In This Issue...

Rising Levels of Proteinuria Associated With Shorter Life Expectancy

Canadian researchers found a substantial and progressive decrease in life expectancy associated with the presence and severity of proteinuria (Am J Kidney Dis 2013;61:644–8). The findings could increase recognition of the health burden associated with proteinuria and help prioritize programs or funding involving this prevalent condition.

The investigators analyzed medical records for adults in Alberta, Canada without end-stage renal disease who had at least one outpatient measurement of proteinuria over a 4-year period. A cohort of 812,386 patients was then followed for at least 3 more years to identify all-cause mortality. The researchers estimated baseline proteinuria via urine albumin-creatinine ratio (ACR) or urine dipstick, with normal by ACR being defined as <30 mg/g, mild as 30–300 mg/g, and heavy as >300 mg/g. Negative urine dipstick was considered normal, trace or 1+ as mild, and 2+ as heavy.

Overall, 9.55% of men had mild and 2.03% had heavy proteinuria, while 7.48% and 1.22% of women had mild or heavy proteinuria, respectively. Life expectancy was substantially shorter for people with higher levels of proteinuria. Life expectancies for 40-year old men with normal, mild, or heavy proteinuria were 31.8, 23.2, and 16.6 years, respectively. Similarly, life expectancies for 40-year old women with normal, mild, or heavy proteinuria were 35.7, 25.2, and 18.2 years, respectively. The results mirror another recent study of the authors' in which they reported that lower levels of kidney function based on estimated glomerular filtration rate were associated with decreased life expectancy for both men and women.

Chimeric PCR Simplifies Testing for Huntington Disease

Researchers at ARUP Laboratories in Salt Lake City developed a chimeric, or triple repeat, primed polymerase chain reaction (PCR) process for determining expression of the Huntington (HTT) gene that provides a simple strategy to differentiate normal from expanded CAG alleles, thereby reducing the number of samples that still require expensive and labor-intensive Southern blot analysis (J Mol Diagn 2013;15:255–62).

Huntington disease is associated with abnormal expansions of the CAG repeat in the HTT gene. Samples that appear homozygous for a normal allele typically undergo additional testing to verify that PCR did not miss a CAG expansion. This approach might include testing the adjacent CCG loci and amplifying over the CCG+CAG region. If the sample still appears homozygous, the next step is Southern blot analysis. In contrast, the chimeric method, which has been described previously in fragile X screening, generates different sized amplicons due to multiple annealing sites on the template. In using the method in Huntington disease, the authors found that it distinguishes true homozygous alleles easily, and that only very large expanded alleles still require Southern blot analysis.

To test how well the chimeric assay performed, the authors analyzed 246 samples that previously had been analyzed by another method, had both homozygous and heterozygous samples, and a range of CAG repeats. The authors found that it correctly genotyped all samples, characterizing them all within ±1 CAG repeat. This gave the chimeric method "perfect" concordance with the other method, with 100% sensitivity and specificity in detecting CAG repeats.

The investigators determined that all adult-onset cases of Huntington disease with <101 CAG repeats can be genotyped easily and correctly sized. In this way, apparent homozygous samples can be detected reliably without additional CAG+CCG or Southern blot analysis.