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Pediatric Nephrology

, Volume 34, Issue 5, pp 777–785 | Cite as

Treating the idiopathic nephrotic syndrome: are steroids the answer?

  • Georges DeschênesEmail author
  • Claire Dossier
  • Julien Hogan
Educational Review

Abstract

The use of steroids in idiopathic nephrotic syndrome is the major discovery of the twentieth century in the field of pediatric nephrology. At onset of the twenty-first century, steroids remain the first line of treatment at first flare. All the protocols to treat the first flare are similar by a common sequence including a first phase of daily prednisolone/prednisone at a dose of 60 mg/m2/day for at least 4 weeks followed by an alternate-day regimen for several weeks. It appears that a cumulated dose of 2240 mg/m2 given in 8 weeks at the first flare without tapering sequence is not inferior to increased dose and duration in terms of prevalence of frequent relapsers and the subsequent cumulated dose of steroids at 24 months of follow-up. A higher cumulated dose might only be interesting in patients aged below 4 years although a formal demonstration is still missing. Several retrospective studies are concordant to suggest that intravenous methylprednisolone pulses are useful to reach a full urinary remission in case of oral resistance to 4 weeks of oral prednisone/prednisolone. A majority of patients have multiple relapses after the treatment of the first flare and half meet the definition of steroid dependency. In those patients, long-lasting alternate-day prednisone/prednisolone therapy does not lead to long-lasting remission, opening the question of the best strategy of immunosuppression.

Keywords

Prednisone Prednisolone Intravenous methylprednisolone Steroid dependency Steroid resistance 

Introduction

The use of steroids in idiopathic nephrotic syndrome is the major discovery of the twentieth century in the field of pediatric nephrology. Steroids both changed the life of 95% of children affected with nephrotic syndrome and also had a major impact on the insight of the disease in the mind of pediatric nephrologists. Although John Luetscher was not the first to report on the use of cortisone in nephrotic children [1, 2], he was the first to clearly note the fall of proteinuria that preceded or accompanied the diuresis and edema recovery [3]. Later on, Keith Drummond reported that most of the children that responded to steroid therapy had minimal renal changes by light microscopy and showed no glomerular IgG deposition in immunofluorescence [4]. This is still the modern definition of idiopathic nephrotic syndrome.

In the early seventies, several groups of pediatric nephrologists around the world and belonging to different nationwide medical societies suggested to treat the first flare of the disease with a common and uniform treatment. Three major protocols were suggested independently by the International Study in Kidney Disease (ISKDC) in the USA, the Arbeitgeimenshaft für Pediatric Nephrologie (APN), and the Société de Néphrologie Pédiatrique (SNP) [5]. Those protocols were elaborated on an empirical basis according to the best rate between efficiency and steroid toxicity. They were quite similar by a common sequence including a first phase of daily prednisolone/prednisone (Fig. 1 and Table 1) at a same dose of 60 mg/m2/day during a fixed period of time followed by a subsequent phase of alternate-day regimen also limited to a fixed period of time (Table 2). By contrast, they were quite different by the length of therapy from 8 to 18 weeks and the cumulated dose of prednisolone/prednisone from 2240 to 3990 mg/m2 in patients weighing less than 30 kg BW. In addition to these two phases, the SNP protocol included a tapering sequence of prednisone in three steps of 45, 30, and 15 mg/m2 in order to test the level of steroid dependence as soon as the first flare. The three European uniform protocols are within the KDIGO (Kidney Disease Improving Global Outcome) recommendations: 60 mg/m2/day during 4 to 6 weeks followed by 40 mg/m2 alternate day during 8 to 20 weeks. KDIGO recommendations also suggest a tapering sequence but without a precise schedule [6]. Half of the European patients are treated according to one of those three uniform protocols, while the other half is treated with in-house protocols where steroids are irrationally overloaded in the majority of cases [5].
Fig. 1

