The kidneys are organs that help clear toxins from the body and balance levels of acid and water in the human body. Water and waste products are turned into urine by the kidneys and excreted from the body. Nephropathy is the general term for renal disease.

Causes

Problems with kidney function in HIV-infected people may be due to medications or HIV itself. HIV-associated nephropathy (HIVAN) is highly prevalent among HIV-positive people in Africa, with recent studies showing rates of between 25 and 50% in Kenya and Uganda (Muloma 2005; Pepper 2005). However, HIVAN is usually reversed after intiation of antiretroviral therapy (Post 2005; Scheurer 2004; Szczech 2004).

Anti-HIV drugs can also cause kidney problems themselves. The nucleotide reverse transcriptase inhibitor tenofovir (Viread) has been identified as one cause of renal toxicity, although recent studies have called this into question. See Tenofovir - overview in Drugs used by people with HIV: Nucleotide reverse transcriptase inhibitors for further details.

Indinavir (Crixivan) is also a known cause of kidney toxicity, while one report has identified the development of kidney stones in 4% of patients taking ritonavir-boosted lopinavir (Kaletra; Thanh 2004). See Indinavir - overview and Lopinavir - overview in Drugs used by people with HIV: Protease inhibitors for further details.

Kidney disease in HIV-infected people has been associated with more advanced HIV disease, low CD4 cell counts, and diabetes. A study of 35 people with nephropathy without hypertension or diabetes found that kidney disease was linked to cidofovir (Vistide), indinavir or co-trimoxazole (Septrin / Bactrim) therapy, systemic chemotherapy for lymphoma, acute bacterial infection of the kidneys and sepsis (Visnegarwala 2003).

A Canadian study of approximately 900 people with normal kidney function who started either tenofovir or abacavir (Ziagen) found that people who began tenofovir had more than twice the risk of creatinine elevation compared with those who started abacavir. Lower CD4 cell counts were also linked to increased risk of kidney toxicity. For every reduction in CD4 cell count of 100 cells/mm³, the risk of creatinine elevation increased 1.5 times (Harris 2003).

A recent study has identified smoking for over ten years, and African or Haitan race, as risk factors for the development of kidney disease in HIV-positive patients (Miguez-Burbano 2004).

Symptoms

Symptoms of kidney toxicity include fatigue, dehydration, polyuria (the passage of a large volume of urine), polydipsia (excessive or abnormal thirst), high blood pressure and a rapid heart rate.

It is usually diagnosed by testing for the presence of protein in the urine or by measuring the levels of a protein called creatinine in the blood. Kidney function is said to be impaired if levels of creatinine in the blood are elevated or if clearance of creatinine is below 60ml/min. A positive diagnosis is usually confirmed with an ultrasound scan and possibly analysis of a sample of kidney tissue.

A measure called glomerular filtration rate is emerging as a more sensitive method for the diagnosis of kidney disease in HIV-positive patients (Becker 2005). This is a measure of the filtering activity of the kidneys, calculated using the creatinine level, age, gender, weight and body size.

Fanconis syndrome is a disorder of the proximal renal tubes of the kidneys, where electrolytes and nutrients are not properly absorbed back into the body. Low levels of phosphorous in the blood (hypophosphataemia) is a sign of kidney impairment associated with Fanconi's syndrome.

Recent guidelines for HIV-positive patients from the Infectious Diseases Society of America have recommended screening for kidney disease at the time of HIV diagosis. Thereafter, patients at high risk of developing kidney disease should be screened every year. These include people of African descent, those with CD4 cell counts below 200 cells/mm³ or viral loads above 4000 copies/ml, and those with diabetes, high blood pressure or hepatitis C co-infection (Gupta 2005).

Treatment

Treatments for kidney impairment depend in part on the cause of the condition. There is not enough evidence to provide a general indication of how best to treat HIV-positive patients with renal disease. Treatments must therefore be tailored to the individual patient's needs and circumstances.

If impairment is severe, antiretrovirals such as tenofovir may be stopped. However, the use of antiretrovirals can improve kidney function by improving general health and removing the damaging effects of co-infections such as fungal infections and their treatments (Reisler 2005; Siwani 2005). The doses of all nucleoside and nucleotide reverse transcriptase inhibitors, with the exception of abacavir, need to be reduced in patients with kidney disease.

Treatment may also be provided to boost phosphorous levels, reduce blood pressure and increase hydration.

In cases of severe or 'end stage' kidney disease, dialysis may be a viable option for HIV-positive patients. This involves filtration of the blood by a dialysis machine, which takes over the function of the kidneys. Transplantation is also an option for HIV-positive patients now that antiretroviral therapy has reduced the risks associated with immunosuppression to prevent rejection of the transplant and the risk of death from HIV itself.

References

Becker S et al. Beyond serum creatinine: identification of renal insufficiency using glomerular filtration: implications for clinical research and care. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 819, 2005.

Gupta SK et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 40: 1559-1585, 2005.

Harris M et al. Increases in creatinine during therapy with tenofovir DF. Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract 55, 2003.

Karras A et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, fanconi syndrome, and nephrogenic diabetes inspididus. Clin Infect Dis 36: 1070-1073, 2003.

Miguez-Burbano MJ et al. Renal disease in HIV infected subjects: the deleterious effect of smoking. Fifteenth International AIDS Conference, Bangkok, abstract MoPeB3274, 2004.

Muloma E et al. Renal disease in antiretroviral naﶥ HIV-infected population in western Kenya. Third International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, abstract MoPe11.6C23, 2005.

Murphy MD et al. Fatal lactic acidosis and acute renal failure after addition of tenofovir to an antiretroviral regimen containing didanosine. Clin Infect Dis 36: 1082-1085, 2003.

Pepper L et al. Prevalence of renal disease in patients attending the HIV/AIDS clinic at Mbarara University Teaching Hospital. Third International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, abstract TuPe15.3C02, 2005.

Reisler R et al. Chronic kidney disease and the use of HAART. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 818, 2005.

Rollot F et al. Tenofovir-related Fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immune deficiency syndrome: the role of lopinavir-ritonavir-didanosine. Clin Infect Dis 37: E174-E176, 2003.

Scheurer D et al. Rapid reversal of renal failure after initiation of HAART: a case report. AIDS Read 14: 443-447, 2004.

Siwani R et al. Complete suppression of HIV viral replication may improve renal outcome in patients with HIV-associated nephropathy (HIVAN). Third International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, abstract TuPe7.8C03, 2005.

Szczech LA et al. The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection. Kidney Int 66: 1145-1152, 2004.

Thanh DC et al. Lopinavir-ritonavir (Kaletra) and lithiasis: seven cases. AIDS 18: 705-706, 2004.

Visnegarwala F et al. Prevalence of renal disease in an inner city HIV-infected cohort. Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris (Antiviral Therapy 8:1), abstract 1147, 2003.