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Focal segmental glomerulosclerosis and HIV

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Related Terms
  • Albumin, antiretroviral, antiretroviral therapy, (ART), edema, end-stage renal disease, ESRD, fluid retention, focal sclerosis with hyalinosis, genetic disorder, genetically inherited, glomerular disease, glomeruli, glomerulosclerosis, glomerulus, HAART, high blood pressure, highly active antiretroviral therapy, histopathology, HIV, human immunodeficiency virus, hyperlipidemia, hypertension, hypoalbuminemia, kidney, kidney disease, kidney disorder, kidney failure, nephrotic syndrome, NS, protein, proteinuria, renal, renal disease, renal failure, viral infection, virus, weakened immune system.

Background
  • Focal segmental glomerulosclerosis (FSGS) is a type of glomerular disease (disease that affects the glomeruli) that can cause permanent kidney disease in children and adults. It affects kidney function by attacking the glomeruli, the tiny structures inside the kidneys where blood is filtered. The term glomerulosclerosis is used to describe the scarring or hardening of the tiny blood vessels inside the kidneys. Consequently, protein and sometimes red blood cells leak into the urine.
  • The most common clinical feature of FSGS is nephrotic syndrome, which is characterized by generalized edema (fluid in the body tissues that causes swelling), proteinuria, hypoalbuminemia (abnormally low levels of albumin, which is normally the most plentiful protein in the blood), and hyperlipidemia (high cholesterol).
  • Patients who have HIV may develop HIV-associated FSGS. In HIV-associated FSGS, renal (kidney) function deteriorates quickly, leading to end-stage renal disease (ESRD) within a few weeks to one year. ESRD is fatal unless treated with dialysis or kidney transplantation.
  • Since the introduction of highly active antiretroviral therapy (HAART), which is used to treat HIV/AIDS, patients are less likely to experience kidney failure when the viral load of HIV decreases.
  • Although the cause of HIV-associated FSGS remains unknown, researchers believe HIV itself may cause it, or the conditions may be genetically inherited because the disease primarily affects African American men.
  • For unknown reasons, men are more likely to develop HIV-associated FSGS. The ratio of men to women is 10 to one. Most patients with HIV-associated FSGS are African American men, with an average age of 33 years. HIV-associated FSGS is rare in Caucasians. Worldwide, more than 95% of HIV-associated FSGS patients are black. About 50% of patients suffering from HIV-associated FSGS are intravenous (injection) drug users and the remaining are homosexual or bisexual men, heterosexual contacts of infected persons, or HIV-infected children.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Kopp JB, Winkler C. HIV-associated nephropathy in African Americans. Kidney Int Suppl. 2003 Feb;(83):S43-9. .
  2. National Kidney Foundation. .
  3. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2007.
  4. The Nephcure Foundation. .

Causes
  • The exact mechanism of action of HIV-associated focal segmental glomerulosclerosis (FSGS) remains unknown. However, some researchers suggests that is the result of a direct HIV infection of kidney cells and toxicity of HIV-1 accessory proteins.
  • HIV-associated FSGS predominantly affects African American men, which suggests that there is a genetic basis for the condition. However, the gene or genes responsible have not yet been identified.

Symptoms
  • Common symptoms of focal segmental glomerulosclerosis (FSGS) include fatigue, nausea, headache, foamy urine, weight gain, and poor appetite.
  • The most common clinical feature of FSGS is nephrotic syndrome, which is characterized by generalized edema (fluid in the body tissues, which causes swelling in the ankles, hands, feet, and eyelids), proteinuria (high levels of protein in the urine), hypoalbuminemia (abnormally low levels of albumin, which is normally the most plentiful protein in the blood), and hyperlipidemia (high cholesterol). Edema generally develops over a few weeks, but initial symptoms may appear suddenly in some patients, with weight gain of 15 to 20 or more pounds. High blood pressure is common among most patients. It is especially common among African American men with renal insufficiency because this population is genetically predisposed to develop high blood pressure.
  • Pleural effusion (fluid in the lung cavity) and ascites (fluid in the abdomen) may occur. Pericardial effusions are rare.
  • Rarely, patients experience severe renal failure. Symptoms may include altered mental status and advanced uremia (build up of waste in the blood due to severe kidney disease). Symptoms of uremia include nausea, vomiting, bleeding, and seizures.

