Assessment of nephrotic syndrome

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Last reviewed: 30 Nov 2025

Last updated: 08 Apr 2025

Nephrotic syndrome is defined as the presence of proteinuria (>3.5 g/24 hours), hypoalbuminaemia (<30 g/L), and peripheral oedema. Hyperlipidaemia and thrombotic disease are also frequently seen.

Despite heavy proteinuria and lipiduria, the urine contains few cells or casts. This differs from nephritic syndrome, which is typically defined as the presence of acute kidney injury (renal dysfunction), hypertension, and an active urinary sediment (red cells and red cell casts).

Nephrotic syndrome is not a single disease; it is a constellation of several symptoms that can be caused by several renal diseases. The challenge is to determine the underlying aetiology causing the nephrotic syndrome in any given patient.

Patients with nephrotic syndrome are at risk of chronic kidney disease and end-stage renal disease. Nephrotic syndrome is associated with significant morbidity and mortality; therefore, these patients require specialised input and assessment.

Pathophysiology

Each kidney has approximately 1 million glomeruli, which are the sites of blood filtration. The layers of the glomeruli include the fenestrated endothelium of the capillary, the glomerular basement membrane, and the foot processes of the podocytes. Together these crucial structures are known as the glomerular filtration barrier, with the connection between adjacent podocyte foot processes called slit diaphragms.

Proteinuria

Glomerular proteinuria develops when the components of the filtration barrier are disrupted by disease. The podocyte is the major target of pathological processes resulting in the development of high-grade glomerular proteinuria.

In focal segmental glomerulosclerosis (FSGS), the podocyte is often the target of an unknown circulating factor.[1] In idiopathic membranous nephropathy, the podocyte is the target of an antibody response, and in genetic causes of steroid-resistant nephrotic syndrome (SRNS), the genetic mutation affects the podocyte or the filtration barrier.[2][3]

Hypoalbuminaemia

Patients become hypoalbuminaemic due to the urinary loss of albumin. The liver tries to compensate for this protein loss by increasing the synthesis of albumin, as well as other molecules including low-density lipoprotein, very low-density lipoprotein, and lipoprotein(a), contributing to the development of lipid abnormalities including hypercholesterolaemia and hypertriglyceridaemia.[4] The lipid abnormalities correlate with the extent of proteinuria. These lipid abnormalities increase the patient’s risk of cardiovascular disease.

Hypercoagulability and thrombosis

Hypercoagulability and thrombosis (deep vein thrombosis, pulmonary emboli, renal vein thrombosis) is a recognised life-threatening complication of nephrotic syndrome.[5] It occurs as a result of loss of antithrombin III, protein C, and protein S in the urine; increased hepatic synthesis of pro-coagulant factors; and increased platelet activation.[6][7]

Oedema

Occurs due to a combination of a decrease in oncotic pressure (also known as colloid osmotic pressure) from hypoalbuminaemia, as well as a primary renal sodium retention in the collecting tubules.[8][9] Patients with nephrotic syndrome are at increased risk of infection due to loss of immunoglobulins, complement, and other compounds in the urine. Immunotherapy may exacerbate the infection risk.[10][11]

Differentials

Common

Minimal change disease
Focal segmental glomerulosclerosis (FSGS)
Membranous nephropathy
Diabetic nephropathy
Multiple myeloma-associated AL amyloidosis
IgA nephropathy

Full details

Uncommon

Membranoproliferative (mesangiocapillary) glomerulonephritis
Amyloidosis
Lupus nephritis
Fabry disease
Alport syndrome
Nail-patella syndrome
Malignant hypertension

Full details

Contributors

Authors

Panduranga Rao, MD, DNB, MS

Richard D Swartz Collegiate Professor of Nephrology

Professor of Medicine

Department of Medicine

University of Michigan

Ann Arbor

Disclosures

PR declares that he has no competing interests.

Benjamin Wagner, MD

Assistant Professor of Medicine

Department of Medicine

University of Michigan

Ann Arbor

Disclosures

BW declares that he is a co-investigator on "An Open Label Phase 1b Study of Felzartamab in Lupus Nephritis", a study sponsored by HI-Bio.

Acknowledgements

Dr Panduranga Rao and Dr Benjamin Wagner would like to gratefully acknowledge Dr Ruth Pepper, Dr John Connolly, Dr David J.A. Goldsmith, Dr Oliver J. Ziff, and Dr Michael S. Gersch, previous contributors to this topic.

Disclosures

RP, JC, DJAG, OJZ, and MSG declare that they have no competing interests.

Peer reviewers

John Feehally, MBBS, FRCP

Professor of Renal Medicine

The John Walls Renal Unit

Leicester General Hospital

Leicester

Disclosures

JF declares that he has no competing interests.

Judith H. Veis, MD, FASN

Associate Director

Nephrology

Washington Hospital Center

Washington

Disclosures

JHV declares that she has no competing interests.

Catherine Clase, BA, MB, MSC, FRCPC

Associate Professor

Department of Medicine

McMaster University

Ontario

Canada

Disclosures

CC declares that she has no competing interests.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

References

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Key articles

Nishi S, Ubara Y, Utsunomiya Y, et al. Evidence-based clinical practice guidelines for nephrotic syndrome 2014. Clin Exp Nephrol. 2016 Jun;20(3):342-70.Full text Abstract

Trautmann A, Boyer O, Hodson E, et al. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2023 Mar;38(3):877-919.Full text Abstract

Kidney Disease Improving Global Outcomes Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021 Oct;100(4S):1-276.Full text

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Guidelines
- IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome
- KDIGO clinical practice guideline for the management of glomerular diseases
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Assessment of nephrotic syndrome

Summary

Pathophysiology

Differentials

Common

Uncommon

Contributors

Authors

Panduranga Rao, MD, DNB, MS

Disclosures

Benjamin Wagner, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

John Feehally, MBBS, FRCP

Disclosures

Judith H. Veis, MD, FASN

Disclosures

Catherine Clase, BA, MB, MSC, FRCPC

Disclosures

Peer reviewer acknowledgements

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Guidelines

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice