Nephrotic Syndrome

0
192
nephrotic syndrome

Nephrotic syndrome is a kidney disorder characterized by proteinuria greater than 40mg/m2/hour or 50mg/kg/day, first morning urine protein to creatinine ratio of greater than or equal to 3mg/mg, hypoalbuminemia less than 3g/dl in the presence of edema and hyperlipidemia greater than 200mg/dl.

Four cardinal features which are hallmark of nephrotic syndrome are:

  • Proteinuria
  • Hypoalbuminemia
  • Edema
  • Hyperlipidemia

Epidemiology

There are approximately 2-7new cases per 100,000 kids in western hemisphere, with peak incidence at around 1.5-6 years of ag. This disease is relatively more common in boys with high prevalence in South East Asia.

Etiology

Nephrotic syndrome can be classified as primary, secondary and genetic. Primary nephrotic syndrome is further classified as idiopathic and post glomerulonephritis nephrotic syndrome.

Primary Nephrotic Syndrome

Primary nephrotic syndrome is associated with glomerular diseases intrinsic to the kidney and not related to systemic causes. Among all the kids diagnosed with nephrotic syndrome, more than 85 percent are found to have minimal change disease.

Different varieties include:

  • Minimal Change Nephrotic Syndrome
  • Focal Segmental Glomerulosclerosis
  • Membranous Nephropathy
  • Membranoproliferative Glomerulonephritis
  • IgA Nephropathy
  • Idiopathic Crescentic Glomerulonephritis

Congenital Nephrotic Syndrome

There is a really long list of congenital nephrotic syndromes but few imp ones are listed here:

  • Finnish Type Congenital Nephrotic Syndrome
  • Focal Segmental Glomerulosclerosis
  • Diffuse Mesangial Sclerosis
  • Denys Drash Syndrome
  • Frasier Syndrome

These are clinically rare entities that result from podocin, nephrin  and cation channel 6 gene mutations and usually present in first 3 months of life.

Secondary Nephrotic Syndrome

By definition secondary causes are the causes that start extrinsic to kidney and later on progress to involve them. They include infections, like hepatitis B and C, HIV, syphilis and malaria, drugs like penicillamine, gold salts and NSAIDs, autoimmune diseases like SLE, various forms of vascultis like Henoch Schonlein Purpura, allergic reaction to bee sting and food allergens and metabolic diseases like diabetes.

Steroid Sensitive Nephrotic Syndrome

Therapeutically speaking nephrotic syndrome is classified on the basis of response to steroid therapy. Features suggesting steroid sensitive disease are age between 1 and 10 years, absence of macroscopic hematuria, normal BP, normal complement levels and normal renal function.

Steroid Resistant Nephrotic Syndrome

Conventionally steroid resistant disease is said to have occurred when urinary remission cannot be achieved within 8 weeks of prednisone therapy of 60mg/m2/day. 

But currently it is defined as when there is failure to achieve urinary remission after 4 weeks of prednisolone therapy and 3 doses of IV methyl prednisolone pulse therapy on alternate days.

Relapse

Relapse of nephrotic syndrome is defined as recurrence of nephrotic range proteinuria in association with recurrence of edema once the patient has become completely asymptomatic.

Frequently Relapsing Disease

Frequently relapsing disease is the one with more than 2 relapses in 6 months or more than 4 relapses in 1 year.

Steroid Dependent Disease

Steroid dependent nephrotic syndrome is defined as relapse of disease on either switching to alternate therapy or within 15 days of stopping steroid therapy.

Pathophysiology

Nephrotic syndrome results from impaired permeability across the glomerular basement membrane resulting in loss of albumin in urine. There is decreased oncotic pressure resulting in edema. Reduced blood volume triggers renin angiotensin 2 aldosterone axis. There is an increased hepatic production of TGs and lipoprotein carriers resulting in hyperlipidemia.

History

95 percent of the kids report with complaints of edema and weight gain. Edema usually appears first in areas of low tissue resistance. It then progresses rapidly or slowly to become generalized and massive.

Other complains include frothy urine, breathlessness secondary to ascites and plueral effusions. Some kids also have a history of respiratory tract infections or a hypersensitivity event like bee sting.

