Urinary Peptides as Potential Non-Invasive Biomarkers for Lupus Nephritis: Results of the Peptidu-LUP Study.

Background: Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). The therapeutic strategy relies on kidney biopsy (KB) results. We tested whether urinary peptidome analysis could non-invasively differentiate active from non-active LN. Design: Urinary samples were collected from 93 patients (55 with active LN and 38 with non-active LN), forming a discovery (n = 42) and an independent validation (n = 51) cohort. Clinical characteristics were collected at inclusion and prospectively for 24 months. The urinary peptidome was analyzed by capillary-electrophoresis coupled to mass-spectrometry, comparing active LN to non-active LN, and assessing chronic lesions and response to therapy. The value of previously validated prognostic (CKD273) and differential diagnostic (LN172) signatures was evaluated. Results: Urinary peptides could not discriminate between active and non-active LN or predict early response to therapy. Tubulo-interstitial fibrosis was correlated to the CKD273. The LN172 score identified 92.5% of samples as LN. Few patients developed new-onset CKD. Conclusions: We validated the CKD273 and LN172 classifiers but did not identify a robust signature that could predict active LN and replace KB. The value of urinary peptidome to predict long-term CKD, or renal flares in SLE, remains to be evaluated.

A randomized trial of low-animal-protein or high-fiber diets for secondary prevention of calcium nephrolithiasis.

BACKGROUND: The purpose of this trial was to evaluate the efficacy of a low-animal-protein diet (LAPD) or a high-fiber diet (HFD) for the prevention of calcium nephrolithiasis recurrence. METHODS: We conducted a 4-year randomized trial comparing the effect of 2 diets in 175 idiopathic calcium stone formers. Fifty-five were assigned to a LAPD (<13% of total energy derived from protein), 60 were assigned to a HFD (>25 g/day fiber) and 60 were placed on a normal diet (control group). The primary outcome measure was the time to the first recurrence of calcium nephrolithiasis. Daily urine compositions were analyzed at baseline, at month 4 (M4), M12, M24, M36 and M48. RESULTS: Seventy-three patients completed the trial (23 in the LAPD group, 27 in the HFD group and 23 in the control group). Recurrence was 48% (11/23) in the LAPD group, 63% (17/27) in the HFD group and 48% (11/23) in the control group (p = not significant). During follow-up, urinary calcium levels and other urine parameters did not change significantly in the 3 groups, except for a significant decrease in 24-hour urinary sulfate in the LAPD group. CONCLUSIONS: In idiopathic calcium stone formers, neither a LAPD nor a HFD appeared to provide protection against recurrence.

Optimized preparation of urine samples for two-dimensional electrophoresis and initial application to patient samples.

OBJECTIVE: We optimized of the preparation of urinary samples to obtain a comprehensive map of urinary proteins of healthy subjects and then compared this map with the ones obtained with patient samples to show that the pattern was specific of their kidney disease. DESIGN AND METHODS: The urinary protein excretion patterns of 49 healthy men and 4 patients with renal disease were obtained by 2D electrophoresis. Silver nitrate stained protein spots were identified by mass spectrometry. RESULTS: Reproductive 2D gels identified 5 classes of proteins systematically found in healthy subjects, irrespective of age. The proteins evidenced included serum albumin and its specific proteolytic products, Tamm-Horsfall, transferrin, zinc-alpha2-glycoprotein, alpha1-microglobulin, haptoglobin, and Ig light chains. CONCLUSIONS: This study of a large panel of healthy individual showed that 2D urinary pattern was constant over time and reveal for the first time the relative abundance of albumin fragments in healthy subjects' urine. The profiles of the 4 patients, were specific of their renal disease.