History

Fact Explanation
Body swelling Nephrotic syndrome is a nonspecific kidney disorder characterised by a number of signs of disease namely proteinuria, hypoalbuminemia and edema. It usually present in children between 3 - 10 years. Males are more susceptible. Glomerular capillary membrane is damaged by several mechanisms which increases the permeability of it. [1,2,3] The exact cause remains unknown. Complex disturbances in immune system or genetic mutations are thought to causes extensive effacement of podocyte foot processes . This leads to increased permeability of the glomerular capillary wall. Therefore proteins such as albumin, antithrombin or immunoglobulins tend to pass through the cell membrane and appear in urine. The subsequent hypoalbuminaemia (less than 25 g/l) reduces capillary oncotic pressure which usually tends to pull water into the circulatory system. In the absence of the pulling force, fluid leaks out of the capillaries resulting in excess fluid buildup in the tissues. Additionally hypovolemia results in reduced renal perfusion pressure. Subsequent activation of the Renin-angiotensin-aldosterone system causes retention of sodium and water which again increases the body swelling. Reduced intravascular volume causes release of ADH hormone which enhance reabsorption of water. Edema in nephrotic syndrome starts in a milder form as a peri orbital puffiness or rarely at lower extremities and progress to a generalized edema, ascites, pleural effusion and genital edema. edema has a diurnal variation. Edema is more prominent in the face during the morning and over lower extremities later in the day. Edema is pitting in nature. [1,2,3,4,5]
Frothy urine In minimally change disease, possible T cell dysfunction leading to alteration of cytokines has been recognized. This causes loss of negatively charged glycoproteins within the glomerular capillary wall. So the usual repulsion forces which had between negatively charged glomerular capillary wall and albumin molecules diminished leading to increase permeability of the wall for protein molecules. Appearance of proteins in "nephrotic levels" causes frothy urine. (more than 40mg/m2/hour or urine protein : creatinine ratio more than 200mg protein/mmol creatinine) [1,2,4,6]
Decreased urine output Hypovolemia and reduced renal perfusion pressure which cause reduced urine output. Activated Renin-angiotensin-aldosterone system and ADH hormone aggravate it. [1,2,3]
Proceeding respiratory tract infection This is frequent. Patient may be febrile, lethargic or irritable. Mothers may complain of difficulty in feeding and reduced appetite. Patient may have diarrhoea too. Atopic children are more prone to idiopathic/primary nephrotic syndrome. They usually have a history of frequent episodes of allergic rhinitis.[1,2,4]
Red colored urine Gross red hematuria occurs rarely when the patient has the membranoproliferative subtype of nephrotic/nephritic syndrome. Membranoproliferative glomerulonephritis involves deposits at the intraglomerular mesangium. These depositions can lead to splitting of the glomerular basement membrane which become permeable to red blood cells. Very rarely it can occur in minimal change nephrotic syndrome as well. [1,2,3,7]
Respiratory distress Massive ascites and thoracic compression, frank pulmonary edema or pulmonary effusions as a result of transudation of fluids in to body cavities may cause difficulty in breathing. Increased prothrombotic state )thrombocytosis, hemoconcentration, relative immobilization) and decreased fibrinolytic factors (urinary loss of antithrombin protein C and S) result increased risk of venous and arterial thromboembolism. Pulmonary embolism risk is also increased. It may also present as respiratory distress and chest pain. [1,2]
Abdominal pain Severe intestinal oedema may occur in nephrotic syndrome as a result of compensatory fluid overload and hypoalbuminaemia. The patient developed abdominal pain. Abdominal pain may present because of several etiologies in nephrotic syndrome. Uncompensated hypovolumia, peritonits (as a result of susceptibility of infection secondary to low immunoglobulin level), cellulitis and renal vein thrombosis are some complications which may present as an abdominal pain.[1,2,3]
Neurological symptoms (Eg -Seizures ,headache) Patients with a nephrotic syndrome are at increased risk of venous and arterial thromboembolism. Sagital sinus thrombosis is one of them. Sudden vascular occlusion can result in neurological manifestations such as headache and seizures and sometimes followed by hemiparesis. [8,9]
