|Year : 2022 | Volume
| Issue : 1 | Page : 29-33
Case-based management of nephrotic syndrome: A review and update
Golam M Uddin, Mst Shanjida Sharmim, Tahmina Jesmin, Abdullah Al Mamun
Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh
|Date of Submission||16-Feb-2022|
|Date of Acceptance||11-Apr-2022|
|Date of Web Publication||31-May-2022|
Prof. Golam M Uddin
Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka
Source of Support: None, Conflict of Interest: None
Nephrotic syndrome (NS) is one of the most common glomerular diseases that affect children. The most common cause of NS is idiopathic NS (INS). Minimal change NS (MCMS) is more than 80% in patients with favorable outcomes. However, a few children have focal segmental glomerulosclerosis along with secondary causes, which are at risk for complications. Complications may be disease-associated or may be drug-related complications. Disease-related complications include infections (e.g., peritonitis, sepsis, cellulitis, chicken pox), thrombo-embolism, hypovolemic crisis, hypercholesterolemia, acute kidney injury (AKI), anemia and other AKIs, hypothyroidism, hypocalcemia, and bone disease. The majority of children with MCNS respond to corticosteroids or cytotoxic agents, alkylating agents, cyclosporine A, and mycophenolate mofetil. Early detection and management of these complications will improve outcome for these patients with NS. This article provides an update of current available therapeutics strategies and case-based management of common complications of NS.
Keywords: Case-based management, child, complications, nephrotic syndrome, proteinuria
|How to cite this article:|
Uddin GM, Shanjida Sharmim M, Jesmin T, Al Mamun A. Case-based management of nephrotic syndrome: A review and update. Paediatr Nephrol J Bangladesh 2022;7:29-33
|How to cite this URL:|
Uddin GM, Shanjida Sharmim M, Jesmin T, Al Mamun A. Case-based management of nephrotic syndrome: A review and update. Paediatr Nephrol J Bangladesh [serial online] 2022 [cited 2022 Dec 3];7:29-33. Available from: http://www.pnjb-online.org/text.asp?2022/7/1/29/346348
| Introduction|| |
Nephrotic syndrome (NS) is a clinical disease characterized by heavy proteinuria (urine protein >40 mg/m2/h or 24 h urinary total protein >1 g/m2), hypoalbuminemia (serum albumin <2.5 g/dL), hyperlipidemia (serum cholesterol >200 mg/dL), and generalized edema. Idiopathic NS (INS) is a disease that occurs in 2–7 cases per 100,000 children per year,,,, and prevalence is approximately 16 cases per 100,000., Children with NS majority have minimal change disease (MCD) and responded to steroids. Kidney biopsy is not recommended in steroid-sensitive NS (SSNS). The etiology of SSNS remains unclear.
Response to steroid varied according to histopathologic type; in case of MCD, 95–98% responded to corticosteroid therapy but in case of focal segmental glomerulosclerosis only 20% responded., About 60–80% of them have frequent relapses, require repeated use of steroids and other immunosuppressive agents, and develop complications. Early detection of complication is essential to prevent patients’ morbidity and mortality associated with NS. These case-based discussions will enrich our knowledge with latest updated management of patients with NS.
| Case-based Management|| |
A 2-year-old girl diagnosed to have NS 1 week back presented to the emergency room with fast breathing, lethargy, and temperature 37°C, blood pressure (BP) 80/50 mmHg, weak pulse. She had history of watery diarrhea for 2 days. She was on treatment with oral steroids. She had hypovolemia and diagnosed by clinical features. These were tachycardia, cold extremities, poor capillary refill and abdominal pain, and hypotension. It was confirmed by low urinary sodium (<10 mmol/L) and raised hydrochlorothiazide (HCT) and uric acid levels. Though UK/UK+UNa is a better predictor, we usually use urinary Na for pre-renal hypovolemia as it is available in our center. She was managed by fluid resuscitation, prompt treatment of infection, 20% human albumin 1 g/kg (5 mL/kg) over 4–6 h followed by i.v. frusemide 1–2 mg/kg.
