Preclinical Detection of Early Glomerular Injury in Children with Kidney Diseases-Independently of Usual Markers of Kidney Impairment and Inflammation.

Glomerular kidney diseases typically begin insidiously and can progress to end stage kidney failure. Early onset of therapy can slow down disease progression. Early diagnosis is required to ensure such timely therapy. The goal of our study was to evaluate protein biomarkers (BMs) for common nephropathies that have been described for children with Alport syndrome. Nineteen candidate BMs were determined by commercial ELISA in children with congenital anomalies of the kidneys and urogenital tract, inflammatory kidney injury, or diabetes mellitus. It is particularly essential to search for kidney disease BMs in children because they are a crucial target group that likely exhibits early disease stages and in which misleading diseases unrelated to the kidney are rare. Only minor differences in blood between affected individuals and controls were found. However, in urine, several biomarker candidates alone or in combination seemed to be promising indicators of renal injury in early disease stages. The BMs of highest sensitivity and specificity were collagen type XIII, hyaluronan-binding protein 2, and complement C4-binding protein. These proteins are unrelated to inflammation markers or to risk factors for and signs of renal failure. In conclusion, our study evaluated several strong candidates for screening for early stages of kidney diseases and can help to establish early nephroprotective regimens.

Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation.

Introduction: Alport syndrome (AS) is a hereditary type IV collagen disease. It starts shortly after birth, without clinical symptoms, and progresses to end-stage kidney disease early in life. The earlier therapy starts, the more effectively end-stage kidney disease can be delayed. Clearly then, to ensure preemptive therapy, early diagnosis is an essential prerequisite. Methods: To provide early diagnosis, we searched for protein biomarkers (BMs) by mass spectrometry in dogs with AS stage 0. At this very early stage, we identified 74 candidate BMs. Of these, using commercial enzyme-linked immunosorbent assays (ELISAs), we evaluated 27 in dogs and 28 in children, 50 with AS and 104 healthy controls. Results: Most BMs from blood appeared as fractions of multiple variants of the same protein, as shown by their chromatographic distribution before mass spectrometry. Blood samples showed only minor differences because ELISAs rarely detect disease-specific variants. However, in urine , several proteins, individually or in combination, were promising indicators of very early and preclinical kidney injury. The BMs with the highest sensitivity and specificity were collagen type XIII, hyaluronan binding protein 2 (HABP2), and complement C4 binding protein (C4BP). Conclusion: We generated very strong candidate BMs by our approach of first examining preclinical AS in dogs and then validating these BMs in children at early stages of disease. These BMs might serve for screening purposes for AS before the onset of kidney damage and therefore allow preemptive therapy.