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Overview

This Guidelines  summary provides clinical guidance for primary care on the management of glomerular diseases in people of all ages. The full guideline has been separated into a series of summaries, as follows:

This summary covers IgAN, IgAV, membranous nephropathy, and NS in children. For recommendations and good practice points on general management of glomerular disease, see part 1. For recommendations and good practice points on further glomerular diseases, see part 3.

This summary consists of recommendations and practice points. Recommendations are presented in bold. Within each recommendation in this summary, the strength of the recommendation is indicated as level 1 (recommended) or 2 (suggested), and the quality of the supporting evidence is shown as A (high), B (moderate), C (low), or D (very low)—further information can be found on page 14 of the full guideline. 

For a complete set of recommendations and practice points, refer to the full guideline.

KDIGO=Kidney Disease: Improving Global Outcomes

View this summary online at guidelines.co.uk/456727.article

IgA nephropathy

Diagnosis

  • Considerations for the diagnosis of IgAN:
    • IgAN can only be diagnosed with a kidney biopsy
    • determine the MEST-C score (mesangial [M] and endocapillary [E] hypercellularity, segmental sclerosis [S], interstitial fibrosis/tubular atrophy [T], and crescents [C]) according to the revised Oxford Classification
    • there are no validated diagnostic serum or urine biomarkers for IgAN
    • assess all patients with IgAN for secondary causes.

Prognosis

  • Considerations for the prognostication of primary IgAN:
    • clinical and histological data at the time of biopsy can be used to risk stratify patients
    • the International IgAN Prediction Tool is a valuable resource to quantify risk of progression and inform shared decision-making with patients[A]
    • the International IgAN Prediction Tool incorporates clinical information at the time of biopsy and cannot be used to determine the likely impact of any particular treatment regimen
    • there are no validated prognostic serum or urine biomarkers for IgAN other than estimated glomerular filtration rate (eGFR) and proteinuria.

Treatment

  • Considerations for treatment of all patients with IgAN who do not have a variant form of primary IgAN:
    • the primary focus of management should be optimised supportive care
    • assess cardiovascular risk and commence appropriate interventions as necessary
    • give lifestyle advice, including information on dietary sodium restriction, smoking cessation, weight control, and exercise, as appropriate
    • other than dietary sodium restriction, no specific dietary intervention has been shown to alter outcomes in IgAN
    • variant forms of IgAN include IgA deposition with minimal change disease (MCD), IgAN with acute kidney injury (AKI), and IgAN with rapidly progressive glomerulonephritis (RPGN), and may require specific immediate treatment.
  • For an algorithm on the initial assessment and management of the patient with IgAN, see Figure 21 in the full guideline
  • KDIGO recommends that all patients have their blood pressure managed, as described in Guidelines summary part 1; if the patient has proteinuria greater than 0.5 g/day, KDIGO recommends that initial therapy is with either an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) [1B]
  • KDIGO recommends that all patients with proteinuria greater than 0.5 g/day, irrespective of whether they have hypertension, are treated with either an ACEi or ARB. [1B]

Patients with IgAN who are at high risk of progressive CKD despite maximal supportive care

