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Diseases

Evaluation of nephrotic syndrome

OVERVIEW

  • Summary
  • Urgent Considerations
  • Etiology

DIAGNOSIS

  • Differential Diagnosis
  • Diagnostic Approach

IMAGES

  • Library

REFERENCES

  • Citations
  • Credits

Summary

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Nephrotic syndrome is defined as the presence of proteinuria (>3.5 g/24 hours), hypoalbuminemia (<3.0 g/dL), and peripheral edema. Hyperlipidemia 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 etiology 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 specialized 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 pathologic 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]
Hypoalbuminemia
Patients become hypoalbuminemic 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 hypercholesterolemia and hypertriglyceridemia.[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 recognized 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 procoagulant factors; and increased platelet activation.[6] [7]
Edema
Occurs due to a combination of a decrease in oncotic pressure (also known as colloid osmotic pressure) from hypoalbuminemia, 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]
content by BMJ Group
Last updated

Citations

    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.[Abstract][Full Text]

    • 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.[Abstract][Full Text]

    • 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]

    Referenced Articles

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    • 3. Sadowski CE, Lovric S, Ashraf S, et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2015 Jun;26(6):1279-89.[Abstract][Full Text]

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    • 27. Mbakop C, DeVita MV, Wahl SJ, et al. Adult primary nephrotic syndrome trends by race: a diminished frequency of focal segmental glomerulosclerosis in non-black patients. Int Urol Nephrol. 2021 Apr;53(4):719-24.[Abstract]

    • 28. Parikh RV, Tan TC, Fan D, et al. Population-based identification and temporal trend of children with primary nephrotic syndrome: the kaiser permanente nephrotic syndrome study. PLoS One. 2021 Oct 14;16(10):e0257674.[Abstract][Full Text]

    • 29. Meyrier A, Niaudet P. Acute kidney injury complicating nephrotic syndrome of minimal change disease. Kidney Int. 2018 Nov;94(5):861-9.[Abstract]

    • 30. Filler G, Young E, Geier P, et al. Is there really an increase in non-minimal change nephrotic syndrome in children? Am J Kidney Dis. 2003 Dec;42(6):1107-13.[Abstract]

    • 31. Vivarelli M, Massella L, Ruggiero B, et al. Minimal change disease. Clin J Am Soc Nephrol. 2017 Feb 7;12(2):332-45.[Abstract][Full Text]

    • 32. Audard V, Larousserie F, Grimbert P, et al. Minimal change nephrotic syndrome and classical Hodgkin's lymphoma: report of 21 cases and review of the literature. Kidney Int. 2006 Jun;69(12):2251-60.[Abstract][Full Text]

    • 33. Farruggia P, Trizzino A, Maringhini S, et al. Hodgkin lymphoma and nephrotic syndrome in childhood. Indian J Pediatr. 2010 Oct;77(10):1147-9.[Abstract]

    • 34. Wenderfer SE. Viral-associated glomerulopathies in children. Pediatr Nephrol. 2015 Nov;30(11):1929-38.[Abstract][Full Text]

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    • 36. de Roij van Zuijdewijn C, van Dorp W, Florquin S, et al. Bisphosphonate nephropathy: a case series and review of the literature. Br J Clin Pharmacol. 2021 Sep;87(9):3485-91.[Abstract][Full Text]

    • 37. Hinkes BG, Mucha B, Vlangos CN, et al. Nephrotic syndrome in the first year of life: two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, WT1, and LAMB2). Pediatrics. 2007 Apr;119(4):e907-19.[Abstract]

    • 38. Nieto-Gañán I, Iturrieta-Zuazo I, Rita C, et al. Revisiting immunological and clinical aspects of membranous nephropathy. Clin Immunol. 2022 Apr;237:108976.[Abstract][Full Text]

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    • 40. Beck LH Jr, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009 Jul 2;361(1):11-21.[Abstract][Full Text]

    • 41. Debiec H, Ronco P. PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med. 2011 Feb 17;364(7):689-90.[Abstract][Full Text]

    • 42. Ruggenenti P, Debiec H, Ruggiero B, et al. Anti-ohospholipase A2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy. J Am Soc Nephrol. 2015 Oct;26(10):2545-58.[Abstract][Full Text]

    • 43. Kim YG, Choi YW, Kim SY, et al. Anti-phospholipase A2 receptor antibody as prognostic indicator in idiopathic membranous nephropathy. Am J Nephrol. 2015;42(3):250-7.[Abstract]

    • 44. Selby NM, Taal MW. An updated overview of diabetic nephropathy: diagnosis, prognosis, treatment goals and latest guidelines. Diabetes Obes Metab. 2020 Apr;22 Suppl 1:3-15.[Abstract][Full Text]

    • 45. Persson F, Rossing P. Diagnosis of diabetic kidney disease: state of the art and future perspective. Kidney Int Suppl (2011). 2018 Jan;8(1):2-7.[Abstract][Full Text]

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    • 56. Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis: pathogenetic heterogeneity and proposal for a new classification. Semin Nephrol. 2011 Jul;31(4):341-8.[Abstract]

    • 57. Salvadori M, Rosso G. Reclassification of membranoproliferative glomerulonephritis: identification of a new GN: C3GN. World J Nephrol. 2016 Jul 6;5(4):308-20.[Abstract][Full Text]

    • 58. Boyer O, Schaefer F, Haffner D, et al. Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group. Nat Rev Nephrol. 2021 Apr;17(4):277-89.[Abstract][Full Text]

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