Microalbuminuria does not reflect increased systemic capillary permeability in septic shock

Molnár, Zsolt; Szakmány, Tamás; Heigl, P.

doi:10.1007/s00134-003-1651-0

Cited by 32 publications

(17 citation statements)

References 22 publications

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“…In healthy individuals, orosomucoid is present in urine in amounts 10-to 20-fold lower than albumin, but in our sepsis patients, orosomucoid excretion reached rates equal to or higher than those of albumin. The observed increase in urinary albumin excretion to amounts within the microalbuminuric range are in quantitative agreement with previous reports on sepsis patients (8 ) and on patients undergoing abdominal surgery (9 ).…”

Section: Description and Classificationsupporting

confidence: 92%

Monitoring Urinary Orosomucoid in Acute Inflammation: Observations on Urinary Excretion of Orosomucoid, Albumin, α1-Microglobulin, and IgG

et al. 2005

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Background: Inflammation-associated proteinuria in acute, nonrenal disease is a common but poorly understood phenomenon. We performed an observational study of the urinary excretion of orosomucoid (␣ 1 -acid glycoprotein), albumin, ␣ 1 -microglobulin (protein HC), and IgG to obtain quantitative and temporal data on these 4 proteins. Methods: Urine samples were collected at daily intervals for up to 23 days from 6 patients with surgeryinduced inflammation and at hourly intervals for a 24-h period from 7 sepsis patients. Urinary protein concentrations were assessed by immunoturbidimetry. Results: During surgery-induced inflammation, the increase and decrease in orosomucoid excretion mirrored changes in plasma C-reactive protein. Values for all 4 urinary proteins were increased in sepsis patients. The observed maximum increases in urinary protein excretion relative to the upper reference values were 280-fold for orosomucoid, 98-fold for ␣ 1 -microglobulin, 33-fold for albumin, and 26-fold for IgG. Conclusions: Orosomucoid, usually present in plasma and urine in much lower concentrations than albumin, is increased in urine to concentrations equal to or higher than albumin in proteinuria associated with acute inflammation. The pathophysiologic mechanisms responsible for this markedly increased excretion are unknown. Monitoring of urinary excretion of orosomucoid and other specific proteins, expressed as protein/creatinine ratios, may provide a window for clinically rele-

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Section: Description and Classificationsupporting

confidence: 92%

Monitoring Urinary Orosomucoid in Acute Inflammation: Observations on Urinary Excretion of Orosomucoid, Albumin, α1-Microglobulin, and IgG

et al. 2005

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“…Although urinary albumin excretion is an important hallmark of septic ARF [2,26,33], the molecular basis of albuminuria is not fully understood. In this regard, we reported that the loss of nephrin, another key molecule of SD [9], becomes evident during sepsis through a loss in nuclear localization of WT1, a key transcriptional factor of nephrin [ 16].…”

Section: Discussionmentioning

confidence: 99%

“…Sepsis-mediated renal injury is a typical phenotype of ARF that is associated with albuminuria [2,33]. During the sepsis, glomerular thrombosis becomes evident via up-regulations of inflammatory cytokines, and then local permeability and hypoxia enhance renal damage, associated with a loss in renal blood flow [26,30]. Even under low glomerular filtration, albuminuria is often noted in septic patients [2,33] and in rodents [31].…”

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confidence: 99%

Decreases in Podocin, CD2-Associated Protein (CD2AP) and Tensin2 May Be Involved in Albuminuria during Septic Acute Renal Failure

Kato

Mizuno-Horikawa

Mizuno

2011

The Journal of Veterinary Medical Science

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ABSTRACT. Podocytes have a peculiar structure constituting slit diaphragm (SD) and foot process (FP), and play essential roles in the glomerular filtration barrier. There is now ample evidence that SD-and FP-associated molecules, such as podocin and CD2-associated protein (CD2AP), are down-regulated during albuminuria of chronic kidney disease. However, it is still unclear whether these molecules are altered during acute renal failure (ARF) with albuminuria. Using lipopolysaccharide (LPS)-treated mice as a model of septic ARF, we provide evidence that the expression of SD-and FP-associated molecules becomes faint, along with albuminuria. In the LPS-treated mice, urinary albumin levels gradually increased, associated with the elevation of blood urea nitrogen levels, indicating the successful induction of albuminuria during septic ARF. In this pathological process, glomerular podocin expression became faint, especially at 36 hr post-LPS challenge (i.e., a peak of albuminuria). Likewise, LPS treatment led to a significant decrease in CD2AP, an anchorage between podocin and F-actin. With regard to this, tensin2 is a novel molecule that stabilizes F-actin extension. Interestingly, glomerular tensin2 expression levels were also decreased during the albuminuric phase, associated with losses of glomerular F-actin and synaptopodin under septic states. As a result, there were some lesions of podocytic FP effacement, as shown by electron microscopy. Based on these data, we emphasize the importance of concomitant decreases in podocin, CD2AP and tensin2 during septic ARF-associated proteinuria.

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“…Postulated mechanisms include acute changes in glomerular capillary permeability 52 and inflammatory insults. 53 In addition, clinical situations that lead to AKI may result in albuminuria due to diminished reabsorption by the injured proximal tubules. The potential utility of albuminuria as a test for the early diagnosis of AKI has not been systematically evaluated.…”

Section: Tubular Proteinuria For the Diagnosis Of Akimentioning

confidence: 99%

Tubular proteinuria in acute kidney injury: a critical evaluation of current status and future promise

Parikh

Coca

et al. 2010

Ann Clin Biochem

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The diagnosis and prognosis of acute kidney injury (AKI) by current clinical means is inadequate. Biomarkers of kidney injury that are easily measured and unaffected by physiological variables could revolutionize the management of AKI. Our objective was to systematically review the diagnostic and prognostic utility of urine and serum biomarkers of AKI in humans. We searched MEDLINE, PubMed and EMBASE databases (January 2000-August 2009) for biomarker studies that could be classified into the following categories: (a) confirmation of the diagnosis of established AKI, (b) early prediction of AKI, and (c) prognostication of AKI. We identified 54 manuscripts published since 2000 that met our inclusion and exclusion criteria. Urinary interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and Nacetyl-b-D-glucosaminidase (NAG) are potentially useful biomarkers for the diagnosis of established AKI. Urinary NGAL, IL-18, and liver-type fatty acid binding protein, and serum NGAL and cystatin C represent the most promising biomarkers for early prediction of AKI. Urinary cystatin C, a1-microglobulin, NAG and retinol-binding protein may be useful to predict severity and outcomes of AKI. In conclusion, we identified several studies of promising biomarkers for the diagnosis, prediction and prognostication of AKI. However, we note several limitations, including small sample sizes, inadequate gold standard, exclusion of patients with chronic kidney disease, incomplete statistical analyses, utilization of research-based assays and a paucity of studies examining prediction for clinical outcomes. Future studies will need to address these limitations in order for further progress to be made.

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Microalbuminuria does not reflect increased systemic capillary permeability in septic shock

Cited by 32 publications

References 22 publications

Monitoring Urinary Orosomucoid in Acute Inflammation: Observations on Urinary Excretion of Orosomucoid, Albumin, α1-Microglobulin, and IgG

Monitoring Urinary Orosomucoid in Acute Inflammation: Observations on Urinary Excretion of Orosomucoid, Albumin, α1-Microglobulin, and IgG

Decreases in Podocin, CD2-Associated Protein (CD2AP) and Tensin2 May Be Involved in Albuminuria during Septic Acute Renal Failure

Tubular proteinuria in acute kidney injury: a critical evaluation of current status and future promise

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