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2017 ; 18
(1
): 172
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Urinary neprilysin in the critically ill patient
#MMPMID28545475
Pajenda S
; Mechtler K
; Wagner L
BMC Nephrol
2017[May]; 18
(1
): 172
PMID28545475
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BACKGROUND: Critically ill patients in intensive care face hazardous conditions.
Among these, acute kidney injury (AKI) is frequently seen as a result of sepsis.
Early diagnosis of kidney injury is of the utmost importance in the guidance of
interventions or avoidance of treatment-induced kidney injury. On these grounds,
we searched for markers that could indicate proximal tubular cell injury.
METHODS: Urine samples of 90 patients admitted to the intensive or intermediate
care unit were collected over 2 to 5 days. The biomarker neprilysin (NEP) was
investigated in urine using several methods such as dot blot, ELISA and
immunofluorescence of urinary casts. Fifty-five healthy donors acted as controls.
RESULTS: NEP was highly significantly elevated in the urine of patients who
suffered AKI according to the KDIGO criteria in comparison to healthy controls.
It was also found to be elevated in ICU patients without overt signs of AKI
according to serum creatinine changes, however they were suffering from potential
nephrotoxic insults. According to our findings, urinary NEP is indicative of
epithelial cell alterations at the proximal tubule. This was elaborated in ICU
patients when ghost fragments and NEP(+) microvesicles were observed in urinary
sediment cytopreparations. Furthermore, NEP(+) immunofluorescence of healthy
kidney tissue showed staining at the proximal tubules. CONCLUSIONS: NEP, a
potential marker for proximal tubular epithelia, can be measured in urine. This
does not originate from leakage of elevated serum levels, but indicates proximal
tubular cell alterations such as brush border severing, which can heal in most
cases.