Indinavir-associated tubulointerstitial renal disease

Indinavir, used for the treatment of HIV disease, forms distinctive crystals in the urine. The crystalluria has been associated principally with several urinary tract abnormalities which may require discontinuation of the drug. We present a case of progressive leucocyturia and renal impairment occurring during indinavir treatment which illustrates vividly the impact of the crystalluria on the tubulointerstitial renal compartment.     

Drug-induced urolithiasis

Drugs can cause renal stone formation either by raising excretion rates of naturally occurring stone components or by directly precipitating within the urinary tract. In large series of analysed renal stones, the overall frequency of drug-induced urolithiasis is less than 0.5%. Five clinical presentations of drug-induced crystallization in the kidneys can be recognized: asymptomatic crystalluria, symptomatic crystalluria; stone passage; obstructive uropathy and tubulointerstitial nephritis. In the current literature review, the protease inhibitors used for treatment of patients infected with the human immunodeficiency virus stand out as a new class of drugs that frequently causes crystallization within the urinary tract. The most widely used compound, indinavir, may lead to crystalluria and renal stone formation in up to 50% of patients, and occasionally also causes acute renal failure caused by obstructive uropathy or tubulointerstitial nephritis. On the other hand, ritonavir appears more often to induce (reversible) acute renal failure than stone formation.     

Renal toxicity of protease inhibitors

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.     

Nephrotoxicity related to new therapeutic compounds

Toxic nephropathy is an important cause of reversible renal injury. This article focuses on the nephrotoxicity of several new therapeutic compounds. Selective cyclooxygenase-2 inhibitor is associated with sodium retention, hypertension, ankle edema, and acute renal failure. The incidence of renal complication is similar to conventional nonsteroidal anti-inflammatory drugs. Bisphosphonates, especially when used in high dose for prolonged duration, can cause toxic acute tubular necrosis and renal failure. Pamidronate is also associated with a specific form of collapsing focal segmental glomerulosclerosis similar to one found in patients with human immunodeficiency virus (HIV) infection. Acyclic nucleoside phosphonate, a new group of antiviral agents, can cause Fanconi-like syndrome and progressive renal impairment. On the other hand, indinavir, a potent protease inhibitor for the treatment of HIV infection, can cause crystalluria, renal stone, acute tubular obstruction and chronic interstitial nephritis. Intravenous immune globulin and hydroxyethyl starch, a new plasma expander, are associated with acute renal failure with characteristic renal histology known as osmotic nephrosis. In short, physicians should be cautious about possible renal toxicity during the use of any new therapeutic agents.     

The natural history of leukocyturia associated with indinavir treatment in HIV+ individuals

Urinary complications observed during indinavir treatment of HIV disease are often attributed to indinavir crystalluria. In a prospective study of urinalysis during the first year of indinavir therapy, 5 of 54 asymptomatic HIV+ individuals presented severe leukocyturia (> or =100 cells/HPF) usually accompanying indinavir crystalluria. The clinical course of these 5 individuals, successfully treated for HIV and monitored for an second follow-up year, suggests that recurrence of severe leukocyturia may be an indicator of renal damage, likely tubulointerstitial disease caused by indinavir crystalluria. This is in contrast to the remaining 49 subjects, including those presenting mild leukocyturia, who did not demonstrate any evidence of renal disease. Regular urinalysis is therefore recommended in the clinical management of indinavir-treated individuals to detect early renal damage secondary to indinavir crystalluria and to prevent further renal impairment.     

Human immunodeficiency virus and IgA nephropathy

Summary: IgA nephropathy (IgAN) in human immunodeficiency virus (HIV)-infected patients has been described with increasing frequency. In contrast to HIV-associated nephropathy, with collapsing variant of focal and segmental glomerulosclerosis and prominent tubular cell changes, a disorder which is more common in black persons, IgAN is a disease mainly of white patients. Most are asymptomatic carriers of HIV although few have acquired immunodeficiency syndrome (AIDS) or ARC at the time the renal disorder is discovered. The clinical manifestations are generally of haematuria, sometimes with proteinuria. In some patients, the finding of IgA reactive with anti-HIV IgG or IgM in circulating immune complexes and in glomerular eluates strongly suggests this glomerulopathy to be an HIV-associated immune complex disorder. Because of the demographic factors, IgAN may evolve to be an important renal lesion in HIV infection.     