Secondary causes Nephrotic syndrome is primary in around 90% of instances. % of cases are secondary to some other cause. Patient may mention of any of those causes in past medical history. eg- Henoch–Schönlein purpura (joint pains, abdominal colicks, rases) Hepatitis B Malaria (Travel to malaria endemic areas) Hodgkin's lymphoma (fever, malaise, generalized lymphadenopathy) Allergy (Bee sting) Secondary nephrotic syndrome should be suspected in patient presents at an age more than 8 years along with hypertension, haematuria, renal dysfunction, rashes or arthralgia. Very rarely nephrotic syndrome can be congenital (Finnish type). It is autosomal recessive in origin and should be suspected when an infant presents within 1-3 months with persistent edema and infection. [1,2,3,4,7,10]
Past history of similar episodes Most patients admit to the ward with relapses of nephrotic syndrome. They may have one or more similar episodes most of the time. [1,2] Primary/ idiopathic nephrotic syndrome has several histopathological sub types. Pediatrics nephrotic syndrome is minimal change sub type in 85% of instances. In minimal change nephrotic syndrome (MCNS), nephrons appear normal when viewed with an optical microscope as the lesions are only visible using an electron microscope. Protienuria is more prominent. [1,2,5,6] Rarely it falls in to focal segmental glomerular sclerosis (5%) or mesangial proliferative glomerulonephritis (5%) sub types. Focal segmental glomerular sclerosis (FSGS) is the commonest type in adults. Pathologically it appears as sclerosis/scarring of parts of some glomeruli. Mesangial proliferative glomerulonephritis (MPGN) is the inflammation of the glomeruli along with the deposit of antibodies in their membranes. Membranous glomerulonephritis and rapidly progressive glomerulonephritis are other rarer sub types. [1,2,3,4,13,14]
References
  1. GIPSON D. S., MASSENGILL S. F., YAO L., NAGARAJ S., SMOYER W. E., MAHAN J. D., WIGFALL D., MILES P., POWELL L., LIN J.-J., TRACHTMAN H., GREENBAUM L. A.. Management of Childhood Onset Nephrotic Syndrome. PEDIATRICS [online] December, 124(2):747-757 [viewed 15 June 2014] Available from: doi:10.1542/peds.2008-1559
  2. CHARLES KODNER, Nephrotic Syndrome in Adults: Diagnosis and Management, Am Fam Physician[online] 2009,80(10).1129-1134, 1136. [viewed 15 June 2014] Available from: http://www.aafp.org/afp/2009/1115/p1129.html
  3. KANG HEE GYUNG. Treatment of steroid-resistant pediatric nephrotic syndrome. Korean J Pediatr [online] 2011 December [viewed 15 June 2014] Available from: doi:10.3345/kjp.2011.54.8.317
  4. OBERWEIS BS, MATTOO A, WU M, GOLDFARB DS. Minimal change disease and IgA deposition: separate entities or common pathophysiology? Case Rep Nephrol [online] 2013:268401 [viewed 15 June 2014] Available from: doi:10.1155/2013/268401
  5. WONG EK, BRADY M, SHEERIN NS. Severe intestinal oedema due to nephrotic syndrome. QJM [online] 2013 Feb, 106(2):191-2 [viewed 12 June 2014] Available from: doi:10.1093/qjmed/hcr236
  6. SHARMA A, GUPTA R, BAGGA A, DINDA AK. Glomerular filtration barrier in pediatric idiopathic nephrotic syndrome. Saudi J Kidney Dis Transpl [online] 2013 Mar, 24(2):286-91 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23538351
  7. SINHA A, HARI P, SHARMA PK, GULATI A, KALAIVANI M, MANTAN M, DINDA AK, SRIVASTAVA RN, BAGGA A. Disease course in steroid sensitive nephrotic syndrome. Indian Pediatr [online] 2012 Nov, 49(11):881-7 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22791676
  8. PILLEKAMP F., HOPPE B., ROTH B., QUERFELD U.. Vomiting, headache and seizures in a child with idiopathic nephrotic syndrome. Nephrology Dialysis Transplantation [online] 1997 June, 12(6):1280-1281 [viewed 12 June 2014] Available from: doi:10.1093/ndt/12.6.1280
  9. BHOOBUN S, JALLOH AA, JACOBSEN KH. Cerebral venous thrombosis in a child with nephrotic syndrome: case report Pan Afr Med J [online] :57 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549447
  10. DIAS OM, COSTA AN, CARVALHO CR, KAIRALLA RA. Transient lymphadenopathy secondary to nephrotic syndrome. Arq Bras Cardiol [online] 2012 May, 98(5):e82-3 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22858659
  11. ITO S. Disease course in childhood steroid sensitive nephrotic syndrome: is it changeable? Indian Pediatr [online] 2012 Nov, 49(11):868-9 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23255697
  12. WEENING JJ. Will laboratory markers replace kidney biopsy in patients with nephrotic syndrome? Neth J Med [online] 2012 Apr, 70(3):107-8 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22516573
  13. TANEDA S, HONDA K, UCHIDA K, NITTA K, YUMURA W, ODA H, NAGATA M. Histological heterogeneity of glomerular segmental lesions in focal segmental glomerulosclerosis. Int Urol Nephrol [online] 2012 Feb, 44(1):183-96 [viewed 15 June 2014] Available from: doi:10.1007/s11255-011-9932-y
