Elevated transrenal DNA (cell-free urine DNA) in patients with urinary tract infection compared to healthy controls

Moreira, Vanessa García; Prieto, Belén; la, Tamara de; Menéndez, Francisco V. Álvarez

doi:10.1016/j.clinbiochem.2008.12.021

Cited by 22 publications

(21 citation statements)

References 10 publications

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“…Our findings are corroborated by previous results which have demonstrated that in hematopoietic stem cell transplant patients, the quantity of donor-derived cf-DNA in urine does not correlate with that of plasma and that the predominant cf-DNA fragment size differs between plasma and urine [44]–[45]. A similar phenomenon regarding the DNA fragment size discrepancy between plasma and urine cf-DNA has also been observed in pregnant women [46].…”

Section: Discussionsupporting

confidence: 91%

“…The former is supported by the observation that patients with urinary tract infection have elevated urine cf-DNA levels [44], whereas the latter has been demonstrated in colorectal cancer patients who displayed tumor-derived mutated K-ras sequences in the transrenal urine cf-DNA [47]–[48]. Likewise, Y-chromosomal DNA sequences have been detected in the urine of pregnant women carrying male fetuses [44]. Based on animal studies, however, it has been estimated that only 0.5–2% of the circulating DNA passes through the kidneys and is excreted into the urine in a polymeric form [44], [49].…”

Section: Discussionmentioning

confidence: 89%

“…In fact, urinary cf-DNA is likely to consist of a heterogeneous mixture of cf-DNA fragments originating from dying cells in the renal system and from the pool of plasma circulating cf-DNA. The former is supported by the observation that patients with urinary tract infection have elevated urine cf-DNA levels [44], whereas the latter has been demonstrated in colorectal cancer patients who displayed tumor-derived mutated K-ras sequences in the transrenal urine cf-DNA [47]–[48]. Likewise, Y-chromosomal DNA sequences have been detected in the urine of pregnant women carrying male fetuses [44].…”

Section: Discussionmentioning

confidence: 93%

“…Likewise, Y-chromosomal DNA sequences have been detected in the urine of pregnant women carrying male fetuses [44]. Based on animal studies, however, it has been estimated that only 0.5–2% of the circulating DNA passes through the kidneys and is excreted into the urine in a polymeric form [44], [49]. The exact mechanism by which cf-DNA crosses the glomerular basement membrane is currently unknown, yet the maximum urinary excretion of cf-DNA is anticipated to be influenced by renal function although our current results do not seem to support this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

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Plasma Cell-Free DNA Levels Are Elevated in Acute Puumala Hantavirus Infection

et al. 2012

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IntroductionPuumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome called nephropathia epidemica (NE). The aim of the present study was to evaluate plasma cell-free DNA (cf-DNA) levels and urinary cf-DNA excretion in acute NE as well as their associations with the severity of the disease.MethodsTotal plasma cf-DNA was quantified directly in plasma of 61 patients and urine of 20 patients with acute NE. We also carried out a qualitative high-sensitivity lab-on-a-chip DNA assay in 20 patients to elucidate the appearance of cf-DNA in plasma and urine.ResultsThe maximum plasma cf-DNA values taken during acute NE were significantly higher than the control values taken after the hospitalization period (median 1.33 µg/ml, range 0.94–3.29 µg/ml vs. median 0.77 µg/ml, range 0.55–0.99 µg/ml, P<0.001). The maximum plasma cf-DNA levels correlated positively with maximum blood leukocyte count (r = 0.388, P = 0.002) and the length of hospital stay (r = 0.376, P = 0.003), and inversely with minimum blood platelet count (r = −0.297, P = 0.020). Qualitative analysis of plasma cf-DNA revealed that in most of the patients cf-DNA displayed a low-molecular weight appearance, corresponding to the size of apoptotic DNA (150–200 bp). The visually graded maximum cf-DNA band intensity correlated positively with the maximum quantity of total plasma cf-DNA (r = 0.513, P = 0.021). Maximum urinary excretion of cf-DNA in turn was not markedly increased during the acute phase of NE and did not correlate with any of the variables reflecting severity of the disease or with the maximum plasma cf-DNA level.ConclusionsThe plasma levels of cf-DNA are elevated during acute PUUV infection and correlate with the apoptotic cf-DNA-band intensity. The plasma cf-DNA concentration correlates with some variables reflecting the severity of the disease. The urinary excretion of cf-DNA does not reflect the degree of inflammation in the kidney.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Plasma Cell-Free DNA Levels Are Elevated in Acute Puumala Hantavirus Infection

et al. 2012

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“…They found out that when the Tr-DNA quantification is used as a marker for clinical monitoring (i.e. follow up of cancer or transplantation patients), it is important to rule out a concomitant UTI, because a secondary cause of increased concentrations of cell free urine DNA could confound clinical decisions (55). …”

Section: Transplantationmentioning

confidence: 99%

Free DNA – new potential analyte in clinical laboratory diagnostics?

Wagner

2012

Biochem Med

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The existence of cell free DNA in the human circulatory system has been known since the 1950s, however, intensive research in this area has been conducted for the last ten years. This review paper brings a short overview of the existing literature concerning the cell free DNA research in various clinical fi elds and pathological states and considers the application possibilities of this new analyte in clinical laboratory diagnostics. At the moment, cell free DNA is most widely used for the purpose of non-invasive prenatal diagnosis of fetal sex or fetal RhD status. The recent discovery of epigenetic changes in placental/fetal DNA and the detection of fetal/placental-specifi c RNAs have made it possible to use this technology in all pregnancies irrespective of the gender of the fetus. With the application of new techniques such as next generation sequencing, digital PCR and mass spectrometry, it is now possible to detect very small amounts of specifi c DNA in the presence of excess of other nonspecifi c nucleic acids. Second most probable application is in oncology, where detection and monitoring of tumors is now possible by the detection of tumor-derived nucleic acids. Third promising fi eld for near future implementation of this analyte is transplantation medicine, where free DNA level could serve as a marker of transplant rejection. Before any further utilization of this new biomarker, pre-analytical and analytical aspects of free DNA analysis remain to be standardized. In the fi eld of noninvasive prenatal diagnosis, important ethical, legal and social questions remain to be discussed.

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