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

Proteinuria or albuminuria are used as tools to screen for chronic kidney disease. Their elevated levels are associated with increased risk of progression to End Stage Renal Disease (ESRD). Proteinuria is quantified in urine using urine protein-to-creatinine ratio (uPCR) or urine albumin-to-creatinine ratio (uACR). However, the existing literature provided poor clinical importance to non-albumin proteinuria (uNAP) and urine albumin-to-protein ratio (uAPR) for detection of other kidney related conditions.

The author David Ray Chang and colleague (2021) tried to fill this gay with their study titled “The ratio and difference of urine protein-to-creatinine ratio and albumin-to-creatinine ratio facilitate risk prediction of all-cause mortality” published in the journal “Nature”. The summary is below:

Objective

To characterize clinical features and adverse outcomes of patients with different levels of uNAP and uAPR.

Method

The study analyzed 2904 patients, between ages of 18 -90 years, 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.

• The study was a 3 × 3 classification matrix based on severity grades of both;
  1. uACR (normal: < 30; microalbuminuria: 30 to < 300; macroalbuminuria:
  ≥ 300 mg/g creatinine) and
  2. uPCR (normal: < 150; moderate: 150 to < 500; severe: ≥ 500 mg/g creatinine).
• Further, the study categorized patients into 3 groups:
  (1) concordant proteinuria,
  (2) non-albumin-predominant proteinuria, and
  (3) albumin-predominant proteinuria.

The authors also compared patients’ characteristics by using the uAPR and uNAP quartiles.

Finding

Most patients had concordant proteinuria quantified using both uACR and uPCR. In concordant group, uAPR increased gradually from 9.0% in patients without albuminuria and proteinuria to 62.7% in patients with severe albuminuria and proteinuria. Whereas, uNAP was gradually increased from 66.8, 164.5, 975.5 across the severity categories. In the non-albumin-predominant group, uAPR was low in patients with severe proteinuria but without albuminuria. Howeveer it elevated in patients with severe albuminuria but without proteinuria. Patients with severe proteinuria and normal albuminuria had the highest risk of all-cause mortality. The authors recommend simultaneous measurements of uPCR and uACR in daily practice to derive uAPR and uNAP, which can provide a better assessment of mortality.

• Clinical characteristics based on the uAPR quartile
  1. Low quartile: young, increased exposure to NSAID and radiocontrast
  2. Highest quartile: greater BMI, higher prevalence of advance CKD (Stage 3–5), diabetes, hypertension, and CVD with use of ACEI, ARB, diuretics, and anti-diabetic medications.
• Clinical characteristics based on the uNAP quartile
  Highest quartile: presence of chronic diseases such as CKD, diabetes, hypertension, and CVD, higher use of anti-hypertensive drugs and oral hypoglycemic medications. Patients in highest quartile with uNAP above 80.3 mg/g creatinine tended to have a higher prevalence and incidence of cancer.

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