Snapshot A 6-year-old boy is brought to the emergency department by his mother due to swelling around his eyes and legs. The mother reports that the patient recently recovered from an upper respiratory tract infection. Physical exam is significant for periorbital and lower extremity edema. Laboratory testing is significant for hypoalbuminemia and normal complement levels. Urinalysis demonstrates 4+ protein. A presumptive diagnosis of minimal change disease is made and the patient is started on steroid therapy. Introduction Clinical definition a type of kidney disease that results in proteinuria, peripheral edema, hyperlipidemia, and hypoalbuminemia Associated conditions chronic kidney disease HBV membranous nephropathy Epidemiology Incidence annually there are 3 cases per 100,000 adults Etiology Primary glomerular disease focal segmental glomerulosclerosis most common cause of nephrotic syndrome in adults membranous nephropathy minimal change disease Secondary causes diabetic nephropathy systemic lupus erythematosus amyloidosis Pathogenesis the glomerulus becomes permeable to large molecules (e.g., albumin) this loss of albumin (proteinuria) results in hypoalbuminemia and edema associated with a hypercoagulable state pathophysiology unclear but may be due to loss of antithrombin and plasminogen proteins increased lipid synthesis secondary to proteinuria this in turn results in hypercholesterolemia and hyperlipidemia Presentation Symptoms edema periorbital, lower extremity, and genital edema frothy urine ascites weight gain fatigue shortness of breath Physical exam hypertension edema leukonychia suggestive of a low albumin state and presents as white streaking on the fingernails Studies Labs hypoalbuminemia (serum albumin of < 2.5 g/dL) hyperlipidemia Urine studies rule out transient / orthostatic proteinuria if no symptoms or signs are present other than proteinuria proteinuria > 3-3.5 g/day or > 300-350 mg/mmol on spot urine protein to creatinine ratio fatty casts with "maltese cross" sign Nephrotic SyndromeTypePathophysiologyRenal BiopsyTreatment and NotesFocal segmental glomerulosclerosisPodocyte injury or decreased glomerular filtration barrier integrityLight microscopysegmental scarringTreat underlying etiology in secondary causesSteroid therapyCan be secondary toHIVsickle cell diseaseheroin abuseinterferon treatmentMinimal change diseaseUnclear but may be due to an immune-related mechanismLight microscopynormal appearingElectron microscopyeffacement of the foot processesSteroid therapyMost common in childrenMay follow recent infection, immunizations, or may be idiopathicCan be associated with Hodgkin lymphomaMembranous nephropathyAntibody-immune complex depositionIgG antibodies target podocyte antigensor antigens in close proximity to the podocytesComplement-mediated podocyte injuryLight microscopyglomerular basement membrane thickeningImmunofluoresenceimmune complex deposition leading to granular appearanceElectron microscopy"spike and dome"subepithelial depositsImmunosuppressive therapy in primary casessteroids and cyclophosphamideMost common cause of primary nephrotic syndrome in Caucasian adultsPrimary causesantibodies targeting phospholipase A2 receptorsSecondary causesmedicationssystemic lupus erythematosusnonsteroidal anti-inflammatory drugsgoldpenicillaminehepatitis B and C infectionAmyloidosisAmyloid deposits in the mesangiumElectronmicroscopyapple-green birefringence on Congo red stain under polarized lightAssociated with multiple myeloma and chronic inflammatory conditions (i.e., rheumatoid arthritis)Treatment involves addressing the plasma cell dyscrasia or management of the underlying inflammatory conditionDiabetic glomerulonephropathyGlomerular hyperperfusion and hyperfiltration result in albumin leakingunder these conditions the glomerulus responds viaglomerular basement membrane thickeningdue to non-enzymetic glycosylationhypertrophysclerosingpodocyte injuryLight microscopyexpansion of the mesangiumKimmelstiel-Wilson lesionsAngiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)Adequately controlling diabetes Prognosis Depends on the underlying cause e.g., patients with minimal change disease typically respond well to steroid therapy