Reliability of different expert systems for profiling proteinuria in children with kidney diseases

Lun, Andreas; Suslovych, Marina; Drube, Jens; Ziebig, Reinhard; Pavičić, Leo; Ehrich, J. H. H.

doi:10.1007/s00467-007-0661-5

Cited by 14 publications

(17 citation statements)

References 23 publications

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“…Total protein (turbidimetry method), albumin, and alpha-1-microglobulin (immunoturbidimetry method) concentrations (mg/l) were measured in the urine and expressed as ratios to the urinary creatinine (Cr) concentration (mg/ mmol). Pathological total proteinuria was defined as urinary protein excretion ≥22 mg/mmol Cr, pathological albuminuria as urinary albumin excretion ≥2.2 mg/mmol Cr, and pathological alpha-1-microglobulinuria as urinary alpha-1-microglobulin ≥0.55 mg/mmol Cr [11]. The type of proteinuria was determined using the alpha-1-microglobulin/albumin algorithm (AAA), which has the highest accuracy (95-99%) for profiling proteinuria and differentiation between tubular and glomerular proteinuria in children with kidney diseases [11].…”

Section: Laboratory Investigationsmentioning

confidence: 99%

Profiling proteinuria in children after renal transplantation

et al. 2009

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Proteinuria is a common complication after renal transplantation (RTx). In adults, tubular proteinuria prevails and is associated with impaired graft survival. In the absence of studies on proteinuria profiling in transplanted children, we aimed at analyzing the types of proteinuria in transplanted children. Fifty-three children (11.8 years) were analyzed in a cross-sectional study. Morning urine was tested for total protein (PROT), albumin (ALB) and alpha-1-microglobulin (AMG). The type of proteinuria was assessed by the alpha-1-microglobulin/albumin algorithm (AAA): [AAA = AMG x 100/(AMG+ALB]. Median PROT, ALB, and AMG (in mg/mmol creatinine) were 20.0, 3.8, and 4.9, respectively. Pathological total proteinuria (>22 mg protein/mmol creatinine) was found in 47% of children (25/53). Only 20% of patients with pathological total proteinuria (5/25) had glomerular proteinuria, whereas 80% (20/25) had tubular proteinuria. Three of five children with glomerular proteinuria had chronic allograft nephropathy. Both AMG and albuminuria negatively correlated with the estimated glomerular filtration rate (eGFR) (p = 0.021 and 0.003, respectively). In conclusion, tubular proteinuria was present in 80% of children post-RTx and may be associated with impaired graft function; glomerular proteinuria is associated mainly with chronic allograft nephropathy.

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Section: Laboratory Investigationsmentioning

confidence: 99%

Profiling proteinuria in children after renal transplantation

et al. 2009

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“…This expert system uses urinary creatinine, albumin and alpha-1-microglobuline. It is able to distinguish between healthy subjects and patients with pathological proteinuria, as well as between patients suffering from glomerular or tubular proteinuria [29]. This expert system was applied to the patients to double check the results of the proteome analysis by a test used in routine diagnosis by us.…”

Section: Sequencing Of Peptidesmentioning

confidence: 99%

“…Proteinuria expert system AAA In addition to the measure of the urinary proteome pattern, we used the proteinuria expert system AAA [29] on the 20 patients used for validating the proteome pattern. This expert system uses urinary creatinine, albumin and alpha-1-microglobuline.…”

Section: Sequencing Of Peptidesmentioning

confidence: 99%

Urinary proteome pattern in children with renal Fanconi syndrome

Drube

Schiffer

Mischak

et al. 2009

Nephrology Dialysis Transplantation

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Background. The renal Fanconi syndrome (FS) is characterized by renal glucosuria, loss of electrolytes, bicarbonate and lactate, generalized hyperaminoaciduria and low-molecular-weight proteinuria. We studied the urinary low-molecular-weight proteome to identify excreted peptides indicative of a pathogenetic mechanism leading to tubular dysfunction. Methods. We established a urinary proteome pattern using capillary electrophoresis mass spectrometry (CE-MS) of 7 paediatric patients with cystinosis and 6 patients with ifosfamide-induced FS as the study group, and 54 healthy volunteers and 45 patients suffering from other renal diseases such as lupus nephritis (n = 8), focal segmental glomerulosclerosis (n = 27), minimal change disease (n = 7) and membranous glomerulonephritis (n = 3) as controls. Consequently, we conducted a blinded study consisting of 11 FS patients and 9 patients with renal disease other than FS. Additionally, we applied this pattern to 294 previously measured samples of patients with different renal diseases. Amino acid sequences of some marker proteins were obtained. Results. Specificity for detecting FS was 89% and sensitivity was 82%. The marker peptides constituting the proteome pattern are fragments derived from osteopontin, uromodulin and collagen alpha-1. Conclusions. CE-MS can be used to diagnose FS in paediatric patients and might be a future tool for the non-invasive diagnosis of FS. The reduced amount of the marker proteins osteopontin and uromodulin indicates loss of function of tubular excretion in all patients suffering from FS regardless of the underlying cause. In addition, the six different fragments of the collagen alpha-1 (I) chain were either elevated or reduced in the urine. This indicates a change of proteases in collagen degradation as observed in interstitial fibrosis. These changes were prominent irrespectively of the stages of FS. This indicates fibrosis as an early starting pathogenetic reason for the development of renal insufficiency in FS patients.

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“…Die differenzier te Proteinuriediagnostik mit etablierten Proteinmarkern, wie z. B. Albumin und α1Mikroglobulin erlaubt eine Differen zierung in glomeruläre und tubuläre Pro teinurie (AAAUrinexpertensystem; [2]). Die Erweiterung dieses Expertensystems mittels UPESSystem ("urine protein ex pert system", PROTIS®) erlaubt zusätzlich eine Differenzierung in renale und post renale Schädigungstypen [3].…”

Section: Etablierte Urinproteindiagnostikunclassified

“…Das spezifische Proteommuster zeigte in der geblinde ten Analyse eine Sensitivität von 82% und eine Spezifität von 89%. Darüber hinaus gewährten die Markerpeptide Einblicke in die Pathogenese der Niereninsuffizienz beim renalen FanconiSyndrom als ge meinsame Endstrecke von Tubulopathien mit unterschiedlichen Auslösern[24].Im Gegensatz zum AAAUrinexper tensystem, das nur zwischen glomerulä rer und tubulärer Proteinurie unterschei den kann[2], kann das Proteommuster das renale FanconiSyndrom von ande ren Tubulopathien unterscheiden[24]. Hiermit liegt also ein Proteommuster vor, mit dessen Hilfe schwere tubuläre Schä den identifiziert werden können, die zur Niereninsuffizienz führen können.…”

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Urinproteomanalytik

Ehrich

Schiffer

Drube

2010

Urologe

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Due to its accessibility and availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics in urology and nephrology. Here, we review the published findings of a reproducible, high-resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins - ranging from 0.8 to 17.0 kDA - using samples from renal patients analyzed by capillary electrophoresis coupled to mass spectrometry (CE-MS). CE-MS identified children with urodynamically relevant ureteric junction obstruction, vesicoureteric reflux of grades IV and V, glomerulopathies, tubulopathies, and chronic kidney disease. Our analysis revealed that the incorporation of urinary proteome analysis in the initial evaluation of children with urinary tract abnormalities will avoid side effects of radiological imaging techniques, reduce costs, and increase the quality-adjusted life years in this patient population. CE-MS can be recommended for clinical prospective studies on the analysis of naturally occurring urinary peptides in children with urinary tract diseases.

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Reliability of different expert systems for profiling proteinuria in children with kidney diseases

Cited by 14 publications

References 23 publications

Profiling proteinuria in children after renal transplantation

Profiling proteinuria in children after renal transplantation

Urinary proteome pattern in children with renal Fanconi syndrome

Urinproteomanalytik

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