Crystalluria

Susceptibility of the kidney to chemically-induced toxicity is related, at least in part, to several unique aspects of renal anatomy and physiology. By virtue of high renal blood flow, active transport processes for secretion and reabsorption, and progressive concentration of the glomerular filtrate following water removal during the 

The precise biochemical mechanisms leading to irreversible cell injury and nephrotoxicity are not well-defined. Many diverse biochemical activities occur within the kidney, and interference with one or more of these functions may lead to irreversible cell injury. Rather than any one single mechanism mediating chemically induced nephrotoxicity, it is likely that a toxicant alters a number of critical intracellular functions, ultimately leading to cytotoxicity and cellular necrosis. 

Bridges, C. C., and Zalups, R. K. Molecular and ionic mimicry and the transport of toxic metals. Toxicol. Appl. Pharmacol. 204, 274-308, 2005. 

Dekant, W. Chemical-induced nephrotoxicity mediated by glutathione -conjugate formation. Toxicol. Lett. 124, 21-36, 2001. 

Eikmans, M., Baelde, H. J., de Heer, E., and Bruijn, J. A. RNA expression profiling as prognostic tool in renal patients toward nephrogenomics. Kidney Int. 62,1125-1135, 2002. Gibbs, A. Comparison of the specificity and sensitivity of traditional methods for assessment of nephrotoxicity in the rat with metabonomic and proteomic methodologies. J. Appl. Toxicol. 25, 277-295, 2005. 

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Antiviral drugs are given systemically or as topical dragp. When used systemically these dm may be administered orally or intravenously (IV). Rapid IV administration can result in crystalluria (presence of crystals in the urine). The most common adverse reactions when these drugp are administered systemically... 

Acyclovir is available for use orally, topically, and par-enterally (for IV use). When given IV, acyclovir can cause phlebitis, lethargy, confusion, tremors, skin rashes, nausea, and crystalluria Side effects when given orally include nausea, vomiting, diarrhea, headache, dizziness, and skin rashes. Topical administration causes transient burning, stinging, and pruritus. 

ACYCLOVIR When given IV, acyclovir can cause crystal-luria (presence of crystals in the urine) and mental confusion. The nurse helps the patient maintain adequate hydration to prevent crystalluria by encouraging the patient to drink 2000 to 3000 mL of fluid each day (if the disease condition permits). In addition, the nurse should give careful attention to assessing the mental status of the patient. 

Fever, rash, paresthesias, photosensitivity, crystalluria, acidosis, urticaria, pruritus, hematuria, weakness, malaise, anorexia, hematologic changes, convulsions... 

Headache, nausea, vomiting, abdominal pain, crystalluria Gastrointestinal disturbances, allergic skin reactions, headache, anorexia, glossitis, hypersensitivity... 

Oral administration of bicarbonate may decrease the absorption of ketoconazole. Increased blood levels of quinidine, flecainide, or sympatiiomimetics may occur when these agents are administered with bicarbonate There is an increased risk of crystalluria when bicarbonate is administered with the fluoroquinolones. Fbssible decreased effects of lithium, methotrexate, chlorpropamide, salicylates, and tetracyclines may occur when these drag s are administered with sodium bicarbonate. Sodium bicarbonate is not administered within 2 hours of enteric-coated drugs the protective enteric coating may disintegrate before the drug reaches the intestine. 

Nephrolithiasis/ urolithiasis/ crystalluria IDV Onset Any time after initiation of therapy, especially if 4- fluid intake Symptoms Flank pain and/or abdominal pain, dysuria, frequency pyuria, hematuria, crystallauria rarely, Tserum creatinine and acute renal failure 1. History of nephrolithiasis 2. Fhtients unable to maintain adequate fluid intake 3. High peak IDV concentration 4. tDuration of exposure Drink at least 1.5-2 L of non-caffeinated fluid per day Tfluid intake at first sign of darkened urine monitor urinalysis and serum creatinine every 3-6 months Increased hydration pain control may consider switching to alternative agent stent placement may be required... 

Adenine phosphoribosyltransferase (APRT) deficiency is an inherited disorder of purine metabolism and is inherited in an autosomal recessive manner (K18, V7). This enzyme deficiency results in an inability to salvage the purine base adenine, which is oxidized via the 8-hydroxy intermediate by xanthine oxidase to 2,8-di-hydroxyadenine (2,8-DHA). This produces crystalluria and the possible formation of kidney stones due to the excretion of excessive amounts of this insoluble purine. Type I, with virtually undetectable enzyme activity, found predominantly in Caucasians, is found in homozygotes or compound heterozygotes for null alleles. Type II, with significant APRT activity, found only in Japan, is related to a missense mu-... 

Cystinuria. Penicillamine reduces excess cystine excretion in cystinuria. Penicillamine with conventional therapy decreases crystalluria and stone formation, and may decrease the size of or dissolving existing stones. This is achieved by disulfide interchange between penicillamine and cystine, resulting in a substance more soluble than cystine and readily excreted. 

