The Italian Society for Pediatric Nephrology (SINePe) consensus document on the management of nephrotic syndrome in children: Part I - Diagnosis and treatment of the first episode and the first relapse
- Andrea Pasini1Email author,
- Elisa Benetti2,
- Giovanni Conti3,
- Luciana Ghio4,
- Marta Lepore4,
- Laura Massella5,
- Daniela Molino6,
- Licia Peruzzi7,
- Francesco Emma5,
- Carmelo Fede3,
- Antonella Trivelli8,
- Silvio Maringhini9,
- Marco Materassi10,
- Giovanni Messina11,
- Giovanni Montini4,
- Luisa Murer2,
- Carmine Pecoraro6 and
- Marco Pennesi12
© The Author(s). 2017
Received: 6 December 2016
Accepted: 7 April 2017
Published: 21 April 2017
This consensus document is aimed at providing an updated, multidisciplinary overview on the diagnosis and treatment of pediatric nephrotic syndrome (NS) at first presentation. It is the first consensus document of its kind to be produced by all the pediatric nephrology centres in Italy, in line with what is already present in other countries such as France, Germany and the USA. It is based on the current knowledge surrounding the symptomatic and steroid treatment of NS, with a view to providing the basis for a separate consensus document on the treatment of relapses. NS is one of the most common pediatric glomerular diseases, with an incidence of around 2–7 cases per 100000 children per year. Corticosteroids are the mainstay of treatment, but the optimal therapeutic regimen for managing childhood idiopathic NS is still under debate. In Italy, shared treatment guidelines were lacking and, consequently, the choice of steroid regimen was based on the clinical expertise of each individual unit. On the basis of the 2015 Cochrane systematic review, KDIGO Guidelines and more recent data from the literature, this working group, with the contribution of all the pediatric nephrology centres in Italy and on the behalf of the Italian Society of Pediatric Nephrology, has produced a shared steroid protocol that will be useful for National Health System hospitals and pediatricians. Investigations at initial presentation and the principal causes of NS to be screened are suggested. In the early phase of the disease, symptomatic treatment is also important as many severe complications can occur which are either directly related to the pathophysiology of the underlying NS or to the steroid treatment itself. To date, very few studies have been published on the prophylaxis and treatment of these early complications, while recommendations are either lacking or conflicting. This consensus provides indications for the prevention, early recognition and treatment of these complications (management of edema and hypovolemia, therapy and prophylaxis of infections and thromboembolic events). Finally, recommendations about the clinical definition of steroid resistance and its initial diagnostic management, as well as indications for renal biopsy are provided.
KeywordsNephrotic syndrome Prednisolone Steroid sensitive Steroid resistant Edema Diuretics Thromboembolism Anticoagulation agents Kidney biopsy
In Italy, shared treatment guidelines were lacking and, consequently, the choice of steroid regimen was based on the clinical expertise of each individual unit. This consensus document is aimed at providing an updated, multidisciplinary overview on the diagnosis and treatment of pediatric nephrotic syndrome (NS) at first presentation, proposing a shared steroid protocol for National Health System hospitals and pediatricians. Furthermore, indications for the prevention, early recognition and treatment of NS complications (management of edema and hypovolemia, therapy and prophylaxis of infections and thromboembolic events), as well as recommendations about the clinical definition of steroid resistance and its initial diagnostic management, and indications for renal biopsy are provided.
It is based on the current knowledge surrounding the symptomatic and steroid treatment of NS, with a view to providing the basis for a separate consensus document on the treatment of relapses and for future research. Before writing the document, the working group conducted a thorough review of the literature in the PubMed database up to August 2015.
Nephrotic syndrome is a rare disease with an incidence of around 2–7 cases per 100,000 children per year and a prevalence of nearly 16 cases per 100,000 . The International Study of Kidney Disease in Childhood (ISKDC) determined the histopathological, clinical and laboratory characteristics of NS in children  and demonstrated that minimal change disease (MCD) accounts for 76% of idiopathic NS (INS) cases. Subjects with MCD have a 95% response rate to steroids, however, 75% will relapse and 50% (frequent relapsers or steroid dependent subjects) will require higher and prolonged doses of steroids thus increasing the risk of side effects . In any case, in terms of renal function, response to steroids is associated with a good long-term prognosis.
