acute renal insufficiency. Many patients who require treatment with these medications have additional risk factors, such as true or effective intravascular volume depletion and underlying renal insufficiency, that increase the likelihood of drug-induced intrarenal crystal deposition. Acute renal failure in this setting may be preventable if it is anticipated by appropriate drug dosing, volume expansion with high urinary flow, and alkalinization of the urine when appropriate. Renal failure may be reversible if the drug is discontinued, and by volume repletion and alkalinization of the urine when appropriate. Management of established renal insufficiency includes volume repletion, dialytic support if necessary, adjustment of drug doses, and avoidance of further exposure to nephrotoxins. [ABSTRACT FROM AUTHOR]

Objective: To review the pathophysiology underlying the predisposition to hyperkalemia in the elderly; the medications that disrupt potassium balance and promote the development of hyperkalemia in the elderly; the prevention of hyperkalemia in elderly patients treated with potassium-altering medications; and the appropriate management of hyperkalemia when it develops.Methods and Main Results: A MEDLINE search of the literature (1966-1996) using the terms hyperkalemia, drugs, elderly, and treatment was conducted and pertinent review articles, textbooks, and personal files were consulted. Elderly subjects appear to be predisposed to the development of hyperkalemia on the basis of both innate disturbances in potassium homeostasis and comorbid disease processes that impair potassium handling. Hyperkalemia in the elderly is most often precipitated by medications that impair cellular uptake or renal disposal of potassium. This electrolyte disorder is best prevented by recognition of at-risk physiology in the aged, avoidance of therapy with certain high-risk medications, and monitoring of plasma potassium concentration and renal function at intervals appropriate for the medication prescribed. Management of hyperkalemia entails identification of the clinical manifestations of severe hyperkalemia, stabilization of cardiac tissue, promotion of cellular potassium uptake, and ultimately removal of potassium from the body.Conclusions: Geriatric patients should be considered at risk of developing hyperkalemia, especially when they are prescribed certain medications. Potassium levels should be monitored at appropriate intervals when these patients are treated with potassium-altering medications. Appropriate management of hyperkalemia in the elderly can avoid life-threatening neuromuscular and cardiac complications. [ABSTRACT FROM AUTHOR]

In summary, patients with HIV infection may develop a bewildering variety of electrolyte and acid-base disturbances. Hyponatremia from many causes is common and associated with an increased mortality. Potassium disorders are frequent, with hyperkalemia, even to life-threatening levels, more common than hypokalemia. Disturbances in calcium and uric acid homeostasis are less frequent. Acid-base disorders also complicate the clinical course of AIDS and, as with the electrolyte perturbations, may result from HIV infection itself, the illnesses associated with AIDS, or medications. [ABSTRACT FROM AUTHOR]

The article presents a case study involving a 61-year-old man who was diagnosed as having calcific uremic arteriolopathy (CUA). Suffering from diabetes mellitus for 25 years and renal failure, he was hospitalized and was injected with low-dose warfarin prophylaxis. Four months later, he presented with a presumed penile infection, and one month later, he returned with complaints of tenderness and a violet rash on the lateral aspect of both thighs. Skin biopsy findings indicated he was suffering from CUA, while Histopathologic studies showed thrombi within arterioles and intimal calcification. Risk factors for CUA include elevated phosphorus levels, increased body mass index, and hypoalbuminemia.

Nephrogenic systemic fibrosis (NSF) was first recognized as a complication of gadolinium-based contrast (GBC) exposure in 2006 and confirmed subsequently by numerous investigators. Early information on the toxicity of free gadolinium (Gd3+) and the pharmacokinetics of this agent in patients with underlying kidney disease were likely unrecognized subtle clues to its potential for adverse effects in humans. Since the recognition of NSF as a complication of GBC exposure, our approach to imaging in patients with kidney disease has been altered. As these patients require various forms of imaging to diagnose associated conditions, we must utilize an evidence-based approach to imaging options. It is our responsibility to identify patients at high risk to suffer this complication and choose between non-GBC imaging modalities, radiocontrast-based imaging modalities, and GBC imaging modalities based on risk:benefit assessment. The benefits of rapid, accurate diagnosis must be weighed against risks associated with CT scan with radiocontrast (radiation exposure, allergic contrast reactions, acute kidney injury), GBC imaging (development of NSF), and missed diagnoses due to use of suboptimal imaging modalities in an effort to avoid radiocontrast and GBC agent exposure.

