Determination of the protein composition of urine is a non-invasive method helping to diagnose renal lesions and evaluate therapeutic interventions. We present here five observations that highlight the performance and relevance of urine protein analysis combining selected glomerular and tubular protein measurements. Total urine protein level and measurements of urinary IgG, albumin, transferrin alpha-1 microglobulin and retinol binding protein were performed on a urine sample by immunonephelometry. The results were normalized for urine creatinine concentration and integrated in the MDI interpretation software that provides a "urine protein profile" (UPP). Sequential UPP were performed in two patients with drug-induced tubular toxicity. One resolved after drug withdrawal. The second concomitantly developped glomerular lesions and repeated UPP was warranted to follow evaluation of the distinct renal lesions. Two cases illustrate two distinct clinical situations in patients with multiple myeloma, respectively myeloma cast nephropathy and toxic acute tubular necrosis. Those differential diagnoses were early anticipated by UPP. In one case, UPP was in favour of the presence of large amount of urinary monoclonal light chain excretion before performing urine electrophoresis analysis and renal biopsy while this was not in the other case. In the last case, we compared sequential UPP, renal function and kidney biopsies in a patient with a diagnosis of membranous nephropathy, and demonstrated a good correlation between urine glomerular and tubular protein excretion and progression of the renal lesions. The use of the UPP in clinical practice, particularly through the accurate quantification of tubular markers, is a more efficient tool for the diagnosis and follow-up of renal diseases than the less sensitive semi-quantitative urine electrophoresis or combined assays of both total proteinuria and albuminuria.