Charlotte, NC
Prabha Bhandari, MD
Gauri Adhikari, MD
A nephrotic syndrome is a group of disorders that damage the filtering units of your kidney, the nephrons. Nephrons are responsible for filtering blood and producing urine. Each kidney contains thousands of nephrons, each consisting of a glomerulus and a tubule. As blood flows through your glomerulus, waste products and excess substances are filtered out of your bloodstream into the renal tubules. [1]
Nephrons retain protein in the body, allowing less than 150 mg of protein to pass into the urine daily. [1]However, when these filtering units are damaged in Nephrotic syndrome, three or more grams of protein are lost in the urine over a 24-hour period, a condition called proteinuria. [2]As more of these proteins are lost, the resulting osmotic imbalance can cause fluids to leak and accumulate in the spaces between cells, leading to swelling. [1]
The estimated annual incidence rate of Nephrotic Syndrome is two to seven new cases per 100,000 in children of age below 18 years and 4.30 per 100,000 person-years in adults. [1,3] The condition affects children and adults of all ages, genders, or races.
Nephrotic syndrome can arise from various conditions that either solely impact the kidneys or those affecting multiple body parts.
In diabetic nephropathy, prolonged high blood sugar levels damage the small blood vessels in your kidneys, particularly the glomeruli. Additionally, if you have diabetes, you might have an increased risk of developing conditions like high blood pressure and cardiovascular disease, which can contribute to nephrotic syndrome. [4]
The glomerulus of your kidney becomes scarred, allowing proteins to leak into urine. It is the leading cause of nephrotic syndrome in African American adults. [1]
Membranous nephropathy leads to protein build-up in your glomerulus, which causes the protein to leak into the urine. This is the predominant cause among white adults. [1]
It is the most common cause of nephrotic syndrome in children and accounts for a significant proportion of cases in adults as well. [5]
SLE, commonly known as lupus, can cause nephrotic syndrome through a condition known as lupus nephritis. In lupus nephritis, the body’s immune system mistakenly attacks your kidneys, leading to inflammation and damage to the kidney tissue, particularly the glomeruli. [6]
Amyloidosis can cause nephrotic syndrome by depositing abnormal proteins called amyloids in your kidneys. These amyloid deposits interfere with the normal functioning of the glomeruli. [7]
Recognizing the symptoms early can lead to prompt treatment, which is critical in managing nephrotic syndrome.
Swelling is a prominent feature resulting from decreased oncotic pressure due to hypoalbuminemia. In children, swelling of the face or puffy eyelids is usually the earliest sign to appear. Later, this swelling extends to the rest of the body. In adults, however, it typically appears in the legs, ankles, feet, lower abdomen, or other areas. [8]
It is one of the frequently reported symptoms and indicates the presence of protein in urine. [8]You can often notice this symptom right away. When it’s in the toilet bowl, it looks like it has bubbles or foam on the surface, more noticeable than the usual bubbles that may appear when urine hits the water.
Retention of fluid in the body causes people with nephrotic syndrome to experience a rapid increase in weight. This weight gain is not related to fat or muscle but is due to the build-up of excess tissue fluid. [2]
Many people with nephrotic syndrome experience a reduced appetite, which can be linked to the body’s overall inflammatory state, hypothalamic dysregulation, edema, or the general discomfort associated with the condition. [9]
Nephrotic syndrome can lead to several serious complications, primarily due to the loss of proteins in the urine and the body’s response to this imbalance. Some of the most common complications are:
Your body might be more susceptible to infections, including serious ones like spontaneous bacterial peritonitis, an infection of the lining of your abdomen. If the infection spreads throughout your body, you might develop sepsis. [10]
Nephrotic syndrome can lead to high cholesterol levels in your blood. The deposition of this cholesterol in your arterial wall might make your arteries narrow and stiff, which can cause heart problems. [10,11]
The loss of protein like antithrombin III, which helps prevent blood clotting, combined with increased production of clotting factors by the liver, can lead to an increased risk of blood clots. These clots can form in the veins or arteries, leading to life-threatening conditions like deep vein thrombosis or pulmonary embolism. [10,12]
The retention of fluid and salt can lead to high blood pressure, further damaging the kidneys and increasing the risk of cardiovascular problems. [13]
The significant loss of proteins in the urine can lead to malnutrition, as the body loses essential proteins faster than they can be replaced. This can result in muscle wasting, weakness, and stunted growth in children. [10]
Diagnosing nephrotic syndrome involves several tests:
A chemically treated paper strip, or dipstick, is dipped into your urine sample to check for the presence of albumin. [8]
This measures the amount of protein lost in the urine over 24 hours. A protein loss greater than 3.5 grams per day indicates nephrotic syndrome.