The molecular structure of cholesterol, natural glucocorticoids, and the main semi-synthetic steroids used in pediatric nephrology. All steroids are derived from cholesterol. Cholesterol is shaped by 27 carbon residues that have been universally numbered, 17 out of them giving the 4 cycles A to D. Glucocorticoids do not have any sugar residue but have been named glucocorticoids because of their effect on glucose balance by opposition to mineralocorticoids that have an effect on sodium and potassium balance. In everyday language, steroid therapy refers to a treatment with glucocorticoids. Cortisone and hydrocortisone are natural glucocorticoids with 21 carbon residues that only differ by a hydroxyl residue on carbon 11. Prednisone and prednisolone are the semi-synthetic forms of cortisone and hydrocortisone, respectively, and differs from their natural counterpart by two double bonds in cycle A. Along with the natural hormones, prednisolone is the active metabolite of prednisone and differs from prednisone by a hydroxyl residue on carbon 11. Methylprednisolone is a prednisolone substituted with a methyl residue in 6, meaning that it contains 22 carbon residues. Triamcinolone is similar to prednisolone, but a fluor replaces a hydrogen residue on carbon 9. Deflazacort is an oxazoline derivative characterized by 25 carbon residues and a fifth cycle containing nitrogen

Table 1

Main characteristics of steroid drugs used in children affected by the idiopathic nephrotic syndrome

 

Route

Dosage forms

Equivalent in prednisone

Prednisone

Oral

Tablets 1, 2.5, 5, 10, 20 mg

1:1

Prednisolone

Oral

Tablets 1, 2.5, 5, 10, 20 mg

1:1

Deflazacort

Oral

Tablets 6, 18, 30, 36 mg

Oral suspension 22.75 mg/mL

1:0.8

Delayed release triamcinolone

Intramuscular

Vial 1 mL = 40 mg

Vial 2 mL = 80 mg

1:30a

a1 mg/month of delayed released triamcinolone is equivalent to 1 mg/day of prednisone × 30 days

Table 2

Main uniformed protocols of treatment of the first flare

 

ISKDC

APN

SNP

Daily full dose

60 mg/m2/day × 4 weeks

60 mg/m2/day × 6 weeks

60 mg/m2/day × 4 weeks

Alternate full dose

40 mg/m2 eod × 4 weeks

40 mg/m2 eod × 6 weeks

60 mg/m2 eod × 8 weeks

Tapering step 1

NA

NA

45 mg/m2 eod × 2 weeks

Tapering step 2

NA

NA

30 mg/m2 eod × 2 weeks

Tapering step 3

NA

NA

15 mg/m2 eod × 2 weeks

Total cumulated dose

2240 mg/m2

3360 mg/m2

3990 mg/m2

Total duration

8 weeks

12 weeks

18 weeks

Type of steroid

Prednisolonea

Prednisonea

Prednisonea

Maximum daily dosage

80 mg/day

80 mg/day

60 mg/day

“MP test”

No

No

IVMP 1000 mg/1.73 m2 × 3

MP test methylprednisolone bolus in case of resistance at 4 weeks of oral prednisone, ISKDC International Study of Kidney Disease in Childhood, APN Arbeitgeimenshaft fur Pediatric Nephrologie, SNP Société de Néphrologie Pédiatrique

aPrednisolone is the active metabolite of prednisone and differs from prednisone by a hydroxyl residue on carbon 11 (see Fig. 1)

Biological effects of glucocorticoids

Glucocorticoid hormones are a vital mammalian systemic hormonal signal that exerts regulatory effects on almost every cell and system of the body, notably affecting carbohydrate metabolism, blood pressure and vascular trophicity, psychic mood and behavior, muscle and skin trophicity, palatability and weight, bone growth, and mineralization [7]. They have no physiological role in the kidney where sodium reabsorption can only be affected by pharmacological concentrations of glucocorticoids leading to hypertension. Glucocorticoids act in a circadian and stress-directed manner to aid in adaptation to an ever-changing environment. Circadian glucocorticoid secretion provides for a daily waxing and waning influence on target cell function. In addition, the daily circadian peak of glucocorticoid secretion serves as a timing signal that helps entrain intrinsic molecular clock phase in tissue cells distributed throughout the body [7]. Stress-induced glucocorticoid secretion also modulates the state of both physiological and psychological stressors [7]. Indeed, they have also a strong impact on immunity due to a physiological key role on T cell sorting in the thymus through the glucocorticoid-induced apoptosis [8].