Survival of human immunodeficiency virus-infected patients on maintenance dialysis

It has recently been reported that patients on maintenance dialysis with the acquired immune deficiency syndrome (AIDS) survive only 1 to 3 months. We studied all patients on maintenance dialysis at the Baumritter Kidney Center who were known to be infected with the human immunodeficiency virus (HIV). Five patients met the criteria for AIDS; another ten had anti-HIV antibodies but no opportunistic infections. The AIDS patients survived 8 to 18 months, and two are still alive. Mean survival in the AIDS group was 13.2 +/- 1.9 months, while the HIV(+) non-AIDS group survived 15.7 +/- 3.0 months. While these data are not statistically different, the survival curve in the AIDS group predicted a shorter survival than for the HIV(+) patients without AIDS. In fact, the survival of our dialyzed AIDS patients was similar to that reported for AIDS patients in general. Our experience suggests that dialysis may have no adverse effect on survival in AIDS. We conclude that dialysis patients with AIDS may survive 8 to 12 months or more and that the approach to such patients should be individualized.     

Urological management of indinavir-associated acute renal failure in HIV-positive patients

Introduction Indinavir, a protease inhibitor that is commonly used to treat HIV infection, may cause crystal formation within the renal tubules when urine pH is above 3.5. Crystallization in the urine may lead to intrarenal crystal deposition and acute renal failure (ARF). Aim To establish the beneficial urological management of acute renal failure caused by indinavir treatment of HIV/AIDS patients. Patients––methods Five HIV positive patients (four men, one woman) with a mean age of 32 years (range 28–36 years) were referred to our Department of Urology from an AIDS outpatient Clinic, because of the development of postrenal acute renal failure with continuously elevated creatinine and urea plasma levels after indinavir therapy. Among the initial therapeutic maneuvers, indinavir administration was interrupted for 1 week while bilateral double-J ureteral stents were inserted in all the HIV/AIDS patients, during the first 24–72 h to secure upper-tract drainage. Concurrently urine has been acidified by oral administration of the amino acid l-methionine and oral fluid intake was increased. Results All the patients responded well to the treatment and their renal function was effortlessly restored to normal within a few days. Conclusion HIV-positive patients receiving indinavir therapy might be complicated by acute renal failure, mainly due to intrarenal crystal deposition (tubules) or urolithiasis (postrenal obstruction). This adverse effect may simply manage by the discontinuation of indinavir administration, urine acidification, as well as the possible early insertion of bilateral double-J ureteral stents.     

Urolithiasis associated with indinavir in a patient with spinal cord injury

OBJECTIVE: To report a case of indinavir-induced urolithiasis, and the greater risk of this occurrence in individuals with spinal cord injury (SCI) who require fluid restriction for an intermittent catheterization program (ICP). METHODS: Case report. RESULTS: A 38-year-old man with a T4 ASIA A SCI (according to the American Spinal Injury Association classification scale) and human immunodeficiency virus (HIV) infection was using an ICP and taking indinavir (a protease inhibitor) as part of his antiviral regimen. Cystoscopy was performed to rule out recurrent urethral condylomata. He was found to have a bladder stone measuring 0.5 cm x 0.5 cm x 0.3 cm, which, on analysis, was composed of indinavir (100% exterior, 90% interior). The bladder stone was removed under direct visualization. The plain abdominal radiograph did not reveal any stones. CONCLUSION: Indinavir is a frequently used drug for the treatment of HIV that has the potential to induce urinary lithiasis. This is particularly problematic for individuals with SCI who are on fluid restriction and an ICP. Therefore, cystoscopy and monitoring for indinavir-induced urolithiasis should be undertaken in individuals with SCI who are taking indinavir. Considerations include switching to a different protease inhibitor or choosing an entirely new HIV drug cocktail with less potential for urolithiasis.     

