Learning objectives

• Definition of nephrotic syndrome
• Management of nephrotic syndrome

Definition and mechanisms

• Nephrotic syndrome is a collection of symptoms due to kidney damage including protein in the urine, low blood albumin levels, high blood lipids, and edema
• Characterized by glomerular injury
• Can be primary, being a disease specific to the kidneys, or secondary to a systemic condition
• Primary causes:
  • Minimal-change disease (nephropathy)
  • Focal segmental glomerulosclerosis
  • Membranous glomerulonephritis
  • Membranoproliferative glomerulonephritis 
  • Hereditary nephropathies
• Secondary causes:
  • Diabetes mellitus
  • Systemic lupus erythematosus
  • Sarcoidosis
  • Amyloidosis and paraproteinemias
  • Viral infections (e.g. hepatitis B, hepatitis C, HIV)
  • Pre-eclampsia
  • Sjögren’s syndrome
  • Multiple myeloma
  • Vasculitis
  • Cancer
  • Medications: penicillin, captopril
• A defect in the glomerular barrier leads to an increased glomerular permeability resulting in proteinuria/albuminuria
• Leading to a decrease in plasma oncotic pressure, retention of sodium and water, peripheral edema, ascites, pleural effusions, and hypovolemia
• Most cases spontaneously remit without treatment, hypertension occurs commonly, and renal failure is rare
• Patients may develop renal failure as well as secondary complications including arterial and venous thromboembolism and infection

Signs and symptoms

• Proteinuria (>3 g/24 h) and foamy urine
• Hypoalbuminemia (< 3.5 g/dl)
• Hypercholesterolemia and hyperlipidemia 
• Thromboembolic episodes
• Puffy eyelids and swelling in the legs, ankles, feet, or lower abdomen
• Weight gain
• Fatigue
• Loss of appetite

Risk factors

• Nephrotoxic medication
• Diabetes mellitus
• Systemic lupus erythematosus
• Amyloidosis
• Reflux nephropathy
• Infections: HIV, hepatitis B, hepatitis C, malaria

Complications

• Arterial and venous thrombosis
• Infections
• Hypertension
• High blood cholesterol and elevated blood triglycerides
• Acute kidney injury
• Chronic kidney disease
• Pulmonary edema
• Hypothyroidism
• Vitamin D deficiency
• Hypocalcemia
• Microcytic hypochromic anemia
• Protein malnutrition
• Growth retardation
• Cushing’s syndrome

Diagnosis

• Urine dipstick test to check for albuminuria
• 24-hour urine collection
• Urine albumin-to-creatinine ratio
• Blood tests: serum albumin level, creatinine concentrations
• Kidney ultrasound
• Kidney biopsy

Treatment

• Diuretics
• ACE inhibitors and angiotensin-receptor blockers are used alone or in combination
• Prednisolone
• Cyclophosphamide
• Mycophenolate
• Cyclosporin
• Low salt diet and limited fluid intake
• Specific treatment depending on etiology:
  • Statins to lower cholesterol
  • Glucocorticosteroids for minimal-change nephropathy
  • Prednisone and cyclophosphamide are useful in some forms of lupus nephritis
  • Secondary amyloidosis with nephrotic syndrome may respond to anti-inflammatory treatment of the primary disease

Management

Suggested reading

• Pollard BJ, Kitchen, G. Handbook of Clinical Anaesthesia. Fourth Edition. CRC Press. 2018. 978-1-4987-6289-2.
• Vishnu D, Tempe D, Arora K, Virmani S, Chander J, Agarwal S.(2012). Anesthetic management of a child with nephrotic syndrome undergoing open heart surgery: Report of a rare case. Annals of cardiac anaesthesia. 15. 305-8.