Native kidney biopsy is still performed primarily with hospital inpatient observation period. Experience with outpatient Computed Tomographic (CT)-guided renal biopsy at Yale New Haven Medical Center was studied to assess efficacy and safety. A total of 146 outpatient native kidney biopsies were identified between 1995 and 2001. Records were reviewed for demographics, clinical, and laboratory data and details of the procedure. Time of admission to the outpatient unit, duration of procedure and post-biopsy observation period were recorded. Complications such as bleeding, infection, admission to the hospital, transfusion, or intervention for continued bleeding were noted. Mean age was 43.9 ± 14.9 years and mean serum creatinine was 1.8 ± 1.4 mg/dl. Renal size averaged 11.4 cm. Post-procedure observation time of 4 - 6 h appeared to be adequate. Diagnostic tissue was successfully sampled in 98.6% of cases. Procedure was well tolerated with no hemodynamically significant changes. Hematocrit and hemoglobin concentration changes averaged 3.6 ± 2.5% and 1.0 ± 0.9 mg/dl, respectively (p < 0.001). There were no instances of death or need for intervention. Transfusion was required in 1 patient while 6 patients had detectable bleeding and were hospitalized for observation. Outpatient CT-guided kidney biopsy provides adequate tissue and appears to be safe with very low complication rates.

Both diagnostic and therapeutic studies frequently utilize radiocontrast media to enhance images. As a result, use of these agents has increased markedly over the past decade with more than 10 million studies performed on a yearly basis in the United States. Development of acute kidney injury (AKI) is a common complication of radiocontrast exposure in patients who possess underlying risk factors. Impor-tantly, radiocontrast-induce nephropathy (RCIN) is associated with increased short- and long-term mortality. Thus, at risk patients should be identified prior to administration of radiocontrast to allow choice of other potential imaging options or employment of prophylactic interventions. Currently, use of isotonic intravenous fluids is the only proven beneficial preventive therapy. Use of low volumes of radiocontrast and avoidance of nephrotoxic medications are also accepted as nephroprotective. Mixed results exist on the utility of N-acetylcysteine (NAC) therapy and low versus iso-osmolar radiocontrast agents in preventing RCIN. While hemodialysis appears to have no beneficial role, a single center's experience with hemofiltration is associated with a reduction in RCIN and other clinical endpoints. Several therapies have no role in the prevention of RCIN and should be avoided. This review will provide an up to date examination of the current status of these issues as they relate to RCIN.

Proton pump inhibitors (PPIs) are widely prescribed to treat a number of gastrointestinal disorders due to excessive acid production. While effective and safe, adverse renal effects have been described. Most concerning is the ever increasing number of cases of acute interstitial nephritis (AIN) associated with PPI therapy. It appears to be a class effect as all PPIs have been documented to cause AIN. Several adverse drug event registries now note PPIs as the most common cause of drug-induced AIN. While most patients recover kidney function, many are left with some level of chronic kidney disease. Hyponatremia is an extremely rare complication and is thought to result from inappropriate ADH secretion. Interactions with calcineurin inhibitors may occur with certain PPIs when used in susceptible patients, particularly those with polymorphisms in the cytochrome P450-2C19 enzyme gene. This paper will critically review the effect of PPIs on the kidney.

Indinavir is a well-known cause of crystal-induced acute renal failure, dysuria and flank pain, and nephrolithiasis. Recently a more insidious tubulointerstitial lesion has been recognized as secondary to the drug. We report a case of a hepatitis C-positive patient on long-term indinavir therapy for human immunodeficiency virus (HIV) who developed a slowly progressive rise in serum creatinine. Renal biopsy revealed a diffuse interstitial infiltrate with numerous eosinophils and scarring. The tubules showed focal necrosis and dilation with elongated crystals present within their lumina. The elevated serum creatinine decreased to a new baseline over several months with the discontinuation of indinavir. We review the literature of renal syndromes associated with indinavir focusing on chronic progressive tubulointerstitial injury and speculate on risk factors and potential mechanisms of indinavir-induced renal injury.