A 3-year-old boy with steroid-resistant NS presented with massive abdominal distension and increasing edema despite being on diuretics; he had tense ascites, tachypnoea, bilateral decreased breath sounds, and scrotal edema. He was managed with fluid (generally two-thirds of maintenance although individual discretion is required) and salt restriction (1500–2000 mg/day), 20% human albumin, and diuretics when volume depletion has been corrected.
A 4-year-old child with NS on treatment with steroids presented with fever, vomiting, abdominal pain, and increase in edema; he is sick-looking, febrile with a heart rate of 130 per minute, there is abdominal tenderness, guarding, and rigidity. He was diagnosed to have peritonitis on the basis of clinical plus peritoneal fluid analysis, which showed neutrophil count of 80/cmm and protein 2.5 g/cmm of peritoneal fluid. He was managed with injection ceftazidime and aminoglycoside.
A 3-year-old child in relapse of NS presented with two episodes of generalized seizures and altered sensorium. There was no fever and no signs of meningeal irritation, and there was paucity of movements of the limbs. Thrombosis was diagnosed by imaging. The patient was managed by low-molecular-weight (LMW) heparin followed by warfarin and anticonvulsant.
A 14-year-old boy presented with shortness of breath and hypoxia within 2 months after diagnosis of NS. Physical examination showed leg edema, temperature 36.5°C, BP 110/70 mmHg, and lung findings are normal. His platelet counts were 750,000/cmm, prolonged activated partial thromboplastin time, prothrombin time, and thrombin time, serum fibrinogen level was >10 mg/dL, quantitative D-dimer level high, serum albumin 9 g/L, urinary protein 2 g/m2/day, CT angiogram pulmonary thrombo-embolism. He was managed with normal calorie diet with low saturated fat, no refined sugar, and added salt and fluid was given as desired. He was given LMW heparin and then warfarin. Subsequently, warfarin was given for the next 6 months.
An 8-year-old boy presented with edema of 1-week duration. He has not passed urine for last 24 h. He is on diuretics and has received some medications for fever. His serum creatinine was 3 mg/dL. He was diagnosed as a case of NS with AKI. He was managed with normal saline bolus, stopping diuretics, and other nephrotoxic agents and prompt treatment of infection.
| Discussion|| |
INS patients have to faced multiple complications either due to disease process or due to drug-related complications. [Table 1] shows the INS-related complication.
Hypovolemia and hypovolemic crisis are a common presentation of INS but difficult to assess. Several risk factors are responsible for hypovolemic crisis such as severely depressed albumin levels, high-dose diuretics, infection, and vomiting. Hypovolemia may occur at disease onset or relapse. Hypovolemic patients may have moderate-to-severe abdominal pain, nausea, vomiting, lethargy, presented with tachycardia, low volume pulses, low BP, postural hypotension, cold extremities, poor capillary refill, and rarely shock. Laboratory tests may show elevated hematocrit, serum uric acid level, blood urea (mg/dL)-to-creatinine (mg/dL) ratio >100, fractional excretion of sodium (FENa) <0.5%, urinary potassium index [urine K+/(urine Na++K+) >0.6], ultrasonography: decreased inferior vena cava diameter, and increased collapsibility index.,,,, Therapy with diuretics should be discontinued. Hypotensive patients should be managed with 1–2 boluses of isotonic saline (10–20 mL/kg infused over 20–30 min) and/or 5% albumin (10–15 mL/kg over 30–60 min). Diuretics should be stopped immediately. Subsequently, patients are managed with i.v. and oral hydration and i.v. albumin (20%; 0.5–1 g/kg over 3–4 h).,, Our patient presented with 2 days diarrhea, fast breathing, lethargy and temperature 37°C, BP 80/50 mmHg, weak pulse, and getting diuretics. Laboratory investigation shows low urinary sodium (<10 mmol/L) and raised HCT. The patient was managed with fluid resuscitation and 20% human albumin 1 g/kg (5 mL/kg) over 4–6 h.