  • Considerations for treatment of patients with IgAN who are at high risk of progressive chronic kidney disease (CKD) despite maximal supportive care:
    • high risk of progression in IgAN is currently defined as proteinuria greater than 0.75–1 g/day despite 90 days or more of optimised supportive care
    • immunosuppressive drugs should be considered only in patients with IgAN who remain at high risk of progressive CKD despite maximal supportive care (the patients enrolled in the only large randomised controlled trial [RCT] suggesting benefit of immunosuppression had an average of 2.4 g/day of proteinuria)
    • in view of the current uncertainty over the safety and efficacy of existing immunosuppressive treatment choices, all patients who remain at high risk of progressive CKD despite maximal supportive care should be offered the opportunity to take part in a clinical trial
    • in all patients in whom immunosuppression is being considered, a detailed discussion of the risks and benefits of each drug should be undertaken with the patient, recognising that adverse treatment effects are more likely in patients with an eGFR less than 50 ml/min per 1.73 m2
    • there is insufficient evidence to support the use of the Oxford Classification MEST-C score in determining whether immunosuppression should be commenced in IgAN
    • there is insufficient evidence to base treatment decisions on the presence and number of crescents in the kidney biopsy
    • the International IgAN Prediction Tool[A] cannot be used to determine the likely impact of any particular treatment regimen
    • dynamic assessment of patient risk over time should be performed, as decisions regarding immunosuppression may change
  • Proteinuria reduction to under 1 g/day is a surrogate marker of improved kidney outcome in IgAN, and reduction to under 1 g/day is a reasonable treatment target
  • KDIGO suggests that patients who remain at high risk of progressive CKD despite maximal supportive care are considered for a 6-month course of glucocorticoid therapy; the important risk of treatment-emergent toxicity must be discussed with patients, particularly those who have an eGFR less than 50 ml/min per 1.73 m2 [2B]
  • Use of glucocorticoids in IgAN:
    • clinical benefit of glucocorticoids in IgAN is not established and should be given with extreme caution or avoided entirely in situations listed:
      • eGFR less than 30 ml/min/1.73 m2[B]
      • diabetes
      • obesity (body mass index [BMI] over 30 kg/m2)
      • latent infections (for example, viral hepatitis, tuberculosis)
      • secondary disease (for example, cirrhosis)
      • active peptic ulceration
      • uncontrolled psychiatric illness
      • severe osteoporosis
    • there is insufficient evidence to support the use of the Oxford Classification MEST-C score in determining when any glucocorticoid therapy should be commenced
    • there are no data to support efficacy or reduced toxicity of alternate-day glucocorticoid regimens, or dose-reduced protocols
    • where appropriate, treatment with glucocorticoid (prednisone equivalent 0.5 mg/kg/day or greater) should incorporate prophylaxis against Pneumocystis pneumonia along with gastroprotection and bone protection, according to local guidelines.

For more information on the management of patients with IgAN who remain at high risk for progression after maximal supportive care, see Figure 24 of the full guideline. For more information on other pharmacologic therapies evaluated in IgAN, see Figure 25 of the full guideline.

  • Tonsillectomy in IgAN:
    • tonsillectomy should not be performed as a treatment for IgAN in Caucasian patients
    • tonsillectomy is suggested in some national guidelines for the treatment of recurrent tonsillitis in patients with IgAN
    • multiple studies from Japan have reported improved kidney survival and partial or complete remission of haematuria and proteinuria following tonsillectomy alone or with pulsed glucocorticoids (see Figure 26 and Supplementary Table S7 in the full guideline).

Special situations

IgAN with nephrotic syndrome

  • Rarely, patients with IgAN present with NS (including oedema and both hypoalbuminaemia and nephrotic-range proteinuria greater than 3.5 g/day)
  • In these cases, mesangial IgA deposition can be associated with light and electron microscopy features otherwise consistent with a podocytopathy resembling MCD
  • It is unclear whether this is a specific podocytopathic variant of IgAN or the existence of MCD in a patient with IgAN
  • Patients with a kidney biopsy demonstrating mesangial IgA deposition and light and electron microscopy features otherwise consistent with MCD should be treated in accordance with the guidelines for MCD (see Chapter 5 of the full guideline)
  • Patients with NS whose kidney biopsy has coexistent features of a mesangioproliferative glomerulonephritis should be managed in the same way as those patients at high risk of progressive CKD despite maximal supportive care
  • Nephrotic-range proteinuria without NS may also be seen in IgAN, and this commonly reflects coexistent secondary focal segmental glomerulosclerosis (for example, obesity, uncontrolled hypertension) or development of extensive glomerulosclerosis and tubulointerstitial fibrosis.