Phenobarbital-like promotion Crystalluria, carbonic anhydrase inhibition, urine pH extremes, melamine, saccharine, carbonic anhydrase inhibitors, dietary phosphates... 

Q20 has a risk of crystalluria with high doses, particularly during parenteral therapy... 

Co-amoxiclav consists of the combination of amoxicillin (penicillin antibacterial agent) and clavulanic acid (beta-lactamase inhibitor) which is associated with a risk of crystalluria in patients with renal impairment who are receiving high doses, particularly during parenteral therapy. 

Adverse reactions may include ataxia, vertigo, fatigue, hyperirritability, emotional disturbances, diplopia, nystagmus, drowsiness, personality deterioration with mood changes, paranoia, nausea, anorexia, vomiting, megaloblastic anemia, thrombocytopenia, impotence, morbilliform or maculopapular skin eruptions, crystalluria. 

Fluid intake Adequate fluid intake must be maintained in order to prevent crystalluria and stone formation. 

Crystalluria may develop and can be prevented by the maintenance of urine at a neutral or alkaline pH. 

Renal/Hepatic function impairment Use with caution. Maintain adequate fluid intake to prevent crystalluria and stone formation. Patients with severely impaired renal function exhibit an increase in the half-lives of both TMP and SMZ, requiring dosage regimen adjustment. 

The short-acting sulfonamides include sulfadimidine, sulfamerazine and sulfathiazole. Sulfadimidine, as the most important representative of this group, is relatively soluble and has therefore a lower risk of causing crystalluria while sulfamerazine and sulfathiazole are less soluble sulfonamides. Sulfadimidine has good oral absorption. It has an elimination half-life between 1.5 and 5 hours, depending on acetylator phenotype. 

Clinical manifestations occur in three phases. In the neurological stage, the patient appears intoxicated, with slurred speech, ataxia, stupor, and hallucinations, and may be comatose, with respiratory depression. The cardiopulmonary stage is delayed by 12-24 hours, when hypotension, tachycardia, muscle tenderness and congestive cardiac failure are seen. After 1-3 days the renal stage supervenes, with loin pain, crystalluria, oliguria and renal failure, as a result of calcium oxalate crystal deposition in the renal tract. Sequestration of calcium can cause profound hypocalcaemia, tetany, and cardiac arrhythmia. 

Sulfonamides, such as sulfadiazine, in combination with pyrimethamine, are considered the treatment of choice of symptomatic toxoplasmosis. Patients should be well hydrated to prevent crystalluria this problem may be reduced with the use of triple sulfas (trisulfapyrimidine). Some regimens have included a sulfonamide (sul-fadoxine) in combination with pyrimethamine (Fansidar) for the treatment of chloroquine-resistant malaria caused by P. falciparum. 

If the concentration of the sulfonamide is sufficiently high and its aqueous solubility is sufficiently low, the free drug or its metabolites may form crystals and cause bleeding or complete obstruction of the kidneys. Combinations of sulfa compounds have been developed for the purpose of lowering the dosage of individual components to reduce the chance of crystalluria (e.g., triple sulfas, such as the trisulfapyrimidines). 

Smith JM, Curi AL, and Pavesio CE. Crystalluria with sulphadiazine. Br J Ophthalmol 2001 85 1265-1269. 

PAS is readily absorbed from the GI tract and is widely distributed throughout body fluids except cerebrospinal fluid. It penetrates tissues and reaches high concentrations in the tuberculous cavities and caseous tissue. Peak plasma levels are reached within 1 to 2 hours of drug administration, and the drug has a half-life of about an hour. PAS is primarily metabolized by hepatic acetylation. When combined with isoniazid, PAS can function as an alternative substrate and block hepatic acetylation of isoniazid, thereby increasing free isoniazid levels. Both the acetylated and unaltered drug are rapidly excreted in the urine. The concentration of PAS in urine is high and may result in crystalluria. 

Nephrotoxicity/hepatotoxicity occurs occasionally, manifested as dark urine/ stools, pain in lower back, jaundice, dysuria, crystalluria, renal colic/calculi. 

Ascorbic acid may acidify urine, leading to crystalluria. 

Metabolic acidosis, electrolyte imbalance, transient myopia, urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity convulsions, and rarely crystalluria, renal calculi... 

Crystalluria can occur when methenamine is given in large doses. Patient/Famiiy Education... 

Vomiting, diarrhea, drymouth, bittertaste, nervousness, drowsiness, insomnia, photosensitivity, tinnitus, crystalluria, rash, fever, seizures... 

Adequate hydration and urinary output are essential to prevent crystalluria and... 

Sulfonamides also cause renal irritation and may precipitate renal colic. Crystalluria, haematuria and albuminuria can also occur which may lead to the development of oliguria and anuria. 

Adverse effects include drowsiness, insomnia, dizziness, agitation, confusion, depression, delusions, vomiting, diarrhoea, crystalluria, elevation in liver enzyme and total serum cholesterol. Serious side effect is skin rash including Stevens Johnson syndrome as in case of nevirapine. 

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