Case 2:NS with tense ascitis
It is another common presentation usually managed with diuretics and albumin as adjuvant therapy. The patient should also need to take restricted amount of salt. Initially, the patient should be managed with 2 mg/kg/day of oral furosemide. Usually, diuresis will be started 2–4 h of furosemide administration and initial target of diuretic therapy is to achieve weight reduction of 1–2% of body weight per day. Dose should be increased up to 6 mg/kg/day if initial target will not be achieved and lack of response required to switch to i.v. administration. Furosemide combined with metolazone should be used if furosemide alone fails to decrease edema. Diuretic resistant edema patients may be benefited with co-administration of albumin and furosemide. Patients with moderate-to-severe edema and also tense edema on diuretics therapy require strict monitoring of body weight, urine output, evidence of hypovolemia, and serum electrolytes 1–2 times daily.,,
Algorithm for management of edema in NS
INS patients are at increased risk of infections. It is one of the major causes of relapse and admission to the hospital accounting to 19–44%.,,,,, Infection is one of the leading causes of morbidity and mortality of INS patients.,, Several contributing factors predispose the patient to infection with encapsulated organisms which include the use of immunosuppressive agents, anasarca, and urinary losses of IgG and complement factors. The annual incidence of invasive bacterial infection is approximately 1–2%. Peritonitis is the most frequent infection followed by pneumonia and cellulitis. Peritonitis most frequently occurred due to pneumococci and Escherichia coli; those causing pneumonia include pneumococci, Haemophilus influenzae, and Staphylococcus aureus. Cellulitis occurred due to staphylococci, group A streptococci, and H. influenzae.,,,,,
Low serum albumin (≤ 1.5 g/dL) and platelet count less than 500 cells/mm3 at presentation are associated with an increased risk of peritonitis among children with NS. Clinically, peritonitis was characterized by abdominal pain, fever, rebound tenderness, nausea, vomiting, and diarrhea.,
Our patient of NS has fever, vomiting, abdominal pain, increase in edema, febrile with tachycardia diffuse abdominal tenderness, guarding, and rigidity. His peritonitis was managed with injection ceftazidime and aminoglycoside and penicillin prophylaxis for 6 months after resolving from peritonitis and vaccination.
INS patients are also at high risk of viral infection. Several viral agents, including respiratory syncytial virus, influenza virus, parainfluenza virus, VZV, and adenovirus, have been identified as potential triggers of disease relapse. Varicella zoster and influenza viral infection in INS are associated with significant mortality and require specific prevention and management.[Table 2] shows the management of serious infection in NS patients.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causes corona virus disease (COVID-19), which is a global pandemic. Management of NS patients with COVID-19 disease creates a new challenge to healthcare personnel. Children has mild-to-moderate course of disease. But patients who receive immunosuppressive therapy constitute a high-risk group. INS patients are usually in hypovolemic state or get diuretics. This group of patients are at high risk to develop AKI if they have COVID-19 disease. Reduction of immunosuppressive therapy is the most acceptable advice to this group of patients.,
Case 4: NS with seizure
NS patients may present with seizure. Common causes are high BB, hyponatremia, meningitis, febrile convulsion, thrombosis, and vasculitis.,
Case 5: NS with pulmonary thrombo-embolism
Pulmonary thrombo-embolism may present in 28% of asymptomatic NS patients. Symptomatic venous thrombo-embolism usually occurs within 3 months of presentation of NS and can manifest as clot in leg veins, inferior vena cava, pulmonary veins, and sagittal sinus., Urgent evaluation was done by Doppler or computed tomography angiogram to confirm the diagnosis. Risk factors are abuse of diuretics, NS with atypical features, dehydration, steroids, hypercholesteremia, indwelling catheter, and CNS.,
The patient was advised LMW heparin followed by warfarin for at least 3 months. It may be supplemented by recombinant antithrombin-III. Prophylactic anticoagulant therapy may be considered in children who relapse after earlier episodes of thrombosis.