Heavy proteinuria: ≥50 mg/kg/day (or ≥40 mg/m2/h), or a proteinuria/creatininuria ratio >2 (mg/mg)
Serum albumin < 25 g/L
Causes of nephrotic syndrome
Primary Nephrotic Syndrome (95% in children 0–12 years)
Idiopathic nephrotic syndrome (80-90% in children 2–8 years)
Steroid-sensitive nephrotic syndrome
Steroid-resistant nephrotic syndrome
Genetic nephrotic syndrome (isolated or syndromic)
(95 -100% in children <3 months
50 - 60% in children 4–12 months)
Secondary Nephrotic Syndrome (5% in children 0–12 years)
- Vasculitides/autoimmune diseases (SLE, Microscopic polyangiitis, Goodpasture, IgA vasculitis)
- Infections (HBV, HCV, HIV, EBV, Mycoplasma, CMV, PVB19, Treponema, Toxoplasma, malaria, parasites)
- Drugs (Tiopronin, Penicillamine, Gold Salts, Pamidronate, Interferon, Everolimus, antiretroviral and chemotherapy drugs)
- Cancer (Lymphoma, Leukemia)
Investigations at initial presentation
NS in the family
Systemic diseases (autoimmune, neurological, metabolic, congenital, cancer)
Timing and characteristics of edema
Other kidney diseases in the family
(macro/microscopic hematuria, fever, oliguria, vomiting, abdominal pain, hypertension, skin rash, arthralgia…),
Other diseases in the family
Age at onset of symptoms
Signs/symptoms of hypovolemia
Signs/symptoms of infectious/systemic disease
▪ Heart rate
▪ Respiratory rate
▪ Blood pressure
▪ O2 saturation
▪ Body weight
▪ Bowel wall edema
▪ Pleural effusion
▪ Pulmonary edema
▪ Abdominal pain
▪ Cold hands/feet
▪ Capillary refill >2 s
▪ Skin rash
▪ Complete Blood Count (CBC)
▪ BUN, creatinine
▪ Electrolytes (including ionized calcium)
▪ Serum total protein, albumin
▪ Cholesterol, triglycerides
▪ Coagulation (including ATIII)
▪ Complement (C3, C4)
▪ Urinalysis (early morning sample)
▪ 24-h proteinuria or Proteinuria/creatininuria (uP/uCr)
▪ Auto-immune markers (ANA, DS-DNA, ENA, ANCA)
▪ Thyroid function
▪ Infections (HBV, HCV, HIV, ParvoB19, CMV, EBV, pneumococcus, salmonella, treponema, mycoplasma…)
▪ Urine sodium
Discharge and follow up
We suggest that, once discharged, patients should perform urine dipstick tests:
every other day during steroid tapering and during the first month after steroid withdrawal, then two/three times weekly.
daily, in the case of infection or positive stick.
immediately, in the case of edema
Corticosteroid use for the first episode of INS
PDN or prednisolone can be used indifferently for the treatment of a first episode of NS
Dosing of prednisone
We suggest that PDN be given at 60 mg/m2/day, with a maximum dose of 60 mg/day.
The optimal time to administer oral PDN treatment in order to maximise anti-inflammatory and immunosuppressive effects and minimize adverse events has yet to be clearly defined. The timing of PDN administration may influence the development of adrenal suppression, with morning and single administrations being potentially less suppressive than evening or divided-dose regimens , but definite improvements clearly need to be established in future clinical trials. Moreover, only one study (not an RCT) has focused on the correlation between timing of oral PDN intake and risk of side effects showing that PDN side effects (including hypertension) were less common in the single-daily-dose patients compared with the divided-dose patients .
We suggest that PDN can either be given in a single daily dose in the morning or in two divided doses (08.00 and 20.00).
We suggest that PDN (60 mg/m2, maximum 60 mg) be given daily in a single dose or divided into 2 doses for 6 weeks, followed by a single dose of 40 mg/m2, maximum 40 mg PDN on alternate days for another 6 weeks, without any tapering of the dose.
Treatment of the first episode
60 mg/m2 (maximum 60 mg)
in single or 2 divided doses
40 mg/m2 (maximum 40 mg)
on alternate days
Treatment of the first relapse
60 mg/m2 (maximum 60 mg)
in a single or 2 divided doses
Until urine protein is negative for 5 days
40 mg/m2 (maximum 40 mg)
on alternate days
In the case of a first relapse, PDN should be given daily at a dose of 60 mg/m2/day (maximum 60 mg/day) in a single dose or divided into 2 doses, until urine protein has been negative 5 days. Thereafter, a single alternate-day dose of 40 mg/m2 (maximum 40 mg) should be continued for 4 weeks and then stopped.
Diagnosis and treatment of edema in nephrotic syndrome
Pathophysiology of edema in nephrotic syndrome
Edema is a predominant clinical feature of NS which occurs with variable severity, from moderate edema localized in particular areas of the body (face, legs, abdomen, genitals) to massive generalized edema . There are two different mechanisms related to the pathogenesis of nephrotic edema. According to the underfill mechanism, the urinary loss of albumin leads to a decrease in plasma oncotic pressure which, with increased capillary ultrafiltration of sodium and water, leads to edema formation. Therefore, the retention of sodium chloride in NS could be a consequence of the activation of the renin-angiotensin-aldosterone system (RAAS) secondary to plasma volume reduction. In contrast, in the overfill mechanism the primary intra-renal sodium and water retention caused by resistance to atrial natriuretic peptide (ANP) and the activation of epithelial sodium channel (ENaC) in the inner medullary collecting duct leads to an expansion of the intravascular compartment and edema . It is important to estimate the potential contribution of both underfilling and overfilling before starting diuretic therapy. Diuretic therapy alone is effective in “overfilled” patients in terms of the management of edema and intravascular volume excess . On the contrary, the use of diuretics in patients with vascular “underfilling” could exacerbate intravascular hypovolemia. As suggested by some authors, intravascular volume can be easily evaluated by determining the fractional excretion of sodium (FENa), however, the FENa can also be influenced by salt and water intake and additional medication such as diuretics or ACE-inhibitors . Kapur suggests that euvolemic patients with FENa >0.2% can only be safely and effectively treated with diuretics . Hypovolemia may occur in patients with severe edema, or following the administration of diuretics in children with poor oral intake, diarrhoea, and vomiting. The clinical features of hypovolemia are abdominal pain, lethargy, dizziness and leg cramps, tachycardia, hypotension, delayed capillary refill, low volume pulses and cool, clammy distal extremities. An elevated blood urea nitrogen/creatinine ratio, rising hematocrit levels and low fractional excretion of sodium (<0.5%) suggest the presence of hypovolemia.