At pharmacological dose, glucocorticoids are immunosuppressant. They induce the apoptosis of immature T cells [9] and either mature or stimulated B cells [10]. On a more functional point of view, they strongly inhibit signaling of Toll-like receptors through the regulation of AP1 and IRF3; they modulate T cell activity through TCR signaling by the inhibition of the main transcription factors (NFƘB, NFAT, and AP1) and control the expression of the molecular species involved in the immune synapse between dendritic cells and naïve T cells (specially MHC class 2 and CD80) [11]. The overall result is a clear inhibition of cytokine production affecting IL-2, Il-4, IL-6, IFN-ɣ, and TNF-α as well as a significant reduction of IgG production [11, 12].

The first flare

The variability of treatment of the first flare among European centers recently showed that a lot of children are overloaded in steroids compared to the load of the European uniform protocols [5]. In addition, an Italian study also demonstrated that patients treated in general pediatric units also received much higher cumulative doses and much longer time of prednisone than dose treated in pediatric nephrology units [13]. These results highlight the need to generate, publicize, and implement European-updated common guidelines in all children to avoid excessive and unnecessary exposure to steroids.

According to the most recent studies and trials based on high standard quality, none of the three protocols demonstrated any superiority (Table 3) [14, 15, 16]. As expected, a same delay of remission (median 9 days) was observed in the three protocols while a same daily dose of prednisone/prednisolone was given to patients (60 mg/m2/day) during the first 4 weeks of the different protocols (Table 3). More relevant, the first relapse occurred in 70 to 80% of patients with a median ranging between 7 and 8 months. In addition, the prevalence of frequent relapsers was similar in the seven studies ranging from 45 to 55% (Table 3). The PREDNOS study released in September 2017 was a randomized controlled trial comparing a cumulated dose of 2240 mg/m2 in 8 weeks to 3150 mg/m2 in 16 weeks. Of note, the results showed no differences in the prevalence of relapsers (81 and 80%), the prevalence of frequent relapsers (50 and 52%), and the cumulated dose of steroids at 24 months of follow-up (5446 and 6645 mg/m2) in both arms [17]. In addition to those clinical results, the outcome of patients is not correlated to the steroid pharmacokinetics at first flare in terms of area under curve of prednisolone [18]. Altogether, these results support that the treatment of the first flare should be limited to 8 weeks and to a cumulated dose of 2240 mg/m2. Most nationwide and KDIGO guidelines suggest to restrain the upper dose of prednisone/prednisolone to 60 mg/day, meaning that patients over 1 m2 (roughly 30 kg) would receive a lower cumulated dose according to body surface (Table 2) [6]. Whatever the protocol, a single dose of prednisone once a day is as effective as multiple divided doses in terms of delay of remission, the frequency of relapses, and the cumulative dose of prednisolone at 9 months of follow-up [19, 20].
Table 3

Outcome of patients in recent prospective trials or epidemiological studies

Author

Year

Number of patients

Age at onset of steroids

Median (IQ)

In years

Cumulated dose of steroids at first flare (mg/m2)

Duration of steroids at first flare (daily/EOD) in weeks

Type of steroids

Duration of follow-up (months)

Median time to relapse (months)

Cumulated dose of steroids (mg/m2)

Patients free of relapse at last follow-up

Frequent relapsers at last follow-up

Yoshikawa [8]

2015

122

NDa

2240

8 (4/4)

Prednisolone

48

8.1

4621 at M24

30%

44%

Sinha [6]

2015

88

3.5 (2.5–5.9)

2800

12 (6/6)

Prednisolone

28

6.9

3420 at M12

31%

55%

Teeninga [7]

2013

62

4.7 (3.2–5.8)

3360

12 (6/6)

Prednisolone

48

6.0

ND

22%

45%

Teeninga [7]

2013

64

3.8 (3.2–6.4)

3390

24 (6/18)