Case 6: NS with AKI
AKI is common in 34% of adults with NS and 8.5% of children with NS who are hospitalized. The common etiologies are hypovolemia, acute tubular necrosis, interstitial nephritis, and drugs such as CNI, ACEi, ARBs, aminoglycosides, renal vein thrombosis. Our patient had edema, anuria, fever, raised creatinine, hypovolemia. He was on diuretic therapy. We immediately stopped diuretics along with other nephrotoxic drugs and replaced volume by normal saline and prompt treatment of infection.
| Conclusion|| |
NS is a common renal disease in children. It has diversity of presentation along with variable complications. Its management is challenging as it has waxing and waning of disease course and required long duration of treatment. So pediatrician as well as pediatric nephrologist should manage NS very cautiously. Parents should also need deep engagement in the management of NS patients.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
The primary nephritic syndrome in children: Identification of patients with minimal change nephritic syndrome from initial response to prednisolone. A report of the International Study of Kidney. Disease in children. J Pediatr 1981;98:561-4.
Eddy AA, Symons JM Nephrotic syndrome in childhood. Lancet 2003;362:629-39.
Valentini RP, Smoyer WE, Kher KK, Schinaper HW, Makker SP Clinical Pediatric Nephrology. Nephrotic syndrome. 2nd ed. Abhindom, Oxon: Informa Healthcare; 2006. p. 155-94.
Anonymous. The primary nephrotic syndrome in children: Identification of patients with minimal change nephrotic syndrome from initial response to prednisolone. A report of the International Study of Kidney in children. J Pediatr 1981;98:561-4.
Ameil GC The nephrotic syndrome. Pediatr Clin North Am 1971;18:547-59.
Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, et al
. Management of childhood onset nephrotic syndrome. Pediatrics 2009;124:747-57.
Koskimies O, Vilska J, Rapola J, Hallman N Long-term outcome of primary nephrotic syndrome. Arch Dis Child 1982;57:544-8.
Noone DG, Iijima K, Parekh R Idiopathic nephrotic syndrome in children. Lancet 2018;392:61-74. Cited by Sinha A, Bagga A, Banerjee S, Mishra K, Mehta A, Agarwal I, et al
. Steroid sensitive nephrotic syndrome: Revised guidelines. Ind Ped 2021;58(5):461-81.
Sinha A, Hari P, Sharma PK, Gulati A, Kalaivani M, Mantan M, et al
. Disease course in steroid sensitive nephrotic syndrome. Indian Pediatr 2012;49:881-7.
Park SJ, Shin JI Complications of nephrotic syndrome. Korean J Pediatr 2011;54:322-8.
Wang SJ, Tsau YK, Lu FL, Chen CH Hypovolemia and hypovolemic shock in children with nephrotic syndrome. Acta Paediatr Taiwan 2000;41:179-83.
Büyükavci MA, Çivilibal M, Elevli M, Selçuk Duru HN Hypo- and hypervolemic edema in children with steroid sensitive nephrotic syndrome. Turk J Med Sci 2015;45:178-83.
Kaku Y, Ohtsuka Y, Komatsu Y, Ohta T, Nagai T, Kaito H, et al
; Japanese Society for Pediatric Nephrology. Clinical practice guideline for pediatric idiopathic nephrotic syndrome 2013: General therapy. Clin Exp Nephrol 2015;19:34-53.
Meena J, Bagga A Current perspectives in management of edema in nephrotic syndrome. Ind J Pediatr 2020;87:633-40.
Taneja K, Kumar V, Anand R, Pemde HK Normative data for IVC diameter and its correlation with the somatic parameters in healthy Indian children. Indian J Pediatr 2018;85:108-12.
