Question Title

* By agreeing to provide feedback on this draft guideline document, you hereby permit KDIGO to acknowledge your participation as a reviewer in the final publication.

*** This survey is a summary of the Recommendation Statements and Practice Points. For the full extended text including the rationale, figures, and tables, please review the full guideline download on the KDIGO Website.***
IMMUNOGLOBULIN A NEPHROPATHY
2.1. Diagnosis

Question Title

* Practice Point 2.1.1: Considerations regarding the diagnosis of immunoglobulin A nephropathy (IgAN):
  • IgAN can only be diagnosed with a kidney biopsy, as there are no validated diagnostic serum or urine biomarkers for IgAN.
  • To ensure an early diagnosis and prompt treatment of IgAN, a kidney biopsy should be performed in all adults with proteinuria ≥0.5 g/d (or equivalent) in whom IgAN is a possible diagnosis and who do not have a contraindication for kidney biopsy.
  • Once a diagnosis of IgAN is made, assess for secondary causes.
  • In cases of primary IgAN, 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.80

2.2. Prognosis

Question Title

Figure 1 | The data elements included in the International Immunoglobulin A Nephropathy (IgAN) Prediction Tools.

<span style="color: #2c7db7;"><em><strong><span style="font-size: 14pt;">Figure 1 | The data elements included in the International Immunoglobulin A Nephropathy (IgAN) Prediction Tools. </span></strong></em></span>
Using clinical and histologic data at the time of kidney biopsy, or up to 2 years post kidney biopsy, users can calculate the risk of a 50% decline in eGFR or kidney failure up to 7 years from kidney biopsy in adults and children. ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; GFR, glomerular filtration rate; MEST, mesangial (M) and endocapillary (E) hypercellularity, segmental sclerosis (S), and interstitial fibrosis/tubular atrophy (T).

Question Title

* Practice Point 2.2.1: Considerations regarding the prognosis of primary IgAN:

  • Clinical and histologic data at the time of kidney biopsy can be used to risk stratify patients.
  • The International IgAN Prediction Tools are a valuable resource to quantify short term (up to 7 years from kidney biopsy) risk of progression and inform shared decision-making with patients.
    • International IgAN Prediction Tool at biopsy – Adults
    • International IgAN Prediction Tool post-biopsy – Adults
    • International IgAN Prediction Tool at biopsy – Pediatrics
    • International IgAN Prediction Tool post-biopsy – Pediatrics
  • The International IgAN Prediction Tools incorporate clinical information at the time of kidney biopsy or at 1 or 2 years post-biopsy (Figure 1).
  • There are no validated prognostic serum or urine biomarkers for IgAN other than estimated glomerular filtration rate (eGFR) and proteinuria.

Question Title

* Practice Point 2.2.2: The initial assessment of the patient with IgAN (Figure 2)

Question Title

Figure 2 | Initial assessment and management of the patient with immunoglobulin A nephropathy (IgAN).

<span style="color: #2c7db7;"><em><strong><span style="font-size: 14pt;">Figure 2 | Initial assessment and management of the patient with immunoglobulin A nephropathy (IgAN). </span></strong></em></span>
GN, glomerulonephritis; HIV, human immunodeficiency virus; IgAN, immunoglobulin A nephropathy; MEST-C, mesangial (M) and endocapillary (E) hypercellularity, segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T), and crescents (C).
2.3. Treatment
2.3.1 Defining patients with IgAN at risk of progressive loss of kidney function requiring treatment

Question Title

* Practice Point 2.3.1.1: A patient with IgAN is at risk of progressive loss of kidney function if they have proteinuria ≥0.5 g/d (or equivalent), while on or off treatment for IgAN, and treatment/additional treatment should be started in all cases.

2.3.2 Defining a treatment goal in patients with IgAN at risk of progressive loss of kidney function

Question Title

* Practice Point 2.3.2.1: The treatment goal in patients with IgAN at risk of progressive loss of kidney function is to reduce the rate of loss of kidney function to <1 ml/min per year for the rest of the patient’s life. The only validated early biomarker to help guide clinical decision-making is urine protein excretion, which should be maintained at <0.5 g/d (or equivalent), preferably <0.3 g/d (or equivalent), accepting that in some patients with extensive kidney scarring this may not be possible and that multiple drugs are likely to be needed to achieve this.

