Variability of Urinary Creatinine in Healthy Individuals

Many urinary biomarkers are adjusted for dilution using creatinine or specific gravity. The aim was to evaluate the variability of creatinine excretion, in 24 h and spot samples, and to describe an openly available variability biobank. Urine and blood samples were collected from 60 healthy non-smoking adults, 29 men and 31 women. All urine was collected at six time points during two 24 h periods. Blood samples were also collected twice and stored frozen. Analyses of creatinine in urine was performed in fresh urine using an enzymatic method. For creatinine in urine, the intra-class correlation (ICC) was calculated for 24 h urine and spot samples. Diurnal variability was examined, as well as association with urinary flow rate. The creatinine excretion rate was lowest in overnight samples and relatively constant in the other five samples. The creatinine excretion rate in each individual was positively correlated with urinary flow rate. The creatinine concentration was highest in the overnight sample and at 09:30. For 24 h samples the ICC was 0.64, for overnight samples it was 0.5, and for all spot samples, it was much lower. The ICC for urinary creatinine depends on the time of day of sampling. Frozen samples from this variability biobank are open for researchers examining normal variability of their favorite biomarker(s).

OR29-07 A Novel Estimate of Creatinine Excretion to Determine Adequacy of 24-Hr Urine Collection

24-hour urine collections are used to assess excretion of various analytes. Although concomitant measurement of creatinine excretion adjusted for body weight (BW) is utilized to determine adequacy of collection, no gold standard exists for determining completeness of a collection. Use of current reference ranges for daily creatinine excretion/BW of 15–20 mg creatinine/kg BW/day in women and 20–25 mg creatinine/kg/d in men established prior to the rising prevalence of obesity has resulted in a large proportion of contemporary individuals appearing to have “incomplete” urine collections. Our objective was to evaluate the range of creatinine excretion in accurately collected urine specimen from adults with a wide spread of age and BW, and to generate an equation that accurately predicts 24-hour urine creatinine excretion rate from readily available clinical parameters to aid in assessing adequacy of a 24-hour urine collection. We analyzed data from participants who completed two consecutive 24-hour urine collections while consuming a fixed metabolic diet during inpatient research admissions. Results from participants with 24-hour urine creatinine excretion rate differing by >10% between the two consecutive collections were excluded. In the initial 115 pairs of inpatient 24-hour urine collections (50 female, 65 male) participants, creatinine excretion/BW fell outside the currently accepted reference ranges in >50% of collections. The proportion below the reference range increased with higher BMI. In this derivation dataset, linear regression models were then constructed to predict 24-hr urine creatinine excretion from race, sex, age, weight and height. Reliable prediction of observed 24-hr urine creatinine excretion was confirmed in a validation dataset that included 50 pairs of 24-hour urine samples similarly collected in an inpatient research setting. This new prediction model performed significantly better than the currently used reference ranges in a large outpatient dataset including 1,399 pairs of 24-hour urine collections. In women, actual creatinine excretion fell within the 95% prediction intervals for our derived equation in 90% of cases using the new interval vs 46% using the current reference range. The corresponding values were 90% and 33% in men. In both genders, the superiority of the new prediction over the current reference range was more pronounced at higher BMI. We therefore propose revision of currently used criteria to define adequacy of 24-hour urine collection to account for the impact of obesity. The proposed equation incorporates readily available demographic parameters to predict urine creatinine excretion. These findings have wide implications on patient care and research studies, and future studies should test this equation in different settings, diets, and populations.

Complementary Biomarker Assessment of Components Absorbed from Diet and Creatinine Excretion Rate Reflecting Muscle Mass in Dialysis Patients

To prevent protein energy malnutrition (PEM) and accumulation of waste products, dialysis patients require diet adjustments. Dietary intake assessed by self-reported intakes often provides biased information and standard 24-h urinary excretion is inapplicable in dialysis patients. We aimed to assess dietary intake via a complementary, less biased biomarker method, and to compare this to dietary diaries. Additionally, we investigated the prospective association of creatinine excretion rate (CER) reflecting muscle mass with mortality. Complete intradialytic dialysate and interdialytic urinary collections were used to calculate 24-h excretion of protein, sodium, potassium, phosphate and creatinine in 42 chronic dialysis patients and compared with protein, sodium, potassium, and phosphate intake assessed by 5-day dietary diaries. Cox regression analyses were employed to investigate associations of CER with mortality. Mean age was 64 ± 13 years and 52% were male. Complementary biomarker assessed (CBA) and dietary assessed (DA) protein intake were significantly correlated (r = 0.610; p < 0.001), but there was a constant bias, as dietary diaries overestimated protein intake in most patients. Correlations were found between CBA and DA sodium intake (r = 0.297; p = 0.056), potassium intake (r = 0.312; p = 0.047) and phosphate uptake/intake (r = 0.409; p = 0.008). However, Bland-Altman analysis showed significant proportional bias. During a median follow-up of 26.6 (25.3–31.5) months, nine dialysis patients (23%) died. CER was independently and inversely associated with survival (HR: 0.59 (0.42–0.84); p = 0.003). Excretion measurements may be a more reliable assessment of dietary intake in dialysis patients, as this method is relatively free from biases known to exist for self-reported intakes. CER seems to be a promising tool for monitoring PEM.