indinavir-sulfate and Urinary-Calculi

Topics: Humans; Indinavir; Radiography; Urinary Calculi

Introduction of several classes of antiviral agents for the treatment of immunodeficiency virus has led to increased survival and improved quality of life for patients with HIV infection. Protease inhibitors have become the mainstays of current therapy in patient with AIDS. Renal intolerance of indinavir is a rare but important complication in HIV positive patients. The renal function of patients receiving indinavir should be closely monitored. Benign and asymptomatic crystalluria occurs in 4-13% of HIV positive patients. Several cases of acute renal failure, renal atrophy and interstitial nephritis have also been reported. A hydration protocol consisting of one to two liters of fluid should be initiated three hours after each indinavir dose. If significant renal insufficiency persists, temporary indinavir withdrawal or switching to another protease inhibitor should be considered.

Topics: Crystallization; HIV Protease Inhibitors; Humans; Indinavir; Nephritis; Renal Insufficiency; Urinary Calculi

Indinavir sulfate is a protease inhibitor that has been found to be extremely effective in increasing CD4+ cell counts and in decreasing HIV-RNA titers in patients with HIV and AIDS. However, patients receiving indinavir also have been noted to have a significant risk for developing urolithiasis. Published reports of indinavir urolithiasis estimate its incidence at between 4 and 13%. Indinavir has a high urinary excretion with poor solubility in a physiologic pH solution. Consequently, patients develop urinary stones that are principally composed of indinavir or of a mixture of indinavir and other substances, such as calcium oxalate. Similar to other forms of urolithiasis, acute flank pain and hematuria are the typical symptoms of indinavir urolithiasis. Indinavir urolithiasis is unique in that computed tomography, which was once thought to be efficacious in identifying all urinary calculi, is not useful in imaging stones that are composed of pure indinavir. Indinavir urolithiasis generally responds to a conservative regimen of hydration, pain control, and the temporary discontinuation of the medication. Only a minority of patients need surgical intervention. Approximately 10% of patients ultimately need to discontinue indinavir therapy altogether. Indinavir is an antiviral agent that has a significant role in the treatment of AIDS. Although urolithiasis is a significant side effect of indinavir use, limiting its clinical application is not the answer. Rather, physicians need to know more about indinavir urolithiasis to help their patients cope with its potential complications.

Topics: HIV Protease Inhibitors; Humans; Indinavir; Urinary Calculi

Drug-induced urolithiasis are observed in 1.6% of the urinary calculi in France. Drugs crystals are identified in two thirds of these stones. Other drugs are responsible for stones which have an apparent metabolic origin (one third of the cases). Stone analysis using physical methods such as infrared spectroscopy is needed to unambiguously identify stones containing drugs. The inquiry is an important step to identify lithogenetic drugs which do not crystallize in the stones. The main substances which were identified in stones over the past decade were indinavir monohydrate (31.4%), triamterene (11.1%), sulphonamides (10.5%) and amorphous silica (4.5%). The main drugs involved in the nucleation and growth of metabolic stones were calcium and vitamin D supplementation (15%) and long-term treatment with carbonic anhydrase inhibitors (8%). Stone prevention is based on drug withdrawal or change in dosage with additional measures including an increase of diuresis and, if necessary, changes in the urine pH.

Topics: Acetazolamide; Allopurinol; Aluminum Hydroxide; Calcium; Cathartics; Diuretics; HIV Protease Inhibitors; Humans; Indinavir; Pyridoxine; Silicates; Sulfonamides; Triamterene; Urinary Calculi; Vitamin D

We report on 4 cases of urinary stone observed in patients treated with the drug Crixivan (Indinavir Sulfate) and review the literature. Comments include stone composition, clinical aspects, treatment and prevention.

Topics: Adult; Anti-HIV Agents; Calcium Oxalate; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Ureteral Calculi; Ureteroscopy; Urinary Calculi

The approximate incidence of indinavir urolithiasis in HIV positive patients receiving the drug is 10%. The exact mechanism of lithogenesis is still unknown. Pure indinavir stones are radiolucent on plane abdominal X-ray or CT scan. Indinavir urolithiasis can be associated with acute unilateral renal colic or severe azotaemia.. 20 HIV patients were treated conservatively by increasing oral fluid intake (urine production of 2 l/day and more), discontinuation of indinavir therapy for 1 week and acidification of urine with l-methionin (urine pH 5,3-5,8). Some patients were additionally treated with endoscopic procedures.. In all patients renal function normalized. Increase of oral fluid intake, especially during the first 2 hours after intake of indinavir and during night prevented recurrence of indinavir urolithiasis.. HIV positive patients with renal colic or renal insufficiency and roentgenological absence of radio-opaque stone formations should make the urologist consider indinavir urolithiasis as a possible diagnosis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Female; Fluid Therapy; HIV Protease Inhibitors; Humans; Indinavir; Male; Methionine; Middle Aged; Treatment Outcome; Urinary Calculi

Indinavir sulfate is a protease inhibitor used of the treatment of primary HIV infection either as monotherapy or as part of antiretroviral treatment schemes. Approximately 10% of all patients develop urolithiasis with radiolucent stones consisting of indinavir. We present our results of the treatment in 11 HIV positive patients (9 men, 2 women), who developed Indinavir lithiasis after 5-8 months of antiretroviral therapy. Following the initial procedures (spasmoanalgetic drugs, ureteroscopy, double J-stent or nephrostomy), the patients were further treated by increasing diuresis and urinary acidification. All the patients responded well to the treatment, the obstruction was releieved and their renal function was restored to normal.

Topics: Adult; Female; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Male; Middle Aged; Urinary Calculi

Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a K(i) value of 0.049 nM. It stops the spread of the HIV(IIIb)-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.