  14. KUTE VB, VANIKAR AV, SHAH PR, GUMBER MR, PATEL HV, TRIVEDI HL. Mesangial proliferative glomerulonephritis with acute tubule interstitial nephritis leading to acute kidney injury in influenza A (H1N1) infection. Indian J Nephrol [online] 2014 Mar, 24(2):114-6 [viewed 15 June 2014] Available from: doi:10.4103/0971-4065.127902

Examination

Fact Explanation
Anthropometry Weight and height are used to calculate body surface area which is on which the dose of prednisolone is calculated. [1,2]
Features of steroid toxicity In a patient who are already on steroid treatment, features of steroid toxicity should be looked in to. (eg- Cushinoid features, weight gain and obesity, hypertension, cataract) [1,2,3,4]
Vasculitic rash Secondary causes of nephrotic syndrome should be suspected if patient has vasculitic rash. (eg- typical palpable purpura appear on the legs and buttocks in Henoch–Schönlein purpura) [1,3,5]
Edema Pitting edema distributes in peri orbital area and at lower extremities. It may progress to a generalized edema later causing ascites, pleural effusion and genital edema. [1,2,3]
Signs of respiratory distress Rapid, shallow breathing, grunting, flaring of the nostrils and intercostal/subcostal recessions are common findings suggestive of respiratory distress. Massive ascites, pulmonary edema, pulmonary effusions or pulmonary embolism can cause respiratory distress. [1,2,3,6]
Hypertension Hypertension in nephrotic syndrome is either due to the extreme vasoconstrictive response to hypovolemia or the nature of the underlying pathology such as in mesangio proliferative sub type. [1,2,6]
Hypotension Hypotension can be caused by extreme extravasation of fluid in to the interstitial space from intravascular compartment. This may lead to hypovolumemic shock. [1,2,6,7]
Abdominal tenderness This may be either due to cellulitis, peritonitis, renal vein thrombosis or hypovolemia. ,[6,8]
References
  1. GIPSON D. S., MASSENGILL S. F., YAO L., NAGARAJ S., SMOYER W. E., MAHAN J. D., WIGFALL D., MILES P., POWELL L., LIN J.-J., TRACHTMAN H., GREENBAUM L. A.. Management of Childhood Onset Nephrotic Syndrome. PEDIATRICS [online] December, 124(2):747-757 [viewed 15 June 2014] Available from: doi:10.1542/peds.2008-1559
  2. CHARLES KODNER, Nephrotic Syndrome in Adults: Diagnosis and Management, Am Fam Physician[online] 2009,80(10).1129-1134, 1136. [viewed 15 June 2014] Available from: http://www.aafp.org/afp/2009/1115/p1129.html
  3. OBERWEIS BS, MATTOO A, WU M, GOLDFARB DS. Minimal change disease and IgA deposition: separate entities or common pathophysiology? Case Rep Nephrol [online] 2013:268401 [viewed 15 June 2014] Available from: doi:10.1155/2013/268401
  4. SHARMA J. Steroid sensitive nephrotic syndrome and steroid toxicity: what to do next. Indian Pediatr [online] 2012 Oct, 49(10):844; discussion 844 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23144112
  5. CHEN O, ZHU XB, REN P, WANG YB, SUN RP, WEI DE. Henoch Schonlein Purpura in children: clinical analysis of 120 cases. Afr Health Sci [online] 2013 Mar, 13(1):94-9 [viewed 15 June 2014] Available from: doi:10.4314/ahs.v13i1.26
  6. PARK SJ, SHIN JI. Complications of nephrotic syndrome. Korean J Pediatr [online] 2011 Aug, 54(8):322-8 [viewed 15 June 2014] Available from: doi:10.3345/kjp.2011.54.8.322
  7. PANAGIOTIDES AM, HEVER A, SIM JJ. An unusual presentation and etiology of hypotension seen in nephrotic syndrome. Perm J [online] 2009 Spring, 13(2):55-7 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/21373231
  8. WONG EK, BRADY M, SHEERIN NS. Severe intestinal oedema due to nephrotic syndrome. QJM [online] 2013 Feb, 106(2):191-2 [viewed 12 June 2014] Available from: doi:10.1093/qjmed/hcr236

Differential Diagnoses

Fact Explanation
Nephritic syndrome This is characterized by hematuria and hyperrtension with headache and visual blurring. The two classic diagnoses of nephritic syndrome are post-streptococcal glomerulonephritis crescentic glomerulonephritis. (also called rapidly progressive glomerulonephritis) [1]
Chronic Renal failure (CRF) CRF is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are non-specific, and might include feeling generally unwell and experiencing a reduced appetite. [2]
Heart failure Children with heart failure usually have a history of cardiac disease in the past. Feeding intolerance, nocturnal cough, Orthopnea, and Paroxysmal Nocturnal Dyspnea are common features. The edema is more dependent and gets worse towards evening. [3]
Protein loosing enteropathy Protein losing enteropathy refers to any condition of the gastrointestinal tract that results in a net loss of protein such as celiac disease, Crohn's disease, short bowel syndrome, intestinal lymphangiectasia, amyloidosis and enteropathy caused by NSAIDs. [4]
