The Kidneys

In the first 15 years of the AIDS pandemic, the medical focus was on preventing and treating life-threatening infections that were commonly seen in AIDS. In the present era, at least in high-income countries, combination therapy for HIV -- called highly active antiretroviral therapy, or HAART -- is widely available. This treatment puts HIV disease into remission. And as long as there are no severe co-existing illnesses, researchers expect that HIV positive people who are engaged in their care and treatment will have near-normal life spans.

But as HIV positive people live longer, researchers, doctors and patients wonder about the long-term impact of HIV on an ageing body as well as potential side effects of HIV treatment. In this issue of TreatmentUpdate, we review studies on the health of the kidneys in HIV.

Focus on the Kidneys

The kidneys are two organs each about the size of a fist, located on either side of the spine, just below the ribs.

These organs perform many vital functions, such as the following:

• maintaining blood pressure
• converting vitamin D that was made in the skin into its active form, vitamin D₃
• monitoring oxygen levels in the blood and stimulating the bone marrow to produce more oxygen-carrying red blood cells should the need arise
• balancing ions and minerals in the body, such as calcium, potassium, phosphorus and magnesium
• filtering waste materials from the blood

Inside each kidney are millions of cells called nephrons. And inside each nephron are tiny filtering units; each unit is called a glomerulus. Each of these filtering units is made up of a blood vessel wrapped around a collection tube.

Filter, Filter

Perhaps the most important function of the kidneys is to filter waste materials from the blood. These are produced from many everyday activities as cells carry out their functions, repair themselves and, in some cases, die. Wastes are also produced when food is broken down to release energy. Cells release their wastes into the blood.

Checking Up on the Kidneys

Kidney health can be assessed in a number of ways. Perhaps the most common way is a method of assessing how efficiently the glomerulus is able to filter blood. This method is called the glomerular filtration rate, written as GFR. However, because measuring the GFR is cumbersome, timeconsuming and expensive, doctors most often order tests to estimate the GFR and the results are the eGFR.

A Bit About Creatinine

Before we can discuss eGFR we must first give you some background information on a substance called creatinine. This is a waste product produced when muscles are broken down. In healthy people, levels of creatinine in the blood are usually fairly constant. Because creatinine is filtered by the kidneys, levels of this substance in the blood can be used to estimate GFR. Creatinine levels are usually put into one of two formulas named as follows:

• MDRD (modification of diet in renal disease)
• Cockcroft-Gault

MDRD is often used to calculate the eGFR because in addition to factors such as age and gender it can take into account race. The Cockcroft-Gault formula does not take into account a person's race.

Sometimes, often for research purposes, levels of a protein called cystatin C are used to estimate eGFR (more about this protein later).

Test Results

eGFR results are expressed as a number followed by the units mL/min (for example, 90 mL/min). In most cases, people with healthy kidneys will usually have a normal eGFR result of 90 or higher. However, lower values for eGFR may stress kidney damage as indicated below:

• An eGFR between 89 and 60 suggests mild kidney disease.
• An eGFR less than 60 for three consecutive months suggests chronic kidney disease.
• An eGFR between 30 and 59 suggests a moderate degree of kidney damage. If this persists, low levels of red blood cells and thin bones can occur. Low levels of red blood cells can lead to fatigue and fewer minerals in the blood can affect the strength of bones.
• An eGFR that falls between 15 and 29 suggests severe kidney damage. Artificial filtration of the blood -- dialysis -- is needed to remove wastes from the body.
• When the eGFR falls below 15 the kidneys have largely stopped working and without dialysis or a kidney transplant death can occur. In Canada, transplanted organs are not available to HIV positive people.

Other Tests

In addition to eGFR, other tests are useful when trying to assess the risk for or the presence of kidney dysfunction. These tests can include the following:

• Blood pressure
  Because the kidneys regulate blood pressure, having high blood pressure may be a sign of kidney damage. Prolonged periods of high blood pressure can also damage the kidneys.
• Urine tests
  Normally, the kidneys send wastes to the urine and reabsorb useful nutrients. However, damaged kidneys can inadvertently leak key nutrients, such as the protein albumin, into the urine. When a small amount of albumin is detected in the urine, this is called microalbuminuria. If the kidneys continue to degrade and more protein leaks into the urine, this is called proteinuria.
• Kidney biopsy
  A small amount of kidney tissue is removed for analysis.
• Scans
  Depending on the situation, ultrasound, CAT scans or MRIs may be taken to assess kidney health.

Signs and Symptoms

In early cases of kidney damage there may be no noticeable symptoms. However, as the kidney degrades the following may occur:

• increased or decreased urination
• decreased appetite
• nausea
• vomiting
• muscle cramps
• itchiness
• difficulty concentrating

Risk Factors for Kidney Disease

There are a number of factors that increase the risk of developing kidney damage, including the following:

• Uncontrolled HIV infection
  This virus infects the cells of the immune system, but it also infects and weakens the kidneys. Moreover, some researchers suggest that the kidneys can become a reservoir for HIV, a place where new copies of HIV are regularly made inside HIV-infected cells. Taking anti-HIV treatment so that levels of HIV fall to very low levels helps reduce viral damage to this organ.
• High blood sugar and high blood pressure
  Diabetes and high blood pressure are the leading causes of kidney disease in HIV negative people and likely play a major role in HIV positive people.
• Race
  For reasons that are not clear, people of African ancestry are at increased risk for HIV-related kidney damage.
• Age
  As people (and their kidneys) age, these organs become less effective at filtering wastes from the body.

The good news is that diabetes, high blood pressure and HIV viral load can often be controlled, which reduces the risk of kidney disease.

References

1. Marras D, Bruggeman LA, Gao F, et al. Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy. Nature Medicine. 2002 May;8(5):522-6.
2. Tandon R, Levental I, Huang C, et al. HIV infection changes glomerular podocyte cytoskeletal composition and results in distinct cellular mechanical properties. American Journal of Physiology. Renal physiology. 2007 Feb;292(2): F701-10.
3. Papeta N, Chan KT, Prakash S, et al. Susceptibility loci for murine HIV-associated nephropathy encode trans-regulators of podocyte gene expression. Journal of Clinical Investigation. 2009 May;119(5):1178-88.
4. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. American Journal of Kidney Diseases. 2002;39(Suppl 1):S1-266.
5. Himmelfarb J, Joannidis M, Molitoris B, et al. Evaluation and initial management of acute kidney injury. Clinical Journal of the American Society of Nephrology. 2008 Jul;3(4): 962-7.
6. Winston J, Deray G, Hawkins T. Kidney disease in patients with HIV infection and AIDS. Clinical Infectious Diseases. 2008 Dec 1;47(11):1449-57.

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