Unlike the 24-hour urine collection, this test uses a single urine sample. It estimates the albumin lost in 24 hours by measuring albumin and creatinine, a byproduct of normal muscle breakdown. [14]
Blood tests for nephrotic syndrome check factors like protein levels, kidney function, cholesterol, electrolytes, lipid levels, and blood clotting parameters to diagnose and monitor the condition. [15]
Kidney ultrasound is a noninvasive imaging test used to assess the size, structure, and presence of abnormalities such as cysts, tumors, or blockages. It also helps to rule out other causes of kidney disease.
A kidney biopsy is a diagnostic procedure where a small sample of your kidney tissue is taken using a needle, and the tissue is then sent for examination under a microscope. This procedure is performed to determine the underlying cause of the nephrotic syndrome and to assess the severity of your kidney damage. [14]
The treatment of nephrotic syndrome is aimed at managing symptoms, addressing the underlying cause, and preventing complications. Here are common treatment options available:
Corticosteroids, such as Prednisone, play an important role in treating nephrotic syndrome, particularly in cases related to minimal change disease. These medications work by suppressing the immune system and reducing inflammation in the kidneys, which helps to restore the integrity of the glomeruli. This reduction in inflammation leads to decreased proteinuria. Initially, a high dose of steroids is prescribed daily for several weeks to achieve rapid control of symptoms. Once the condition improves, the dosage is gradually tapered down over several months. Steroids are one of the most effective treatments of nephrotic syndrome, but side effects such as weight gain, increased blood sugar levels, and increased risk of infections make monitoring essential. [16]
These medications suppress the immune system. Drugs like cyclophosphamide, cyclosporin, or mycophenolate mofetil are commonly used, particularly in conditions like FSGS, lupus nephritis, or membranous nephropathy. In children, immunosuppressants are used if nephrotic syndrome recurs frequently or does not respond well to treatment. [16,17]
This is a monoclonal group of medications that are used in cases of steroid-resistant nephrotic syndrome and in patients with frequent relapses. [16,17]
Diuretics, often known as water pills, such as furosemide and spironolactone, help reduce fluid retention and swelling by increasing urine output. [18]
Angiotensin-converting enzyme (ACE) inhibitor or Angiotensin II Receptor Blocker (ARB) can lower blood pressure and reduce proteinuria by decreasing the pressure in the glomeruli.
Blood thinners like warfarin or heparin may reduce the risk of blood clots, a common complication of nephrotic syndrome. [18]
Children with nephrotic syndrome should receive pneumococcal vaccination, including the 23-valent pneumococcal polysaccharide vaccine, to protect against severe pneumococcal infections. [19]Annual influenza vaccination is recommended for children with nephrotic syndrome and their household contacts, as it has been shown to reduce both influenza infections and relapses of nephrotic syndrome significantly. SARS-CoV-2 mRNA vaccines have proven safe and effective in these patients, though those on mycophenolate mofetil may exhibit lower antibody levels.[20] Inactivated, recombinant, and toxoid vaccines can be safely administered, with the varicella-zoster virus vaccine being given more frequently without significant side effects. [19,21]
Live vaccines should be postponed until the child’s prednisone dose is below 1 mg/kg daily (less than 20 mg/day) or 2 mg/kg on alternate days (less than 40 mg on alternate days). [19] Live vaccines are contraindicated for children receiving corticosteroid-sparing immunosuppressive agents, and the child should also avoid close contact with the child vaccinated with live vaccine for 3-6 weeks. [22]
Dietary management for nephrotic syndrome consists of several key considerations. Protein intake depends on the type of nephrotic syndrome. A daily intake of 1.0-1.1 g/kg is recommended for minimal change nephrotic syndrome. Other types may require a lower intake of 0.8 g/kg/day to avoid exacerbating proteinuria and renal damage. [23,24]Sodium intake should be restricted to 5-7 grams daily to help manage edema and hypertension. [8]You should watch out for high-sodium seasonings and condiments that often get ignored to have the right amount of salt.