Angioedema It manifests as rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. Angioedema should be treated as a medical emergency, as airway obstruction and suffocation can occur. The skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue, swell up over the period of minutes to hours. [5]
References
  1. BARRIOS JE, DURAN BOTELLO C, GONZáLEZ VELáSQUEZ T. Nephrotic syndrome with a nephritic component associated with toxoplasmosis in an immunocompetent young man. Colomb Med (Cali) [online] 2012 Jul, 43(3):226-9 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24893197
  2. AL SALLOUM AA, MUTHANNA A, BASSRAWI R, AL SHEHAB AA, AL IBRAHIM A, ISLAM MZ, AL HASAN K. Long-term outcome of the difficult nephrotic syndrome in children. Saudi J Kidney Dis Transpl [online] 2012 Sep, 23(5):965-72 [viewed 15 June 2014] Available from: doi:10.4103/1319-2442.100877
  3. HILTON PJ, JONES NF, TIGHE JR. Nephrotic syndrom with heart disease: a reappraisal. Br Med J [online] 1968 Sep 7, 3(5618):584-6 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/5667991
  4. IWASA T, MATSUBAYASHI N. Protein-loosing enteropathy associated with rotavirus infection in an infant. World J Gastroenterol [online] 2008 Mar 14, 14(10):1630-2 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18330961
  5. RYE RASMUSSEN EH, BINDSLEV-JENSEN C, BYGUM A. Angioedema--assessment and treatment. Tidsskr Nor Laegeforen [online] 2012 Nov 12, 132(21):2391-5 [viewed 15 June 2014] Available from: doi:10.4045/tidsskr.12.0470

Investigations - for Diagnosis

Fact Explanation
Urine ward test This test offers a qualitative assessment of Urine protein to creatinine ratio. It is usually more than 3+ in nephrotic syndrome. [1,2,3,4,5]
Urine full report Protienuria equal or more than 2+, microscopic hematuria and hyaline casts are usual findings of urine full report. [1,2,3,6,7]
24 hours urine collection for protein estimation A level of more than 40 mg per square meter per hour defines nephrotic-range proteinuria. [1,2,3]
Serum protein Serum albumin level is less than 25g per liter. [1,2,3]
Lipid profile Elevated total cholesterol, low-density lipoproteins and triglycerides are transient changes that are sometimes occur in nephrotic syndrome. Hypoprotienimia is thought to trigger increased production of lipoproteins in liver as a compensatory reaction. [1,2,5]
Urine protein to creatinine ratio A urine protein/creatinine ratio of more than 3 mg/mg or more than 200 mg/mmol is equivalent with nephrotic-range proteinuria. [1,2]1,2,3,4,5]
Urine culture and antibiotic sensitivity test (ABST) This test is useful to exclude any co existing urinary tract infection. [1,2]
Serum electrolytes and glomerular filtration rate Investigations such as GFR, blood urea nitrogen and serum electrolytes are useful to assess the renal function of the patient. This is important as intravascular volume depletion and/or bilateral renal vein thrombosis can cause acute kidney failure. [1,2,5]
Serum compliments (C3, C4) Low complement levels (C3, C4) are found in post-infectious nephritis, mesangial proliferative glomerulonephritis (MPGN), and lupus nephritis. To exlude all those differentials Serum compliments (C3, C4) test is useful. [1,2,4]
Anti-nuclear antibody (ANA) To exclude secondary causes of nephrotic syndrome such as connective tissue disorders which are postive for Anti-nuclear antibody. (eg - SLE) [1,2,5,6]
Hepatitis B surface antigen To exclude Hepatitis B which is a secondary cause of nephrotic syndrome. [1,7,8,9]
Renal biopsy In clinical practice the renal histology is less important than the response to the steroid therapy. Renal biopsy is needed in nephrotic syndrome if a patient fulfill following recommendations. Early onset (before 6 months), initial macroscopic hematuria without an infection, persistent microscopic hematuria with hypertension, renal failure not attributed to hypovolemia, persistantly low C3 and C4 levels, steroid resistance. [7,10,11]
References
  1. GIPSON D. S., MASSENGILL S. F., YAO L., NAGARAJ S., SMOYER W. E., MAHAN J. D., WIGFALL D., MILES P., POWELL L., LIN J.-J., TRACHTMAN H., GREENBAUM L. A.. Management of Childhood Onset Nephrotic Syndrome. PEDIATRICS [online] December, 124(2):747-757 [viewed 15 June 2014] Available from: doi:10.1542/peds.2008-1559
  2. KANG HEE GYUNG. Treatment of steroid-resistant pediatric nephrotic syndrome. Korean J Pediatr [online] 2011 December [viewed 15 June 2014] Available from: doi:10.3345/kjp.2011.54.8.317
  3. CHARLES KODNER, Nephrotic Syndrome in Adults: Diagnosis and Management, Am Fam Physician[online] 2009,80(10).1129-1134, 1136. [viewed 15 June 2014] Available from: http://www.aafp.org/afp/2009/1115/p1129.html