Treatment of edema in nephrotic syndrome
Management of edema
Management of edema in nephrotic syndrome
▪ sodium restriction
▪ fluid restriction
▪ sodium restriction
▪ fluid restriction
▪ loop diuretic
▪ potassium sparing diuretic for prolonged therapy
▪ sodium restriction
▪ fluid restriction
▪ loop diuretic +/− potassium sparing diuretic
▪ thyazide diuretic
▪ albumin, followed by a bolus of furosemide
We suggest that mild edema be managed with salt and fluid restriction only
We suggest that moderate edema be treated with a loop diuretic, with the addition of a potassium-sparing diuretic in the case of prolonged therapy
We suggest the co-administration of a thiazide diuretic in cases of severe edema unresponsive to oral or i.v. loop diuretics.
We suggest albumin infusions in patients with severe edema unresponsive to oral or i.v. loop diuretics
We suggest interrupting diuretic therapy immediately in case of hypovolemia and its prompt intravenous correction if clinical signs are present.
Infections and immunization in children with INS
Patients with NS, especially children, are susceptible to infection. Thanks to the use of antibiotics, the cumulative incidence of infection-related mortality has dropped from 40% to 1.5% , yet infections still represent one of the most frequent complications of NS worldwide. There are several predisposing factors of contracting an infection, such as the urinary loss of immunoglobulins, defective opsonization (reduced factor B and D concentrations), impaired T-lymphocyte function, the presence of edema and the effects of immunosuppressive therapy. Encapsulated organisms (mainly Streptococcus pneumoniae) and Gram-negative enteric organisms (predominantly Escherichia coli) are the most frequently involved; bacterial peritonitis is the most commonly occurring serious infection, with an incidence of 2-6% [1, 33]. Sepsis, meningitis, cellulitis and pneumonia may also occur and, although not severe, urinary tract infections and viral infections of the upper respiratory tract are common [34, 35]. Viral infections are generally well tolerated, with the exception of chickenpox, which can cause severe complications and be potentially lethal . In the case of a severe viral infection, steroid therapy should be reduced or stopped.
We do not recommend administering either i.v. immunoglobulin or prophylactic antibiotics to children.
We suggest that rapid diagnosis and antibiotic treatment of infections are the most effective interventions.
Varicella-zoster virus infections
We suggest the use of oral acyclovir following exposure to chickenpox in non-immune patients.
Patients with a diagnosis of varicella should be started on acyclovir promptly (80 mg/kg/day divided into 4 doses for 5 days, with a maximum 800 mg/dose) in order to reduce the risk of visceral dissemination . VZIG can be used either prophylactically or therapeutically, according to availability, epidemiology and local practice. In Italy, for instance, VZIG is not available.
We suggest that patients on high-dose steroids should not be given live attenuated vaccines.
Once first episode treatment has been completed, the varicella vaccine is recommended three months after corticosteroid discontinuation.
High dose steroids
Low dose steroids
H. Influenzae type B
We suggest that all unimmunized children with NS should receive the pneumococcal vaccine.
Thromboembolism in INS
We do not suggest thrombophilia screening in children with INS at presentation unless there is a family history of thrombotic events at a young age (<50 years) or known abnormalities of pro-thrombotic coagulation factors.
There are no indications for anticoagulant/antiplatelet prophylaxis in children with INS at presentation.
We suggest the use of anticoagulant/antiplatelet prophylaxis in children with a concomitant cardiovascular abnormality (who would usually already be under prophylactic anticoagulant/antiplatelet treatment) or a central venous catheter (CVC) (almost impossible at the onset of illness).
The greatest care must also be taken in patients with NS and a concomitant septic state, and/or in the presence of a CVC, for whom an antiplatelet/anticoagulant therapy should be considered.
In cases of a persistent nephrotic condition in children with SRNS and whose edema is difficult to control, thrombophilia screening, as well as antiplatelet/anticoagulant prophylaxis may be considered.
Secondary thrombocytosis usually does not require treatment. In the presence of active NS and a platelet count >1.000.000/mmc, we suggest aspirin prophylaxis.
Thromboembolic events: therapy and prophylaxis
Begin at the time of the acute event and continue for 5–10 days.
Suspend on day 6 after OAT start, if INR on target. (Grad 1C +).
Minor use in the last decade.
75 UI/kg bolus in10 min
Initial maintenance dose:
>1 year: 28 UI/Kg/h
>1 year. 20 UI/Kg/h
Then adjust to maintain aPTT between 60–85 s.
Therapeutic target: between 60–85 s.
Low molecular weight heparin (LMWH)
More used in the last decade in the treatment of thromboembolism in children
Enoxaparin Dosage (>2 months)
Therapeutic: 100 UI/kg every 12 h
Prophylactic: 50 UI/ kg every 12 h
If clearance <60 ml/min) dosage must be adjusted on renal function
Anti Xa: blood samples 4 h after drug administration
Therapeutic target: 0.5.1 UI/mL
Prophylactic target: 0.3-0.5 UI/mL
Begin with heparin therapy until the target INR(2–3) is reached.