Diagnosis
  • General: A kidney biopsy is the most definitive diagnostic test for focal segmental glomerulosclerosis (FSGS). In many patients, physical examination findings are normal except for swelling in some or most areas of the body, which is caused by edema (fluid in the tissues).
  • Kidney biopsy: A kidney biopsy is the standard diagnostic test for FSGS. During the procedure, a needle is inserted into the kidney and a small sample of tissue is removed. The tissue sample is then analyzed under a microscope for scarring, which indicates FSGS.
  • Urinalysis: A urinalysis, also called a urine sample test, is used to measure the levels of protein in the urine. Elevated levels of protein in the urine (with or without small amounts of blood) may suggest FSGS. However, since many other conditions may cause proteinuria, further testing is necessary for a diagnosis to be made.

Treatment
  • General: The goals of focal segmental glomerulosclerosis (FSGS) treatment are to maintain adequate nutrition, minimize or eliminate proteinuria, and prevent complications resulting from edema, such as difficulty breathing, anxiety, or excessive sweating. It is important to control high blood pressure because, if left untreated, high blood pressure may cause heart disease, stroke, brain damage, kidney damage, or hardening of the arteries. Lowering of lipid levels is necessary to reduce cardiovascular risk and to possibly delay the progression of renal disease.
  • Highly active antiretroviral therapy (HAART), which suppresses HIV, is associated with remission of proteinuria (high levels of protein in the blood) and prevention of kidney damage. In some patients with HIV-associated FSGS, corticosteroid therapy is associated with a significant improvement of FSGS.
  • Anti-hypertensives (ACE inhibitors): Anti-hypertensives (drugs that lower blood pressure) have been used to treat high blood pressure. One type of drug for high blood pressure called ACE inhibitors reduces proteinuria by reducing the amount of pressure and resistance on blood as it circulates through the body.
  • Corticosteroids: Corticosteroids like prednisone (Deltasone®, Orasone®, or Meticorten®) have been associated with significant improvement in renal function in some patients with HIV-associated FSGS.
  • Dialysis: If the patient does not respond to treatment and develops kidney failure, dialysis may be necessary. There are two types of dialysis - hemodialysis and peritoneal dialysis. Both types filter the blood to remove harmful waste products, extra salt and water. Hemodialysis accomplishes this with a machine, while peritoneal dialysis uses the lining of the abdomen (peritoneal membrane) to filter the blood.
  • Diet: A salt restricted diet (6 grams of salt a day) is recommended for FSGS patients. Reducing the amount of salt intake will reduce the amount of fluid retained (edema) in the body. As a result, the swelling from edema will also be reduced. Eating a large amount of proteins may make the proteinuria worse, which will subsequently worsen kidney function. Therefore, patients are encouraged to reduce their protein intake to 1-1.3 grams of high biological value protein per kilogram of body weight. The biological value of a protein is a value that measures how well the body absorbs and uses a protein. The higher the value, the more the body can absorb, use and retain. Food items such as eggs, milk and soy have high biological value proteins. In addition, patients are encouraged to reduce their consumption of fat to reduce clinical signs of hyperlipidemia.
