Understanding the Mechanisms of Proteinuria: Therapeutic Implications

Abstract

A large body of evidence indicates that proteinuria is a strong predictor of morbidity, a cause of inflammation, oxidative stress and progression of chronic kidney disease, and development of cardiovascular disease. The processes that lead to proteinuria are complex and involve factors such as glomerular hemodynamic, tubular absorption, and diffusion gradients. Alterations in various different molecular pathways and interactions may lead to the identical clinical end points of proteinuria and chronic kidney disease. Glomerular diseases include a wide range of immune and nonimmune insults that may target and thus damage some components of the glomerular filtration barrier. In many of these conditions, the renal visceral epithelial cell (podocyte) responds to injury along defined pathways, which may explain the resultant clinical and histological changes. The recent discovery of the molecular components of the slit diaphragm, specialized structure of podocyte-podocyte interaction, has been a major breakthrough in understanding the crucial role of the epithelial layer of the glomerular barrier and the pathogenesis of proteinuria. This paper provides an overview and update on the structure and function of the glomerular filtration barrier and the pathogenesis of proteinuria, highlighting the role of the podocyte in this setting. In addition, current antiproteinuric therapeutic approaches are briefly commented.

Predicting the development of acute kidney injury in liver cirrhosis – an analysis of glomerular filtration rate, proteinuria and kidney injury biomarkers

“…The aetiology of cirrhosis was alcohol (37%), immune‐mediated (autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis) (23%), viral hepatitis (17%), cryptogenic cirrhosis (11%) and miscellaneous causes (12%). All patients had Child‐Pugh B or C liver disease, 65% (22 of 34) had grade 2 to 3 ascites . Of the 34 patients enrolled, 18 (53%) developed AKI based on serum creatinine ( n = 16) or urine volume criteria ( n = 2).…”

“…All patients had Child-Pugh B or C liver disease, 65% (22 of 34) had grade 2 to 3 ascites. 24 Of the 34 patients enrolled, 18 (53%) developed AKI based on serum creatinine (n = 16) or urine volume criteria (n = 2). Ninety-four per cent of the patients (17/ 18) had stage 1 AKI and one patient (1/18) had stage 3 AKI at the time of sample analysis.…”

“…Ninety-one per cent of patients (29/32) had baseline proteinuria as defined by an enrolment urine protein: creatinine ratio greater than normal (>15). It was significantly higher in those who developed AKI [AKI median urine protein:creatinine ratio 55 (36-189) vs. No-AKI 17 (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), P = 0.0005].…”

Benefits of pomegranate (Punica granatum Linn) fruit extracts to weight changes, total protein, and uric acid in white rats (Rattus norvegicus) as an animal model of acute renal failure

“…The damage of the glomerulus causes the glomerular selectivity walls fail to prevent proteins with large molecular weight to be out of the urine. It induces the leakage of plasma proteins which leads to urine and generates a condition of proteinuria [25]. …”

“…P2 gets the treatment with the best results to reduce the levels of the TPs even though the outcome of the four treatment groups is still within the normal values. The normal levels of the total blood serum proteins of male strain Wistar rats range from 5.0 to 8.0 g/dL [25]. It shows that the combination of various active ingredients in pomegranates has a good effect because it can form a synergistic formulation [26].…”