Continue for 3 months, in absence of predisposing factors like NS.
Continue for 6 months in presence of predisposing factors, like NS, or in cases of recurrent thrombosis.
Vitamin K antagonists more used for older children (frequent blood check)
In pediatric patients > 10 Kg: 0.2 mk/Kg/day
INR Target: 2-3
If PLT >1.000.000 /mmc with concomitant NS
Empirical antiplatelet dosage in pediatrics: 1–5 mg/kg/day
No data on fibrinolytic treatment of thrombotic events in pediatric patients with NS.
We do not recommend the routine use of prophylactic PPIs in combination with steroid therapy in NS.
We suggest that PPIs should be used only in selected cases manifesting with gastric symptoms resistant to treatment with malgadrate or alginate, or with any other risk factor (gastroesophageal reflux, esophageal disease, concomitant need for other gastrotoxic therapies).
Supplementation with calcium and vitamin D
We do not suggest calcium and vitamin D supplementation in children at first episode or in SSNS unless vitamin D deficiency has been predicted or demonstrated.
Treatment of hyperlipidemia
We do not recommend the use of lipid-lowering treatments at INS onset
We do not recommend low fat diets for children at INS onset
Steroid Resistant Nephrotic Syndrome (SRNS)
It is reasonable to define SRNS as a lack of remission despite 4 weeks of treatment with PDN at the dose of 60 mg/m2/day, followed by 3 high-pulse doses of Methylprednisolone (500 mg/m2) and another two weeks of PDN at the dose of 60 mg/m2/day
We suggest that kidney biopsy be performed after the first four weeks of therapy; the continuation of steroid treatment depends on the histological findings.
We suggest that mutational analysis should be offered to patients with congenital, early onset (<12 m) NS or sporadic, familial SRNS or syndromes associated with NS
Genes associated with nephrotic syndrome
Characteristic signs and features
CNS,NS - childhood and adult onset
Adult onset NS
Adult onset NS, Denys-Drash and Fraiser Syndromes
Nail-Patella Syndrome/NS only
Schimke immuno-osseous dysplasia
Early-onset NS and mental retardation
NS with co-segregating heart block disorder
Adult onset NS
Adult onset NS
Adult onset NS
Adult onset NS
Adult onset NS
Early or Adult onset NS
Adult onset NS
Adult onset NS
Intermittent nephritic range proteinuria and epilepsy
Adult onset NS
Early or Adult onset NS
NS with tubulointerstitial involvement
MELAS syndrome; NS+/− deafness and diabetes
Deafness, NS, epilepsy, and dilated cardiomyopathy
Multiorgan failure and NS
Mitochondrial cytopathy and NS
Mitochondrial disease/isolated nephropathy
NS with sensorineural deafness
Mandibulosacral dysplasia with NS
NS, IgA nephropathy
Pierson S.; CNS with ocular abnormalities; isolated early-onset NS
NEP syndrome-NS, epidermolysis bullosa and pulmonary disease
Epidermolysis bullosa and pyloric atresia + NS
Famlial partial lipodystrophy + NS
NS, pretibilial bullous skin lesions, neurosensory deafness, bilateral lacrimal duct stenosis, nail dystrophy, thalassemia minor
Indications for kidney biopsy
Indications for renal biopsy in children with NS
• Onset at less than 12 months or more than 12 years of age
• Initial macroscopic hematuria
• Persistent hypertension and/or microscopic hematuria and/or low plasma C3
• Secondary NS (Henoch-Schoenlein purpura, systemic lupus erythematosus, etc.)
• NS associated with syndromes
• Renal failure not related to hypovolemia
• Steroid Resistance
A renal biopsy should be recommended in patients <12 months or >12 years of age at the onset of NS or when secondary NS is suspected.
Differently, in African or African-American children, it is reasonable to perform the kidney biopsy at NS onset, before starting treatment. In fact, in these races the mean age for presentation of NS is higher than in Caucasians and Hispanics and there is a higher prevalence of FSGS or histological types different from MCD [4, 87–89]. However, the most important predictive factor of renal survival in pediatric NS is not the histological lesion but the achievement and the maintenance of remission after steroid therapy . Kidney biopsy in children with FR- or SDNS is not required before initiating corticosteroid-sparing therapies because response to therapy is cited as the most important predictor of kidney survival.
This consensus document is aimed at providing an updated, multidisciplinary overview on the diagnosis and treatment of pediatric NS at first presentation.
Until now, shared treatment guidelines were lacking in Italy and, consequently, the choice of steroid regimen was based on the clinical expertise of each individual unit. On the basis of a retrospective study evaluating the different therapeutic strategies adopted by pediatricians and pediatric nephrologists in a large number of Italian centers, the 2015 Cochrane systematic review, KDIGO Guidelines and a thorough review of the literature in the PubMed database, this working group (with the contribution of all the pediatric nephrology centres in Italy and on the behalf of the Italian Society of Pediatric Nephrology) has produced a shared steroid protocol that will be useful for National Health System hospitals and pediatricians.
