Correlation between 24-hour proteinuria and spot urine albumin to creatinine ratio in systemic light chain amyloidosis.

Abstract

8549 Background: Proteinuria evaluation is essential for diagnosing and monitoring of renal involvement in light chain (AL) amyloidosis. A 24 hour protein collection (24h UP) is the gold standard for proteinuria assessment however it is cumbersome and can be inaccurate. A spot urine albumin to creatinine ratio (uACR) has been proposed as a convenient method to estimate 24hUP. We aimed to validate the correlation between uACR and 24hUP in a large cohort of patients. Methods: We retrospectively studied systemic AL amyloidosis patients evaluated between 2010 and 2019 at Mayo Clinic, with a uACR and 24hUP collected less than 7 days apart. Linear regression analysis was used to construct a prediction model for 24hUP with uACR as the primary predictor. Possible confounders (age, gender, body mass index, morning versus afternoon spot urine collection, estimated glomerular filtration rate) for the primary relationship between uACR and 24h UP were evaluated in the model. We used receiver operating characteristic (ROC) analysis to identify the best uACR cutoff to predict significant proteinuria (defined as a 24hUP > 500mg). Results: We included 665 patients, with a median age of 66 years (IQR 59-72). The spot urine was collected in the morning (before 1200 hours) in 382 (57%) patients, and in the afternoon in 283 (43%) patients. The median 24hUP was 321 (IQR 129-2512.5) mg, median uACR was 107 (IQR 13.5-1845) mg/g, and median serum creatinine was 1.2 (IQR 1-1.8) mg/dL. The uACR correlated well with 24h UP (Pearson’s r= 0.83, 95% CI 0.80-0.85). Linear regression showed that E (24h UPi) = 362 + 1.05(uACRi), and this model was statistically and clinically significant (p < 0.001 and R2 of 0.68, respectively). Age, gender, body mass index, eGFR, and time of day of spot urine collection did not confound the primary relationship between uACR and 24hUP, and no collinearity was observed. A uACR cutoff of > 280 mg/g was the best predictor of a 24hUP > 500 mg (area under the ROC curve 0.98, sensitivity 92%, specificity 97%). For simplicity, we assessed the predictive value of uACR > 300 mg/g for 24h UP > 500 mg. Among patients with 24huACR > 300 mg/g 264 (96%) had a 24hUP > 500 mg, and 31 (7%) of patients with uACR < 300 mg/g had a 24h UP > 500 mg (p < 0.001). Conclusions: In systemic AL amyloid patients, we showed that uACR on a random urine sample correlated well with 24h UP, and can be used to estimate proteinuria with a linear regression model. Based on these findings, and the convenience of uACR testing for patients, we propose that uACR should be used to monitor renal response to AL amyloidosis therapy.