Urological manifestations of HIV-related disease. A case of AIDS-associated testicular seminoma, Kaposi's sarcoma and possible intracranial lymphoma

A wide variety of pathologies afflicting the genitourinary tract can be displayed by patients infected with the human immunodeficiency virus (HIV), including both infective and neoplastic conditions. Treatment can often be offered for such conditions using a combination of therapeutic approaches. These conditions should be looked for specifically in patients with HIV infection as treatment may improve their quality of life. A case is presented of a testicular seminoma (appearing in association with an intracranial mass and Kaposi's sarcoma) in a male patient with the acquired immune deficiency syndrome (AIDS); he made a good response to orchiectomy and radiotherapy for his seminoma. A short review is also given of the range of HIV-associated genitourinary pathologies which have been described to date.     

Imaging characteristics of indinavir calculi

PURPOSE: Indinavir sulfate is an effective protease inhibitor of the human immunodeficiency virus type 1. Use is associated with a significant incidence of crystallization and stone formation in the urinary tract, and these calculi are not visible on plain radiographs. Previously all urinary stones, including uric acid and matrix, were believed to be radiodense on computerized tomography (CT). We conducted a retrospective study to evaluate the radiographic appearance of indinavir calculi. MATERIALS AND METHODS: Retrospective chart review of 36 patients taking indinavir sulfate and presenting with renal colic was performed with attention to presentation, urinalysis, radiographic evaluation and management. Specifically, imaging characteristics on CT were addressed. RESULTS: All patients complained of ipsilateral flank pain and 35 had nausea and/or vomiting. Of 30 patients with dysuria or urgency the majority had hematuria, and most had pyuria and/or proteinuria. No stones were visualized on abdominal radiography. Diagnosis was confirmed on 1 of 13 excretory urograms and 4 of 11 renal ultrasounds. None of 12 CT scans was diagnostic of renal lithiasis. CONCLUSIONS: Indinavir sulfate is a protease inhibitor with poor solubility and significant urinary excretion. Crystallization and stone formation are demonstrated in as many as 20% of patients taking the medication. Most patients present with flank pain, nausea or vomiting and hematuria. Previously CT was thought to identify all urinary calculi with clarity but it cannot reliably confirm the presence of indinavir calculi.     

Human immunodeficiency virus infection in end-stage renal disease patients

Human immunodeficiency virus (HIV) infection in patients with end-stage renal disease (ESRD) offers many diagnostic and therapeutic challenges to nephrologists. Renal failure may be a direct consequence of viral infection (HIV-associated nephropathy), or intrinsic renal diseases may occur in previously infected individuals. Patients receiving renal replacement therapy (RRT) may acquire HIV infection from blood transfusions, renal allografts, sexual contacts, or needle sharing by drug addicts. In the early 1980s, the overall prognosis of patients with the acquired immunodeficiency syndrome (AIDS) was very poor, and survival of those with ESRD was dismal. Consequently many even questioned the value of providing maintenance dialysis to patients with AIDS. With advances in diagnostic techniques in serologic and viral markers of disease, and deployment of highly effective antiretroviral agents, the prognosis of HIV-infected patients has dramatically improved. Over the past two decades, experiences in the management of HIV patients with ESRD is accumulating. Both peritoneal dialysis and hemodialysis are effective modes of therapy and many centers are now beginning to perform renal transplantation in HIV-infected patients. This article deals with various aspects of HIV infection in patients with ESRD.     

获得性免疫缺陷综合征患者骨质疏松脆性骨折研究进展

获得性免疫缺陷综合征（AIDS）在普通人群中的发病率逐渐增加,随着高效抗逆转录病毒治疗（HAART）的应用,AIDS患者的病死率逐渐降低,但骨质疏松脆性骨折的发生率显著高于健康人群。本综述主要介绍AIDS患者骨质疏松脆性骨折的发生率和危险因素等,人类免疫缺陷病毒（HIV）和HAART对成骨细胞、破骨细胞OPG/RANK/RANKL系统的作用机制和不良反应;简述AIDS患者骨质疏松脆性骨折药物预防和治疗方法。     

Hepatitis C virus-associated glomerular disease in patients with human immunodeficiency virus coinfection.