  • Diuretics: Diuretics like furosemide have been used to treat edema. These drugs stimulate the kidney to increase urine output. This reduces the amount of fluid in the bloodstream, which subsequently lowers blood pressure.
  • Highly active antiretroviral therapy (HAART): It is common for healthcare providers to recommend a combination of antiretroviral drugs known as HAART for HIV/AIDS patients. This drug treatment usually combines drugs from at least two different classes of antiretroviral drugs, which has been shown to suppress the virus.
  • Individuals infected with HIV have less effective immune systems, which can make them vulnerable to opportunistic infections (OIs) and AIDS-associated co-infections. A wide-range of microorganisms such as protozoa, viruses, fungi, and bacteria cause the infections. Hepatitis C virus (HCV) infection is just one example. However, HIV therapies like HAART have dramatically slowed the progression of OIs and AIDS associated co-infections in HIV infected individuals. As a result, patients with HIV stay healthier for longer because their immune systems function better.
  • Currently, the U.S. Food and Drug Administration (FDA) has approved 28 antiretroviral drugs to treat HIV patients. These drugs fall into three major classes: reverse transcriptase (RT) inhibitors (including non-nucleoside reverse transcriptase inhibitors and nucleoside/nucleotide reverse transcriptase inhibitors), fusion inhibitors, and protease inhibitors. In July 2006, the FDA approved a multi-class combination called Atripla®. This drug contains three nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitor.
  • Fusion inhibitors prevent the virus from fusing with the cellular membrane, thus blocking entry into the cell. Only one fusion inhibitor, Fuzeon®, is FDA-approved.
  • Protease inhibitors (PIs) interfere with the protease enzyme that HIV uses to produce infectious viral particles. They are a class of medication used to treat or prevent viral infections, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of protease. This enzyme is essential during the last phase of viral replication inside human cells. The protease binds to a substrate and splits it up to produce more virons. FDA approved protease inhibitors include Agenerase®, Aptivus®, Crixivan®, Invirase®, Kaletra®, Lexiva®, Norvir®, Prezista®, Reyataz®, and Viracept®.
  • Reverse transcriptase (RT) inhibitors disrupt the reverse transcription stage in the HIV lifecycle. During this stage, an HIV enzyme, known as reverse transcriptase, converts HIV RNA to HIV DNA. This drug prevents the virus from copying its genetic code, which prevents the virus from replicating. There are two main types of RT inhibitors - non-nucleoside reverse transcriptase inhibitors and nucleosdie/nucleotide reverse transcriptase inhibitors.
  • Non-nucleosidereverse transcriptase inhibitors (NNRTIs) bind to reverse transcriptase, preventing HIV from converting the HIV RNA into HIV DNA. Approved non-nucleoside RT inhibitors include Rescriptor®, Sustiva®, and Viramune®.
  • Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) contain faulty DNA building blocks. Once the NRTIs are incorporated into the HIV DNA, the DNA chain cannot be completed. Therefore, the drugs prevent HIV from replicating inside a cell. Approved antiretrovirals include Combivir®, Emtriva®, Epivir®, Epzicom®, Hivid®, Retrovir®, Trizivir®, Truvada®, Videx EC®, Videx®, Viread®, Zerit®, and Ziagen®.
  • Kidney transplant: If the patient does not respond to treatment and develops kidney failure, a kidney transplant may be necessary.