IgAN with acute kidney injury

  • AKI can occur in patients with IgAN in the context of severe visible haematuria, commonly in association with an upper respiratory tract infection—a repeat kidney biopsy should be considered in patients who fail to show improvement in kidney function within 2 weeks following cessation of the haematuria; immediate management of AKI with visible haematuria should focus on supportive care for AKI
  • IgAN may also present with AKI either de novo or during its natural history due to an RPGN with extensive crescent formation, commonly in the absence of visible haematuria; in the absence of visible haematuria and when other causes of an RPGN (for example, antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis [AAV], antiglomerular basement membrane [anti-GBM] disease) and reversible causes (for example, drug toxicity, common pre- and post-kidney causes) have been excluded, a kidney biopsy should be performed as soon as possible.

IgAN with rapidly progressive glomerulonephritis

  • Rapidly progressive IgAN is defined as a 50% or greater decline in eGFR over 3 months or less, where other causes of an RPGN (for example, AAV, anti-GBM disease) and reversible causes (for example, drug toxicity, common pre- and post-kidney causes) have been excluded
  • A kidney biopsy is essential in these cases and will commonly demonstrate mesangial and endocapillary hypercellularity, and a high proportion of glomeruli affected by crescents with areas of focal necrosis
  • The presence of crescents in a kidney biopsy in the absence of a concomitant change in serum creatinine does not constitute rapidly progressive IgAN; however, these patients require close follow-up to ensure prompt detection of any glomerular filtration rate (GFR) decline—if this occurs, a second kidney biopsy may be considered
  • Patients with rapidly progressive IgAN should be offered treatment with cyclophosphamide and glucocorticoids in accordance with the guidelines for AAV (see Chapter 9 of the full guideline)
  • Prophylactic measures that should accompany immunosuppression are discussed in Chapter 1 of the full guideline
  • There is insufficient evidence to support the use of rituximab for the treatment of rapidly progressive IgAN.

IgAN and pregnancy planning

  • IgAN is a disease predominantly of young adults, and all women of childbearing potential should be offered preconception counselling when appropriate
  • Preconception counselling should include a discussion on cessation of renin–angiotensin system (RAS) blockade
  • Blood pressure control should be optimised with alternative antihypertensive medications prior to conception
  • In those women at high risk of progressive CKD (see recommendation 2.3.1.1 in the full guideline) despite maximal supportive care, a trial of immunosuppression to optimise immunologic activity and reduce proteinuria prior to conception may be preferable to emergent initiation of immunosuppression during pregnancy.

IgAN in children

  • General considerations
    • for the purposes of this practice point, children are defined as those aged under 18 years; it is acknowledged that postpubertal children in some respects may have a similar course and response to treatment as adults with IgAN, but there are insufficient data currently to recommend that they be managed as adults with IgAN
    • visible haematuria is more frequent in children than in adults, and this may account for earlier diagnosis in children
    • children generally have higher eGFR, lower urine protein excretion, and more haematuria than adults at diagnosis
  • Kidney biopsy in children
    • a kidney biopsy is usually performed at presentation of symptoms (haematuria, proteinuria, normal C3) in order to confirm the diagnosis (and rule out other diagnoses) and assess the degree of inflammation/presence of necrosis
    • inflammation, mesangial, and endocapillary hypercellularity tend to be more prevalent in kidney biopsies of IgAN in children than in those of adults
  • Treatment
    • there is strong evidence suggesting a benefit of RAS blockade in children; all children with IgAN and proteinuria over 200 mg/day or protein:creatinine ratio (PCR) over 200 mg/g (more than 0.2 g/g [20 mg/mmol]) should receive ACEi or ARB blockade, advice on a low-sodium diet, and optimal lifestyle and blood pressure control (systolic blood pressure [SBP] under 90th percentile for age, sex, and height)
    • it is widely acknowledged that treatment of IgAN with immunosuppression differs between adults and children, and that in children, the use of immunosuppressants is more widespread, particularly the use of glucocorticoids; however, RCTs and specific expert consensus-driven indications are lacking
    • evidence derived mostly from retrospective studies suggests that treatment with glucocorticoids (plus second-line immunosuppression) leads to improved kidney survival
    • in children with proteinuria greater than 1 g/day or PCR greater than 1 g/g (100 mg/mmol) and/or mesangial hypercellularity, most paediatric nephrologists will treat with glucocorticoids in addition to RAS blockade from time of diagnosis—duration of treatment is not established, but usually 4 weeks of 1–2 mg/kg/day of oral prednisolone (or equivalent) followed by alternate-day tapering over 4–6 months is employed; regimens including intravenous methylprednisolone are also used
    • evidence for the use of nonglucocorticoid immunosuppressants in addition to glucocorticoids is scarce, but this approach may be considered in more severe cases
    • as for adults, IgAN with MCD may be found, and it should be treated as steroid-sensitive NS (see Chapter 4 of the full guideline)
    • as in adults, children with rapidly progressive IgAN have a poor outcome, and despite limited evidence, this subgroup should be offered treatment with glucocorticoids (usually as methylprednisolone pulses) and cyclophosphamide
  • Follow-up
    • aim for proteinuria 200 mg/day or under (400 mg/1.73 m2/day or under) or PCR 200 mg/g or under (0.2 g/g [20 mg/mmol] or under)
    • aim for blood pressure at SBP under the 90th percentile for age, sex, and height
    • continue to follow patients even after complete remission, as they can relapse even after many years.

IgAV

Diagnosis

  • Considerations for the diagnosis of IgAV:
    • unlike children, there are no internationally agreed-upon criteria for the diagnosis of IgAV in adults, although a clinical diagnosis of IgAV is often made based on the criteria described for children
    • in adults with a vasculitic rash typical of IgAV, a kidney biopsy should be performed in the setting of features consistent with a persistent and/or significant nephritis, RPGN, proteinuria over 1g/day, and/or impaired kidney function
    • assess all adult patients with IgAV for secondary causes
    • assess all adult patients with IgAV for malignancy, with age- and sex-appropriate screening tests.

Prognosis

  • Considerations for the prognostication of IgAV:
    • retrospective data from a limited number of small registries have identified uncontrolled hypertension and the amount of proteinuria at presentation, and hypertension and mean proteinuria during follow-up, as predictors of a poor kidney outcome in adults with IgAV
    • the Oxford Classification has not been validated for IgAV
    • the International IgAN Prediction Tool[A] is not designed for prognostication in IgAV.

Treatment

Prevention of nephritis in IgAV

  • KDIGO recommends not using glucocorticoids to prevent nephritis in patients with isolated extrarenal IgAV [1B]
  • Considerations for the treatment of all patients with IgAV-associated nephritis (IgAVN) who do not have an RPGN:
    • assess cardiovascular risk and commence appropriate interventions as necessary
    • give lifestyle advice, including information on smoking cessation, weight control, and exercise, as appropriate
    • no specific dietary intervention has been shown to alter outcomes in IgAVN
    • treat to nationally agreed-upon blood pressure targets; KDIGO suggests treating to an SBP target of under 120 mmHg measured using standardised office blood pressure measurement (see Figure 8 in the full guideline)
    • treat with maximally tolerated dose of ACEi or ARB if proteinuria greater than 0.5 g/day
    • offer participation in a clinical trial if one is available.

Patients with IgAVN who are at high risk of progressive CKD despite maximal supportive care

  • Considerations for the treatment of patients with IgAVN who are at high risk of progressive CKD despite maximal supportive care:
    • there is insufficient evidence to support the use of the Oxford Classification MEST-C score in determining whether immunosuppression should be commenced in patients with IgAVN
    • the presence of crescents in the kidney biopsy is not in itself an automatic indication for commencement of immunosuppression
    • in all patients in whom immunosuppression is being considered, a detailed discussion of the risks and benefits of each drug should be undertaken with the patient with a recognition that adverse treatment effects are more likely in patients with an eGFR less than 50 ml/min per 1.73 m2
  • In those patients who wish to try immunosuppressive therapy, treatment with glucocorticoids is as described above for IgAN.

Special situations

  • IgAV with RPGN:
    • the potential risks and benefits of immunosuppression should be evaluated at the individual patient level and discussed with the patient
    • patients agreeing to treatment should be treated in accordance with the guidelines for AAV (see Chapter 9 of the full guideline)
    • IgAV with RPGN as well as other IgAVN may be associated with significant extrarenal involvement (pulmonary, gastrointestinal, and skin), which may dictate alternative immunosuppressive strategies
    • there are insufficient data to determine the efficacy of plasma exchange in IgAVN with RPGN; however, uncontrolled case series describe the potential role for the addition of plasma exchange to glucocorticoid therapy to accelerate recovery in patients with life- or organ-threatening extrarenal complications of IgAV—clinicians are referred to the guidelines of the American Society for Apheresis regarding recommendations regarding plasma exchange for IgAV.

IgAV-associated nephritis in children

  • For the purposes of this practice point, children are defined as those aged under 18 years; it is acknowledged that postpubertal children in some respects may have a similar course and response to treatment as adults with IgAN, but there are insufficient data currently to recommend that they be managed as adults with IgAN
  • Indications for management of IgAVN in children have recently been published as the result of a European consortium initiative; briefly:
    • there are no data supporting the use of glucocorticoids to prevent nephritis in children with IgAV but mild or absent evidence of kidney involvement
    • children over 10 years of age more often present with non-nephrotic-range proteinuria and impaired kidney function, and they may suffer more chronic histologic lesions with delay in biopsy and delay in treatment longer than 30 days
    • the majority of children who will develop nephritis will do so within 3 months of presentation; urinary monitoring is necessary for 6 months or longer and optimally 12 months from initial presentation of systemic disease
    • children with IgAVN and persistent proteinuria for over 3 months should be treated with an ACEi or ARB; a paediatric nephrologist should be consulted
    • a kidney biopsy should be performed in children with nephrotic-range proteinuria, impaired GFR, or persistent moderate (over 1 g/day) proteinuria
    • oral prednisone/prednisolone or pulsed intravenous methylprednisolone should be used in children with mild or moderate IgAVN
    • children with IgAVN with NS and/or rapidly deteriorating kidney function are treated in the same way as those with rapidly progressive IgAN.

Membranous nephropathy

Diagnosis

  • A kidney biopsy is not required to confirm the diagnosis of membranous nephropathy (MN) in patients with NS and a positive anti-phospholipase A2 receptor (anti-PLA2R) antibody test
  • Patients with MN should be evaluated for associated conditions, regardless of whether anti-PLA2R antibodies and/or anti-thrombospondin type-1 domain-containing 7A antibodies are present or absent (see Figure 29 in the full guideline).

Prognosis

  • In patients with MN, use clinical and laboratory criteria to assess the risk of progressive loss of kidney function (see Table 1).

Table 1: Clinical criteria for assessing risk of progressive loss of kidney function in membranous nephropathy

Low riskModerate riskHigh riskVery high risk
  • Normal eGFR, proteinuria <3.5 g/day, and serum albumin >30 g/l OR
  • Normal eGFR, proteinuria <3.5 g/day, or a decrease >50% after 6 months of conservative therapy with ACEi/ARB
  • Normal eGFR, proteinuria >3.5 g/day, and no decrease >50% after 6 months of conservative therapy with ACEi/ARB AND
  • Not fulfilling high-risk criteria
  • eGFR <60 ml/min/1.73 m2[A] and/or proteinuria >8 g/day for >6 months OR
  • Normal eGFR, proteinuria >3.5 g/day, and no decrease >50% after 6 months of conservative ACEi/ARB AND at least one of the following:
    • serum albumin <25 g/l[B]
    • PLARab >50 RU/ml[C]
    • urinary α1 -microglobulin >40 mcg/min
    • urinary IgG >1 mcg/min
    • urinary β2 -microglobulin >250 mg/day
    • selectivity index >0.20[D]
  • Life-threatening nephrotic syndrome OR
  • Rapid deterioration of kidney function not otherwise explained

 

 

Abbreviations: ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; BCP=bromocresol purple; eGFR=estimated glomerular filtration rate; IgG=immunoglobulin G; PCR=protein:creatinine ratio; PLA2Rab=antibodies against the M-type phospholipase A2 receptor; SCr=serum creatinine

eGFR and PCR are used in routine clinical care. Other biomarkers may not be available in all centres; this table provides an overview of useful biomarkers

[A] Most studies have used SCr values to guide management, and SCr values >1.5 mg/dl (133 mcmol/l) are often used to define kidney insufficiency. An eGFR value of 60 ml/min per 1.73 m2  defines kidney insufficiency in a young adult. It is important to realise that eGFR decreases with age, and an SCr value of 1.5 mg/dl (133 mcmol/l) reflects an eGFR of 50 ml/min per 1.73 m2  in a 60-year-old male patient and 37 ml/min per 1.73 m2  in a 60-year-old female patient. Thus, when using eGFR in risk estimation, age should be taken into account

[B] Serum albumin should be measured by BCP or immunometric assay

[C] Cutoff values are not validated. Anti-PLA2R antibodies should be measured at 3–6-month intervals, the shorter interval being performed in patients with high anti-PLA2R antibodies levels at baseline. Changes in anti-PLA2R antibodies levels during follow-up likely add to risk estimation. Disappearance of anti-PLA2R antibodies precedes clinical remission and should lead to refraining from additional therapy. Detailed data are lacking

[D] Selectivity index is calculated as clearance of IgG/clearance of albumin

Treatment

  • Considerations for treatment of patients with primary MN:
    • all patients with primary MN and proteinuria should receive optimal supportive care
    • immunosuppressive therapy should be restricted to patients considered at risk for progressive kidney injury (see Algorithm 1).

Algorithm 1: Risk-based treatment of membranous nephropathy

risk-based treatment of membranous nephropathy v3

  • Immunosuppressive therapy is not required in patients with MN, proteinuria less than 3.5 g/day, serum albumin over 30 g/l by bromocresol purple or immunometric assay, and eGFR greater than 60 ml/min per 1.73 m2
  • Immunosuppressive therapy is not required in patients with MN, NS, and normal eGFR, unless at least one risk factor for disease progression is present or serious complications of NS (for example, AKI, infections, thromboembolic events) have occurred
  • For patients with MN and at least one risk factor for disease progression, KDIGO recommends using rituximab or cyclophosphamide and alternate month glucocorticoids for 6 months, or calcineurin inhibitor (CNI)-based therapy for 6 months or more, with the choice of treatment depending on the risk estimate (see Figures 30 and 31 in the full guideline) [1B]
  • Longitudinal monitoring of anti-PLA2R antibody levels at 6 months after start of therapy may be useful for evaluating treatment response in patients with MN, and can be used to guide adjustments to therapy (see Figure 33 in the full guideline).

Special situations

For algorithms on the treatment of patients with MN and initial relapse after therapy, management of patients with treatment-resistant MN, evaluation of a kidney transplant recipient with MN, and management of children with MN, see Figures 34–37 in the full guideline.

  • Prophylactic anticoagulant therapy in patients with MN and NS should be based on an estimate of the risk of thrombotic events and the risk of bleeding complications (see Figure 38 in the full guideline).

Nephrotic syndrome in children

Diagnosis

The definitions relating to NS in children are based on the clinical characteristics outlined in Figure 39 in the full guideline.

Prognosis

  • The prognosis for childhood NS is best predicted by the patient’s response to initial treatment and frequency of relapse during the first year after treatment; therefore, a kidney biopsy is not usually needed at initial presentation, and instead is reserved for children with resistance to therapy or an atypical clinical course.

Treatment

Initial treatment of NS in children

  • KDIGO recommends that oral glucocorticoids are given for 8 weeks (4 weeks of daily glucocorticoids followed by 4 weeks of alternate-day glucocorticoids) or 12 weeks (6 weeks of daily glucocorticoids followed by 6 weeks of alternate-day glucocorticoids) [1B]
  • The standard dosing regimen for the initial treatment of NS is daily oral prednisone/prednisolone 60 mg/m2/day or 2 mg/kg/day (maximum 60 mg/day) for 4 weeks followed by alternate day prednisone/prednisolone, 40 mg/m2, or 1.5 mg/kg (maximum of 50 mg) for another 4 weeks, or prednisone/prednisolone 60 mg/m2/day (maximum 60 mg/d) for 6 weeks followed by alternate day prednisone/prednisolone, 40 mg/m2, or 1.5 mg/kg (maximum of 50 mg), for another 6 weeks.

Prevention and treatment of relapses of NS in children

  • For children with frequently relapsing and steroid-dependent NS who are currently taking alternate-day glucocorticoids or are off glucocorticoids, KDIGO recommends that daily glucocorticoids 0.5 mg/kg/day are given during episodes of upper respiratory tract and other infections for 5–7 days to reduce the risk of relapse [1C]
  • The initial approach to relapse should include oral prednisone/prednisolone as a single daily dose of 60 mg/m2/day or 2 mg/kg/day (maximum 60 mg/day) until the child remits completely for 3 days or more
  • After achieving complete remission, reduce oral prednisone/prednisolone to 40 mg/m2 or 1.5 mg/kg (maximum 50 mg) on alternate days for 4 weeks or more
  • For children with frequently relapsing NS or steroid-dependent NS without glucocorticoid toxicity, the same glucocorticoid regimen may be employed in subsequent relapses
  • For children with frequently relapsing NS without serious glucocorticoid-related adverse effects, low-dose alternate-day oral prednisone/prednisolone (optimally 0.5 mg/kg/day or less) can be prescribed to prevent relapse
  • For children with frequently relapsing NS who develop serious glucocorticoid-related adverse effects and for all children with steroid-dependent NS, KDIGO recommends that glucocorticoid-sparing agents are prescribed, rather than no treatment or continuation with glucocorticoid treatment alone [1B]
  • Patients should ideally be in remission with glucocorticoids prior to the initiation of glucocorticoid-sparing agents such as oral cyclophosphamide, levamisole, mycophenolate mofetil (MMF), rituximab, or CNIs; co-administration of glucocorticoids is recommended for 2 weeks or more following initiation of glucocorticoid-sparing treatment
  • Choosing the most appropriate glucocorticoid-sparing agent from among oral cyclophosphamide, levamisole, MMF, rituximab, and CNIs is a decision that requires careful consideration of specific patient-related issues such as resources, adherence, adverse effects, and patient preferences—oral cyclophosphamide and levamisole may be preferable glucocorticoid-sparing therapies in frequently relapsing NS; MMF, rituximab, CNIs and, to a lesser extent, oral cyclophosphamide may be preferable to glucocorticoid-sparing therapies in children with steroid-dependent NS (see Figure 41 in the full guideline).

Steroid-resistant nephrotic syndrome in children

Treatment

  • KDIGO recommends using ciclosporine or tacrolimus as initial second-line therapy for children with steroid-resistant NS. [1C]

Special situations

Figure 43 in the full guideline outlines the general principles in children with NS.

Footnotes

[A] Calculate by QxMD website. International IgAN Prediction Tool at biopsy—adults. qxmd.com/calculate/calculator_499/international-igan-prediction-tool-at-biopsy-adults?_branch_match_id=656546875419766679 (accessed 5 January 2022)

[B] The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study included patients with eGFR 20–30 ml/min per 1.73 m2, but only 26 patients in total had this range of kidney function. Prespecified subgroup analyses for signals of efficacy and toxicity were underpowered and did not distinguish patients with eGFR less than 30 ml/min per 1.73 m2

[C] High BMI in the TESTING study was not specifically considered an exclusion, but the mean BMI was under 24 kg/m2

 

Full guideline:

Kidney Disease Improving Global Outcomes. KDIGO 2021 Clinical practice guideline for the management of glomerular diseases. Kidney Int 2021; 100 (4S): S1–S276. Available at: kdigo.org/wp-content/uploads/2017/02/KDIGO-Glomerular-Diseases-Guideline-2021-English.pdf  

Published date: October 2021.

Credit:

Lead image: krishnacreations/stock.adobe.com

KDIGO general management of glomerular diseases guideline