Prednisolone

48

8.0

ND

20%

53%

Sinha [6]

2015

92

3.7 (2.9–6.2)

3500

24 (6/18)

Prednisolone

28

9.4

3741 at M12

32%

48%

Yoshikawa [8]

2015

124

NDa

3885

24 (4/20)

Prednisolone

48

8.1

6484 at M24

23%

48%

Nephrovir study

2017

174

4.1 (2.8–6.8)

3990

18 (4/14)

Prednisone

48

8.0

ND

19%

52%

M months after the first pill of steroids at first flare, ND not determined, EOD every other day

aAge is given in mean (SD): 6.7 (4.1) years for the arm at 2240 mg/m2 and 6.3 (4.1) years for the arm treated with 3885 mg/m2 of prednisolone

Nevertheless, the issue of the duration and the cumulated dose of prednisone/prednisolone is not exhausted by this apparently very complete set of results. Patients below 4 years of age who are at higher risk of relapse and steroid dependency [21] showed a significant benefit of receiving 4620 mg/m2 in 28 weeks (6/11 patients free of relapse at 24 months) compared to 3360 mg/m2 in 12 weeks (0/10 of patients free of relapse at 24 months) [22]. Although this result has been obtained with a post hoc analysis in short samples of patients (11 and 10 patients, respectively), the same trend has been observed in a trial comparing 2800 mg/m2 in 12 weeks and 3500 mg/m2 in 24 weeks for the children aged below 3 years of age [14]. The formal demonstration of the increased efficiency of higher dosage in very young patients is still missing, and randomized control trials have to be carried out prior to the generalization of this schedule.

The association of prednisone/prednisolone to a second drug targeting the immune system might be a promising way to improve the results of the treatment of the first flare in terms of prevalence of definite remission and steroid dependency. Of note, a trial testing 8 weeks of cyclosporine in association to the standard APN protocol showed a transient benefit in patients below 7 years of age [23]. Trials testing either mycophenolate or levamisole are currently in progress in Deutschland (EudraCT 2014-001991-76), The Netherlands (EudraCT 2017-001025-41), and France (Clinicaltrials.gov #NCT02818738 and EudraCT 2016-002324-92).

Relapse and steroid dependency

The most standard treatment schedule of the relapse of idiopathic nephrotic syndrome consists of 60 mg/m2 prednisolone daily until complete remission is achieved for three consecutive days, followed by 40 mg/m2 prednisolone on alternate days for 4–6 weeks. This schedule is only based on clinical empirics and blindly repeated in quite all nationwide or international guidelines. A shorter protocol (the RESTERN study; Clinicaltrials.gov #NTR5670, EudraCT 2016-002430-76) is prospectively compared to the classical protocol in the Netherlands [24]. By contrast, infrequent relapsers with one or less relapse by year are commonly treated with the protocol of the first flare.

The definition of steroid dependency is obviously based on the need of patients for prednisone. Historically, steroid dependency has been introduced to differentiate among frequent relapsers those with a history of relapse under prednisone or a failure to stop prednisone more than 14 days after the treatment from the other frequent relapsers. Curiously, this cutoff of 14 days relied on the better results of cyclophosphamide in patients that relapse over this delay (non-steroid-dependent frequent relapsers) compared to those who relapse within this delay (steroid-dependent frequent relapsers) [25]. Nowadays, the definition is far from to be universal. The KDIGO retained a definition based on two consecutive relapses either occurring under prednisone or within 14 days of the withdrawal of prednisone [26]. Nevertheless, other publications consider any patient relapsing under prednisone or within 14 days after withdrawal as steroid dependent. A subset of patients excluded by this definition will need immunosuppressive drugs in the course of the disease [15], meaning that the morbidity of idiopathic nephrotic syndrome is not restrained to the rigid definition of steroid dependency. Indeed, patients that have the need of intravenous methylprednisolone to obtain a remission either at first flare or at a relapse, those patients relapsing under 40 mg/m2 alternate day of prednisone/prednisolone at the first flare, those frequent relapsers that does not strictly fit with the criteria of steroid dependency but have two or three relapses by year will be steroid exposed to a long duration of the disease and to heavy immunosuppression. Once-a-year relapsers with a discouraging duration of the disease over 5 or 10 years, although less severe than those listed upper, might be also treated with immunosuppressive drugs, especially those associated with a remnant effect.

