Pathophysiology of kidney disease in inborn errors of (energy) metabolism

Pathophysiology of kidney disease in inborn errors of (energy) metabolism2024-05-13T12:13:15+02:00

Anke Schumann, MD/PhD

Senior physician
Medical head of the Metabolic Diagnostic Laboratory
European Certificate in Pediatric Metabolic Medicine

T: +49 761 270 43730
F: +49 761 270 45270

Medical Center– University of Freiburg
Center for Pediatrics
Department of General Pediatrics, Adolescent Medicine and Neonatology
Mathildenstr. 1
79106 Freiburg


Monogenetic inborn errors of metabolism (IEM) are complex multisystemic diseases affecting the kidney as a prime target organ.

Our research focusses on pathomechanisms driving kidney disease in IEM of different origin (e.g. Organic acidurias, Fabry disease) using human and murine model systems. Our special interest lies on the crosstalk between different organelles and cellular compartments. We furthermore aim at the identification of potentially targetable aims to modify affected pathways with special regards on renal cellular energy metabolism. Our final goal is the generation of a comprehensive kidney map allowing to screen for generalizable pathomechanisms in both rare and common kidney disease.

Inborn errors of energy metabolism (IEM) are monogenic defects typically presenting with acute, potentially live threatening metabolic crisis in the neonatal period. Due to improved medical care patients grow older and long-term complications emerge, selectively affecting only specific organs, while the defective enzyme is expressed in all tissues.

Due to its unique role the kidney is a prime target organ in IEM. Based on the hypothesis that its vulnerability is based on high energetic demands, we aim to elucidate how different metabolic defects impact on renal cellular homeostasis and metabolism. Strikingly, our investigations revealed that the perturbations caused by monogenic enzyme deficiency extend the compartment directly affected by far and lead to more extensive cellular metabolic dysfunction and damaging patterns.

Our group is currently working on projects addressing the pathophysiology of chronic kidney disease (CKD) in organic acidurias (methylmalonic and propionic aciduria) caused by mitochondrial enzyme deficiency and lysosomal Fabry disease as disease examples.

The aim of the investigations is to understand how the impairment of different organelles leads to a disruption of renal cellular mitochondrial (energy) metabolism and which (intra-) cellular communication pathways are modulated in a disease-specific manner. We have supporting evidence that IEM affect different subsets of the nephron, e.g. not only glomerular but also epithelial cells and cell-type specific injury might explain why damage patterns occur at different time points as CKD progresses.

Of note, the investigated diseases have existing therapeutic interventions (e.g., protein reduced diet and enzyme replacement therapy) which are neither curative nor sufficiently hindering CKD progression. This underlines the need for deep metabolic and molecular profiling of distinct kidney cell populations.

A better insight into underlying pathomechanisms might point towards new therapeutic options and help to identify potentially targetable aims with high translational potential. Our final goal is to establish a broadly applicable translational approach for hereditary metabolic kidney diseases.


Karina Zeyer
Role of renal epithelial mesenchymal transition in organic acidurias and Fabry disease

Johannes Kowalzik
Towards unraveling the toxic metabolite hypothesis in organic acidurias

Jonathan Köhler
Clinical phenotype in complex III deficiency (mitoNET registry)

Ilona Skatulla
Renal phenotype in a hypomorphic murine model of propionic aciduria: common pathomechanisms in organic acidurias (submitted)

Marion Brutsche
The impact of metabolic stressors on mitochondrial homeostasis in a renal epithelial cell model of methylmalonic aciduria. Sci Rep. 2023 May 11;13(1):7677

Véronique Belche
Mitochondrial damage in renal epithelial cells is potentiated by protein exposure in propionic aciduria. J Inherit Metab Dis. 2021 Nov;44(6):1330-1342

Kristin Schaller
Defective lysosomal storage in Fabry disease modifies mitochondrial structure, metabolism and turnover in renal epithelial cells. J Inherit Metab Dis. 2021 Jul;44(4):1039-1050


Véronique Belche (MD student)
Marion Brutsche (MD student)
Jonathan Köhler (MD student)
Johannes Kowalzik (MD student)
Kristin Schaller (MD student)
Ilona Skatulla (Technician)
Karina Zeyer (Fellow)


For a complete publication list for Anke Schumann, please click here:


Berta Ottenstein Advanved Clinician Scientist Program University of Freiburg
DFG, Collaborative Research Center 1453 Nephrogenetics, Research associate
Research Commission University of Freiburg
Research award of the German Society for Pediatric Metabolic Diseases
Nutricia metabolic research grant


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