Protein Excreted In Urine May Be Help In Diagnosing Kidney Disease Caused By HIV

New data collected at Columbia University Medical Center and by the Mount Sinai School of Medicine are helping researchers understand the extent to which a certain protein – NGAL – can play a significant role in marking chronic kidney disease resulting from HIV while at the same time distinguishing nephropathy from more common causes such as diabetes and hypertension.

It's well-known that Human Immunodeficiency Virus-associated nephropathy (HIVAN) is an important cause of kidney disease in HIV-infected patients. Antiretroviral therapy plays an important role in the treatment of HIVAN, yet despite advances in understanding HIVAN, current recommendations for treatment have largely been based on observational data and can only definitively made after a kidney biopsy.

The current study, spearheaded by Columbia University's Jonathan Barasch, M.D., Ph.D., along with Ali Gharavi M.D., Ph.D., Neal Paragas M.S., Thomas Nickolas M.D., M.S., and Vivette D'Agati M.D., together with Paul Klotman, M.D., Christina Wyatt M.D., and Susan Morgello M.D., of the Mount Sinai School of Medicine and Landino Allegri in Parma, Italy, and Prasad Devarajan in Cincinnati Childrens Hospital, represents the examination of data from human cohorts in New York and Parma, and from mouse models created by Dr. Klotman.

The team noted that NGAL, or Neutrophil Gelatinase Associated Lipocalin, a protein they previously discovered in damaged kidneys, was prominently expressed in kidney tissue and in the urine of humans and in mouse models of HIVAN. The high levels of the urine protein were out of proportion to the degree of chronic renal failure, for example that typifies patients with other types of chronic glomerular diseases of both mice and humans. Most strikingly, Paragas, Barasch, and Gharavi noticed that the rise in urinary NGAL levels was in conjunction with the development of a specific type of lesion, namely tubular cysts that typify HIVAN. The association with these cysts consequently may justify their biopsy or an aggressive treatment with antiretroviral drugs when high levels of urine NGAL are discovered.

"From what we can tell, NGAL is unexpectedly expressed in great abundance by kidney cysts allowing the clinician to potentially identify HIVAN among other types of chronic kidney diseases and hopefully to intervene to prevent a kidney from ultimately dying from what physicians refer to as ESRD, or 'end-stage renal disease,'" Dr. Barasch says.

Dr. Barasch cautions that studying a much larger human cohort would be needed in order to determine the precise relationship of NGAL to HIVAN and whether the protein is a good enough predictor of tubular cysts, but he finds the results of the study unexpected and intriguing.

The research appears in an upcoming Journal of the American Society of Nephrology and was funded in part by the Emerald Foundation, the March of Dimes, the National Institutes of Health and the Glomerular Center of Columbia University.

Not adequately diagnosing kidney problems can be life-threatening and NGAL expression which is induced in kidney disease and damage can help identify patients at risk of kidney failure even in those without HIV. Last year, Dr. Barasch and Nickolas found that approximately 65 percent of patients with NGAL protein in the urine upon presentation to the Emergency Department will require care by a nephrologist, another 32 percent will need dialysis, and 29 percent will require care in the intensive care unit, over the course of a week following the subsequent hospitalization. That study was published in the June 3, 2008, issue of the Annals of Internal Medicine.

Prevalence of Lower Urinary Tract Symptoms Related with Benign Prostatic Hyperplasia. Study of 1804 Men Aged 40 or Older in Madrid - Abstract

Unidad de Apoyo a la Investigación, Servicio de Medicina Preventiva, Hospital Clínico San Carlos, Madrid.

Lower urinary tract symptoms (LUTS) related with benign prostatic hyperplasia (BPH) are present nowadays in approximately 20 to 30% of the Spanish male population from the age of 50 onwards. The purpose of this study was to assess clinical and epidemiological characteristics of patients with LUTS.

A cross-sectional study was performed, between 1999 and 2000, among 1,804 men aged 40 or older who were living in Madrid. Subjects were interviewed by telephone; socio-demographic information was requested and the presence of LUTS was assessed using the International Prostate Symptoms Score. Informed consent was requested, Association between qualitative variables was evaluated by chi2 or Fisher's test. A logistic regression model was performed to control confusion.

Prevalence of moderate/severe LUTS was 16.6% (95%CI: 14.8-18.3). Nearly 90% of the subjects consumed olive oil, 71.5% alcohol, 63.1% did not smoke and 96.9% did not consume drugs. A 27.7% of the subjects had hypertension and 8.8% referred diabetes. Men aged 70 or older had a threefold increased frequency of serious symptoms compared to younger men (OR: 3.31; 95%CI: 2.10-5.22). Low level of studies increased this frequency by a factor of 2.2 (95%CI: 1.42-3.46) and men who consumed only seed oil had twice more serious symptoms than those who consumed olive oil (OR: 1.86; 95%CI: 0.98-3.55).

Family history of urological diseases, age, low level of studies, hypertension, diabetes and seed oil consumption were independently associated with more serious symptoms, while medium alcohol consumption and mild smoking habit were associated with slighter symptoms.

Integrative Medicine: Reduce risk from prostate

Prostate cancer is the second-leading cause of cancer death in American men, and millions of men also suffer from the symptoms of an enlarged prostate. In fact, by age 70, about 90 percent of men will have prostate enlargement. Is this an inevitable part of growing older for the male of the species?

The answer is no. Men in Asia are much less likely to develop prostatic enlargement and prostate cancer than their American counterparts. This is probably because of differences in our lifestyles, especially our diets, which are higher in fat and lower in antioxidants in the West.

So what can you or your loved ones do? Eating fruits and vegetables that are high in antioxidants is probably beneficial. A recent study published in the Journal of Urology reported on the long-term follow-up of a group of men with prostate cancer who were treated with pomegranate juice.

In this study, which began in 2003, 48 men over age 60 who had been treated for localized prostate cancer were given 8 ounces of pomegranate juice to drink every day. Prior to the start of the study, these men were found to have rising PSA levels, which can indicate a recurrence of cancer.

The results of the initial study, as well as recently published follow-up data, suggested that pomegranate juice significantly reduced the rise of PSA – the men who got the juice took four times as long to double their PSA levels as expected. The limitations of this study: It was small, it did not have a control group, and mortality was not assessed.

What else can you do for prostate health?

• Eat more soy: A recent review in the American Journal of Clinical Nutrition showed that regular intake of soy foods, especially non-fermented soy foods such as tofu and soy milk, resulted in a 30 percent reduction in the risk of prostate cancer.

• Get your vitamin D: Adequate vitamin D levels may help to prevent prostate cancer, and studies are also under way to look at the use of vitamin D analogs as treatments for prostate cancer. Many people are deficient in vitamin D and not aware of it. Talk to your doctor.

• Eat more plants: Men who eat diets that are low in animal fat and high in fruits and vegetables seem to be at lower risk of prostate cancer. Try cruciferous veggies like broccoli and cauliflower .

• Keep your weight normal: Several studies suggest a higher risk of prostate cancer in men with a large waist-to-hip ratio.

• Stay active: Studies suggest that vigorous exercise can help reduce prostate cancer risk.

• Consider aspirin: Regular intake of aspirin may help to prevent prostate cancer. Talk with your doctor before starting.