Protein-Spilling Kidney Diseases – A New Educational Primer Article

Podocytopathies in focus

Podocytopathies are kidney diseases in which injury to podocytes (key cells of the glomerulus, which is the filter in the kidney) results in proteinuria (loss of protein in the urine) or nephrotic syndrome (a condition characterized by swelling, usually in the extremities, and reduced albumin protein and increased lipids in the blood). This group of diseases is a major contributor to end-stage kidney disease worldwide.

A new Primer article in the journal Nature Reviews Disease Primers, authored by a group of leading international experts, has just been published — endorsing the idea that these diseases should be described based on their underlying cause rather than their appearance on biopsy. A Primer article describes worldwide epidemiology, molecular mechanisms, diagnosis and management, and it provides a global and authoritative overview of research on these diseases, as well as of the challenges facing the research community as it strives towards a better understanding of this condition.

Visual Summary of Podocytopathies (Protein-Spilling Kidney Diseases)

Click on the image above to be taken through to the PrimeView on Podocytopathies.

“Patients are often told they have ‘focal segmental glomerulosclerosis’ or ‘diffuse mesangial sclerosis’, but these are not diagnoses per se,” explains the Chief Editor of the journal, Clemens Thoma, DPhil, ORCID. “They are patterns that are revealed when the kidneys are biopsied.” The real challenges lie in understanding what causes these patterns and selecting the most effective and least toxic therapy for each patient, which is the goal of precision medicine.


A broad spectrum of causes of podocyte injury can also produce relatively uniform clinical patterns (namely, proteinuria and nephrotic syndrome). “Because of this, these diseases manifest various degrees of proteinuria and risks of progressive kidney scarring,” explains Paola Romagnani, MD, PhD, lead author of the Primer.

The Primer explains that distinct contributing factors with different relative contributions can combine to reach a threshold to induce podocyte injury and loss. Such factors include genetic predisposition, low birth weight, prematurity, increased body mass index and exposure to certain viruses and drugs. “Once we define the genetic factors and mechanisms underlying podocyte injury, then targeted personalized management of patients may become a reality,” says senior investigator Jeffrey Kopp, MD, a co-author of the Primer.

All too often, current treatments are non-specific in that they address clinical manifestations rather than the underlying causes. “Recent work of ours and other groups suggest that patients with apparently identical ‘diseases’ do not respond similarly to treatments because they have different and unexpected genetic mutations as the underlying cause,” explains Professor Romagnani.

“Novel diagnostic approaches involving nephrologists, geneticists and pathologists can identify these causes in more patients.”

In the future, targeting specific forms and mechanisms of podocyte injury to promote podocyte repair and resilience may be possible using novel, precision medicine strategies. Professor Romagnani is optimistic for the future. “We hope the Primer will enhance understanding of the podocytopathies and will stimulate new approaches to research and therapeutics.”

Read the Primer without access control here. The accompanying Primeview can be accessed here.

Nature Reviews Disease Primers (@DiseasePrimers) is a Nature Research journal that was launched in 2015 to provide broad review articles on various health fields.

The research described here is conducted in part by the Division of Intramural Research at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health. The content in this release is the sole responsibility of the authors and does not necessarily represent the official views or imply endorsement of the National Institutes of Health.

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