History
In 1984, physicians in New York and Miami reported HIV-infected adult patients with heavy proteinuria and rapid progression to end-stage renal disease. These patients showed large edematous kidneys with combination of focal segmental glomerulosclerosis (FSGS) and tubulointerstitial lesions. This renal syndrome, named HIV-associated nephropathy (HIVAN), was found predominantly in African Americans. Subsequent studies confirmed the presence of HIVAN in children in America & Africa, who frequently develop nephrotic syndrome in association with focal segmental glomerulosclerosis (FSGS) and/or mesangial hyperplasia with microcystic tubular dilatation. Subsequent studies have documented a range of renal manifestations in HIV infected children.
Glomerulopathy occurs in up to 15% of children with HIV infection whereas the occurrence of tubular dysfunction is less well defined.
HIV and renal involvement
A variety of renal abnormalities among HIV-infected patients have been described. These include HIV associated nephropathy (HIVAN), HIV-related immune complex disease, nephropathy secondary to antiretroviral therapy (ART) or antibiotics, thrombotic microangiopathy, and diseases related to common comorbidities such as opportunistic infections. The broad spectrum of clinical presentation includes acute renal failure (ARF), nephrotic syndrome, progressive chronic renal dysfunction, proteinuria, tubular function abnormalities and electrolyte disturbances. Several studies have found that HIV associated renal disease is seen with low CD4 + count and increased viral loads. Thus, all children with advanced HIV disease should be screened for renal disease.
HIV and proteinuria
A variety of renal abnormalities among HIV-infected patients have been described. These include HIV associated nephropathy (HIVAN), HIV-related immune complex disease, nephropathy secondary to antiretroviral therapy (ART) or antibiotics, thrombotic microangiopathy, and diseases related to common comorbidities such as opportunistic infections. The broad spectrum of clinical presentation includes acute renal failure (ARF), nephrotic syndrome, progressive chronic renal dysfunction, proteinuria, tubular function abnormalities and electrolyte disturbances. Several studies have found that HIV associated renal disease is seen with low CD4 + count and increased viral loads. Thus, all children with advanced HIV disease should be screened for renal disease.
HIV-associated nephropathy (HIVAN)
HIVAN is a unique form of collapsing focal segmental glomerulosclerosis which is the most common histological presentation. Other histological patterns include mesangial hyperplasia, focal necrotizing glomerulonephritis and minimal change disease. It has been predominantly reported in African – American children. It has been rarely reported in Indian children. Patients usually present with advanced HIV infection, renal insufficiency and marked proteinuria (nephrotic range proteinuria) and usually is seen with other AIDS – related illnesses such as encephalopathy and cardiomyopathy. Thus, all children presenting with nephrotic range proteinuria should be screened for underlying HIV disease.
Several mechanisms for pathogenesis have been implicated. The pathogenesis of HIVAN is not exactly established though viral infection of renal cells have been postulated to play a key role in the pathogenesis of HIVAN by partially affecting the growth and differentiation of glomerular and tubular epithelial cells and enhancing the renal recruitment of infiltrating mononuclear cells and cytokines. These changes enhance the infectively of HIV-1 in the kidney and induce injury and proliferation of intrinsic renal cells. Low CD4 count is associated with subsequent development of chronic renal disease. Other agents that can lead to associated renal disease are opportunistic infections, nephrotoxic agents and immunological abnormalities.
Highly active antiretroviral therapy (HAART) is effective in preventing end-stage renal disease and angiotensin converting enzyme (ACE) inhibitors also have a role.
References- Shah Ira. Response of HIV Associated Proteinuria to Antiretroviral Therapy in HIV-1 Infected Children. Braz J Infect Dis. 2006;10:408-410.
- Shah Ira, Gupta S, Shah D, Dhabe H, Lala M. Renal manifestation in HIV infected HAART naive Children: A preliminary study from India. World Journal of Pediatrics. Accepted for publication, August 2011
- Shah I. Nephrotic Proteinuria and Renal Involvement in HIV Infected Children. Indian Journal of Sexually Transmitted Diseases and AIDS. Accepted for publication, July 2011
- Ray PE, XU L, Rakusan T, Liu XH. A 20 year history of children HIV-associated nephropathy. Pediatr Nephrol 2004; 19: 1075-1092.
- Ahuja TS, Abbott KC, Pack L, Kuo YF. HIV-associated nephropathy and end-stage renal disease in children in the United States. Pediatr Nephrol 2004; 19 :808-811.
- Anochie IC, Eke FU, Okpere AN. Human immunodeficiency virus-associated nephropathy (HIVAN) in Nigerian children. Pediatr Nephrol 2008; 23: 117-122.
- Choi AI, Rodriguez RA. Renal manifestations of HIV. 2008 Jan. Available at http://hivinsite.ucsf.edu/InSite?page=kb-04-01-10 (Accessed on 17/12/2008)
- Viani RM, Danker WM, Muelenaer, PA, Spector SA. Resolution of HIV-associated nephropathy nephrotic syndrome with highly active antiretroviral therapy delivered by gastrostomy tube. Pediatrics 1999; 104: 1394-1396.
- Kimmer PL, Mishkin GJ, Umana WO. Captopril and renal survival in patients with human immunodeficiency virus nephropathy. AM J Kidney Dis. 1996; 28: 202-208.
- Eustace JA, Nuermberger E, Choi M, Scheel PJ, Moore R, Briggs WA. Cohort study of the treatment of severe HIV-associated nephropathy with corticosteroids. Kidney Int 2000; 58: 1253-1260.