Chronic infection with hepatitis C virus (HCV) has been linked to the development of glomerular disease. HCV infection is highly prevalent among intravenous drug users, a population that is also at risk for HIV coinfection. This study reports the clinical-pathologic features and outcome of HCV-associated glomerular disease (HCV-GD) in 14 patients with HIV coinfection. All were intravenous drug users and all but one were African-Americans. Renal presentations included renal insufficiency, microscopic hematuria with active urine sediment, hypertension, and nephrotic syndrome or nephrotic-range proteinuria without hypercholesterolemia. Hypocomplementemia and cryoglobulinemia were present in 46 and 33% of patients, respectively. The predominant renal biopsy findings were membranoproliferative glomerulonephritis type 1 or type 3 (Burkholder subtype) in 79% of patients and membranous glomerulopathy with atypical features in 21% (including overlap with collapsing glomerulopathy in one patient). The clinical course was characterized by rapid progression to renal failure requiring dialysis. The overall morbidity and mortality were high with median time of 5.8 mo to dialysis or death. Although most patients died in renal failure, cause of death was primarily attributable to long-term immunosuppression and advanced AIDS. Patients with AIDS had shorter survival than those without (median survival time of 6.1 mo versus 45.9 mo, log-rank test P = 0.02). Only two patients were alive with stable renal function at follow-up of 28.5 mo. In patients with HCV-GD, coinfection with HIV leads to an aggressive form of renal disease that can be easily confused with HIV-associated nephropathy. Although hypocomplementemia, cryoglobulinemia, and more prominent hypertension and microscopic hematuria may provide clues to the presence of HCV-GD, renal biopsy is essential to differentiate HCV-GD from HIV-associated nephropathy.     

Human immunodeficiency virus-associated Kaposi's sarcoma in a pediatric renal transplant recipient

An 11-year-old boy developed Kaposi's sarcoma and progressive T lymphocyte deficiency 5 years after cadaveric kidney transplantation for end-stage renal disease. He had received 17 individual red blood cell transfusions prior to and during transplantation in 1980. Human immunodeficiency virus (HIV) was cultured from blood in cerebrospinal fluid and HIV antibodies were detected with enzyme immunoassay and immunoblot techniques. The recipient of the donor's other kidney was well and HIV antibody-negative. The patient was treated with etoposide with excellent although transient regression of tumor. Allograft function has remained stable despite minimal immunosuppressive therapy and the need for high-dose anticonvulsant therapy. This case represents the first pediatric patient with acquired immune deficiency syndrome (AIDS) and Kaposi's sarcoma following kidney transplantation.     

Human immunodeficiency virus: anesthetic and obstetric considerations

The pandemic of acquired immune deficiency syndrome (AIDS) is on the threshold of its third decade of existence. The World Health Organization-United Nations statistics show that human immunodeficiency virus (HIV)/AIDS pandemia is set to get much worse. Women of reproductive age are the fastest growing population with HIV. Common signs and symptoms have become more moderate or subclinical, and new clinical presentations have emerged. It is quite apparent that HIV-disease affects multiple organ systems. Advances have been made in elucidating the pathogenesis of HIV. In addition, the molecular technique of viral load determination and the CD + 4 T-lymphocyte count enable evaluation of the disease, its prognosis, and its response to therapy. There is limited specific information concerning the overall risk of anesthesia and surgery of HIV/AIDS patients. However, as far as can be determined, surgical interventions do not increase the postoperative risk for complications or death and should therefore not be withheld. There is also little evidence to suggest that HIV or antiretroviral drugs increase the rate of pregnancy complications or that pregnancy may alter the course of HIV infection. General anesthesia is considered safe, but drug interactions and their impact on various organ systems should be considered preoperatively. Regional anesthesia is often the technique of choice. Yet, one must take into consideration the presence of neuropathies, local infection, or blood clotting abnormalities. It should be emphasized that all practicing anesthesiologists should be familiar with the disease and should use prenatal anesthesia consultations and a team approach to assure optimal treatment for HIV patients.     