Treatment of symptomatic intradialytic hypotension (IDH) is a difficult task for the practicing nephrologist. Minimizing patient factors that precipitate IDH as well as dialysis procedure-related components that lower blood pressure are the initial approaches to this problem. However, despite these maneuvers, hypotension often persists in a group of high-risk patients. Pharmacologic interventions are often used to reduce IDH. Unfortunately, many of the available therapies are marginally effective and/or poorly tolerated. A few therapies appear to be efficacious and well tolerated-carnitine, sertraline, and midodrine. This article reviews the various pharmacologic therapies used for IDH and makes recommendations for treatment of this difficult problem.

Prostaglandins produced by the COX-2 isoform of cyclooxygenase may be important for renal function--and perhaps even more so in diseases that render the kidney highly prostaglandin-dependent. COX-2 inhibitors may thus have much the same renal risks that a standard NSAID does. Several clinical trials have already focused on the new drugs' renal effects.

Selective cyclooxygenase-2 (COX-2) inhibitors have provided relief for patients suffering from chronic pain and other inflammatory conditions and have reduced adverse gastrointestinal effects. The documented reduction in gastric erosions, ulcerations, and perforations during the use of COX-2-selective inhibitors raises the question: would the kidney be similarly spared? Our understanding of these enzyme isoforms in the kidney is incomplete. However, kidney tissue seems to possess "constitutive" or homeostatic COX-2 enzyme, suggesting a role for prostaglandins produced by this isoform. In addition, studies evaluating the renal effects of the selective nonsteroidal anti-inflammatory drugs (NSAIDs) are inconclusive, and available data on the renal effects of COX-2-selective inhibitors are conflicting. Inadequate numbers, varied baseline patient characteristics, and different doses and lengths of drug treatment hampers comparison of the small number of clinical investigations available for review. Therefore, this article reviews the role of cyclooxygenase enzyme activity and associated prostaglandins in the kidney and the adverse renal effects of nonselective NSAIDs. We also touch on the COX-1/COX-2 selectivity of NSAIDs, the localization of COX enzymes in kidneys, and clinical studies examining the renal effects of selective COX-2 inhibitors.

Treatment of intradialytic hypotension (IDH) in the end-stage renal disease population has been a difficult task for nephrologists caring for these patients. The presence of multiple pathogenic factors contributes to hemodynamic instability and explains why therapies that modulate only a specific aspect of the problem are only partially effective. Cool dialysate (34.5 degrees C to 35.5 degrees C) and midodrine may provide hemodynamic stability through an increase in peripheral vascular resistance, whereas high dialysate calcium concentration (HDCa; 3.5 mEq/L) improves intradialytic blood pressure through preservation of cardiac output. Theoretically, the combination of these two types of therapies might further reduce the frequency and severity of hypotension during hemodialysis (HD). We undertook a study to evaluate the effect of HDCa added to midodrine and/or cool dialysate in the treatment of patients with severe IDH. Twenty-eight patients met the entry criteria, and 23 patients completed the prospective crossover study. Five patients dropped out of the study secondary to hypercalcemia. The addition of HDCa significantly improved post-HD mean arterial pressure (MAP; 95.6 +/- 12.7 versus 90.8 +/- 12.5 mm Hg; P = 0.002). The decreases in MAP from pre-HD to lowest intradialytic (16.3 +/- 8.2 versus 20.6 +/- 10.0 mm Hg; P = 0.009) and pre-HD to post-HD (2.0 +/- 8.5 versus 8.15 +/- 10.8 mm Hg; P = 0.002) were significantly reduced with HDCa compared with low dialysate calcium. However, there were no significant improvements in symptoms of or interventions for IDH. Thus, it appears that the addition of HDCa to midodrine and/or cool dialysate further improves blood pressure in patients with IDH. However, this therapy did not reduce symptoms or interventions required for IDH. In addition, hypercalcemia complicated this therapy in 22% of the patients.

Acute renal failure is a well-described renal syndrome observed in patients infected with the human immunodeficiency virus (HIV). Underlying glomerular disease and disturbances in renal tubular function predispose these patients to a number of hemodynamic and nephrotoxic insults. Prerenal azotemia from both "true" and "effective" depletion of intravascular volume is the most common cause of acute renal insufficiency in patients infected with HIV. Direct damage to the renal tubules from both nephrotoxic medications and prolonged ischemic processes occurs frequently in hospitalized patients. Injury to the tubulointerstitium of the kidney may also result from allergic reactions to medications prescribed to patients. Deposition of crystals in the tubular lumens, and rarely in the glomerular capillaries, will cause acute renal failure in the setting of tumor lysis syndrome or during therapy with medications associated with crystal nephropathy. Finally, obstruction of the urinary system will rarely cause postrenal azotemia in patients infected with HIV.

