Association of urinary laminin G-like 3 and free K light chains with disease activity and histological injury in IgA nephropathy.

BACKGROUND AND OBJECTIVES: IgA nephropathy has variable clinical presentation and progression. Its definitive diagnosis and prognosis require renal biopsy. The identification of new biomarkers allowing noninvasive diagnosis and monitoring of disease activity would be advantageous. This study analyzed the urine proteome of IgA nephropathy patients at an early stage of disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urine from 49 IgA nephropathy patients, 42 CKD patients, and 40 healthy individuals was analyzed by surface-enhanced laser desorption/ionization time of flight/mass spectrometry. Differentially excreted proteins were identified by matrix-enhanced laser desorption/ionization time of flight/mass spectrometry, confirmed by immunologic methods, and validated in an independent set of patients (14 IgA nephropathy and 24 CKD). All patients were recruited at the Division of Nephrology of the University of Foggia from January of 2005 to March of 2007. RESULTS: Two proteins, with 21,598 and 23,458 m/z, were significantly decreased in IgA nephropathy and identified as Perlecan laminin G-like 3 peptide and Ig κ light chains, respectively. Western blot analysis confirmed the lower urinary excretion of laminin G-like 3 in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunonephelometry analysis confirmed the lower urinary excretion of free κ light chains in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunohistochemistry analysis justified the urinary excretion profile of such proteins in IgA nephropathy. Finally, urinary free κ light chains and laminin G-like 3 concentration inversely correlated with severity of clinical and histologic features of our IgA nephropathy cohort. CONCLUSIONS: Laminin G-like 3 and free κ light chains can contribute to the noninvasive assessment of IgA nephropathy disease activity.

Kidney biopsy in the elderly.

Renal biopsy continues to play an essential role in the clinical assessment of hematuria, proteinuria and kidney failure. Nonetheless, the indications for renal biopsy are still controversial. The best determination of the potential benefit of an invasive diagnostic procedure comes from the demonstration that knowledge of a specific diagnosis guides the selection of treatments that produce improved outcomes. The size of the aging population is growing. In the years between 1980 and 1997, an 18% increase occurred in the number of individuals more than 65 years of age in the USA, and a 73% increase of those more than 85 years of age. Elderly patients are surviving longer with both acute and chronic disease, they are adapting to functional limitations in positive ways and they are choosing life-prolonging treatments that were not available to this population in the past. Despite these changes, several authors discuss physician biases that influence care of the elderly, and they argue that criteria for diagnosis and treatment should be the same as in younger patients. Many of the diagnoses made are treatable, and when treated, the outcome improves. Although comparison of survival data for patients with the general population would have been informative, data showing that loss of renal function correlates with shortened survival imply that interventions that delay progression to end-stage renal disease should significantly impact mortality. Thus, a bias toward limited diagnosis based on age alone is not justified. Histology is essential to precisely characterize the glomerular diseases underlying nonspecific clinical pictures and to direct the best therapeutic strategies. Our experience supported by larger studies from the United States showed that native kidney biopsy is safe and essential for diagnosis of renal disease and to direct the best therapeutic strategies in elderly patients.