It is the first consensus document of its kind to be produced by all the pediatric nephrology centres in Italy, in line with what is already present in other countries such as France, Germany and the USA. It is based on the current knowledge surrounding the symptomatic and steroid treatment of NS, with a view to providing the basis for a separate consensus document on the treatment of relapses and for future research.
American Academy of Pediatrics
Atrial natriuretic peptide
Arbeitsgemeinschaft für Pädiatrische Nephrologie
Complete Blood Count
Congenital nephrotic syndrome
Central venous catheter
Diffuse mesangial sclerosis
Fractional excretion of sodium
Frequently relapsing nephrotic syndrome
Focal segmental glomerulosclerosis
Idiopathic nephrotic syndrome
The International Study of Kidney Disease in Childhood
Kidney Disease Improving Global Outcomes
Low density lipoprotein
Minimal change disease
Mesangial proliferative glomerulonephritis
7-valent pneumococcal conjugated vaccine
Proton pump inhibitors
23-valent pneumococcal polysaccharide vaccine
Randomized controlled trials
Steroid dependent nephrotic syndrome
Steroid sensitive nephrotic syndrome
Very low density lipoprotein
The authors thank Alexandra Teff for her linguistic assistance.
No funding was obtained
Availability of data and materials
AP conceived the concept, conducted the literature search and drafted the section on corticosteroid use for the first episode. EB conceived the concept, conducted the literature search drafted sections on diagnosis, investigations at initial presentation, discharge and follow up. DM conceived the concept, conducted the literature search and drafted the section on the treatment of edema. LG conceived the concept, conducted the literature search and drafted the section on infections and immunization. LM conceived the concept, conducted the literature search and drafted the section on thromboembolism. LP conceived the concept, conducted the literature search and drafted the section on gastroprotection, calcium and vitamin D supplementation and treatment of hyperlipidemia. GC conceived the concept, conducted the literature search and drafted the section on steroid resistant NS and indications for kidney biopsy. All the authors read and approved the final manuscript. This article was also read and approved by the Steering Committee: FE, CF, AT, SM, MM, GM, GM, LM, CP, MP and members of the Italian Society of Pediatric Nephrology (SINePe).
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003;362(9384):629–39.View ArticlePubMedGoogle Scholar
- Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int. 1978;13(2):159–65.
- Niaudet P. Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. Clin J Am Soc Nephrol. 2009;4(10):1547–8.View ArticlePubMedGoogle Scholar
- KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. Kidney Int Suppl. 2012;(2):139–274.
- Hari P, Bagga A, Mantan M. Short term efficacy of intravenous dexamethasone and methylprednisolone therapy in steroid resistant nephrotic syndrome. Indian Pediatr. 2004;41(10):993–1000.PubMedGoogle Scholar
- Tsuzuki K, Tanabe M, Satoh C, et al. Betamethasone “pulse” therapy for children with idiopathic nephrotic syndrome -especially for fresh cases (author transl). Nihon Jinzo Gakkai Shi. 1981;23(11):1405–13.PubMedGoogle Scholar
- McLean TLK RH, Rasoulpour M. Intravenous methylprednisolone treatment of steroid responsive nephrotic syndrome. Pediat Res. 1980;14(8):1006.
- Broyer M, Terzi F, Lehnert A, Gagnadoux MF, Guest G, Niaudet P. A controlled study of deflazacort in the treatment of idiopathic nephrotic syndrome. Pediatr Nephrol. 1997;11(4):418–22.View ArticlePubMedGoogle Scholar
- Ehrich JH, Brodehl J. Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Eur J Pediatr. 1993;152(4):357–61.View ArticlePubMedGoogle Scholar
- Syndrome Néphrotique Idiopathique de l’Enfant. Protocole national de disgnostic et de soins pour une maladie rare. France: Haute Autorité de Santé; 2008.Google Scholar
- Feber J, Al-Matrafi J, Farhadi E, Vaillancourt R, Wolfish N. Prednisone dosing per body weight or body surface area in children with nephrotic syndrome: is it equivalent? Pediatr Nephrol. 2009;24(5):1027–31.View ArticlePubMedGoogle Scholar
- Saadeh SA, Baracco R, Jain A, Kapur G, Mattoo TK, Valentini RP. Weight or body surface area dosing of steroids in nephrotic syndrome: is there an outcome difference? Pediatr Nephrol. 2011;26(12):2167–71.View ArticlePubMedGoogle Scholar
- Mehls O, Hoyer PF. Dosing of glucocorticosteroids in nephrotic syndrome. Pediatr Nephrol. 2011;26(12):2095–8.View ArticlePubMedGoogle Scholar
