Renal manifestations in HIV-infected Jamaican children / Manifestaciones renales en niños jamaicanos infectados por el VIH

BACKGROUND: Documentation regarding the renal complications of paediatric HIV infection from developing countries is scarce. In the era prior to highly active antiretroviral therapy (HAART), HIV-infected children in Jamaica who developed HIV-associated nephropathy (HIVAN) progressed to end stage renal disease (ESRD) and death within a few months of diagnosis. With increased public access to antiretroviral therapy since 2002 and subsequent survival, renal complications are increasingly recognized among the surviving cohort of infected children. METHODS: A cohort of 196 HIV-infected children was followed in four multicentre ambulatory clinics from September 1, 2002 to August 31, 2005 as part of the Kingston Paediatric and Perinatal HIV/AIDS Programme, Jamaica. We describe the clinical presentations and natural history of those patients who developed renal complications. RESULTS: Urinary tract infections were the most common diagnosis, occurring in 16.8% of patients, with a high recurrence rate and the most common organism was Escherichia coli. Four of seven patients who started indinavir developed complications of nephrolithiasis and tubulointerstitial nephropathy. Six patients (3%) fulfilled the criteria for HIVAN, five of whom were male. Median age at diagnosis was five years; all presented with advanced HIV disease, nephrotic syndrome or nephrotic range proteinuria and three with chronic renal failure. Patients received standard medical management and were initiated on angiotensin-converting enzyme (ACE) inhibitors and HAART. While the mortality ratio was 50%, only one death was associated with HIVAN and the median survival time was 3.1 years. CONCLUSIONS: HIV-infected children present with a variety of renal complications. With improved survival since the introduction of HAART, the incidence of HIVAN is expected to increase among this maturing paediatric cohort. Early detection and treatment will optimize the outcomes for these children.

ANTECEDENTES: La documentación en relación con las complicaciones renales de la infección pediátrica por VIH en países en vías de desarrollo, es escasa. En la era de la terapia antiretroviral pre-altamente activa (TARAA), los niños infectados por VIH en Jamaica que desarrollaron nefropatía asociada con VIH evolucionaron hacia la enfermedad renal en fase terminal (ERFT) y la muerte dentro de pocos meses de hecho el diagnóstico. Con el aumento del acceso público a la terapia antiretroviral a partir de 2002 y la subsiguiente supervivencia, cada vez más las complicaciones renales se observan entre la cohorte sobreviviente de niños infectados. MÉTODOS: A una cohorte de 196 niños infectados con VIH, se le practicó un seguimiento en cuatro clínicas ambulatorios multicentros, desde septiembre 1 de 2002 hasta agosto 31 de 2005, como parte del Programa VIH/SIDA Prenatal y Pediátrico de Kingston, Jamaica. El trabajo describe las presentaciones clínicas y la historia natural de los pacientes que desarrollaron complicaciones renales. RESULTADOS: Las infecciones de las vías urinarias fueron el diagnóstico más común en 16.8% de los pacientes, acompañadas de una alta tasa de recurrencia, y el organismo más común fue el Escherichia coli. Cuatro de siete pacientes que comenzaron tratamiento con indinair, desarrollaron complicaciones de nefrolitiasis y nefropatía tubulointersticial. Seis pacientes (3%), cinco de ellos varones, satisfacían los criterios de NAVIH. La edad promedio al momento del diagnóstico fue de cinco años. Todos representaron con la enfermedad de VIH avanzada, síndrome nefrótico o proteniuria de rango nefrótico, y tres con fallo renal crónico. Los pacientes recibieron tratamiento médico estándar y se iniciaron en el uso de inhibidores de enzimas convertidoras de angiotensina (IECAs) y el TARAA. Si bien la proporción de la mortalidad fue 50%, sólo una muerte estuvo asociada con NAVIH y el tiempo medio de supervivencia fue 3.1 años. CONCLUSIONES: Los niños infectados con VIH se presentaron con una variedad de complicaciones renales. Con el mejoramiento de la supervivencia a partir de la introducción del TARAA, se espera que la incidencia de NAVIH aumente entre la cohorte pediátrica en maduración. La detección precoz y el tratamiento temprano optimizarán los resultados obtenidos con estos niños.

Indinavir-associated toxicity mimicking urinary tuberculosis in a patient with AIDS

This case reported to a patient with AIDS who presented persistent sterile leukocyturia and hematuria, lower back pain, bladder suffering symptoms, and renal papillary necrosis which were thought to be secondary to urinary tuberculosis but were demonstrated to be indinavir-associated side effects. The intention of this report is to remind medical professionals involved in the care of HIV+ patients of this possible association in order to avoid unnecessary investigation and to stress the need of careful periodical assessment of renal function and urinalysis in patients treated with indinavir.

Urinary NO3 excretion and renal failure in indinavir-treated patients

Treatment with indinavir (IDV), a protease inhibitor, is frequently associated with renal abnormalities. We determined the incidence of renal failure (creatinine clearance <80 mL min-1 1.73 (m²)-1) in HIV patients treated with highly active antiretroviral therapy, including IDV, and investigated the possible mechanisms and risk factors of IDV nephrotoxicity. Thirty-six patients receiving IDV were followed for 3 years. All were assessed for age, body weight, duration of infection, duration of IDV treatment, sulfur-derivative use, total cholesterol, triglycerides, magnesium, sodium, potassium, creatinine, and urinalysis. We also determined renal function in terms of creatinine clearance, urine osmolality and fractional excretion of sodium, potassium, and water. Urinary nitrate (NO3) excretion was measured in 18 IDV-treated patients and compared with that of 8 patients treated with efavirenz, a drug without renal side effects. Sterile leukocyturia occurred in 80.5 percent of the IDV-treated patients. Creatinine clearance <80 mL min-1 1.73 (m²)-1 was observed in 22 patients (61 percent) and was associated with low body weight and the use of sulfur-derivatives. These patients also had lower osmolality, lower urine volume and a higher fractional excretion of water compared to the normal renal function group. Urinary NO3 excretion was significantly lower in IDV-treated patients (809 ± 181 æM NO3-/mg creatinine) than in efavirenz-treated patients (2247 ± 648 æM NO3-/mg creatinine, P < 0.01). The lower NO3 excretion suggests that IDV decreases nitric oxide production.