Cerebellar abscess due to Rhodococcus equi in an immunocompetent patient: case report and literature review

Rhodococcus equi (R. equi) is a facultative, intracellular, nonmotile, non-spore-forming, gram-positive coccobacillus, primarily causes zoonotic infections that affect grazing animals, mainly horses and foals and is a rare opportunistic pathogen found in severely compromised patients, and most commonly in recent years, in human immunodeficiency virus (HIV)-infected persons. Early cases, most in patients receiving immunosuppressant therapy, were more likely to be successfully treated with antimicrobial agents than cases in AIDS patients, it is emerging as an important pathogen in patients with cellular immune deficiency. We report a case of an immunocompetent 37 year-old patient with cerebellar abscess location that seems to be the only thin to today described in the literature. R. equi is a facultative, intracellular, nonmotile, non-spore-forming, gram-positive coccobacillus, primarily causes zoonotic infections that affect grazing animals, mainly horses and foals and is a rare opportunistic pathogen found in severely compromised patients, and most commonly in recent years, in human immunodeficiency virus (HIV)-infected persons. Early cases, most in patients receiving immunosuppressant therapy, were more likely to be successfully treated with antimicrobial agents than cases in AIDS patients, it is emerging as an important pathogen in patients with cellular immune deficiency. We report a case of an immunocompetent 37 year-old patient with cerebellar abscess location that seems to be the only thin to today described in the literature.     

Pyuria in patients treated with indinavir is associated with renal dysfunction

BACKGROUND: Indinavir therapy is associated with a continuum of crystal-related syndromes, including nephrolithiasis, renal colic, flank pain without recognizable stone formation, dysuria and asymptomatic crystalluria. A frank nephropathy has been recognized recently as part of the spectrum. METHODS: A retrospective analysis of 72 HIV-infected individuals receiving indinavir was performed to identify the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals treated with nucleoside analogues alone served as controls. RESULTS: Mean serum creatinine levels rose from 1.03 +/- 0.16 mg/dl to 1.11 +/- 0.22 mg/dl at week 12 and 1.15 +/- 0.27 mg/dl at week 24 (both, p < 0.01). Thirteen individuals developed serum creatinine levels > or =1.4 mg/dl. Increased serum creatinine levels were found more frequently in women (p < 0.01) and were associated with pyuria and microhematuria (p < 0.01). Frank renal colic and/or nephrolithiasis (seven patients) and urinary pH were not associated with serum creatinine levels > or =1.4 mg/dl. The mean duration of indinavir treatment, until sterile pyuria occurred, were 22 weeks and 32 weeks until the first rise of serum creatinine levels to > or =1.4 mg/dl. Ten patients showed both findings, pyuria preceded the first rise in serum creatinine levels to > or = 1.4 mg/dl (18 vs. 27 weeks, p = 0.02). Renal biopsy, done in three patients, revealed tubulointerstitial disease with crystals in collecting ducts. In 21 patients, among them 11 with pyuria, indinavir was replaced for various reasons and pyuria disappeared in nine. In these patients mean serum creatinine levels decreased from 1.43 mg/dl at withdrawal of indinavir to 1.04 mg/dl three months later (p < 0.01). CONCLUSION: Indinavir therapy is associated with a decrease in renal function which is reversible after withdrawal. In addition, indinavir-associated tubulointerstitial disease does no in patients taking indinavir may help to identify patients being at risk for nephrotoxicity.     

Oral malignancies in HIV disease: changes in disease presentation, increasing understanding of molecular pathogenesis, and current management.

Infection with human immunodeficiency virus (HIV) and progression to acquired immune deficiency syndrome (AIDS) are associated with a vide variety of morbidities. Local and systemic diseases can develop in association with HIV infection and may manifest themselves as malignancies of the oropharynx. Advances in HIV management, fueled by increasing understanding of molecular pathogenesis, have resulted in marked changes in the prevalence of oral malignant disease. This paper discusses recent trends in the presentation and treatment of malignancies related to HIV and AIDS with an emphasis on malignancies seen in the oral cavity.