In the past, long-lasting steroid therapy has been suggested to maintain the remission of steroid-dependent patients and to limit the yearly total dose of prednisone/prednisolone. In fact, data are scarce while only two studies have been released in the literature (Table 4), one using an alternate-day regimen (0.25 mg/kg eod), and the other a daily treatment (0.25 mg/kg/day) during a period of 25 and 18 months, respectively [27, 28]. Although the daily treatment provides a better control of the disease, the rate of relapses either during the treatment or after withdrawal remains significant (100 and 50% within 12 months after initiation, respectively). The daily administration of the maintenance doses of prednisolone during intercurrent upper respiratory tract infections significantly reduces the relapse rate [29, 30] as well as in infrequent relapsers without maintenance steroid therapy [31]. It is still accepted that a limited subset of mild frequently relapsing children who can be maintained in remission on low-dose steroid may be candidates for long-term steroid therapy instead of giving “heavier” immunosuppression. The family choice also needs to be considered in this situation as some of them may opt for low-dose steroids although being informed of all the potential side effects. Deflazacort, the only oxasoline derivative of prednisone, has been precisely reported to have fewer side effects than prednisone at long term. An encouraging result has been obtained after a randomized controlled trial comparing deflazacort and prednisone (Fig. 1 and Table 1) on an alternate-day basis in steroid-dependent patients: no patients remained in stable remission under prednisone during 1 year of treatment compared to 60% of patients under deflazacort given at a ratio of equivalence prednisone/deflazacort = 0.8 (meaning that 5 mg of prednisone is equivalent to 6 mg of deflazacort) [32]. Side effects of the steroid therapy were less marked in the patients treated by deflazacort compared to those treated with prednisone at 6 and 12 months, but growth velocity remained similar in both groups. In addition, another trial comparing prednisolone to deflazacort (with the same equipotent ratio of 0.8) at the first flare has also showed a significant reduction of the delay of urinary remission [33]. The lack of commercial availability until 2016 has prevented the general use of this drug that is still only available in the USA and explains why this trial has not been replicated yet. The lower toxicity of deflazacort on bone structure has been recognized early, but the mechanism by which it works remains obscure. It is supposed that the oxasoline core confers less cross reactivity with vitamin D receptor [34].
Table 4

Outcome of patients under long-lasting alternate-day steroid therapy

 

Broyer 1978

Srivastava 1992

Type of steroids

Prednisone

Prednisolone

Number of patients

29

21

Dose in mg/kg BW

0.25 eod

0.25/day

Duration of treatment in months

25 [12–45]

18

Patients relapsing during treatment

21/29

8/20

Patients relapsing after withdrawal

25/29 at 6 months

6/12 at 12 months

eod every other day (alternate-day regimen)

Precisely, complications of long-lasting steroids therapy frequently occur as soon as 3 to 5 years of steroid therapy: increasing weight and body mass index [35], growth retardation [36, 37, 38], early posterior subcapsular cataracts [39], bone demineralization [40], hypertension and cardiovascular damage [41], gastric mucosal inflammatory changes associated, and increased prevalence of Helicobacter pylori [42]. Sleep disturbance, aggressive behavior, and attention problems in young children, as well as depression and internalizing behavior in teenagers, are often understated [43]. In addition, steroid-dependent patients are often discouraged by long-lasting treatment, while half of them with a long course of alternate-day prednisone were likely to be non-compliant and responded to a treatment with triamcinolone (Fig. 1 and Table 1) given by the intramuscular route [44].

