Ratio of Urinary Proteins to Albumin Excretion Shifts Substantially during Progression of the Podocytopathy Alport Syndrome, and Spot Urine Is a Reliable Method to Detect These Pathologic Changes
Jan Boeckhaus,
Lea Mohr,
Hassan Dihazi,
Burkhard Tönshoff,
Lutz T. Weber,
Lars Pape,
Kay Latta,
Henry Fehrenbach,
Baerbel Lange-Sperandio,
Matthias Kettwig,
Hagen Staude,
Sabine König,
Ulrike John-Kroegel,
Jutta Gellermann,
Bernd Hoppe,
Matthias Galiano,
Dieter Haffner,
Heidrun Rhode,
Oliver Gross
Affiliations
Jan Boeckhaus
Clinic for Nephrology and Rheumatology, University Medical Center Goettingen, 37075 Goettingen, Germany
Lea Mohr
Clinic for Nephrology and Rheumatology, University Medical Center Goettingen, 37075 Goettingen, Germany
Hassan Dihazi
Clinic for Nephrology and Rheumatology, University Medical Center Goettingen, 37075 Goettingen, Germany
Burkhard Tönshoff
Department of Pediatrics I, University Children’s Hospital Heidelberg, 69120 Heidelberg, Germany
Lutz T. Weber
Pediatric Nephrology, Children’s and Adolescents’ Hospital, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany
Lars Pape
Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, 30625 Hannover, Germany
The urinary albumin- and protein-to-creatinine ratios (UACR and UPCR, respectively) are key endpoints in most clinical trials assessing risk of progression of chronic kidney disease (CKD). For the first time, the current study compares the UACR versus the UPCR head-to-head at early stages of CKD, taking use of the hereditary podocytopathy Alport syndrome (AS) as a model disease for any CKD. Urine samples originated from the prospective randomized, controlled EARLY PRO-TECT Alport trial (NCT01485978). Urine samples from 47 children with confirmed diagnoses of AS at very early stages of CKD were divided according to the current stage of AS: stage 0 (UACR 300 mg/g). The range of estimated glomerular filtration rate was 75–187.6 mL/min. The mean age was 10.4 ± 4.5 years. In children at stage 0, proteinuria in spot urine, confirmed in 24 h urine, was almost ten times higher than albuminuria (106.4 ± 42.2 vs. 12.5 ± 9.7; p p p = 0.36). In 17 children, UACRs and UPCRs were measured simultaneously in 24 h urine and spot urine in the same study visit. Interestingly, the UACR (and UPCR) in 24 h urine vs. in spot urine varied by less than 10% (266.8 ± 426.4 vs. 291.2 ± 530.2). In conclusion, our study provides the first evidence that in patients with normal glomerular filtration rate (GFR) and low amounts of albuminuria, especially in children with podocytopathies such as AS, measuring the UACR and UPCR in spot urine is a reliable and convenient alternative to 24 h urine collection. Our study advocates both the UACR and the UPCR as relevant diagnostic biomarkers in future clinical trials in children with glomerular diseases because the UPCR seems to be a very significant parameter at very early stages of podocytopathies. The German Federal Ministry of Education and Research funded this trial (01KG1104).
