Urinary congophilia in women with hypertensive disorders of pregnancy and preexisting proteinuria or hypertension

Abstract

Congophilia indicates the presence of amyloid protein, which is an aggregate of misfolded proteins, that is implicated in the pathophysiologic condition of preeclampsia. Recently, urinary congophilia has been proposed as a test for the diagnosis and prediction of preeclampsia. The purpose of this study was to determine whether urine congophilia is present in a cohort of women with preeclampsia and in pregnant and nonpregnant women with renal disease. With the use of a preeclampsia, chronic hypertension, renal disease, and systemic lupus erythematosus cohort, we analyzed urine samples from healthy pregnant control subjects (n= 31) and pregnant women with preeclampsia (n= 23), gestational hypertension (n= 10), chronic hypertension (n= 14), chronic kidney disease; n= 28), chronic kidney disease with superimposed preeclampsia (n= 5), and chronic hypertension and superimposed preeclampsia (n= 12). Samples from nonpregnant control subjects (n= 10) and nonpregnant women with either systemic lupus erythematosus with (n= 25) and without (n= 14) lupus nephritis were analyzed. For each sample, protein concentration was standardized before it was mixed with Congo Red, spotted to nitrocellulose membrane, and rinsed with methanol. The optical density of the residual Congo Red stain was determined; Congo red stain retention was calculated, and groups were compared with the use of the Mann-Whitney test or Kruskal-Wallis analysis of Variance test, as appropriate. Congophilia was increased in urine from women with preeclampsia (median Congo red stain retention, 47%; interquartile range, 22-68%) compared with healthy pregnant control subjects (Congo red stain retention: 16%; interquartile range, 13-21%; P= .002), women with gestational hypertension (Congo red stain retention, 20%; interquartile range, 13-27%; P= .008), or women with chronic hypertension (Congo red stain retention, 17%; interquartile range, 12-28%; P= .01). There were no differences in Congo red retention between pregnant women with chronic hypertension and normal pregnant control subjects (Congo red stain retention, 17% [interquartile range, 12-28%] vs 16% [interquartile range, 13-21%], respectively; P= .72). Congophilia was present in pregnant women with chronic kidney disease (Congo red stain retention, 32%; interquartile range, 14-57%), being similar to values found in women with preeclampsia (P= .22) and for women with chronic kidney disease and superimposed preeclampsia (Congo red stain retention, 57%; [interquartile range, 29-71%; P= .18). Nonpregnant women with lupus nephritis had higher congophilia levels compared with nonpregnant female control subjects (Congo red stain retention, 38% [interquartile range, 17-73%] vs 9% [7-11%], respectively; P < .001) and nonpregnant women with systemic lupus erythematosus without nephritis (Congo red stain retention, 38% [interquartile range, 17-73%] vs 13% [interquartile range, 11-17%], respectively; P= .001). A significant positive correlation was observed between congophilia and protein:creatinine ratio (Spearman rank correlations, 0.702; 95% confidence interval, 0.618-0.770; P < .001). This study confirms that women with preeclampsia and chronic kidney disease without preeclampsia have elevated urine congophilia levels compared with healthy pregnant women. Nonpregnant women with lupus nephritis also have elevated urine congophilia levels compared with healthy control subjects. An elevated Congo Red stain retention may not be able to differentiate between these conditions; further research is required to explore the use of congophilia in clinical practice.