Consistently, non-steroid immunosuppressive drugs give the possibility to limit the chronic use of prednisone. Roughly, prednisone/prednisolone can be steadily stopped in one fourth of the patients either treated with mycophenolate or levamisole [45, 46, 47]. However, in patients relapsing despite ongoing mycophenolate and levamisole treatment, the exposure to prednisone can be reduced from 2 to 3-fold [45, 46, 47, 48]. Those two drugs have no remnant effect, and 95% of patients are relapsing after the withdrawal, forcing to resume steroids [45, 47]. Cyclosporine allows to steadily stop prednisone/prednisolone in 80% of frequent relapsers, but 97% of patients have a relapse in the weeks that follow the withdrawal of the drug, even after two or more years of treatment [49]. In addition, patients treated over 3 years of duration are exposed to the development of renal fibrosis [50]. Similar results and limits can be expected from the use of tacrolimus although data are more limited. Conversely to those drugs, cyclophosphamide and rituximab have a protracted effect of relapse prevention after the withdrawal of drug. Prednisone can be stopped in 50% of patients treated with cyclophosphamide, and 30% of patients have a long-lasting if not a definite remission after a cure of cyclophosphamide [51, 52] with the standard total dose of 168 mg/kg. Rituximab allows stopping prednisone in more than 90% of patients, but the remnant effect is dependent of the length of B cell depletion [53, 54]. As a matter of fact, a single cure of rituximab, independently of the number of injection and the cumulated dose, is followed by a risk of relapse up to 95% by 24 months while a continuous B cell depletion over 20 months is associated with a remission rate of 60% by 30 months [53, 54]. The delay of prednisone/prednisolone withdrawal is obviously variable according to the choice of the non-steroid drug. Although data and consensus are largely lacking, this delay can be shortened to a few weeks (a reasonable suggestion might be 4 to 12 weeks) with cyclosporine and rituximab that are the most powerful drugs that allow stopping steroids. By contrast, a prudent strategy of dose tapering on a monthly basis can be proposed for the other non-steroid drugs [48]. Similarly to the treatment of the first flare, a high variability has been reported in the management of frequent relapsers among European centers of pediatric nephrology supporting the establishment of European guidelines in the use of steroid sparing agents.

Steroid resistance

Steroid resistance is universally defined by the lack of response to prednisone. Nevertheless, the delay of non-response is quite variable among schedules [5], from 4 to 8 weeks of daily prednisone/prednisolone. Moreover, a lot of teams worldwide are completing the oral course by a treatment with one to three intravenous methylprednisolone infusions with a high unitary dosage from 500 to 1000 mg/1.73 m2 in patients who did not fully respond to the oral course of prednisone [5]. As a matter of fact, intravenous methylprednisolone infusions lead to a full remission in 29 to 62% of patients who did not respond to oral prednisone (Table 5) [55, 56, 57]. Moreover, intravenous methylprednisolone infusions seem to improve the rate of remission of steroid resistant patients after the initiation of cyclosporine [58].
Table 5

Gain of remission after intravenous methylprednisolone in case of resistance to 4 weeks of oral daily prednisone/prednisolone

Author

Year

N patients

N pulses

Dose (g/1.73 m2)

% Remission

Hari [29]

2004

22

6

1

33

Shenoy [30]

2010

16

3–5

0.5

62

Nephrovir study

2007–10

24

3

1

42

Zhang [31]

2016

28

3

0.5–1

29

Conclusions and recommendations on steroids in idiopathic nephrotic syndrome

As a conclusion, yes, steroids remain the answer to obtain a rapid and full urinary remission of the flares in idiopathic nephrotic syndrome, but their efficiency to prevent a chronic disease after the first flare is closely limited, warranting the trials of non-steroid drugs in association to prednisone during the first flare. In view of the very relative efficiency to prevent relapses, the burden of complications, and the decreasing compliance of patients along with the duration of the treatment, long-lasting steroid therapy, either daily or alternate, is not an appropriate treatment in most frequent relapsers.

Several recommendations can be suggested from this review to optimize the use of steroids:
  1. 1-

    Either daily prednisolone or prednisone at 60 mg/m2 remains the first-line treatment for the first flare of idiopathic nephrotic syndrome, and there are no arguments for a difference in efficiency between both drugs.

     
  2. 2-

    In terms of full urinary remission, 4 weeks of daily prednisone are enough at the first flare and no more benefit can be expected of a longer period of daily prednisone.

