Withstanding the test of time: Morning versus afternoon/evening urine protein-to-creatinine ratios in preeclampsia

Preeclampsia is a hypertensive disorder in pregnancy that comprises 2–8 % of pregnancy complications worldwide [1]. Renal components in the pathophysiology of preeclampsia, such as proteinuria and protein-to-creatine ratios, contribute an essential role in the diagnosis and timely management of preeclampsia [2]. Diagnosis of preeclampsia occurs when there is proteinuria of 300 mg or more per 24-hour urine collection, urine dipstick reading of 2+, or a urine protein to creatinine ratio (UPCR) of 0.3 or more [3].

The gold-standard laboratory test for determining the renal pathology of preeclampsia is analysis of all urine voided during a 24-hour time period [2]. It is often challenging in clinical practice to obtain all urine voided during a 24-hour time period due to high rates of patient nonadherence, poor collection techniques, and testing costs [4]. Spot UPCR collection is used instead as a surrogate measure [5]. Specific gravity is also calculated from the spot urine sample to ensure that the urine sample concentration is adequate for the determination of the UPCR, as specific gravity ranges that are either too concentrated or too dilute are likely to overestimate or underestimate UPCR [6]. In addition, increased uric acid concentration is commonly utilized as an indicator of altered kidney function in both pregnant patients with preeclampsia and non-pregnant patients with chronic renal diseases and hypertension [7].

Proteinuria, UPCR, and urine dipstick readings are essential in evaluating renal function in the nephrology of non-pregnant patients [8]. For non-pregnant patients, the collection of spot urine samples is an acceptable surrogate measure and widely used instead of the gold standard of 24-hour urine collection to estimate daily protein excretion and renal status [6]. In non-pregnant patients, there are mixed findings regarding time of day and urine creatinine measured levels. Some studies report better values for the morning, as creatinine concentration and urine specific gravity had the highest levels overnight and at 9:30 ante meridiem (AM) as compared to other morning and afternoon times [9]. Also, morning or first-void urine collection samples of protein and creatinine had higher correlations than non-morning samples with 24-hour urine protein and creatinine samples among those with renal disease [10]. Some studies report better values for the evening, as urine electrolytes including creatinine collected in the evening approximated 60 % of actual 24-hour urine samples [11]. Also, 12-hour evening urine creatinine samples had similar values to 24-hour collection samples [12]. Some studies report no difference for collection time as one study did not find any differences between morning and evening urine creatinine measurements [13]. Another study did not find any difference between morning or midday UPCR ratios from random samples when compared to 24-hour urine collection [14].

Similar to chronic renal diseases, pregnancy-induced renal changes in the setting of preeclampsia facilitate the increase in tubular permeability, renal blood flow, and glomerular filtration rates which correlate with an increase in serum creatinine and a decrease in urine creatinine [5], [8]. These laboratory findings may potentially be affected by the timing of collection secondary to time-sensitive filtration patterns of normal renal physiology [5], [8]. There does not appear to be any literature on the comparison of spot UPCR values regarding morning versus afternoon and/or evening collection times in pregnancy. There also does not appear to be any literature on the comparison of either urine specific gravity or serum uric acid values regarding morning versus afternoon and/or evening collection times in either non-pregnant patients or pregnant patients. The primary aim of this study is to compare the morning spot UPCR to combined afternoon and evening spot UPCR in pregnant patients diagnosed with preeclampsia. The secondary aims of this study are to compare urine specific gravity and serum uric acid values of morning to combined afternoon and evening values in pregnant patients diagnosed with preeclampsia.

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