  4. ADELEKE SI, ASANI MO. Urinary tract infection in children with nephrotic syndrome in Kano, Nigeria. Ann Afr Med [online] 2009 Jan-Mar, 8(1):38-41 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19763005
  5. SINHA A, HARI P, SHARMA PK, GULATI A, KALAIVANI M, MANTAN M, DINDA AK, SRIVASTAVA RN, BAGGA A. Disease course in steroid sensitive nephrotic syndrome. Indian Pediatr [online] 2012 Nov, 49(11):881-7 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22791676
  6. INDIAN PEDIATRIC NEPHROLOGY GROUP, INDIAN ACADEMY OF PEDIATRICS, BAGGA A, ALI U, BANERJEE S, KANITKAR M, PHADKE KD, SENGUTTUVAN P, SETHI S, SHAH M. Management of steroid sensitive nephrotic syndrome: revised guidelines. Indian Pediatr [online] 2008 Mar, 45(3):203-14 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18367765
  7. WEENING JJ. Will laboratory markers replace kidney biopsy in patients with nephrotic syndrome? Neth J Med [online] 2012 Apr, 70(3):107-8 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22516573
  8. INDIAN SOCIETY OF PEDIATRIC NEPHROLOGY, GULATI A, BAGGA A, GULATI S, MEHTA KP, VIJAYAKUMAR M. Management of steroid resistant nephrotic syndrome. Indian Pediatr [online] 2009 Jan, 46(1):35-47 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19179716
  9. BAGGA A. Revised guidelines for management of steroid-sensitive nephrotic syndrome. Indian J Nephrol [online] 2008 Jan, 18(1):31-9 [viewed 16 June 2014] Available from: doi:10.4103/0971-4065.41289
  10. MEHRAZMA M, OTUKESH H, MADANI A, HOOMAN N, BEDAYAT A, DIANATI MALEKI N, EHTESHAMI AFSHAR A, HOSEINI R. Histopathologic and clinical findings of congenital nephrotic syndrome in Iranian children: a study of two centers. Iran J Kidney Dis [online] 2012 Nov, 6(6):426-31 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23146979
  11. TANEDA S, HONDA K, UCHIDA K, NITTA K, YUMURA W, ODA H, NAGATA M. Histological heterogeneity of glomerular segmental lesions in focal segmental glomerulosclerosis. Int Urol Nephrol [online] 2012 Feb, 44(1):183-96 [viewed 15 June 2014] Available from: doi:10.1007/s11255-011-9932-y

Investigations - Followup

Fact Explanation
White blood cell count Most of the immunosppressive treatment regimes should be closely monitored with white blood cell count due to the risk of neutropenia. When the patient is on Cyclophosphamide, if leukopenia occurs the therapy should be discontinued and recommenced once the recovers. If neutropenia appears, permanent discontinuation of levamisole should be done. [1,2,3,4,5]
Renal function tests Renal function tests should be done when the patient is on cyclosporine. [1,2]
Fasting blood sugar Serum glucose level should be checked frequently (3-6 months) due to the diabetogenic effect of prednisolone. [1,3,4]
Serum calcium Hypocalcemia is a side effect of prednisolone due to its hypercalciuric effect. So, serum calcium should be checked once in 3-6 months. [1,3,4]
Method of checking urine protein at home This can be done using commercial urine strips for protein or by urine heat coagulation test. Urine should be collector to fill 2/3 of test tube. The upper part of the tube should be heated. If a turbidity is formed few drops of sodium salicilate or vinegar and see if the turbidity disappears. Quantification of the amount of protein can be done according to the following scale. Nil - No turbidity. Trace - Turbid but no difficulty in reading print. 1+ - Turbid. 2+ - Turbid, can't read, but can notice black. 3+ - Turbid, can't notice black. 4+ - Precipitate. This can also be done with urine dipstick test. [1,2,4,6]
References
  1. GIPSON D. S., MASSENGILL S. F., YAO L., NAGARAJ S., SMOYER W. E., MAHAN J. D., WIGFALL D., MILES P., POWELL L., LIN J.-J., TRACHTMAN H., GREENBAUM L. A.. Management of Childhood Onset Nephrotic Syndrome. PEDIATRICS [online] December, 124(2):747-757 [viewed 15 June 2014] Available from: doi:10.1542/peds.2008-1559
  2. KANG HEE GYUNG. Treatment of steroid-resistant pediatric nephrotic syndrome. Korean J Pediatr [online] 2011 December [viewed 15 June 2014] Available from: doi:10.3345/kjp.2011.54.8.317
  3. SINHA A, HARI P, SHARMA PK, GULATI A, KALAIVANI M, MANTAN M, DINDA AK, SRIVASTAVA RN, BAGGA A. Disease course in steroid sensitive nephrotic syndrome. Indian Pediatr [online] 2012 Nov, 49(11):881-7 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22791676
  4. INDIAN PEDIATRIC NEPHROLOGY GROUP, INDIAN ACADEMY OF PEDIATRICS, BAGGA A, ALI U, BANERJEE S, KANITKAR M, PHADKE KD, SENGUTTUVAN P, SETHI S, SHAH M. Management of steroid sensitive nephrotic syndrome: revised guidelines. Indian Pediatr [online] 2008 Mar, 45(3):203-14 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18367765
