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The ratio and difference of urine protein-to-creatinine ratio and albumin-to-creatinine ratio facilitate risk prediction of all-cause mortality.

ABSTRACT: The role of the difference and ratio of albuminuria (urine albumin-to-creatinine ratio, uACR) and proteinuria (urine protein-to-creatinine ratio, uPCR) has not been systematically evaluated with all-cause mortality. We retrospectively analyzed 2904 patients with concurrently measured uACR and uPCR from the same urine specimen in a tertiary hospital in Taiwan. The urinary albumin-to-protein ratio (uAPR) was derived by dividing uACR by uPCR, whereas urinary non-albumin protein (uNAP) was calculated by subtracting uACR from uPCR. Conventional severity categories of uACR and uPCR were also used to establish a concordance matrix and develop a corresponding risk matrix. The median age at enrollment was 58.6 years (interquartile range 45.4-70.8). During the 12,391 person-years of follow-up, 657 deaths occurred. For each doubling increase in uPCR, uACR, and uNAP, the adjusted hazard ratios (aHRs) of all-cause mortality were 1.29 (95% confidence interval [CI] 1.24-1.35), 1.12 (1.09-1.16), and 1.41 (1.34-1.49), respectively. For each 10% increase in uAPR, it was 1.02 (95% CI 0.98-1.06). The linear dose-response association with all-cause mortality was only observed with uPCR and uNAP. The 3 × 3 risk matrices revealed that patients with severe proteinuria and normal albuminuria had the highest risk of all-cause mortality (aHR 5.25, 95% CI 1.88, 14.63). uNAP significantly improved the discriminative performance compared to that of uPCR (c statistics: 0.834 vs. 0.828, p-value = 0.032). Our study findings advocate for simultaneous measurements of uPCR and uACR in daily practice to derive uAPR and uNAP, which can provide a better mortality prognostic assessment.

SUBMITTER: Chang DR

PROVIDER: S-EPMC8041921 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceAlthough cumulative evidence suggests that elevated urinary albumin-to-creatinine ratio (UACR) in the normal range (<30 mg/g) may be associated with an increased risk of mortality, few studies have investigated whether cardiovascular health (CVH) modifies the harmful outcomes of high-normal UACR.ObjectiveTo investigate associations of traditionally normal UACR and CVH with all-cause mortality.Design, setting, and participantsThis cohort study used National Health and Nutrition Examination Survey data from 2005 through 2018 and linked mortality information until 2019. Data were analyzed from March 1 through October 31, 2023. The study included adult participants aged 20 to 79 years with a normal UACR (<30 mg/g) based on Kidney Disease: Improving Global Outcomes criteria.ExposuresThe UACR was treated as a continuous variable and categorized into tertiles delineated as low (<4.67 mg/g), medium (4.67-7.67 mg/g), and high (7.68 to <30 mg/g). Cardiovascular health was assessed using Life's Essential 8 scores and grouped as poor (0-49 points), moderate (50-79 points), and ideal (80-100 points).Main outcomes and measuresMultivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of UACR with all-cause mortality in total participants and as stratified by CVH groups.ResultsThe study included 23 697 participants (mean [SD] age, 45.58 [15.44] years; 11 806 women [49.7%] and 11 891 men [50.3%]). During the median 7.8 years (range, 4.5-11.1 years) of follow-up, 1403 deaths were recorded. Near-linear associations were observed for continuous UACR and CVH with all-cause mortality. Compared with the low UACR group, high UACR in the normal range showed an increased mortality risk in the moderate and poor CVH groups (CVH [50-79]: HR, 1.54 [95% CI, 1.26-1.89]; CVH [0-49]: HR, 1.56 [95% CI, 1.10-2.20]), with a significant multiplicative interaction of UACR and CVH (P < .001).Conclusions and relevanceThe findings suggest that high UACR within the normal range is associated with a significantly increased risk of all-cause mortality, with the association more pronounced in adults with poor CVH status. These findings highlight the importance of risk management for early kidney dysfunction, particularly among individuals with poor CVH.