Vande Walle JG, Donckerwolcke RA Pathogenesis of edema formation in the nephrotic syndrome. Pediatr Nephrol 2001;16: 283-93.
Ellis D Pathophysiology, evaluation, and management of edema in childhood nephrotic syndrome. Front Pediatr 2015;3:111.
Lilova MI, Velkovski IG, Topalov IB Thromboembolic complications in children with nephrotic syndrome in Bulgaria (1974–1996). Pediatr Nephrol 2000;15:74-8.
McCaffrey J, Lennon R, Webb NJ The non-immunosuppressive management of childhood nephrotic syndrome. Pediatr Nephrol 2016;31:1383-402.
Alfakeekh K, Azar M, Sowailmi BA, Alsulaiman S, Makdob SA, Omair A, et al
. Immunosuppressive burden and risk factors of infection in primary childhood nephrotic syndrome. J Infect Public Health 2019;12:90-4.
Manta M, Singh S Infection associated relapses in children with nephrotic syndrome: A short-term outcome study. Saudi J Kidney Dis Transpl 2019;30:1245-53.
Wei CC, Yu IW, Lin HW, Tsai AC Occurrence of infection among children with nephrotic syndrome during hospitalizations. Nephrology 2012;17:681-8.
Kumar M, Ghunawat J, Saikia D, Manchanda V Incidence and risk factors for major infections in hospitalized children with nephrotic syndrome. J Bras Nefrol 2019;41:526-33.
Ajayan P, Krishnamurthy S, Biswal N, Mandal J Clinical spectrum and predictive risk factors of major infections in hospitalized children with nephrotic syndrome. Indian Pediatr 2013;50: 779-81.
Kronbichler A, Gauckler P, Windpessl M, Il Shin J, Jha V, Rovin BH, et al
. Covid-19: Implications for immunosuppression in kidney disease and transplantation. Nat Rev Nephrol 2020;16:365-7.
Vasudevan A, Mantan M, Krishnamurthy S, Pais P, Mathew G, Hari P, et al
; Indian Society of Pediatric Nephrology. Managing children with renal diseases during the Covid-19 pandemic. Indian Pediatr 2020;57:641-51.
Alhassan A, Mohamed WZ, Alhaymed M Patterns of childhood nephrotic syndrome in Aljouf region, Saudi Arabia. Saudi J Kidney Dis Transpl 2013;24:1050-4.
Wang CS, Yan J, Palmer R, Bost J, Wolf MF, Greenbaum LA Childhood nephrotic syndrome management and outcome: A single center retrospective analysis. Int J Nephrol 2017;2017:1-7.
Zhang LJ, Wang ZJ, Zhou CS, Lu L, Luo S, Lu GM Evaluation of pulmonary embolism in pediatric patients with nephrotic syndrome with dual energy Ct pulmonary angiography. Acad Radiol 2012;19:341-8.
Kerlin BA, Blatt NB, Fuh B, Zhao S, Lehman A, Blanchong C, et al
. Epidemiology and risk factors for thromboembolic complications of childhood nephrotic syndrome: A Midwest Pediatric Nephrology Consortium (MWPNC) study. J Pediatr 2009;155:105-10, 110.e1.
Andrew M, Brooker LA Hemostatic complications in renal disorders of the young. Pediatr Nephrol 1996;10:88-99.
Kerlin BA, Haworth K, Smoyer WE Venous thromboembolism in pediatric nephrotic syndrome. Pediatr Nephrol 2014;29:989-97.
Zaffanello M, Franchini M Thromboembolism in childhood nephrotic syndrome: A rare but serious complication. Hematology 2007;12:69-73.
Chen T, Lv Y, Lin F, Zhu J Acute kidney injury in adult idiopathic nephrotic syndrome. Ren Fail 2011;33:144-9.
[Table 1], [Table 2]