Key test of kidney function has poor accuracy in patients with HIV

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Urine dipsticks may be a poor way of telling if HIV-positive patients have protein in their urine, an important marker of kidney disease, according to US research published in the February 1st edition of the Journal of Acquired Immune Deficiency Syndromes.

The investigators paired dipstick tests with protein-to-creatinine ratio tests obtained from the same patient within 24 hours and found that over a fifth of dipstick tests were failing to detect significant levels of protein in urine. They call for further research to find the best method of screening for kidney disease in HIV-positive patients.

Kidney disease is an increasingly important cause of illness and death in patients with HIV. A number of factors are responsible for this, including the general ageing of patients with HIV and a high prevalence amongst HIV-positive patients of other conditions capable of causing kidney disease.

Glossary

protein

A substance which forms the structure of most cells and enzymes.

creatinine

Breakdown product of creatine phosphate in muscle, usually produced at a fairly constant rate by the body (depending on muscle mass). As a blood test, it is an important indicator of the health of the kidneys because it is an easily measured by-product of muscle metabolism that is excreted unchanged by the kidneys.

renal

Relating to the kidneys.

false negative

When a person has a medical condition but is diagnosed as not having it.

sensitivity

When using a diagnostic test, the probability that a person who does have a medical condition will receive the correct test result (i.e. positive). 

Many individuals with kidney disease have protein in their urine, and this is often called proteinuria.

Compared with the general population, patients with HIV are significantly more likely to have proteinuria. A study conducted in HIV-positive women before effective anti-HIV treatment became available, found that significant levels of proteinuria (dipstick > 1+) were associated with a doubling in the risk of death. Another study found that proteinuria increased HIV-positive individuals’ risk of hospitalisation by 50%and their risk of cardiovascular illness by 40%.

Guidelines for the management of chronic kidney disease in patients with HIV issued by the Infectious Diseases Society of America recommend that urine dipstick tests should be used to detect kidney abnormalities in this population. This test should have the ability to detect kidney disease with a threshold of 1+ proteinuria.

But dipstick tests measure levels of albumin, and if urine is diluted the accuracy of these tests is affected. Furthermore, some forms of kidney disease, including tubular disorders, cannot be accurately diagnosed using dipstick tests.

Early detection is vital to the appropriate management of kidney disease in HIV-positive patients. It is therefore essential that healthcare staff are using the most accurate tests to detect such disorders.

Investigators from Johns Hopkins University compared the accuracy of two tests to measure protein in urine: a urine dipstick test and a protein-to-creatinine ratio test.

Their study included 165 HIV-positive patients who were receiving care at the Johns Hopkins Nephrology Clinic between 1995 and 2005. The patients included in the study had these two tests within the space of 24 hours.

The dipstick tests had a sensitivity to detect proteinuria of above 1+. The protein-to-creatinine ratio selected for comparison was 0.30 to 0.99.

Patients had a mean age of 45 years, 59% were male and 94% were African American.

Results showed that 13 of 64 patients (21%) with abnormally low protein-to-creatinine ratios had normal urine dipstick results.

“The results of our study suggest that the urine dipstick may not be an adequate tool for screening proteinuria in HIV-positive patients”, comments the investigators.

They add, “at clinically relevant lower levels of proteinuria…a threshold of >1+ proteinuria had a false-negative rate of 21%.”

This could have serious clinical consequences for a significant number of patients. The investigators write, “as many as one in five patients with proteinuria in this range may not be recognised and may be subject to delayed workup and treatment.”

The investigators conclude, “in sum, despite recommendations to use urine dipsticks for screening of renal disease in the HIV-positive population, poor validity of qualitative testing prevents any reliable single cutoff from serving as a reliable marker for predicting proteinuria at ranges where HIV providers may consider further workup of renal involvement.”

They therefore recommend, “it might be prudent to revisit guidelines that recommend using the dipstick as a screening tool. Further investigation of protein measurements, including comparison of random and 24-hour protein measurements, may help to determine the best method for screening and monitoring renal disease in HIV-infected patients.”

References

Siedner MJ et al. Poor validity of urine dipstick as a screening tool for proteinuria in HIV-positive patients. J Acquir Immune Defic Syndr 47: 261 – 263, 2008.