Unravelling the enigma of proteinuria in burn patients

Hu and coworkers in the previous issue of Critical Care provide evidence for the clinical relevance of proteinuria in the outcome of burn patients. Proteinuria is a common finding after severe burns, appears within a short period and is detectable for several weeks. Proteinuria ranging from 0.5 to 3 to 4 g/day is initially of mixed type, then, after a week, gradually changes to tubular proteinuria. The clinical role of proteinuria is still unclear, mainly due to a lack of data on its pathogenesis. Recent studies have demonstrated an association between proteinuria and incidence of inhalation injury, sepsis, acute kidney injury and mortality rate. Proteinuria is considered the mirror of increased systemic capillary permeability, and possibly a direct marker of glomerular and tubular injury. Circulating plasma inflammatory mediators and pro-apoptotic factors reflecting burn injury, sepsis and acute kidney injury can affect the viability and function of tubular cells and podocytes. These studies highlight that proteinuria in burn patients should receive due consideration.


Proteinuria and clinical outcome in burn patients
In the past 10 years many reports have focused on the relationship between severe burns, acute kidney injury (AKI; staged using RIFLE or AKI classifi cation) and proteinuria. Th ese studies demonstrated a high incidence of AKI in burn patients, an association of AKI with dysfunction of other organs, a pathogenetic role of sepsis in AKI and, in particular, a direct correlation between AKI and mortality [4,5].
Th e study of Hu and coworkers [1] in the previous issue of Critical Care provides additional evidence on the clinical relevance of proteinuria on the outcome of burn patients. It explores in a large cohort of 369 severe burn patients (total burned surface area >30%) the determinants of proteinuria, and its infl uence on AKI staged according to the RIFLE classifi cation and on clinical outcome. Proteinuria, evaluated as positive urine dipstick readings, was absent in 31.5% of patients, mild (5 to 20 mg/dl) in 45.5% and heavy (>100 mg/dl) in 23%. Patients with proteinuria were older, with a higher incidence of inhalation injury, more severe burns and more incidence of sepsis (67%) than in patients with mild (46%) or absent (15%) proteinuria. In addition, proteinuric patients were more prone to develop AKI (incidence of 55%). In contrast, none of the patients without proteinuria developed AKI, suggesting that the persistent absence of proteinuria excludes the development of AKI. Th e mortality rate of patients with AKI was 29%, signifi cantly higher than that observed in patients without AKI (12.50%). Finally, patients with proteinuria had significantly longer mechanical ventilation durations, longer

Abstract
Hu and coworkers in the previous issue of Critical Care provide evidence for the clinical relevance of proteinuria in the outcome of burn patients. Proteinuria is a common fi nding after severe burns, appears within a short period and is detectable for several weeks. Proteinuria ranging from 0.5 to 3 to 4 g/day is initially of mixed type, then, after a week, gradually changes to tubular proteinuria. The clinical role of proteinuria is still unclear, mainly due to a lack of data on its pathogenesis. Recent studies have demonstrated an association between proteinuria and incidence of inhalation injury, sepsis, acute kidney injury and mortality rate. Proteinuria is considered the mirror of increased systemic capillary permeability, and possibly a direct marker of glomerular and tubular injury. Circulating plasma infl ammatory mediators and pro-apoptotic factors refl ecting burn injury, sepsis and acute kidney injury can aff ect the viability and function of tubular cells and podocytes. These studies highlight that proteinuria in burn patients should receive due consideration.

© 2010 BioMed Central Ltd
Unravelling the enigma of proteinuria in burn patients

Pathogenesis of proteinuria in burn patients
Proteinuria in thermally injured patients is considered the mirror of increased systemic capillary permeability [6]. However, proteinuria (or preferably proteinuria/ creatininuria ratio to correct for variation of urinary fl ow rate) is possibly a direct marker of renal injury. In fact, it has been demonstrated that proteinuria negatively correlates with both decreased creatinine and urea clearance as an index of loss of glomerular function and positively correlates with both Na+ and K+ fraction excretion refl ecting loss of tubular function [7]. A plethora of infl ammatory mediators (cyto kines, polypeptides, lipid mediators) targeting endothelial cells have been implicated in glomerular and peritubular capillary dysfunction [8]. Indeed, the plasma of burn patients contains proapoptotic factors at levels refl ecting the presence of sepsis and AKI [7]. Th ese circulating pro-apoptotic factors reduce the viability and function of tubular cells and podocytes by a mechanism dependent on up-regulation of pro-infl ammatory and pro-apoptotic genes and downregulation of apoptosis inhibitors. More over, they alter permeability by disrupting tight junctions and the polarity of tubular cells and by inducing nephrin loss in podocytes [7]. Th erefore, proteinuria refl ects a direct negative infl uence of plasma factors on renal paren chymal cells and requires further studies on new extra corporeal therapeutic approaches in burn patients [9][10][11].
In conclusion, the study of Hu and colleagues reminds us that proteinuria in burn patients should receive due consideration.