Integrative therapies
  • Chelation therapy: Chelation therapy involves infusing a chemical called ethylene diamine tetraacetic acid (EDTA) into the blood. According to preliminary research, repeated chelation therapy may improve renal function and slow the progression of renal insufficiency. Further research is needed to confirm these results.
  • Avoid with heart disease, liver disease, kidney disease, immune system disorders, bleeding disorders, or if taking agents that increase the risk of bleeding. Avoid if pregnant or breastfeeding due to potential toxic effects.
  • Omega-3 fatty acids: More research is needed to determine whether omega-3 fatty acids can effectively treat nephrotic syndrome.
  • Avoid if allergic or hypersensitive to fish, omega-3 fatty acid products that come from fish, nuts, or linolenic acid. Avoid during active bleeding. Use cautiously with bleeding disorders, diabetes, low blood pressure , or if taking drugs, herbs, or supplements that treat any such conditions. Use cautiously before surgery. The Environmental Protection Agency (EPA) recommends that intake be limited in pregnant/nursing women to a single six-ounce meal per week, and in young children to less than two ounces per week. For farm-raised, imported, or marine fish, the U.S. Food and Drug Administration (FDA) recommends that pregnant/breastfeeding women and young children avoid eating types with higher levels of methylmercury and less than 12 ounces per week of other fish types. Women who might become pregnant are advised to eat seven ounces or less per week of fish with higher levels of methylmercury or up to 14 ounces per week of fish types with about 0.5 parts per million (such as marlin, orange roughy, red snapper, or fresh tuna).
  • Reishi mushroom: One clinical trial was conducted to evaluate the effect of reishi mushroom (Ganoderma lucidum) in treating kidney disorder patients with persistent proteinuria that is resistant to steroids with or without immunosuppressant therapy. Ganoderma lucidum treatment decreased proteinuria in the small number of patients in this study. This trial provides good preliminary data, but long-term studies with a larger amount of patients are needed to evaluate the effect of Ganoderma lucidum on proteinuria.
  • Avoid if allergic or hypersensitive to any constituents of Ganoderma lucidum or any member of its family. Use cautiously with diabetes, blood disorders (including hemophilia), low blood pressure, or ulcers. Avoid if pregnant or breastfeeding.
  • Soy: Due to limited human study, there is not enough evidence for or against the use of soy in the treatment of kidney diseases, such as nephrotic syndrome. People with kidney disease should speak to their healthcare providers about recommended amounts of dietary protein, and should bear in mind that soy is a high-protein food, which may worsen proteinuria in FSGS patients.
  • Avoid if allergic to soy. Breathing problems and rash may occur in sensitive people. Soy, as a part of the regular diet, is traditionally considered to be safe during pregnancy and breastfeeding, but there is limited scientific data. The effects of high doses of soy or soy isoflavones in humans are not clear, and therefore are not recommended. There has been a case report of vitamin D deficiency rickets in an infant nursed with soybean milk (not specifically designed for infants). People who experience intestinal irritation (colitis) from cow's milk may experience intestinal damage or diarrhea from soy. It is not known if soy or soy isoflavones share the same side effects as estrogens, like increased risk of blood clots. The use of soy is often discouraged in patients with hormone-sensitive cancers, such as breast, ovarian, or uterine cancer. Other hormone-sensitive conditions such as endometriosis may also be worsened. Patients taking blood-thinners like warfarin should check with a doctor and pharmacist before taking soy supplementation.
  • Traditional Chinese medicine (TCM): TCM herbs have been reported to improve the therapeutic effectiveness and counteract adverse reactions to hormone therapy in treating nephrotic syndrome and reduce the recurrence of symptoms.
  • Acupuncture is generally considered safe. Side effects with cupping are rare. Chinese herbs can be potent and may interact with other herbs, foods, or drugs. Side effects with moxibustion are rare. Reported side effects with TMC include acute hepatitis, death, dizziness, and headache. A qualified healthcare professional, including a pharmacist, should be consulted for recommendations of safe herbal products. Avoid with caffeine.
  • Vitamin E: It has been suggested that proteinuria (protein in the urine) may be reduced with the use of vitamin E in patients with focal segmental glomerulosclerosis, which is refractory to standard medical management. However, further research is necessary before a clear conclusion can be drawn.
  • Avoid if allergic or hypersensitive to vitamin E. For short periods of time, vitamin E supplementation is generally considered safe at doses up to 1,000 milligrams per day. Avoid doses higher than 1,000 milligrams a day. Avoid with Retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders. The recommended dose of vitamin E for pregnant women of any age is 15 milligrams and for breastfeeding women of any age, the recommended dose is 19 milligrams. Use beyond this level in pregnant women is not recommended.

Prevention
  • Since little is known about the exact cause of HIV-associated focal segmental glomerulosclerosis (FSGS), there is currently no known method of prevention.

Complications
  • In HIV-associated FSGS, renal (kidney) function deteriorates quickly, leading to end-stage renal disease (ESRD) within a few weeks to one year. ESRD typically occurs after the patient experiences chronic kidney failure. ESRD is fatal unless treated with dialysis or kidney transplantation. Common symptoms include unintentional weight loss, nausea or vomiting, general feeing of discomfort, fatigue, decreased urination, generalized itching, easy bruising or bleeding, blood in vomit or stools, muscle twitching or seizures, increased skin pigmentation, nail abnormalities, headache, frequent hiccups, and decreased sensation in the hands, feet, or other areas.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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