  5. CHARLES KODNER, Nephrotic Syndrome in Adults: Diagnosis and Management, Am Fam Physician[online] 2009,80(10).1129-1134, 1136. [viewed 15 June 2014] Available from: http://www.aafp.org/afp/2009/1115/p1129.html
  6. AGARWAL I, KIRUBAKARAN C, MARKANDEYULU, SELVAKUMAR. Quantitation of proteinuria by spot urine sampling. Indian J Clin Biochem [online] 2004 Jul, 19(2):45-7 [viewed 16 June 2014] Available from: doi:10.1007/BF02894256

Management - General Measures

Fact Explanation
Monitoring Following the admission, several parameters should be monitored. They are daily weight, abdominal girth, input - output charts, abdominal tenderness, temperature, blood pressure thrice a day, regular pulse examination for rate and volume. This are recorded in order to assess the disease progression and predict complications such as infections, renal failure and shock. [1,2,3,4,5]
Bed rest Bed rest is not usually recommended as it can pose an added risk of thromboembolism during a hypercoagulable state such as nephrotic syndrome. But bed rest is acceptable if only the patient has severe edema or severe hypertension. [1,2,3,4,5]
Diet and fluids Normal protein diet with adequate calories and restricted salt content is recommended until the resolution of the relapse. High protein diet or fluid restriction are not encouraged. [1,2,5]
Antibiotics Prophylactic oral penicillin (250mg twice a day) for 10 days is the usual dose to prevent primary bacterial peritonitis. [1,5]
Vaccination Pneumococcal vaccination has been recommended for patients with nephrotic syndrome due to their immunocompromised state as a result of prolonged prednisolone therapy.[1,2,3,4,5]
Diuretics Diuretics are beneficial to control edema but should be used cautiously. They should only be used after correction of hypovolemia. Frusemide can be administered in a dose of 1-2 mg/kg in divided doses orally or intravenously. It can also be used along with colloids (albumin or cryo-poor plasma) infusion. Spironolactone can be used as an adjunct provided the renal function is normal. [1,2,4,6,7]
Antihypertensives If blood pressure exceeds the normal limits, a short course of antihypertensives could be prescribed once euvolemia is established. Recommended antihypertensives are nifedipine, hydralazine and atenolol. Diuretics are useful when hypertension is due to fluid overload. [2,4,6,7,8]
Lipid lowering agents As the hypercholesterolemia occurs in the nephrotic syndrome is transient and unlikely to have long term complications, lipid lowering drugs are not routinely recommended. [1,2,8]
Management of hypovolemic shock Hypovolemia commonly occurs with the development of edema or in the presence of diarrhea, vomiting, sepsis or injudicious use of diuretics. If the patient develops hypovolemic shock he/ shu should be infused with normal saline bolus 20ml/kg within 20 minutes followed by a salt free 20% albumin infusion. Urine output should be kept below 0.5ml/kg/hour. [1,2,3,4]
Management of thromboembolism Patients with clinical and radiological evidence of thrombosis should be treated with heparin or low molecular weighr heparin. Initial therapy with heparin is followed by oral warfarin for 6 monthsor longer. Prophylactic use of these agents for prevention of thrombosis is currently not recommended. [1,2,3,6]
Management of peritonitis In a patient who developed peritonitis parenteral benzyl penicillin 250mg twice a day and a third generation cephalosporin should be started. [1,2,7,8]
Management of varicella infection A patient who develops overt disease while receiving immunocompressive medication should be treated with intravenous acyclovir. Patient should be advised to avoid contact and in case of contact avised to seek medical advice immediately. Varicella zoster immunoglobulin, is recommended within 96 hours of exposure, preferably as early as possible. [1,2,8,9]
Management of addisonian crisis Patients on long term steroids can rarely have circulatory failure due to adrenal suppression during intercurrent illness. They should be managed with intravenous fluids, correction of blood sugar and intravenous hydrocortisone. [1,2,3,4,10]
Parent education regarding the disease Parents or care givers should be thoroughly educated regarding the disease, prognosis, drugs and side effects, life style modifications and complications of the disease as the knowledge of a chronic disease like nephrotic syndrome is paramount in successful management. Nephrotic syndrome should be introduced as an chronic relapsing disease. And they must be reassured that progression of this disease to a chronic kidney disease is extremely rare with adequate management. [1,2,3,4,5]