Adequate caloric intake is also crucial to prevent malnutrition, with a recommended energy intake of over 35 kcal/kg/day to meet increased metabolic demands and prevent muscle wasting. [8]To manage hyperlipidemia, patients should limit saturated and trans fats, opting for a diet rich in monounsaturated and polyunsaturated fats. [18]
It is often challenging to manage fluid intake and water balance in children. Fluid intake should be adjusted based on the patient’s edema and overall fluid balance, though strict fluid restriction is generally only necessary in cases of significant fluid overload. [25] A balanced diet that provides sufficient calories and protein while limiting salt and fluids is important for regulating fluid levels. [23]
To help manage your child’s fluid intake and maintain their comfort, you start by determining the size of their favorite glass or cup to measure all the fluid they take properly. [25]You should remember all room-temperature liquids like milk, water, and juice should be counted as fluid intake. [25]
You should avoid giving your child salty foods, which can increase thirst. [25]If your child feels thirsty, you can choose iced tea, lemonade, or frozen fruits, such as melon or berries, to avoid giving them too much fluid. [25]Offering chewing gum or hard candy can also help alleviate thirst, and rinsing the mouth with cold water (without swallowing) can provide relief. Sucking on a lemon wedge can further moisten the mouth. [25,26]
[1] Tapia C, Bashir K. Nephrotic Syndrome. StatPearls [Internet] 2023.
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[3] Vestergaard SV, Birn H, Jensen SK, Sørensen HT, Nitsch D, Christiansen CF. Twenty-four-Year Trends in Incidence and Mortality of Nephrotic Syndrome: A Population-Based Cohort Study. Epidemiology 2023;34:411–20. https://doi.org/10.1097/EDE.0000000000001576.
[4] Samsu N. Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment. Biomed Res Int 2021;2021:1–17. https://doi.org/10.1155/2021/1497449.
[5] Vivarelli M, Massella L, Ruggiero B, Emma F. Minimal Change Disease. Clinical Journal of the American Society of Nephrology 2017;12:332–45. https://doi.org/10.2215/CJN.05000516.
[6] Nawata A, Hisano S, Shimajiri S, Wang K, Tanaka Y, Nakayama T. Podocyte and endothelial cell injury lead to nephrotic syndrome in proliferative lupus nephritis. Histopathology 2018;72:1084–92. https://doi.org/10.1111/his.13454.
[7] Karam S, Kaushal A, Abu Amer N, Royal V, KItchlu A. Non-Immunoglobulin Amyloidosis-Mediated Kidney Disease: Emerging Understanding of Underdiagnosed Entities. Advances in Kidney Disease and Health 2024;31:334–45. https://doi.org/10.1053/j.akdh.2024.02.001.
[8] Kodner C. Diagnosis and Management of Nephrotic Syndrome in Adults. Am Fam Physician 2016;93:479–85.
[9] Ueno H, Miyamoto T, Sanada K, Nakazono K, Tanaka K, Nishimura H, et al. Changes in gene expressions of hypothalamic neuropeptides controlling feeding behaviors in bilateral nephrectomized rats. Neurosci Lett 2019;711:134426. https://doi.org/10.1016/j.neulet.2019.134426.
[10] Claudio P, Gabriella M. Nephrotic syndrome: pathophysiology and consequences. J Nephrol 2023;36:2179–90. https://doi.org/10.1007/S40620-023-01697-7.