Angiotensin-converting enzyme (ACE) inhibitors may exacerbate anemia in patients with chronic renal failure, as well as in dialysis patients. To better answer this question, a prospective, crossover study was conducted to evaluate the effect of ACE inhibitors on recombinant human erythropoietin (rHuEPO) requirements in hemodialysis patients. Patients administered an ACE inhibitor when entering the study remained on this drug for the initial 4 months and were then switched to another antihypertensive agent for 4 more months. Patients not initially administered an ACE inhibitor were switched to lisinopril at 4 months. rHuEPO doses were adjusted using a sliding scale based on weekly laboratory hematocrit values. The inclusion criteria were met by 51 patients undergoing dialysis. Demographics were as follows: 61% were women, 64% were black, 46% had diabetes, average age was 53.2 +/- 13.3 years, and time on hemodialysis was 38.0 +/- 44.5 months. Thirty-three patients completed the study. Hematocrit averaged 32.7% +/- 1.9% while on ACE inhibitor therapy and 33.1% +/- 2.1% off ACE inhibitor therapy (P = 0.217). There was no difference in rHuEPO dose per treatment during each period (3,500 +/- 1,549 U on ACE inhibitor therapy versus 3,312 +/- 1,492 U off ACE inhibitor therapy; P = 0.300). No significant differences were found in degree of blood pressure control or various clinical and laboratory parameters that might be associated with rHuEPO resistance between the two periods. Similarly, no differences were found in hospitalization days, duration of infections, or transfusion requirements. These findings suggest that ACE inhibitors do not contribute to rHuEPO resistance in hemodialysis patients.

Nonsteroidal anti-inflammatory drugs are well-known culprits in the development of acute renal insufficiency in high-risk patients. The recent release of the selective cyclooxygenase-2 enzyme inhibitors for the treatment of inflammatory diseases and pain syndromes has been associated with a clear-cut decrease in adverse gastrointestinal effects. However, the nephrotoxic potential of these agents in patients with prostaglandin-dependent states and chronic renal impairment is unknown. Many clinicians commonly wonder if these agents can be safely prescribed to such high-risk patients. We present two cases of acute renal failure complicating the course of therapy with celecoxib in patients with chronic renal insufficiency.

Cotrimoxazole (trimethoprim-sulfamethoxazole) is a combination antimicrobial that is frequently used to treat a wide variety of infections. Only recently has hyperkalaemia been recognised as a relatively common complication of therapy with trimethoprim. Hyperkalaemia has been demonstrated to occur with the administration of both high and standard dosages of trimethoprim. The recognition of this disorder of potassium homeostasis prompted the investigation and ultimate description of the mechanism by which trimethoprim causes hyperkalaemia. Trimethoprim was found to reduce renal potassium excretion through the competitive inhibition of epithelial sodium channels in the distal nephron, in a manner identical to the potassium-sparing diuretic amiloride. Increased risk for hyperkalaemia with trimethoprim treatment appears to be related to both higher dosages and underlying renal impairment. It is probable that other disturbances in potassium homeostasis, such as hyopoaldosteronism and treatment with medications that impair renal potassium excretion, are also risk factors for hyperkalaemia with trimethoprim therapy. Prevention of this adverse reaction depends upon recognition of patients at risk of developing hyperkalaemia as well as proper dosage selection of trimethoprim for the patient's prevailing glomerular filtration rate. Management of hyperkalaemia often mandates discontinuation of the drug, volume repletion with isotonic fluids, and other therapies specific to hyperkalaemia. In circumstances where continued treatment with trimethoprim is required, induction of high urinary flow rates with intravenous fluids and a loop diuretic, as well as alkalinisation of the urine, have been shown to block the antikaliuretic effect of trimethoprim on distal nephron cells.

