HIV-related nephropathy: new aspects of an old paradigm

SUMMARY The scenario of infection by the human immunodeficiency virus (HIV) has been undergoing changes in recent years, both in relation to the understanding of HIV infection and regarding the treatments available. As a result, the disease, which before was associated with high morbidity and mortality, is now seen as a chronic disease that can be controlled, regarding both transmission and symptoms. However, even when the virus replication is well controlled, the infected patient remains at high risk of developing renal involvement, either by acute kidney injury not associated with HIV, nephrotoxicity due to antiretroviral drugs, chronic diseases associated with increased survival, or glomerular disease associated to HIV. This review will cover the main aspects of kidney failure associated with HIV.

RESUMO O panorama da infecção pelo vírus da imunodeficiência humana (HIV) vem sofrendo alterações nos últimos anos, tanto em relação ao entendimento da infecção pelo HIV quanto aos tratamentos disponíveis. Como resultado, a doença, que antes estava associada a alta morbimortalidade, é agora considerada uma doença crônica que pode ser controlada, tanto em relação à transmissão quanto aos sintomas. No entanto, mesmo quando a replicação viral é bem controlada, o paciente infectado tem um alto risco de desenvolver complicações renais, seja através de lesão renal aguda não relacionada ao HIV, por nefrotoxicidade causada por drogas antirretrovirais, por doenças crônicas associadas com o aumento da sobrevida ou por doença glomerular associada ao HIV. Esta revisão abordará os principais aspectos da insuficiência renal associada ao HIV.

Multiple facets of HIV-associated renal disease

HIV infection has a broad spectrum of renal manifestations. This study examined the clinical and histological manifestations of HIV-associated renal disease, and predictors of renal outcomes. Sixty-one (64% male, mean age 45 years) HIV patients were retrospectively evaluated. Clinical presentation and renal histopathology were assessed, as well as CD4 T-cell count and viral load. The predictive value of histological lesion, baseline CD4 cell count and viral load for end-stage renal disease (ESRD) or death were determined using the Cox regression model. The outcomes of chronic kidney disease (CKD) and ESRD or death were evaluated by baseline CD4 cell count. The percent distribution at initial clinical presentation was non-nephrotic proteinuria (54%), acute kidney injury (28%), nephrotic syndrome (23%), and chronic kidney disease (22%). Focal segmental glomerulosclerosis (28%), mainly the collapsing form (HIVAN), acute interstitial nephritis (AIN) (26%), and immune complex-mediated glomerulonephritis (ICGN) (25%) were the predominant renal histology. Baseline CD4 cell count ≥200 cells/mm3 was a protective factor against CKD (hazard ratio=0.997; 95%CI=0.994-0.999; P=0.012). At last follow-up, 64% of patients with baseline CD4 ≥200 cells/mm3 had eGFR >60 mL·min-1·(1.73 m2)-1 compared to the other 35% of patients who presented with CD4 <200 cells/mm3 (log rank=9.043, P=0.003). In conclusion, the main histological lesion of HIV-associated renal disease was HIVAN, followed by AIN and ICGN. These findings reinforce the need to biopsy HIV patients with kidney impairment and/or proteinuria. Baseline CD4 cell count ≥200 cells/mm3 was associated with better renal function after 2 years of follow-up.

Compromiso renal en pacientes HIV+ / Renal abnormalities in HIV infected patients

Varias complicaciones nefrológicas pueden ocurrir durante la infección por el virus de la inmunodeficiencia humana (HIV) especialmente en estadios avanzados de la enfermedad o relacionadas con otras infecciones o drogas. Poco conocida es la prevalencia de alteraciones renales subclínicas de pacientes HIV+ surgidas como complicación o relacionadas a la infección y/o tratamiento. Realizamos un corte transversal de pacientes asintomáticos HIV+ referidos en forma consecutiva al consultorio de nefrología para la detección de alteraciones nefrológicas. Se estudiaron 52 pacientes adultos mediante exámenes de sangre y orina, ultrasonido y biopsia renal. Edad media 39.9 ± 10.6 años, 88% varones, tiempo de diagnóstico de la infección: 53.2 ± 41.2 (2-127) meses. El 71% tenían síndrome de inmunodeficiencia adquirida (HIV-sida) y el 77% recibían con antirretrovirales. La carga viral al momento del estudio fue 7043 ± 3322 copias y el recuento de CD4+ 484 ± 39 cel/mm³. El 30.7% presentó alteraciones del sedimento urinario: albuminuria: 16.6%, hematuria microscópica: 11.5%, hipercalciuria: 10.8% y cristaluria 6%. La media del filtrado glomerular fue 102.2 ± 22.9 ml/min (rango: 34-149). El 41% presentó anormalidades que corresponderían a enfermedad renal crónica (estadios 1 a 3). Los pacientes con alteraciones tenían mayor edad, con duración más prolongada de la infección. Las anomalías renales no se asociaron con mayor prevalencia de HIV-sida. Dos pacientes fueron biopsiados, con hallazgos de nefritis túbulo-intersticial crónica con cristales y glomerulonefritis por IgA. No hubo hallazgos de nefropatía por HIV. El amplio espectro y la alta prevalencia de anormalidades nefrológicas subclínicas encontradas sugieren que los pacientes asintomáticos HIV+ deberían realizar evaluaciones nefrológicas de rutina.