[11] Agrawal S, Zaritsky JJ, Fornoni A, Smoyer WE. Dyslipidaemia in nephrotic syndrome: mechanisms and treatment. Nat Rev Nephrol 2018;14:57–70. https://doi.org/10.1038/nrneph.2017.155.
[12] Vestergaard SV, Birn H, Darvalics B, Nitsch D, Sørensen HT, Christiansen CF. Risk of Arterial Thromboembolism, Venous Thromboembolism, and Bleeding in Patients with Nephrotic Syndrome: A Population-Based Cohort Study. Am J Med 2022;135:615-625.e9. https://doi.org/10.1016/j.amjmed.2021.11.018.
[13] Ray EC, Rondon-Berrios H, Boyd CR, Kleyman TR. Sodium Retention and Volume Expansion in Nephrotic Syndrome: Implications for Hypertension. Adv Chronic Kidney Dis 2015;22:179–84. https://doi.org/10.1053/j.ackd.2014.11.006.
[14] Kodner C. Nephrotic syndrome in adults: diagnosis and management. Am Fam Physician 2009;80:1129–34.
[15] Stoycheff N, Stevens LA, Schmid CH, Tighiouart H, Lewis J, Atkins RC, et al. Nephrotic Syndrome in Diabetic Kidney Disease: An Evaluation and Update of the Definition. American Journal of Kidney Diseases 2009;54:840–9. https://doi.org/10.1053/j.ajkd.2009.04.016.
[16] Vivarelli M, Gibson K, Sinha A, Boyer O. Childhood nephrotic syndrome. The Lancet 2023;402:809–24. https://doi.org/10.1016/S0140-6736(23)01051-6.
[17] Nagai K. Immunosuppressive Agent Options for Primary Nephrotic Syndrome: A Review of Network Meta-Analyses and Cost-Effectiveness Analysis. Medicina (B Aires) 2023;59:601. https://doi.org/10.3390/medicina59030601.
[18] Appel GB. Improved outcomes in nephrotic syndrome. Cleve Clin J Med 2006;73:161–7. https://doi.org/10.3949/ccjm.73.2.161.
[19] Kamei K, Miyairi I, Ishikura K, Ogura M, Shoji K, Funaki T, et al. Prospective Study of Live Attenuated Vaccines for Patients with Nephrotic Syndrome Receiving Immunosuppressive Agents. J Pediatr 2018;196:217-222.e1. https://doi.org/10.1016/j.jpeds.2017.12.061.
[20] Kamei K, Ogura M, Sato M, Nishi K, Shoji K, Funaki T, et al. Immunogenicity and safety of SARS-CoV-2 mRNA vaccine in patients with nephrotic syndrome receiving immunosuppressive agents. Pediatric Nephrology 2023;38:1099–106. https://doi.org/10.1007/s00467-022-05633-y.
[21] Angeletti A, Lugani F, La Porta E, Verrina E, Caridi G, Ghiggeri GM. Vaccines and nephrotic syndrome: efficacy and safety. Pediatric Nephrology 2023;38:2915–28. https://doi.org/10.1007/s00467-022-05835-4.
[22] Nephrotic syndrome in children – NHS n.d. https://www.nhs.uk/conditions/nephrotic-syndrome/ (accessed August 11, 2024).
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[24] Polderman N, Cushing M, McFadyen K, Catapang M, Humphreys R, Mammen C, et al. Dietary intakes of children with nephrotic syndrome. Pediatric Nephrology 2021;36:2819–26. https://doi.org/10.1007/s00467-021-05055-2.
[25] National Kidney Foundation. KDOQI Clinical Practice Guideline for Nutrition in Children with CKD: 2008 Update. American Journal of Kidney Diseases 2009;53:S11–104. https://doi.org/10.1053/j.ajkd.2008.11.017.
[26] Nutrition and Nephrotic Syndrome – Stanford Medicine Children’s Health n.d. https://www.stanfordchildrens.org/en/topic/default?id=nutrition-and-nephrotic-syndrome-90-P03099 (accessed August 11, 2024).