- Ekka BK, Bagga A, Srivastava RN. Single- versus divided-dose prednisolone therapy for relapses of nephrotic syndrome. Pediatr Nephrol. 1997;11(5):597–9.View ArticlePubMedGoogle Scholar
- Li X, Li Z, Cheng Z. Treatment of children with simple nephrotic syndrom using prednison once per day. Acta Academiae Medicinae Hubei. 1994;15(4):386–8.Google Scholar
- Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2015;3:Cd001533.Google Scholar
- Nephrotic syndrome in children: a randomized trial comparing two prednisone regimens in steroid-responsive patients who relapse early. Report of the international study of kidney disease in children. J Pediatr. 1979;95(2): 239–43
- Hodson EM, Knight JF, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2000;4, CD001533.Google Scholar
- Teeninga N, Kist-van Holthe JE, van Rijswijk N, et al. Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. J Am Soc Nephrol. 2013;24(1):149–59.View ArticlePubMedGoogle Scholar
- Sinha A, Saha A, Kumar M, et al. Extending initial prednisolone treatment in a randomized control trial from 3 to 6 months did not significantly influence the course of illness in children with steroid-sensitive nephrotic syndrome. Kidney Int. 2015;87(1):217–24.View ArticlePubMedGoogle Scholar
- Yoshikawa N, Nakanishi K, Sako M, et al. A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment. Kidney Int. 2015;87(1):225–32.View ArticlePubMedGoogle Scholar
- Hoyer PF. New lessons from randomized trials in steroid-sensitive nephrotic syndrome: clear evidence against long steroid therapy. Kidney Int. 2015;87(1):17–9.View ArticlePubMedGoogle Scholar
- Pasini A, Aceto G, Ammenti A, et al. Best practice guidelines for idiopathic nephrotic syndrome: recommendations versus reality. Pediatr Nephrol. 2015;30(1):91–101.View ArticlePubMedGoogle Scholar
- Bagga A, Ali U, Banerjee S, et al. Management of steroid sensitive nephrotic syndrome: revised guidelines. Indian Pediatr. 2008;45(3):203–14.PubMedGoogle Scholar
- Gipson DS, Massengill SF, Yao L, et al. Management of childhood onset nephrotic syndrome. Pediatrics. 2009;124(2):747–57.View ArticlePubMedGoogle Scholar
- Sinha A, Bagga A. Nephrotic syndrome. Indian J Pediatr. 2012;79(8):1045–55.View ArticlePubMedGoogle Scholar
- Humphreys MH. Mechanisms and management of nephrotic edema. Kidney Int. 1994;45(1):266–81.View ArticlePubMedGoogle Scholar
- Bockenhauer D. Draining the edema: a new role for aquaretics? Pediatr Nephrol. 2014;29(5):767–9.View ArticlePubMedGoogle Scholar
- McCaffrey J, Lennon R, Webb NJA. The non-immunosuppressive management of childhood nephrotic syndrome. Pediatr Nephrol. 2016;31:1383–402.View ArticlePubMedGoogle Scholar
- Kapur G, Valentini RP, Imam AA, Mattoo TK. Treatment of severe edema in children with nephrotic syndrome with diuretics alone--a prospective study. Clin J Am Soc Nephrol. 2009;4(5):907–13.View ArticlePubMedPubMed CentralGoogle Scholar
- Joles JA, Rabelink TJ, Braam B, Koomans HA. Plasma volume regulation: defences against edema formation (with special emphasis on hypoproteinemia). Am J Nephrol. 1993;13(5):399–412.View ArticlePubMedGoogle Scholar
- Minimal change nephrotic syndrome in children: deaths during the first 5 to 15 years’ observation. Report of the International Study of Kidney Disease in Children. Pediatrics. 1984;73(4): 497–501.
- Uncu N, Bülbül M, Yildiz N, et al. Primary peritonitis in children with nephrotic syndrome: results of a 5-year multicenter study. Eur J Pediatr. 2010;169(1):73–6.View ArticlePubMedGoogle Scholar
- Gulati S, Kher V, Arora P, Gupta S, Kale S. Urinary tract infection in nephrotic syndrome. Pediatr Infect Dis J. 1996;15(3):237–40.View ArticlePubMedGoogle Scholar
- Alwadhi RK, Mathew JL, Rath B. Clinical profile of children with nephrotic syndrome not on glucorticoid therapy, but presenting with infection. J Paediatr Child Health. 2004;40(1–2):28–32.View ArticlePubMedGoogle Scholar
- Nyerges G, Meszner Z, Gyarmati E, Kerpel-Fronius S. Acyclovir prevents dissemination of varicella in immunocompromised children. J Infect Dis. 1988;157(2):309–13.View ArticlePubMedGoogle Scholar
- Wu HM, Tang JL, Cao L, Sha ZH, Li Y. Interventions for preventing infection in nephrotic syndrome. Cochrane Database Syst Rev. 2012;4:Cd003964.Google Scholar
- Hirst C, Owusu-Ofori S. Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease. Cochrane Database Syst Rev. 2012;9:Cd003427.Google Scholar
- McIntyre P, Craig JC. Prevention of serious bacterial infection in children with nephrotic syndrome. J Paediatr Child Health. 1998;34(4):314–7.View ArticlePubMedGoogle Scholar
