History

The first sign of nephrotic syndrome in children is usually swelling of the face; this is followed by swelling of the entire body. Adults can present with dependent edema. Foamy urine may be a presenting feature. Fatigue and loss of appetite are common symptoms. A thrombotic complication, such as deep venous thrombosis of the calf veins or even a pulmonary embolus, may be the first clue to nephrotic syndrome.

Additional historical features can be related to the cause of nephrotic syndrome. Thus, the recent start of a nonsteroidal anti-inflammatory drug (NSAID) suggests such drugs as the cause and a more than 10-year history of diabetes with symptomatic neuropathy indicates diabetic nephropathy.

Physical Examination

Edema is the salient feature of nephrotic syndrome and initially develops around the eyes and legs. With time, the edema becomes generalized and may be associated with an increase in weight, the development of ascites, or pleural effusions.

Hematuria and hypertension manifest in a minority of patients.

Additional features on exam will vary according to cause and as a result of whether or not renal function impairment exists. Thus, in the case of longstanding diabetes, the patient may have diabetic retinopathy, which correlates closely with diabetic nephropathy. If the kidney function is reduced, the patient may have hypertension, anemia, or both.

Differential Diagnoses

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Media Gallery

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx). Primary urine is formed through the filtration of plasma fluid across the glomerular barrier (arrows); in humans, the glomerular filtration rate (GFR) is 125 mL/min. The plasma flow rate (Qp) is close to 700 mL/min, with the filtration fraction being 20%. The concentration of albumin in serum is 40 g/L, while the estimated concentration of albumin in primary urine is 4 mg/L, or 0.1% of its concentration in plasma. Courtesy of the American Physiological Society (www.the-aps.org) and reproduced from Haraldsson B, Nystrom J, Deen WM. Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev. 2008 Apr;88(2):451-87.
Incidence of important causes of nephrotic syndrome, in number per million population. The left panel shows systemic causes, and the right panel lists primary renal diseases that can cause nephrotic syndrome. fgs = focal glomerulosclerosis, MN = membranous nephropathy, min change = minimal-change nephropathy. Data are in part from Swaminathan et al and Bergesio et al.
A schema of the average patient age at presentation in various common forms of nephrotic syndrome. (Timeline not to scale.)
Forces determining capillary filtration

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#author-disclosures{display:block}#author-disclosures.modal-layer{position:relative}#author-disclosures .modal-content{max-height:none}#author-disclosures .close-modal{display:none}

Author

Ramapriya Sinnakirouchenan, MD, MBBS Assistant Professor, Department of Medicine, Division of Nephrology, Medical College of Wisconsin; Medical Director of Dialysis Unit, Fresenius Kidney Care

Ramapriya Sinnakirouchenan, MD, MBBS is a member of the following medical societies: American Society of Nephrology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc.

Chief Editor

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Eric P Cohen, MD Professor, Department of Medicine, Division of Nephrology, University of Maryland School of Medicine; Nephrology Section Chief, Baltimore Veterans Affairs Hospital

Eric P Cohen, MD is a member of the following medical societies: American Society of Nephrology, International Society of Nephrology, Radiation Research Society, Société Francophone de Dialyse

Disclosure: Nothing to disclose.

Laura Lyngby Mulloy, DO, FACP Professor of Medicine, Chief, Section of Nephrology, Hypertension, and Transplantation Medicine, Glover/Mealing Eminent Scholar Chair in Immunology, Medical College of Georgia, Georgia Regents University

Disclosure: Nothing to disclose.

Cassiopia Lippold, MD Resident Physician, Department of Internal Medicine, Pinnacle Health Hospitals

Cassiopia Lippold, MD is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Nephrotic Syndrome Clinical Presentation

History

Physical Examination

References

Tables

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