     
  3. 3-

    A cumulated dose of 2240 mg/m2 given in 8 weeks at the first flare without tapering sequence is not inferior to increased dose and duration in terms of prevalence of frequent relapsers.

     
  4. 4-

    Intravenous methylprednisolone pulses are useful to reach a full urinary remission in case of oral resistance to 4 weeks of oral prednisone and seem to improve the delay of remission after the initiation of cyclosporine in true steroid-resistant patients.

     
  5. 5-

    Long-lasting alternate-day prednisone therapy is still an acceptable treatment during a few years in the minority of relapsing patients that are fully controlled with low doses. The total cumulated dose and the length of this treatment without major risk of developing secondary complications at adult age remain to be defined.

     

Key summary points

1

Either daily prednisolone or prednisone at 60 mg/m2 remains the first-line treatment for the first flare of idiopathic nephrotic syndrome

2

4 weeks of daily prednisone are enough at the first flare, and no more benefit can be expected of a longer period of daily prednisone in terms of full urinary remission

3

A cumulated dose of 2240 mg/m2 given in 8 weeks at the first flare without tapering sequence is not inferior to increased dose and duration in terms of prevalence of frequent relapsers

4

Intravenous methylprednisolone pulses are useful to reach a full urinary remission in case of oral resistance to 4 weeks of oral prednisone and seems to improve the delay of remission after the initiation of cyclosporine in true steroid-resistant patients

5

Long-lasting alternate-day prednisone therapy does not lead to long-lasting remission in the majority of steroid-dependent patients

Multiple choice questions (answers are provided following the reference list)

  1. 1.
    The first-line treatment of the first flare of idiopathic nephrotic syndrome in childhood is based on
    1. a)

      Triamcinolone

       
    2. b)

      Prednisone or prednisolone

       
    3. c)

      Angio-converting enzyme inhibitors

       
    4. d)

      Dexamethasone

       
    5. e)

      Thyroid extracts

       
     
  2. 2.
    What is the optimal duration of the daily dose of steroids at first flare?
    1. a)

      2 weeks

       
    2. b)

      3 weeks

       
    3. c)

      4 weeks

       
    4. d)

      5 weeks

       
    5. e)

      At least 6 weeks

       
     
  3. 3.
    The morbidity of idiopathic nephrotic syndrome is due to
    1. a)

      Any relapse after the first flare

       
    2. b)

      Steroid dependency

       
    3. c)

      Steroid resistance

       
    4. d)

      Exposure to immunosuppressive drugs

       
    5. e)

      The need of intravenous methylprednisolone pulses to obtain a full urinary remission

       
     
  4. 4.
    Long-lasting steroid therapy at low doses
    1. a)

      Can prevent the occurrence of relapses

       
    2. b)

      Is useful in steroid resistant patients

       
    3. c)

      Is mandatory after thromboembolism to prevent a further episode

       
    4. d)

      Is complicated by steroid intoxication and growth failure

       
    5. e)

      Can shorten the duration of the disease

       
     
  5. 5.
    Intravenous methylprednisolone pulses allow
    1. a)

      To stop the disease after the first relapse

       
    2. b)

      To prevent end stage renal failure

       
    3. c)

      To reduce the prevalence of steroid dependency

       
    4. d)

      To reduce the prevalence of steroid resistance

       
    5. e)

      To treat patients with vomiting and oral intolerance

       
     

Notes

Compliance with ethical standards

Conflict of interest

Georges Deschênes declares that he has no conflict of interest in the field of the paper. Claire Dossier and Julien Hogan received a grant from Délégation de la Recherche Clinique for randomized control trials in patients with Idiopathic Nephrotic Syndrome (PHRCI-15-015 and PHRCN-16-0547, respectively).

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Copyright information

© IPNA 2018

Authors and Affiliations

  • Georges Deschênes
    • 1
    Email author
  • Claire Dossier
    • 1
  • Julien Hogan
    • 1
  1. 1.Department of Pediatric Nephrology, APHP Robert-DebréSorbonne Paris Cité UniversityParisFrance

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