Increased Urinary Excretion of Podocyte Markers in Normoalbuminuric Patients with Diabetes.
BACKGROUND
Podocyte injury plays a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). We investigated whether patients with diabetes mellitus (DM) without overt DN present podocyte markers in urine suggestive of early podocyte injury.


METHODS
We studied 71 patients with DM type 2 and normal urine albumin excretion (UAE) and 39 non-diabetic controls. The mRNA abundance of 3 podocyte-specific markers in urinary sediment (nephrin, podocin and synaptopodin) was measured with real-time quantitative PCR. All the subjects were categorized according to their urinary podocyte marker profile into 2 groups, those with only synaptopodin mRNA presence (synaptopodin only group) and those with nephrin and/or podocin mRNA presence in addition to synaptopodin in their urine (nephrin and/or podocin group).


RESULTS
Synaptopodin mRNA was detected in the urine of all the diabetics and controls. The presence of nephrin and/or podocin mRNA in urine was more frequent among DM patients compared to controls (53.5 vs. 30.8%, respectively; p = 0.022). Binary logistic regression analysis revealed that the only significant predictor of the presence of nephrin and/or podocin mRNA in urine was the presence of DM (OR 2.59, 95% CI 1.14-5.91, p = 0.024, adjusted for all risk factors). A strong correlation between nephrin and podocin urinary mRNA levels was noted (r = +0.796, p < 0.001).


CONCLUSIONS
This study demonstrated that urinary podocyte markers are more prevalent in diabetic patients with normal UAE compared to controls, and this may reflect early podocyte injury. DM is the only significant determinant of the presence of nephrin and/or podocin mRNA in urine in this population. Therefore, urinary podocyte markers may emerge as a valuable tool in the early diagnosis of DN.
Department of Acute Medicine, King's College Hospital, London, UK.
Eirini
E
Lioudaki
Konstantinos G
KG
Stylianou
Ioannis
I
Petrakis
Georgios
G
Kokologiannakis
Andreas
A
Passam
Dimitri P
DP
Mikhailidis
Eugene K
EK
Daphnis
Emmanouil S
ES
Ganotakis
D000368:Aged; D000419:Albuminuria / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000652:urine*; D003928:Diabetic Nephropathies / Q000473:pathology* / Q000652:urine*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000652:urine; D008297:Male; D008565:Membrane Proteins / Q000652:urine; D008840:Microfilament Proteins / Q000652:urine; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D015995:Prevalence; D012333:RNA, Messenger / Q000652:urine; D012307:Risk Factors
D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C407223:NPHS2 protein; D012333:RNA, Messenger; C503967:SYNPO protein, human; C113267:nephrin