Physical Exam

On physical examination the edema is pitting and typically dependent in nature. Blood pressure is usually normal in minimal change disease. Many children have significant respiratory distress secondary to ascites and pleural effusions. Abdominal tenderness might indicate peritonitis.

Investigations

Various urine and blood studies are performed to confirm the diagnosis of nephrotic syndrome.

Urine Studies

First morning urine protein/creatinine ratio is more easily obtained than 24-hour urine studies and is more reliable as well. Other urinary investigations include urine dipstick test, urine microscopy and culture.

Blood Studies

Serum albumin levels are low. Pateints have an elevated total cholesterol, triglycerides and LDL levels.

Serum sodium and calcium levels are typically low. In addition there is marked hemoconcentration due to intravascular volume depletion.

Complement levels and renal function tests are normal in minimal change disease.

Some investigations to rule out secondary causes include serology for hepatitis B and C, blood screening for malaria, ASO titres and throat swab to check for poststreptococcal glomerulonephritis and anti nuclear antibodies to rule out SLE.

Imaging Studies

Kidney ultrasonographic findings are usually nonspecific. CXR may show pleural effusions and pulmonary edema.

Kidney Studies

Indications to perform renal biopsy in a patient of nephrotic syndrome are:

  • Age < 1 Year or > 10 Years at Presentation
  • Gross or Persistent Microscopic Hematuria
  • Low Complement Levels
  • Hypertension
  • Impaired Renal Function
  • Steroid Resistant Nephrotic Syndrome

Differential Diagnosis

Differential diagnosis includes acute glomerulonephritis and other entities causing generalized edema like hereditary angioedema, protein losing enteropathy, heart failure and malnutrition if supported by  history and physical examination.

Treatment

Treatment of nephrotic syndrome aims at providing supporting and specific relief to patients.

Infections

Upper respiratory tract infections are treated with appropriate antibiotic therapy.

Edema

Patient is advised to use no added salt diet, diuretics and albumin infusions  are advised only when there is significant respiratory distress due to massive ascites or bilateral plueral effusions.

Hyperlipidemia

Hyperlipidemia goes away on its own mostly.

Specific Treatment for Minimal Change Nephrotic Syndrome

Oral corticosteroids are mainstay in the treatment of minimal change disease. One must exclude active infections, tuberculosis and other contraindications before prescribing steroid therapy. Patients are also checked for their vaccination status against Pneumococci, Meningococci and Hemophilus influenzae.

Longer regimens of steroids are preferred because of lower relapse rates. Total duration of this regimen is 4.5 months. We start by giving 60mg/m2/day prednisolone until proteinuria is gone. The same dose is continued for 30 days and then switch to alternate day therapy for another 2 months. After 2 months steroids are tapered off by 15mg/m2 every 2 weeks.

Steroid Resistant Nephrotic Syndrome

For steroid resistant disease steroid intake duration is prolonged and steroid sparing agents are added.

Frequently Relapsing and Steroid Dependent Nephrotic Syndrome

To tackle frequently relapsing nephrotic syndrome and to treat steroid dependent disease low dose steroid therapy is given for an increased duration.

Congenital Nephrotic Syndrome

For congenital nephrotic syndrome unilateral nephrectomy is carried out for the control of hypoalbuminemia, followed by dialysis for renal failure until the child is large and fit for renal transplantation.

Secondary Nephrotic Syndrome

Secondary nephrotic syndrome is managed by identifying and treating the underlying cause.

Complications of Nephrotic Syndrome

Various complications of nephrotic syndrome include

  • Peritonitis
  • Thromboembolism and CVS Disease
  • Pleural Effusion and Ascites
  • Anasarca
  • Renal Insufficiency
  • Vitamin D deficiency
  • Hypothyroidism
  • Impaired Growth

Complications of Medical Therapy

Prolonged steroid therapy may lead to

  • Cushing Syndrome
  • Growth Suppression
  • Decreased Bone Mineral Density
  • Peptic Ulceration
  • Increased Risk of Infections
  • Impaired Glucose Tolerance
  • Cataracts
  • Depression

 

SHARE
Previous articleHistopathology Images: Adenocarcinoma Prostate
Next articleCo-Trimoxazole
The writer enjoys medical education and has special interest in community medicine.