Topics: Animals; Antiviral Agents; Cattle; Cell Culture Techniques; Dogs; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Haplorhini; HIV Protease Inhibitors; HIV-1; Humans; Indans; Male; Piperazines; Protein Binding; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Urinary Calculi

To evaluate specific urological abnormalities in patients treated with the protease inhibitor indinavir.. A series of 155 consecutive human immunodeficiency virus-positive patients were treated with indinavir 800 mg p.o. three times a day. Of these, 14 (9%) treated for 1-321 (average 110) days experienced severe flank pain and were subjected to clinical and laboratory examinations.. Abdominal X-ray was consistently negative for stones. Ultrasonography showed upper-tract dilatation in 12 patients. Intravenous urography showed obstruction above a radiolucent obstacle in 7 patients; in 2 cases, there was a marked delay in urine excretion on the obstructed side. The mean urine pH was 6. Urine culture was negative. Serum uric acid, phosphorus, and calcium levels were normal. In 8 patients there was slight renal insufficiency, and 4 patients required ureteral stenting. In all cases, hyperhydration and oral analgesia led to a favorable outcome. In 3 patients, chemical analysis of the stone demonstrated monohydrate indinavir crystals.. In our experience, indinavir therapy is associated with urolithiasis in 9% of the cases. Hydration, analgesia, and acidification of the urine usually lead to a favorable clinical outcome. Prophylactic hydration and acidification of the urine are extremely important.

Topics: Adult; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Prospective Studies; Urinary Calculi

We evaluated the radiographic characteristics as well as the clinical management of urolithiasis induced by systemic therapy with indinavir sulfate, a protease inhibitor utilized in the treatment of HIV infection.. Fifteen consecutive HIV-positive male patients (average age 41.3 years) who presented with urolithiasis while being treated with indinavir sulfate (average time 11.1 months) were studied.. All patients presented with flank pain, and eight had gross hematuria. All but one patient had microscopic hematuria. The location of the stones was the kidney in three, the proximal ureter in four, and the distal ureter in nine. One patient had both a renal and a proximal ureteral stone. The stones were radiolucent on CT imaging in five patients and could not be seen in five. In the five cases in which a stone was not definitely identified, a diagnosis of urolithiasis was established on the basis of ureteral obstruction and periureteral/renal streaking noted on CT. Treatment included observation with hydration in eight patients, ureteral stent placement in two patients, ureteroscopy in three patients, and extracorporeal shockwave lithotripsy in two patients. Stones were analyzed in five patients and proved to be 100% indinavir in three and a mixture of indinavir, calcium oxalate monohydrate, and calcium oxalate dihydrate in two.. Urolithiasis is a recognized complication of treatment with indinavir sulfate. Pure indinavir stones cannot be seen on CT unless intravenous contrast medium is utilized. Mixed calcium and indinavir stones can occur and may be radiopaque. The majority of HIV-positive patients with symptomatic urolithiasis can be treated conservatively with hydration. Metabolic evaluation of these patients with identification and correction of factors predisposing to stone formation may minimize future recurrences. Administration of this effective medication thus can continue uninterrupted.

Topics: Adult; Endoscopy; Follow-Up Studies; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lithotripsy; Male; Middle Aged; Stents; Tomography, X-Ray Computed; Ureteroscopy; Urinary Calculi

Topics: Acute Kidney Injury; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Drug Therapy, Combination; Humans; Indinavir; Male; Urinary Calculi

Topics: Diagnostic Imaging; HIV Protease Inhibitors; Humans; Indinavir; Laparoscopy; Lithotripsy; Urinary Calculi

Topics: Adult; Anti-HIV Agents; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Time Factors; Urinary Calculi

Topics: Adult; Anti-HIV Agents; Female; HIV Protease Inhibitors; HIV Seropositivity; HIV-1; Humans; Indinavir; Male; Middle Aged; Urinary Calculi

We discuss the specific urological abnormalities associated with protease inhibitor therapy.. We report on a human immunodeficiency virus positive patient who was on protease inhibitor therapy and presented with renal colic.. The stone passed spontaneously. Stone analysis was not consistent with any known composition of urinary calculus.. The positive effects of protease inhibitors in human immunodeficiency virus positive patients mandate that the urological community become familiar with these drugs and the specific urological complications as the use of these drugs becomes widespread.

Topics: Adult; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Male; Urinary Calculi

Anti-proteases, a new class of anti-HIV drugs used in combination with reverse transcriptase inhibitors have led to spectacular improvement in the patients' clinical status. Since April 1996, indinavir is the most widely prescribed anti-protease in France.. From July 1996 to July 1997, we analyzed 46 spontaneously expulsed stones in 45 HIV+ patients (35 men and 10 women; age range 25 to 64 years) given indinavir in combination with other drugs since one week to ten months. Only six patients were known to have a past history of renal lithiasis.. Forty-one calculi contained indinavir monohydrate (INDM) identified by mass spectrometry and infrared spectrophotometry. INDM was the only component excepting proteins in 39/45 calculi. In the 12 others, other compounds were also identified. Among the 114 urine samples collected 2 to 3 hours after an 800 mg dose of indinavir, 38 (33%) monohydrate indinavir crystals, identified by infrared microscopy. Mean urinary pH was significantly higher than in samples without INDM crystals (6.53 +/- 0.68 versus 5.96 +/- 0.71, p < 0.001).. Two measures could possibly reduce the risk of crystalization: administration of urine acidifiers and increased fluid intake to raise diuresis. Alkalinisation is not indicated. Long-term increased fluid intake should be preferred over acidification which could be reserved solely for the treatment of drug-induced lithiasis.

Topics: Adult; Aged; Ambulatory Care; Crystallization; Female; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Male; Middle Aged; Risk Factors; Urinary Calculi