Consensus Document. Implication of proteinuria in the diagnosis and monitoring of the chronic kidney disease (CKD)

Abstract

Chronic kidney disease (CKD) is a clinical entity secondary to multiple etiologies, characterized for being still in early stages and, without an adequate treatment, it frequently follows a progressive course that leads to an irreversible failure of the organ function and requires a substitute treatment (dialysis or renal transplant). CKD is a risk factor for cardiovascular disease (CV); this is the most frequent complication, including the principal cause of death for these patients. The two most prevalent causes of CKD are diabetes mellitus and arterial hypertension. CKD constitutes a problem in Public Health, not only because of its potential need for dialysis and transplant in the long run, but also for the cardiovascular co-morbidity implicated from its initial stages. Our Scientific and Professional National Societies have recommended, in a previous document published in 2010, that the evaluation of the renal function be estimated by means of the glomerular filtrate index (GFI) by a formula, taking into account the measure of plasmatic creatinine. For our societies, the recommended formula in adults is MDRD (Modification of Diet in Renal Disease). In this one, the only parameter that is measured is the determination of creatinine in blood; although recient opinions highlight the potential superiority of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), particularly when the renal function is slightly affected. Anyway, and despite which is the best formula to be used, the evaluation of the renal function is an image of the functional condition of the kidney at a specific time, and the accumulated evidences offer little or no possibility of knowing the evolution of the functional and clinical situation. The persistent presence of increased concentrations of protein or albumin in urine is a signal of renal injury and constitutes, together with GFI, the best strategy on which both the diagnosis and prediction of CKD rely on.
In order to determine the loss of proteins or albumin in urine, test strips in urine samples taken at ramdom or from first urine morning samples or from 24-hours urine samples were used depending on the clinical situation. It depends whether we are performing a population screening, a specialized diagnostic confirmation, the monitoring of a classic treatment or the evaluation of a new antiproteinuric strategy.
It should be highlighted that the use of test strips for the screening of total proteins in urine has already been evaluated by different means. These have compared the diagnostic precision of the test strip with the measure of protein in a 24-hour urine in populations with a high prevalence of proteinuria. However, the results show a variable sensitivity and specificity. That is why the majority of the clinical practice guides suggest the confirmation of a positive result by means of a quantitative measure. On the other hand, the semiquantitative measure of albumin by means of test strips based on immunological or non-immunological procedures is capable of detecting small concentrations of albumin (the mean of limit of detection is 20 mg/l). Moreover, the positive and negative predictive value is variable depending on the concentration used to define albuminuria.
Taking into account the concepts mentioned above, in those cases that are considered necessary to evaluate small amounts of protein loss in the urine, the determination of urinary albumin and of the ratio albumin/creatinine should be requested; preferably in the first morning urine.
Each clinical situation requires preferential handlings and methodologies, when we try to perform diagnostic confirmation or monitoring of the already existing kidney disease the use of the Albumin/Creatinin ratio or the Protein/Creatinin ratio in urine is recommended in the first morning urine in adults and little children, and in the 24-hour urine in children with adequate control of sphincters. It is recommended that the concentration of protein or albumin in urine be referred to the concentration of urinary creatinine to minimize the errors depending on the volume and on the hydration status of the patient.
The results will be expressed in mg/g, or else mg/mmol, depending on the types of units used by each laboratory. The results should be expressed without decimals (mg/g) or with one decimal (mg/mmol). If the samples are not processed the same day of their obtainment, should be stored at temperatures between 2 °C and 8 °C for 7 days. It is also advisable to quit the use of the terms microalbuminuria and macroalbuminuria, and replace them instead for albuminuria, as the urinary loss of albumin constitutes a continuous variable of renal and cardiovascular risk. This document provides a general and updated vision of the role of proteinuria in the diagnosis and monitoring of the CKD.