Controversies in Nephrology

Timed Urine Collections Are Not Needed to Measure Urine Protein Excretion in Clinical Practice

All of the methods for quantitative evaluation of proteinuria (or albuminuria) suffer from some methodological flaw. A new modification that improves the accuracy of the urine protein-to-creatinine ratios for predicting 24-hour urinary protein excretion has been examined in a well-characterized cohort of patients with glomerular disease. This approach needs to be systematically compared with other techniques before it can be universally recommended to replace the time-honored 24-hour urine collection.

Urine 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.

Cross-sectional study.

3,481 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study.

ACR and PCR.

We examined the association between ACR and PCR with measures of common CKD complications: serum hemoglobin, bicarbonate, parathyroid hormone, phosphorus, potassium, and albumin.

Restricted 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.

Mean 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.

Participants largely had moderate CKD with low values for ACR and PCR, so results may not be generalizable to all CKD populations.

In 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.

A previous study has shown that shorter bevacizumab infusions (0.5 mg/kg/min) can be safely administered without increasing the risk of infusion-related hypersensitivity reactions (HSRs). However, the risk of proteinuria and hypertension in patients receiving shorter infusions of bevacizumab is undetermined.

This was a multicenter, prospective, observational study in patients receiving <10 mg/kg of bevacizumab infused over 0.5 mg/kg/min. Patients were observed until discontinuation of bevacizumab for progression of cancer or toxicity. The incidence of hypertension and proteinuria was compared with a prior cohort of patients who had received standard duration infusions of bevacizumab.

Sixty-three patients received a total of 392 doses of shorter bevacizumab infusions. Nineteen (30.2%) patients experienced proteinuria while receiving bevacizumab. Out of 19 patients, 13 had grade 1 and 6 had grade 2 proteinuria. None of the patients experienced grade 3 or 4 proteinuria. Hypertension was reported in 32 (50.8%) patients receiving bevacizumab. Twelve (19%) patients developed grade 3 or greater hypertension on bevacizumab. The incidence of proteinuria and hypertension was 38.3% and 56.6%, respectively, in patients (N = 120, 1347 infusions) receiving standard duration infusions of bevacizumab.

Shorter bevacizumab infusions (0.5 mg/kg/min) do not increase the risk of proteinuria and hypertension.

The 24-h urine protein-to-creatinine ratio is the gold standard in evaluating proteinuria in lupus nephritis; however, the urine collection is inconvenient to the patient. Random spot urine protein-to-creatinine ratios, although convenient, have poor agreement with the 24-h ratios in these patients. Here, we sought to define a timed collection interval providing accurate and precise data and patient convenience. Urine from 41 patients, in 2 medical centers, with biopsy-proven lupus nephritis was collected at 6-h intervals for 24 h. The protein-to-creatinine ratio of each short collection was then compared with that of a 24-h collection made by combining the 6-h samples. A first morning void and spot urine samples were collected before and after the 24-h collection, respectively. There was significant diurnal variation with peak proteinuria at 6–12 h and nadir at 18–24 h. Each 6-h collection showed excellent correlation and concordance with the 24-h protein-to-creatinine ratio, but the 12–24-h interval had the best agreement. In contrast to the random spot urines, the first morning void also had excellent correlation and concordance, but underestimated the 24-h protein-to-creatinine ratio. Our study shows that a 12-h overnight urine collection is the best surrogate, with excellent agreement with the 24-h protein-to-creatinine ratio, and it is convenient for patients. There was little variability between centers, an important feature for clinical trials.