Education regarding follow up Diet should be normal with reduced fat and refined sugar. The method of urine ward test should be thoroughly familiarized. Examination of urine at home should be done every morning during a relapse, during intercurrent infection or if child has even mild peri-orbital edema. Urine test should be done 2/3 times a week during the remission period. Maintenance a diary for protein testing, infections, management changes, school activities is helpful to ease the follow up. Early medical attention should be obtained in case of an infection. Patient should avoid crowded places due to risk of infections. And he/she should be admitted to the hospital if there is edema or protein greater than or equal to 2 for more than 2 days at home. patient should be followed up at clinic frequently with urine protein test records. [1,2,3,4,5]
Education regarding steroids Patient should be educated regarding prednisolone. They should be informed regarding possible adverse reactions of prednisolone such as irritability, behavioral changes, cushinoid features, gastric irritation, growth faltering, cataract, obesity, recurrent infections and complications such as addisonian crisis. The important of steroids even in the presence of side effects should be emphasized. The risk of addisonian crisis if abrupt withdrawal of steroids should be informed. Live vaccinations should be stopped until 3 months after stopping of steroids. During every other day regimen, killed vaccines can be given. [1,2,3,4,5]
Ophthalmology referral Frequent eye check ups should be done when the patient is on prednisolone as it increases risk of developing scleritis and corneal thinning. [1,2,3]
Calcium supplementation Hypocalcemia is a side effect of prednisolone due to its hypercalciuric effect. So calcium supplementation is recommended for patients with long term steroid therapy. [1,2,5,11]
References
  1. GIPSON D. S., MASSENGILL S. F., YAO L., NAGARAJ S., SMOYER W. E., MAHAN J. D., WIGFALL D., MILES P., POWELL L., LIN J.-J., TRACHTMAN H., GREENBAUM L. A.. Management of Childhood Onset Nephrotic Syndrome. PEDIATRICS [online] December, 124(2):747-757 [viewed 15 June 2014] Available from: doi:10.1542/peds.2008-1559
  2. KANG HEE GYUNG. Treatment of steroid-resistant pediatric nephrotic syndrome. Korean J Pediatr [online] 2011 December [viewed 15 June 2014] Available from: doi:10.3345/kjp.2011.54.8.317
  3. CHARLES KODNER, Nephrotic Syndrome in Adults: Diagnosis and Management, Am Fam Physician[online] 2009,80(10).1129-1134, 1136. [viewed 15 June 2014] Available from: http://www.aafp.org/afp/2009/1115/p1129.html
  4. ADELEKE SI, ASANI MO. Urinary tract infection in children with nephrotic syndrome in Kano, Nigeria. Ann Afr Med [online] 2009 Jan-Mar, 8(1):38-41 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19763005
  5. SINHA A, HARI P, SHARMA PK, GULATI A, KALAIVANI M, MANTAN M, DINDA AK, SRIVASTAVA RN, BAGGA A. Disease course in steroid sensitive nephrotic syndrome. Indian Pediatr [online] 2012 Nov, 49(11):881-7 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22791676
  6. INDIAN PEDIATRIC NEPHROLOGY GROUP, INDIAN ACADEMY OF PEDIATRICS, BAGGA A, ALI U, BANERJEE S, KANITKAR M, PHADKE KD, SENGUTTUVAN P, SETHI S, SHAH M. Management of steroid sensitive nephrotic syndrome: revised guidelines. Indian Pediatr [online] 2008 Mar, 45(3):203-14 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18367765
  7. AL SALLOUM AA, MUTHANNA A, BASSRAWI R, AL SHEHAB AA, AL IBRAHIM A, ISLAM MZ, AL HASAN K. Long-term outcome of the difficult nephrotic syndrome in children. Saudi J Kidney Dis Transpl [online] 2012 Sep, 23(5):965-72 [viewed 16 June 2014] Available from: doi:10.4103/1319-2442.100877
  8. OTUKESH H, OTUKESH S, MOJTAHEDZADEH M, HOSEINI R, FERESHTEHNEJAD SM, RIAHI FARD A, SADIGH N, HESHMATZADE BEHZADI A, JAVADI R, HOOMAN N, MEHRAZMA M. Management and outcome of steroid-resistant nephrotic syndrome in children. Iran J Kidney Dis [online] 2009 Oct, 3(4):210-7 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19841524
  9. BAGGA A. Revised guidelines for management of steroid-sensitive nephrotic syndrome. Indian J Nephrol [online] 2008 Jan, 18(1):31-9 [viewed 16 June 2014] Available from: doi:10.4103/0971-4065.41289
  10. D'SILVA C, WATSON D, NGAAGE D. A strategy for management of intraoperative Addisonian crisis during coronary artery bypass grafting. Interact Cardiovasc Thorac Surg [online] 2012 Apr, 14(4):481-2 [viewed 16 June 2014] Available from: doi:10.1093/icvts/ivr139
  11. MASSRY SG, GOLDSTEIN DA. Calcium metabolism in patients with nephrotic syndrome. A state with vitamin D deficiency. Am J Clin Nutr [online] 1978 Sep, 31(9):1572-80 [viewed 16 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/685872

Management - Specific Treatments

Fact Explanation