Intradialytic hypotension (IDH) is a morbid complication of hemodialysis (HD). Both midodrine, an oral selective alpha1 agonist, and cool dialysate have been reported as useful therapies for this problem. We performed this prospective crossover study to compare the efficacy of these two therapies, alone and in combination, for IDH. The study consisted of a control phase and three treatment phases: midodrine phase (10 mg oral dose pre-HD), cool dialysate phase (35.5 degrees C), and combination therapy phase (midodrine, 10 mg, and dialysate temperature, 35.5 degrees C). Each phase consisted of nine consecutive HD treatments. Eleven patients (six men, five women; mean age, 67.5 years) with known symptomatic IDH were studied. This cohort was followed up in terms of blood pressure measurements (pre-HD blood pressure, lowest intradialytic blood pressure, post-HD blood pressure), weights, laboratory values, and interventions for IDH. The lowest intradialytic blood pressures were significantly better with midodrine and cool dialysate compared with the control phase (systolic blood pressure [SBP], 103.9 +/- 4.1 [mean +/- standard error of the mean] and 102.6 +/- 2.9 v 90.6 +/- 2.5 mm Hg, respectively; P < 0.001), as were the post-HD blood pressures (SBP, 116.9 +/- 4.0 and 118.2 +/- 3.5 v 109.0 +/- 2.1 mm Hg; P < 0.01). In addition, the lowest intradialytic blood pressures were significantly better with the combination phase compared with the control phase (SBP, 103.7 +/- 4.2 v 90.6 +/- 2.5 mm Hg; P < 0.001), as were the post-HD blood pressures (SBP, 122.1 +/- 4.6 v 109.0 +/- 2.1 mm Hg; P < 0.01). There was a significant reduction in the number of nursing interventions performed and volume of saline infused for IDH with midodrine and cool dialysate compared with control. There was a trend toward amelioration of hypotensive symptoms with both therapies. Laboratory values, including Kt/V, did not change significantly with either midodrine or cool dialysate. This prospective study shows that both midodrine and cool dialysate are effective therapies for symptomatic IDH. There does not seem to be additional benefit when these two therapies are used in combination.

Epsilon-aminocaproic acid (Amicar) is used to treat severe hemorrhage refractory to usual medical management. This antifibrinolytic drug has been associated with a number of renal complications. However, there are no descriptions of this medication causing hyperkalemia. This report describes the development of hyperkalemia in a patient with underlying chronic renal insufficiency treated with intravenous epsilon-aminocaproic acid. The patient, who underwent coronary artery bypass grafting, had no other obvious cause for the acute increase in serum potassium concentration. Based on data in animals and humans, the cationic amino acids lysine and arginine have been shown to enter muscle cells in exchange for potassium and lead to hyperkalemia through a shift of potassium from the intracellular to the extracellular space. Epsilon-aminocaproic acid, a synthetic amino acid structurally similar to lysine and arginine, also has been noted to cause an acute increase in serum potassium in anephric dogs infused with this medication. It is probable that the mechanism underlying the increase in serum potassium with epsilon-aminocaproic acid is also based on the shift of potassium from the intracellular to the extracellular space. Hence, it appears that intravenous epsilon-aminocaproic acid can also cause hyperkalemia in humans.

Intravenous immune globulin (IVIG) therapy has been used more commonly to treat a number of clinical disorders. During the past 10 years, IVIG infusion has been associated with a variety of complications. Acute renal failure, which was not described in the initial drug trials, was recognized as an adverse effect of IVIG therapy in 1987. Since the original report, a number of cases have been described in the literature. Older age and preexisting renal impairment appear to predispose to the development of acute renal failure. Acute renal insufficiency develops within days and resolves over several days to weeks. However, in some cases, recovery is delayed and initiation of renal replacement therapy is required. Chronic renal insufficiency requiring maintenance dialysis is extremely rare. The precise cause of IVIG-associated acute renal failure is unknown but may be attributable to either the direct effects of the immunoglobulin or the stabilizing agent used in the IVIG preparation.

Indinavir has been described to cause crystalluria and nephrolithiasis in a variable number of treated patients. Acute renal failure, often reversible with discontinuation of the medication, induction of a diuresis and correction of urinary obstruction if present, occurs in a smaller percent of patients. One recent report described renal biopsy findings, indinavir crystals within cellular casts in the collecting tubules, in a patient receiving this antiretroviral agent. We report a second case of a patient with mild renal insufficiency and pyuria following indinavir therapy and describe similar renal biopsy findings.