- Overturf GD. American Academy of Pediatrics. Committee on Infectious Diseases. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis. Pediatrics. 2000;106(2 Pt 1):367–76.View ArticlePubMedGoogle Scholar
- Goldstein SL, Somers MJ, Lande MB, Brewer ED, Jabs KL. Acyclovir prophylaxis of varicella in children with renal disease receiving steroids. Pediatr Nephrol. 2000;14(4):305–8.View ArticlePubMedGoogle Scholar
- Furth SL, Arbus GS, Hogg R, Tarver J, Chan C, Fivush BA. Varicella vaccination in children with nephrotic syndrome: a report of the Southwest Pediatric Nephrology Study Group. J Pediatr. 2003;142(2):145–8.View ArticlePubMedGoogle Scholar
- Alpay H, Yildiz N, Onar A, Temizer H, Ozcay S. Varicella vaccination in children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2002;17(3):181–3.View ArticlePubMedGoogle Scholar
- Shroff A, Frank R, Vergara M, Gauthier B, Trachtman H. Prevention of serious bacterial infections in new-onset nephrotic syndrome: a survey of current practices. Clin Pediatr (Phila). 2002;41(1):47–9.View ArticleGoogle Scholar
- Ulinski T, Leroy S, Dubrel M, Danon S, Bensman A. High serological response to pneumococcal vaccine in nephrotic children at disease onset on high-dose prednisone. Pediatr Nephrol. 2008;23(7):1107–13.View ArticlePubMedGoogle Scholar
- Bogaert D, Hermans PW, Adrian PV, Rumke HC, de Groot R. Pneumococcal vaccines: an update on current strategies. Vaccine. 2004;22(17–18):2209–20.View ArticlePubMedGoogle Scholar
- Fedson DS. The clinical effectiveness of pneumococcal vaccination: a brief review. Vaccine. 1999;17 Suppl 1:S85–90.View ArticlePubMedGoogle Scholar
- Tinaztepe K, Buyan N, Tinaztepe B, Akkök N. The association of nephrotic syndrome and renal vein thrombosis: a clinicopathological analysis of eight pediatric patients. Turk J Pediatr. 1989;31(1):1–18.PubMedGoogle Scholar
- Lilova MI, Velkovski IG, Topalov IB. Thromboembolic complications in children with nephrotic syndrome in Bulgaria (1974–1996). Pediatr Nephrol. 2000;15(1–2):74–8.View ArticlePubMedGoogle Scholar
- Andrew M, Brooker LA. Hemostatic complications in renal disorders of the young. Pediatr Nephrol. 1996;10(1):88–99.View ArticlePubMedGoogle Scholar
- Kerlin BA, Ayoob R, Smoyer WE. Epidemiology and pathophysiology of nephrotic syndrome-associated thromboembolic disease. Clin J Am Soc Nephrol. 2012;7(3):513–20.View ArticlePubMedPubMed CentralGoogle Scholar
- Suri D, Ahluwalia J, Saxena AK, et al. Thromboembolic complications in childhood nephrotic syndrome: a clinical profile. Clin Exp Nephrol. 2014;18(5):803–13.View ArticlePubMedGoogle Scholar
- Dame C, Sutor AH. Primary and secondary thrombocytosis in childhood. Br J Haematol. 2005;129(2):165–77.View ArticlePubMedGoogle Scholar
- Mittal A, Aggarwal KC, Saluja S, Aggarwal A, Sureka B. Platelet functions and coagulation changes in Indian children with nephrotic syndrome. J Clin Diagn Res. 2013;7(8):1647–50.PubMedPubMed CentralGoogle Scholar
- Remuzzi G, Marchesi D, Mecca G, de Gaetano G, Silver M. Platelet hypersensitivity in the nephrotic syndrome. Proc Eur Dial Transplant Assoc. 1979;16:487–94.PubMedGoogle Scholar
- Walter E, Deppermann D, Andrassy K, Koderisch J. Platelet hyperaggregability as a consequence of the nephrotic syndrome. Thromb Res. 1981;23(6):473–9.View ArticlePubMedGoogle Scholar
- Kerlin BA, Blatt NB, Fuh B, et al. Epidemiology and risk factors for thromboembolic complications of childhood nephrotic syndrome: a Midwest Pediatric Nephrology Consortium (MWPNC) study. J Pediatr. 2009;155(1):105–10. 10.e1.View ArticlePubMedPubMed CentralGoogle Scholar
- Tkaczyk M, Baj Z. Surface markers of platelet function in idiopathic nephrotic syndrome in children. Pediatr Nephrol. 2002;17(8):673–7.View ArticlePubMedGoogle Scholar
- George FD. Microparticles in vascular diseases. Thromb Res. 2008;122 Suppl 1:S55–9.View ArticlePubMedGoogle Scholar
- Monagle P, Chan A, Massicotte P, Chalmers E, Michelson AD. Antithrombotic therapy in children: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):645S–87S.View ArticlePubMedGoogle Scholar
- Monagle P, Chan AK, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e737S–801S.View ArticlePubMedPubMed CentralGoogle Scholar
- Chan AK, Monagle P. Updates in thrombosis in pediatrics: where are we after 20 years? Hematology Am Soc Hematol Educ Program. 2012;2012:439–43.PubMedGoogle Scholar
- Law C, Raffini L. A guide to the use of anticoagulant drugs in children. Paediatr Drugs. 2015;17(2):105–14.View ArticlePubMedGoogle Scholar
- Guslandi M. Steroid ulcers: Any news? World J Gastrointest Pharmacol Ther. 2013;4(3):39–40.PubMedPubMed CentralGoogle Scholar