Steroid therapy Oral prednisolone 2 mg/kg/d with a maximum of 60 mg per day for 4 -6 weeks is the recommended induction regimen. It has been found that a longer period of initial steroid treatment reduces the rate of relapse. So treatment for 6 weeks is preferable. This should be given as a single dose in the morning. This induction therapy is followed by a maintenance therapy with oral prednisolone 1.5 mg/kg/d with a maximum of 40 mg per day given as a single dose on every other day for 4 weeks. Alternate day treatment should be started on the next day after the daily regimen stops. Patients with steroid sensitive nephrotic syndrome usually achieve remission with this regimen. They are labeled as steroid-sensitive nephrotic syndrome. (Remission - urinary protein excretion less than 4mg/m2/h or urine protein negative or trace for 3 days ) But relapses occur in majority of the patients. A relapse is treated as same as the above regimen. Steroid-sensitive nephrotic syndrome (SSNS) with two or more relapses occurring within 6 months, or four or more relapses occurring within a 12-months is defined as Frequently relapsing nephrotic syndrome (FRNS). SSNS with two or more consecutive relapses during tapering, or within the first 14 days following stopping steroids is defined as Steroid-dependent nephrotic syndrome (SDNS) With frequent and prolonged steroids treatment, the risk of steroid toxicity is increased. Therefore, in FRNS and SDNS, a steroid-sparing alternative agent is introduced once remission of proteinuria has been achieved with usual steroid regimen. Possible side-effects of prednisolone include Adrenal suppression, Acne, delayed wound healing, ulcerative esophagitis, GI perforation, peptic ulcer, hypokalemic alkalosis, myopathy, insomnia, psychosis, seizure, urticaria, vertigo and weight gain [1,2,3]
Alternative therapy Indications for alternative agents are frequent relapse, steroid dependence, steroid resistance, an steroid toxicity. Cyclophosphamide, cyclosporine, Levamisole and cyclosporine are common drugs which are used in alternative therapy. [1,4,5]
Cyclophosphamide Cyclophosphamide prolongs the duration of remission and reduces the number of relapses in children with frequently relapsing and steroid-dependent nephrotic syndrome. Leukopenia, alopecia, hepatic function disorder, hemorrhagic cystitis and sterility are common side effects. Patient should be adequately hydrated before commencement. hite blood cell count should be monitored freequently. If leukopenia occurs the therapy should be discontinued and recommenced once the recovers. 2-3 mg/kg/day for up to 12 weeks is the recommended dose. [5]
Cyclosporine It is effective in maintaining prolonged remissions in children with nephrotic syndrome and is useful as steroid-sparing agents. 5mg/kg/day for 1-3 years is recommended. Hypertension, nephrotoxicity, hirsutism and gingival hyperplasia are common side effects. Renal function should be monitored closely. [1,4]
Levamisole It is an antihelminthic and immunomodulator belonging to a class of synthetic imidazothiazole derivatives. Patient should be monitored with white blood cell count. If neutropenia appears, permanent discontinuation should be done. [6]
References
  1. GIPSON D. S., MASSENGILL S. F., YAO L., NAGARAJ S., SMOYER W. E., MAHAN J. D., WIGFALL D., MILES P., POWELL L., LIN J.-J., TRACHTMAN H., GREENBAUM L. A.. Management of Childhood Onset Nephrotic Syndrome. PEDIATRICS [online] December, 124(2):747-757 [viewed 15 June 2014] Available from: doi:10.1542/peds.2008-1559
  2. CHARLES KODNER, Nephrotic Syndrome in Adults: Diagnosis and Management, Am Fam Physician[online] 2009,80(10).1129-1134, 1136. [viewed 15 June 2014] Available from: http://www.aafp.org/afp/2009/1115/p1129.html
  3. SINHA A, HARI P, SHARMA PK, GULATI A, KALAIVANI M, MANTAN M, DINDA AK, SRIVASTAVA RN, BAGGA A. Disease course in steroid sensitive nephrotic syndrome. Indian Pediatr [online] 2012 Nov, 49(11):881-7 [viewed 15 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22791676
  4. KANG HEE GYUNG. Treatment of steroid-resistant pediatric nephrotic syndrome. Korean J Pediatr [online] 2011 December [viewed 15 June 2014] Available from: doi:10.3345/kjp.2011.54.8.317
  5. CAMMAS B, HARAMBAT J, BERTHOLET-THOMAS A, BOUISSOU F, MORIN D, GUIGONIS V, BENDEDDOUCHE S, AFROUKH-HACINI N, COCHAT P, LLANAS B, DECRAMER S, RANCHIN B. Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. Nephrol Dial Transplant [online] 2011 Jan, 26(1):178-84 [viewed 15 June 2014] Available from: doi:10.1093/ndt/gfq405
  6. MADANI A, ISFAHANI ST, RAHIMZADEH N, FERESHTEHNEJAD SM, HOSEINI R, MOGHTADERI M, MOHSENI P, ATAIEE N. Effect of levamisole in steroid-dependent nephrotic syndrome. Iran J Kidney Dis [online] 2010 Oct, 4(4):292-6 [viewed 13 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20852369