Antiretroviral Clinical Trials – Breaking News

Kidney Diseases Associated with Human Immunodeficiency Virus Infection
Cohen SD, et al.
N Engl J Med. 2017 Dec 14;377(24):2363-2374

3rd january 2018, by Pr Anton Pozniak

Highly active ART has led to dramatic improvement in the life expectancy of persons with HIV infection.

Approximately 36.7 million people live with HIV infection worldwide, and there were approximately 2.1 million cases of incident HIV infection globally in 2015. Almost three quarters of HIV-infected persons live in sub-Saharan Africa. Although 18.2 million people worldwide were receiving ART by 2016, only 40% of HIV-infected persons in sub-Saharan Africa received ART as of 2014. The prevalence of HIV infection is much lower in the USA than in sub-Saharan Africa. Approximately 1.2 million persons in the USA have HIV infection, and the annual incidence has been stable at approximately 50,000 infections over the past decade.

Kidney disease, which is a common complication of HIV infection and its treatment, may shorten the lifespan of patients. Soon after the index cases of the AIDS were identified in 1980, various kidney diseases associated with AIDS were recognized. The spectrum of HIV-associated renal diseases includes diseases that are directly associated with infection, those that are linked to the systemic immune response to infection, those that develop as a consequence of superinfections, and those that are associated with the treatment of HIV infection (Table 1). Since the introduction of molecular tools to detect HIV within tissues, our understanding of the pathogenesis of common kidney diseases, such as focal segmental glomerulosclerosis and immune complex renal disease, in persons with HIV infection has improved.

Over the past two decades, antiretroviral therapy has converted HIV infection to a chronic illness, with associated changes in the incidence, type, and severity of HIV-associated kidney diseases. Current antiretroviral therapy regimens suppress viral replication, but this treatment may result in chronic inflammation, premature aging, and metabolic disorders (e.g., diabetes, hyperlipidemia, and abnormal body fat composition) - conditions that are associated with chronic kidney disease.

Table 1. Kidney Diseases in Patients with Human Immunodeficiency Virus Infection

Acute kidney injury Chronic kidney disease Opportunistic infections of the kidney parenchyma Infiltrative lesions of the kidney
Prerenal azotemia
Acute tubular necrosis
ART-associated acute kidney injury
TI nephritis (IRIS)
HIV immune-complex kidney disease (Ig A nephropathy, postinfectious GN, mesangial proliferative GN, lupus-like GN, membranoproliferative GN, cryoglobulinemic GN, Other)
Thrombotic microangiopathies
Urinary tract obstruction (bladder outlet obstruction, ureteral obstruction : fungus balls, blood clots, retroperitoneal fibrosis, lymphadenopathy)
HIV immune-complex kidney disease
ART-associated chronic kidney disease (TI nephritis, crystal nephropathy, TDF-induced nephrotoxicity)
TI renal disease (diffuse infiltrative lymphocytosis syndrome)
Viral (CMV, HSV, Parvovirus, Other)
Mycobacterial, typical and atypical
Bacterial pyelonephritis
Kaposi's sarcoma

HIVAN : HIV-associated nephropathy ; GN : glomerulonephritis ; TI : tubulointerstitial

Table 2. Approaches to Evaluating Kidney Disease in Patients with HIV Infection

Pre-renal   Volume depletion
Bland urine sediment
Fractional excretion of Na < 1%
Intrinsic renal Acute tubular necrosis (sepsis, medications, pigment) Granular or muddy brown casts
Fractional excretion of Na > 2%
Thrombotic microangiopathy Microangiopathic hemolytic anemia
Acute interstitial nephritis (sepsis, medications) Active urine sediment
White-cell casts
HIV-associated immune-complex disease Active urine sediment
Microscopic hematuria
Red-cell casts Hypocomplementemia
Screen for hepatitis and other infections
HIVAN Nephrotic-range proteinuria
HIV viral load
Low CD4 count
cART nephropathy (insterstitial nephritis, crystalluria, mitochondrial toxicity, Fanconi's syndrome) Subnephrotic proteinuria
Controlled viral load and CD4 count
Other kidney syndromes Diabetes
Focal segmental glomerulosclerosis
Post-renal   Obstruction

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