- Dorlo TP, Jager NG, Beijnen JH, Schellens JH. Concomitant use of proton pump inhibitors and systemic corticosteroids. Ned Tijdschr Geneeskd. 2013;157(19):A5540.PubMedGoogle Scholar
- Munson JC, Wahl PM, Daniel G, Kimmel SE, Hennessy S. Factors associated with the initiation of proton pump inhibitors in corticosteroid users. Pharmacoepidemiol Drug Saf. 2012;21(4):366–74.View ArticlePubMedPubMed CentralGoogle Scholar
- Weinstein RS. Clinical practice. Glucocorticoid-induced bone disease. N Engl J Med. 2011;365(1):62–70.View ArticlePubMedGoogle Scholar
- Gulati S, Sharma RK, Gulati K, Singh U, Srivastava A. Longitudinal follow-up of bone mineral density in children with nephrotic syndrome and the role of calcium and vitamin D supplements. Nephrol Dial Transplant. 2005;20(8):1598–603.View ArticlePubMedGoogle Scholar
- Gruppen MP, Davin JC, Oosterveld MJ, et al. Prevention of steroid-induced low bone mineral density in children with renal diseases: a systematic review. Nephrol Dial Transplant. 2013;28(8):2099–106.View ArticlePubMedGoogle Scholar
- Querfeld U. Should hyperlipidemia in children with the nephrotic syndrome be treated? Pediatr Nephrol. 1999;13(1):77–84.View ArticlePubMedGoogle Scholar
- Kong X, Yuan H, Fan J, Li Z, Wu T, Jiang L. Lipid-lowering agents for nephrotic syndrome. Cochrane Database Syst Rev. 2013;12, CD005425.Google Scholar
- Cochat P, Fargue S, Mestrallet G, et al. Disease recurrence in paediatric renal transplantation. Pediatr Nephrol. 2009;24(11):2097–108.View ArticlePubMedPubMed CentralGoogle Scholar
- Gulati A, Bagga A, Gulati S, Mehta KP, Vijayakumar M. Management of steroid resistant nephrotic syndrome. Indian Pediatr. 2009;46(1):35–47.PubMedGoogle Scholar
- The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr. 1981;98(4):561–4.
- KDIGO Clinical Practice Guideline Chapter 4: Steroid-resistant nephrotic syndrome in children. Kidney Int Suppl. 2012;2(2):172–6.
- Prospective, controlled trial of cyclophosphamide therapy in children with nephrotic syndrome. Report of the International study of Kidney Disease in Children. Lancet. 1974;2(7878):423–7.
- Trautmann A, Bodria M, Ozaltin F, et al. Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort. Clin J Am Soc Nephrol. 2015;10(4):592–600.View ArticlePubMedPubMed CentralGoogle Scholar
- Bierzynska A, Soderquest K, Koziell A. Genes and podocytes - new insights into mechanisms of podocytopathy. Front Endocrinol (Lausanne). 2014;5:226.Google Scholar
- KDIGO Clinical Practice Guideline. Chapter 3: Steroid-sensitive nephrotic syndrome in children. Kidney Int Suppl. 2012;2(2):163–71.
- Nammalwar BR, Vijayakumar M, Prahlad N. Experience of renal biopsy in children with nephrotic syndrome. Pediatr Nephrol. 2006;21(2):286–8.View ArticlePubMedGoogle Scholar
- Corwin HL, Schwartz MM, Lewis EJ. The importance of sample size in the interpretation of the renal biopsy. Am J Nephrol. 1988;8(2):85–9.View ArticlePubMedGoogle Scholar
- KDIGO Clinical Practice Guideline. Chapter 2: General principles in the management of glomerular disease. Kidney Int Suppl. 2012;2(2):156–62.
- Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children. Kidney Int. 1981;20(6): 765–71.
- McKinney PA, Feltbower RG, Brocklebank JT, Fitzpatrick MM. Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire. UK Pediatr Nephrol. 2001;16(12):1040–4.View ArticlePubMedGoogle Scholar
- Gulati S, Sharma AP, Sharma RK, Gupta A, Gupta RK. Do current recommendations for kidney biopsy in nephrotic syndrome need modifications? Pediatr Nephrol. 2002;17(6):404–8.View ArticlePubMedGoogle Scholar
- Gulati S, Sural S, Sharma RK, Gupta A, Gupta RK. Spectrum of adolescent-onset nephrotic syndrome in Indian children. Pediatr Nephrol. 2001;16(12):1045–8.View ArticlePubMedGoogle Scholar
- Baqi N, Singh A, Balachandra S, et al. The paucity of minimal change disease in adolescents with primary nephrotic syndrome. Pediatr Nephrol. 1998;12(2):105–7.View ArticlePubMedGoogle Scholar
- Sorof JM, Hawkins EP, Brewer ED, Boydstun II, Kale AS, Powell DR. Age and ethnicity affect the risk and outcome of focal segmental glomerulosclerosis. Pediatr Nephrol. 1998;12(9):764–8.View ArticlePubMedGoogle Scholar
- Bonilla-Felix M, Parra C, Dajani T, Ferris M, Swinford RD, Portman RJ, Verani R. Changing patterns in the histopathology of idiopathic nephrotic syndrome in children. Kidney Int. 1999;55(5):1885–90.View ArticlePubMedGoogle Scholar
- Gipson DS, Chin H, Presler TP, et al. Differential risk of remission and ESRD in childhood FSGS. Pediatr Nephrol. 2006;21(3):344–9.View ArticlePubMedGoogle Scholar