Project description:BackgroundUrine albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR) are important markers of kidney damage and are used for prognosis in persons with chronic kidney disease (CKD). Despite how commonly these measurements are done in clinical practice, relatively few studies have directly compared the performance of these 2 measures with regard to associations with clinical outcomes, which may inform clinicians about which measure of urinary protein excretion is best. We studied the association of ACR and PCR with common complications of CKD.Study designCross-sectional study.Setting & participants3,481 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study.PredictorsACR and PCR.OutcomesWe examined the association between ACR and PCR with measures of common CKD complications: serum hemoglobin, bicarbonate, parathyroid hormone, phosphorus, potassium, and albumin.MeasurementsRestricted cubic spline analyses adjusted for estimated glomerular filtration rate (eGFR; calculated by the MDRD [Modification of Diet in Renal Disease] Study equation) were performed to study the continuous association with our predictors with each outcome.ResultsMean eGFR was 43±13 (SD)mL/min/1.73 m2 and median values for PCR and ACR were 140 and 46 mg/g, respectively. In continuous analyses adjusted for eGFR, higher ACRs and PCRs were similar and both were associated with lower serum hemoglobin, bicarbonate, and albumin levels and higher parathyroid hormone, phosphorus, and potassium levels. Across all outcomes, the associations of ACR and PCR were similar, with only small absolute differences in the outcome measure. Similar associations were seen in patients with diabetes mellitus.LimitationsParticipants largely had moderate CKD with low values for ACR and PCR, so results may not be generalizable to all CKD populations.ConclusionsIn persons with CKD, ACR and PCR are relatively similar in their associations with common complications of CKD. Thus, routine measurement of PCR may provide similar information as ACR in managing immediate complications of CKD.

Project description:Background and objectivesBecause there is substantial biologic intraindividual variation in albumin excretion, randomized trials of albuminuria-reducing therapies may need multiple urine samples to estimate daily urinary albumin excretion. Mailing spot urine samples could offer a convenient and cost-effective method to collect multiple samples, but urine albumin-to-creatinine ratio stability in samples stored at ambient temperatures for several days is unknown.Design, setting, participants, & measurementsPatients with kidney disease provided fresh urine samples in two tubes (with and without boric acid preservative). Reference aliquots from each participant were analyzed immediately, whereas remaining aliquots were subject to different handling/storage conditions before analysis, including delayed processing for up to 7 days at three different storage temperatures (4°C, 18°C, and 30°C), multiple freeze-thaw cycles, and long-term frozen storage at -80°C, -40°C, and -20°C. We calculated the mean percentage change in urine albumin-to-creatinine ratio for each condition, and we considered samples stable if the 95% confidence interval was within a ±5% threshold.ResultsNinety-three patients provided samples with detectable albuminuria in the reference aliquot. Median (interquartile range) urine albumin-to-creatinine ratio was 87 (20-499) mg/g. The inclusion of preservative had minimal effect on fresh urine albumin-to-creatinine ratio measurements but reduced the changes in albumin and creatinine in samples subject to processing delay and storage conditions. The urine albumin-to-creatinine ratio was stable for 7 days in samples containing preservative at 4°C and 18°C and 2 days when stored at 30°C. It was also stable in samples with preservative after three freeze-thaw cycles and in frozen storage for 6 months at -80°C or -40°C but not at -20°C.ConclusionsMailed urine samples collected with preservative and received within 7 days if ambient temperature is ≤18°C, or within 2 days if the temperature is higher but does not exceed 30°C, are suitable for the measurement of urine albumin-to-creatinine ratio in randomized trials. Preserved samples frozen to -40°C or -80°C for 6 months before analysis also seem suitable.

Project description:BackgroundAlthough measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead.ObjectiveTo develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging.DesignIndividual participant-based meta-analysis.Setting12 research and 21 clinical cohorts.Participants919 383 adults with same-day measures of ACR and PCR or dipstick protein.MeasurementsEquations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g).ResultsMedian ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR.LimitationDiverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample.ConclusionUrine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis.Primary funding sourceNational Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

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The ratio and difference of urine protein-to-creatinine ratio and albumin-to-creatinine ratio facilitate risk prediction of all-cause mortality.

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