A further investigation on a MALDI-based method for evaluation of markers of renal damage.

The validity of the urinary protein profile to characterize the pathological states of diabetic, nephropathic and diabetic-nephropathic patients was considered on the basis of previously obtained results by MALDI/MS, showing a different abundance ratio of the collagen alpha1 and alpha5 chain precursor fragments at m/z 1219 and 2049 and of the uromodulin precursor fragment at m/z 1912 observed in healthy subjects and patients; a larger number of subjects was examined and the obtained results were statistically evaluated. The p values related to the observed differences indicate that they are statistically significant when comparing all patients versus healthy controls, diabetic with normo or microalbuminuria versus nephropathic with advanced renal disease patients and diabetic with normo or microalbuminuria versus diabetic with advanced nephropathy patients. The scatter plot matrix gives evidence of the strict inverse relationship between the abundances of ions at m/z 1912 and 1219, the correlation coefficient being particularly high (r = 0.921, p < 0.001). The relationship between the true positive rate (sensitivity) and false positive rate (1-specificity) for every possible cutoff value in abundance of the considered ionic species was investigated through the receiver-operating characteristic (ROC) curve. The obtained data indicate that a good differentiation of nephropathic patients with advanced renal disease and diabetic patients with advanced nephropathy versus healthy subjects can be easily obtained by this approach.

Non-invasive markers of ureteropelvic junction obstruction.

Non-invasive prognosis of the clinical progression of disease is of high interest, especially in newborn and children. Neonatal ureteropelvic (UPJ) junction obstruction needs close and invasive surveillance to determine the necessity of pyeloplasty. A number of groups have initiated research with the aim to find non-invasive biomarkers for UPJ obstruction. Two different strategies have been followed. One strategy, based on the knowledge obtained in animal models of UPJ obstruction, has identified a number of individual urinary markers of severe UPJ obstruction. Combining these markers might allow prediction of which patients will require surgery and in which patients UPJ obstruction will spontaneously resolve. The other strategy is based on urinary proteomics. In this strategy the entire urinary proteome is probed for a set of biomarkers that correlates with the degree of UPJ obstruction. In subsequent steps, these sets of urinary biomarkers are used for prediction of the clinical evolution of UPJ obstruction patients. This proteomic-based strategy allowed prediction, several months in advance, of the clinical evolution of neonates with UPJ-obstruction. Both strategies will be complementary and will hopefully replace in the near future the invasive follow-up of newborns with UPJ obstruction.