Several renal complications may occur during HIV infection, especially in advanced stages related to HIV, to other infectious agents and/or drugs. Little is known about the prevalence of renal diseases that may occur as a complication of or related to HIV infection in asymptomatic patients. This is a single center cross-sectional study of asymptomatic HIV+ patients referred to a nefrology care service at an Argentine hospital to look for the presence of renal abnormalities. Fifty two consecutive patients were studied between April and November 2008. Patients underwent plasma and urine analysis, ultrasound, and kidney biopsy as needed. Mean age was 39.9 ± 10.6 years, 88% were male, time from HIV diagnosis 53.2 ± 41.2 months (2-127); 71% had HIV-disease and 77% were on antiretroviral therapy. Mean plasma HIV-RNA copies number was 7.043 ± 3.322 and CD4+ cell count: 484 ± 39. Pathologic findings in urine analysis were present in 30.7% of patients: albuminuria 16.6%, microscopic hematuria 11.5%, hypercalciuria 10.8% and crystalluria 6%. Mean glomerular filtration rate was 102.2 ± 22.95 ml/min (34-149) and 41% of patients could be classified in stages 1 to 3 of chronic kidney disease. Renal abnormalities prevaled in older patients without relationship with presence of HIV-disease. Two patients were biopsied and the findings included: tubulointerstitial nephritis with presence of crystal deposition in one and IgA nephropathy in the other. No HIV-associated nephropathy was detected. The broad spectrum and the high prevalence of lesions found in this series suggest that asymptomatic HIV-infected patients should routinely undergo renal evaluation.

Human immunodeficiency virus-associated nephropathy.

Human immunodeficiency virus-associated nephropathy (HIVAN) is a clinicopathological entity characterised by proteinuria, rapidly developing azotemia and histologically by collapsig variant of focal and segmental glomerulosclerosis with acute tubular necrosis and mild interstitial inflammation. Untreated, it may result in end stage renal disease (ESRD) in as little as four months. The incidence of HIVAN continues to increase and is the single most common cause of chronic renal disease in HIV-1 seropositive patients. It affects predominantly black individuals. Exact pathogenesis is still not clear but a great deal of progress has been made in the recent past by studies on transgenic mouse model, renal cell cultures and from study of human biopsy material. Current considerations revolve around the role of HIV or protein in renal epithelium and the effects of cytokines, including transforming growth factor-beta and basic fibroblast growth factor on renal structures. Different modalities of treatment with corticosteroids, zidovudine or angiotensin converting enzyme inhibitors have been tried with modest success.

Renal lesions associated with AIDS--an autopsy study.

Kidneys from 55 cases (20 with HIV infection and 35 with AIDS) were studied by routine Haematoxylin and Eosin stains and special stains (PAS, PASM GMS, ZN, Mucicarmine and Congo red) to evaluate, glomerular, interstitial and vascular pathology. Twenty-four of the 35 (68.6%) cases of AIDS showed infective aetiology which included 17 cases (48.5%) of tuberculosis, 5 cases (14.4%) of fungal infection (3 cryptococcus neoformans and 2 candida species) and 2 cases (5.7%) of CMV infection. Other lesions noted were amyloidosis and tubular calcinosis. HIV associated nephropathy (HIVAN) was not detected in any of the cases. Intravenous drug abuse was not a risk factor in our cases which probably explains the absence of HIV associated nephropathy in the present study.

Renal lesions in AIDS: a biopsy and autopsy study.

We studied renal lesions at biopsy (20 cases) and at autopsy (21 cases) among patients with the acquired immune deficiency syndrome (AIDS). Nephrotic syndrome with concomitant renal insufficiency was most common indication for biopsy. 85 percent of biopsies showed features of HIV associated nephropathy (HIVAN) which include: Focal segmental glomerulosclerosis (FSGS), glomerular collapse and mesangial hyperplasia. These glomerular changes were always accompanied by tubular microcysts and ultrastructurally, tubuloreticular inclusions (TRI) within the glomerular endothelium were often noted. Changes of HIVAN were also seen in two cases who were HIV negative at the time of biopsy but were positive on repeat testing. Minimal change disease, mesangiocapillary glomerulonephritis and diffuse proliferative lupus nephritis were other biopsy lesions. Autopsy findings were HIVAN (33 percent), tubular necrosis and opportunistic infections. We conclude that HIVAN is a distinct clinicopathologic entity that may sometimes be the first manifestation of the underlying disease state.

Nefropatia relacionada ao HIV / HIV related nephrophaty

A sindrome de Imunodeficiencia Adquirida (SIDA) foi descrita pela primeira vez em 1981. Tres anos mais tarde RAO associada a Nefropatia ao HIV (NRHIV), caracterizando-a pelos achados de proteinuria e glomeruloesclerose focal, na ausencia de outras causas. A NRHIV acomete com maior frequencia homens negros e viciado em droga. Sua patogenese e desconhecida e clinicamente, tanto os portadores do HIV como os pacientes com SIDA podem apresenta-la...