Association of urinary proteomics with the graft failure risk and left ventricular dysfunction
Irena Rambabova-Bushljetik1, Lada Trajceska1, Harald Mischak2, Goce Spasovski1, Oliver Bushljetikj3.
1Transplantation, University Clinic for Nephrology, Skopje, Macedonia, The Former Yugoslav Republic of; 2Mosaiques Diagnostic, Hanover, Germany; 3Cardiology, University Clinic for Cardiology, Skopje, Macedonia, The Former Yugoslav Republic of
Introduction: Kidney transplantation is the best treatment option for end stage renal disease, but is still associated with a long term graft failure. To identify grafts with high failure risks before eGFR starts declining and irreversible graft changes occurs, as well as prevent cardiovascular morbidity is a challenge for transplant professionals. Transplantation medicine is facing emerged need for identification of novel disease-specific biomarkers, with practical application in preventive screening, early diagnostic and improve prognostic and therapeutic possibilities.
Material and methods: We evaluate 55 living donor kidney transplant patients (genetically and emotionally related). All patients underwent clinical examination and had a routine laboratory screening at the same time points (3,6,12,24,48 months), including determination of serum creatinine, blood urea nitrogen, blood glucose, blood cell counts, protein status, and 24/h proteinuria. Graft function was estimated by Nankivell equitation. Urine samples was collected according to the defined standard operation procedure (SOP) at 24 and 48 months for urinary proteomic classifier analysis of CKD273, HF1 and HF2. All patients underwent transthoracic echocardiography to evaluate left ventricular function.
Results: Our study showed a significant positive correlation between CKD 273 classifier and serum creatinine at 12, 24 and 48 months, urinary protein excretion at 48 months expressed as g/24h (r=0.34, p=0.04) and a negative correlation with GFR slope ml/min/year (r=--0,42, p<0,05) determined by Nankivell equation.
Patients with lower CKD score (<0,175) have better graft function, with lower serum creatinine in the follow up period from 12 to 48 months with higher eGFR at 24 and 48 months. Patients with proteinuria above 0,44 g/24h at 48 months was associated with GFR decline of -7,82± 2,1 ml/min/year and -10,81±4,1 %/year. Our analysis do not confirmed positive correlation between urinary proteomic classifiers with left ventricular changes (Diastolic dysfunction and subclinical systolic dysfunction).
Conclusion: Urinary proteomes improve early diagnosis in progression of kidney disease and diagnosis of LV dysfunction in general population. Positive results in our analysis of CKD 273 were observed in kidney transplant recipients, whereas urinary proteomics for early diagnosis of LV function in renal transplant recipients does not have positive results. Further studies for urinary proteomic analysis in renal transplant recipients need to be done.