High prevalence of indinavir-associated renal complications in Thai HIV-infected patients.

BACKGROUND: Indinavir (IDV) is the protease inhibitor (PI) used most often in resource-limited countries. The present study aimed to determine the prevalence of IDV-associated renal complications as well as their clinical characteristics. MATERIAL AND METHOD: The authors reviewed all patients participating in cohorts of indinavir-containing regimens at the HIV-NAT research center during the period of indinavir treatment. Patients who had pre-existing renal diseases were excluded. Renal toxicities included presence of urologic symptoms, nephrolithiasis, abnormal urine sediments, crystalluria and loss of renal function. Radiological studies of KUB system were reviewed as well. RESULTS: Two-hundred and four patients treated with IDV were included. Median (IQR) follow up period was 216 (150-312) weeks. One hundred and eighty patients were treated with ritonavir-boosted regimens at some point, and 24 patients were treated only with unboosted regimens. Leukocyturia (51.9%) was the most common finding of IDV-associated renal complications. Thirty-five percent of patients had urologic symptoms such as flank pain or dysuria. Almost half of the patients had significant loss of renal function that was associated with prolonged use of IDV The most common radiological finding was nephrolithiasis. Less common, but of greater clinical importance, are nephrocalcinosis or renal atrophy. CONCLUSION: A high prevalence of IRC was found in Thai HIV-infected patients. As long as no other cost-effective boosted PI regimens are available, strategies to prevent irreversible loss of renal function are warranted.

Nefrolitíase associada ao uso de indinavir: relato de caso / Nephrolithiasis triggered by indinavir use: case report

O sulfato de indinavir, em associação com inibidofores d transcripfase reversa, promove, de forma efetiva, aumento da contagem de células CD4+ e redução da carga viral (ARN-VIH) em pacientes com sindrome de imunodeficiência adquirida. Esse inibidor da protease provoca nefrolitiase em até 34,4% dos pacientes. Em decorrência do uso ainda freqüente deste antiretroviral, seus efeitos adversos devem ser prontamente reconhecidos e prevenidos, quando possível. Este trabalho descreve a associação de litíase urinária com manifestações clínicas exuberantes com o uso de indinavir.

A case of nephrolithiasis related to the use of indinavir sulfate is described. This drug, in association with reverse transcriptase inhibitors, effectively promotes a rise in the CD4+ T cell count and a decrease in the levels of HIV RNA in AIDS patients. This protease inhibitor elicits the development of nephrolithiasis in up to 34.4% of patients. Since indinavir sulfate is a frequently prescribed drug, its side effects should be well known and avoided whencver possibie.

Osteoporosis asociada a indinavir en paciente infectado por virus de inmunodeficiencia humana: comunicación de un caso y revisión de la literatura / Osteoporosis associated to indinavir in an HIV infected patient. case report and review

Se presenta el caso de un paciente de 45 años portador de VIH que desarrolló osteoporosis secundaria a 33 meses de exposición a sulfato de indinavir como parte de su terapia antiretroviral (TAR). Su manejo consistió en alendronato, calcio y vitamina D junto con modificación de su TAR: suspensión de indinavir e inicio de efavirenz. Luego de 16 meses de tratamiento se verificó un incremento en la densidad mineral ósea de 11 por ciento en promedio. No ocurrieron fracturas ni se constató efectos adversos o interacciones medicamentosas. Se revisa la literatura.

Indirect hyperbilirubinemia with indinavir.

Indinavir is a protease inhibitor used in the treatment of HIV infected individuals and as post-exposure prophylaxis. Indinavir is associated with various adverse effects including gastrointestinal, a lipodystrophy syndrome and nephrolithiasis. We describe indirect hyperbilirubinemia as an adverse effect of indinavir in a person on post-exposure prophylaxis (PEP).

Paroniquia secundaria al uso de inhibidores de proteasas: nuestra experiencia / Paronychie during the use of antiretroviral protease inhibitors: our experience

Presentamos cinco pacientes HIV positivos que desarrollaron inflamación periungueal dolorosa en uñas de pies durante el tratamiento con antirretrovirales inhibidores de proteasas (indinavir). La paroniquia asociada a indinavir y lamivudina en pacientes HIV fue recientemente reportada. Su patogenia no es bien conocida

Lipodistrofia secundaria al uso de antirretrovirales inhibidores de proteasas / Lipodistrophy secondary to the use of antiretrovirals pretease inhibitors

El uso de inhibidores de proteasas en el tratamiento de la infección por HIV-1, ha revolucionado la sobrevida de éstos enfermos. Pero también se lo ha asociado a diabetes mellitus de nuevo comienzo, hiperlipidemia y lipodistrofia. Presentamos tres pacientes con lipodistrofia secundaria y comentamos la fisiopatogenia y tratamiento