Clinical Characteristics And The Role Of KIM-1on Dengue Patients With Kidney Injury

Dengue is considered as one of the most important arthropod-borne infectiousdiseases worldwide, causing a spectrum of illnesses ranging from acute hightemperature, joint pain, a transient rash, hemorrhagic multiple organ functionlesion such as liver damage and kidney injury. Recently more and more cases havebeen reported that dengue patients have proteinuria,hematuria,even acute renalfailure. There are different possible mechanisms implicated in the pathogenesis ofdengue with kidney injury,including immune complexes mediated renal injuryand direct role of dengue virus. Renal biopsy showed renal tubular injury indengue patients and some fatal cases. Kidney injury molecule-1is a cellmembrane glycoprotein,expressed in the apical membrane of proximal tubuleswhen injuried. Thus, Kidney injury molecule-1is the biomarker of kidney tubularinjury showed in multiple studies.Little is known about the clinicalcharacteristics,risk factors and the pathogenesis of dengue with kidney injury inChina. Aims of this study are to summarize the clinical manifestation and explorethe role of kidney injury molecule-1on dengue patients with kidney injury. 1. ObjectivesTo better understand the clinical characteristics in dengue patients with kidneyinjury in China and explore the role of kidney injury molecule-1on its pathogenesis.2. Methods2.1Retrospective study of dengue with kidney injury was conducted based on theclinical data of1150dengue patients,hospitaled in Guangzhou No.8People’sHospital from May2002to December2013.2.2KIM-1and1-microglobulin(1-MG) were detected and compared inurines of65dengue patients grouped according to renal function and bloodpotassium. The abnormal renal function was defined as the estimated endogenouscreatinine clearance rate(eGFR) for each patient by the simplified equation of theModification is not less than70ml/min. We also evaluated the role of KIM-1onearly kidney injury in dengue patients by ROC curve.2.3Urine pottasium(Uk),urinary potassium-urinary creatinine ratio(UK-UCr) andacross the tube potassium concentration gradient(TTKG) were used as the evaluationof the secretion of K+in urines. In order to study the possible cause of denguepatients with hypokalemia,15dengue patients were out of the65adults by thefactors contributed to potassium shift,then the comparasions of variables like fever,ashift of K+into cells,renal glomerular functio and KIM-1,1-MG betweenhypokalemia and control group were performed.3. Results3.1Retrospective study of clinical data from1150dengue patients.3.1.1The incidence of dengue with kidney injury was24.6%and acute renal failurewas0.43%. It is showed that anuria/hypourocrinia (0.7%), nasty waist bursting(2.81%), hypersthenuria(3.70%), proteinuria(32%), elevated serum creatinine(4.24%)and elevated blood urea nitrogen(3.53%) in dengue patients with kidney injury. It isalso showed that the incidence of dengue with kidney injury was41.1%in severedengue patients whereas23.3%in dengue patients.3.1.2Significantly high risk factors were found between dengue patients with kidneyinjury and those without kidney injury included femal sex (54.40%versus 43.90%:P=0.002), age (mean±SD,56.20±14.04versus32.77±13.12years;P=0.001),severe dengue fever (13.10%versus6.10%;P=0.00), hypokalemia (56.50%versus43.0%;P=0.00), liver damage (59.4%versus51.4%;P=0.02), dengue myocarditis(4.20%versus2.10%;P=0.047).Spearman analysis had showed that renal functionlevels were positively correlated with severe dengue fever (r=0.112,P=0.034) andhypokalemia (r=0.116,P=0.029).3.2Detection of KIM-1and1-microglobulin in dengue patients3.2.1KIM-1and1-MG levels were significantly higher in dengue with kidneyinjury than without kidney injury (medians are0.59ng/ml versus0.35ng/ml，P=0.001and P=0.001respectively).The renal funtcton levels were negativelycorrelated with KIM-1(r=0.552,P=0.0001) and1-MG（r=0.517,P=0.0002）.3.2.2The receiver-operating characteristic curve analyses (ROC) were performed toevaluate the diagnostic value of serum creatinine, proteinuria(the presence of≥2+protein on a urine strip test), KIM-1and1-MG. The area under curves (AUC) wascompared among these variables, with the highest AUC of KIM-1(AUC=0.898,P=0.00). The AUC of other three variables were0.873(P=0.00),0.783(P=0.00),0.660(P=0.031), respectively.3.3The possible cause of dengue with hypokalemia15dengue patients were out of the65adults by the factors contributed topotassium shift, then the compaasions of variables between hypokalemia and controlgroups were performed. No significantly difference were found between two groupsin the onset of disease (6versus6days, P=0.922), the course of fever (7versus6days, P=0.922), the peak temperature (39.4versus39℃, P=0.05), creatine kinase(189versus137U/L,P=0.976), serum creatinine (86.9versus75.8μmol/L,P=0.232).The patients with hypokalemia had significantly higher urine potassium levels (urinepottasium medians are28versus16.7mmol/L,P=0.023;TTKG medians are4.91versus2.84, P=0.027), KIM-1(median,0.48versus0.36ng/ml, P=0.027),1-MG(median,16.1versus10.0ng/ml, P=0.036). Besides,secrum potassium levels indengue patients were positvely correated with KIM-1(r=0.24, P=0.02) and1-MG (r=0.23, P=0.03). 4. Conclusions4.1The incidence of dengue with kidney injury was24.6%,with most denguepatients suffering kidney injury showed proteinuria.Dengue patients who were olderfemal,severe stroke and complicated withe hypokalemia,liver damage and denguemyocarditis had risk of suffering kidney injury.4.2The kideny injury molecule-1in urine may be a be a predictor for denguepatients with kidney injury.