Question Title

* Practice Point 2.3.2.2: Treatment of patients with IgAN who are at risk of progressive kidney function decline and do not have a variant form of primary IgAN (Figure 3):
  • The focus of management in most patients should be to simultaneously:
    • Prevent or reduce IgA immune complex formation and immune complex-mediated glomerular injury.
    • In parallel, manage the consequences of existing IgAN-induced nephron loss.
  • Reduction or prevention of IgA immune complex formation should incorporate treatments that have been proven to reduce pathogenic forms of IgA (commonly measured as galactose deficient IgA1 [gd-IgA1]).
  • Prevention of immune complex-mediated injury should incorporate treatments with proven anti-inflammatory effects, and ideally should be used in combination with, and not as a replacement for, treatments that prevent or reduce IgA immune complex formation.
  • Management of the consequences of IgAN-induced nephron loss should include:
    • Lifestyle advice, including information on dietary sodium restriction, smoking cessation, weight control, and exercise, as appropriate,
    • Control of blood pressure with a target of ≤120/70 mm Hg,
    • Measures to reduce glomerular hyperfiltration and the impact of proteinuria on the tubulointerstitium, using singly or in combination, renin-angiotensin system (RAS) blockade or dual endothelin angiotensin receptor antagonism (DEARA), and sodium-glucose cotransporter-2 inhibition (SGLT2i), and
    • A thorough cardiovascular risk assessment and commencement of appropriate interventions as necessary.
  • The key factors to consider when making treatment choices are summarized in Tables 1 and 2 (Refer to Tables in the full guideline).
  • Issues related to accessibility and affordability of newly approved treatments for IgAN, alongside the requirement for continual or cyclical dosing, mean that it is unlikely that these treatments will be used in resource-limited settings, where cheaper and more easily resourced drugs will be used.
  • In all patients in whom treatments that target the production of pathogenic forms of IgA or glomerular inflammation are being considered, a detailed discussion of the risks and benefits of each drug should be undertaken.
  • There is insufficient evidence to support the use of the Oxford Classification MEST-C score in determining which drug should be commenced in IgAN.
  • There is insufficient evidence to base treatment decisions on the presence and number of crescents in the kidney biopsy alone. Histopathological features must be interpreted in the context of clinical features, in particular, the rate of change of eGFR.
  • The International IgAN Prediction Tool 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 the relative merits of different treatments may change.

Question Title

Figure 3 | Treatment targets in immunoglobulin A nephropathy (IgAN) and available to-date approved treatment options.

<span style="color: #2c7db7;"><em><strong><span style="font-size: 14pt;">Figure 3 | Treatment targets in immunoglobulin A nephropathy (IgAN) and available to-date approved treatment options. </span></strong></em></span>
*Measures to reduce glomerular hyperfiltration and the impact of proteinuria on the tubulointerstitium, using singly or in combination, renin-angiotensin system (RAS) blockade or dual endothelin angiotensin receptor antagonism (DEARA), and sodium-glucose cotransporter-2 inhibition (SGLT2i). RASi, renin-angiotensin system inhibitors.
2.3.3 Managing the IgAN-specific drivers for nephron loss
2.3.3.1 Reducing the production of pathogenic forms of IgA and IgA immune complex formation

Question Title

* Recommendation 2.3.3.1.1: We suggest treatment with a 9-month course of nefecon for patients who are at risk of progressive kidney function loss with IgAN (2B).

Question Title

* Practice Point 2.3.3.1.1: Factors to consider before using nefecon in patients with IgAN
  • A single 9-month treatment course of nefecon is unlikely to produce a sustained clinical response in terms of proteinuria reduction or stabilization of eGFR and it is likely that many patients will need either repeated 9-month treatment cycles or a reduced-dose maintenance regimen
  • The approval status, labelled indication and availability vary globally.

Question Title

* Practice Point 2.3.3.1.2: Other pharmacologic therapies evaluated in IgAN:
  • Multiple agents have been evaluated in often small studies, in restricted populations and have failed to show a consistent benefit in IgAN (Figure 4)

Question Title

Figure 4 | Other pharmacologic therapies evaluated in immunoglobulin A nephropathy (IgAN).

<span style="color: #2c7db7;"><em><strong><span style="font-size: 14pt;">Figure 4 | Other pharmacologic therapies evaluated in immunoglobulin A nephropathy (IgAN). </span></strong></em></span>
1Tang et al.28, 2Tang et al.29, 3Hou et al.30, 4Hou et al. 31, 5Maes et al.32, 6Frisch et al.33, 7Hogg et al.34, 8Liu et al.35, ACEi, angiotensin-converting enzyme inhibitor; aHR, adjusted hazard ratio; ARB, angiotensin II receptor blocker; CKD, chronic kidney disease; CI, confidence interval; IgAN, immunoglobulin A nephropathy; KRT, kidney replacement therapy; MMF, mycophenolate mofetil; RCT, randomized controlled trial; SC, standard of care; SCr, serum creatinine.

Question Title

* Practice Point 2.3.3.1.3: Tonsillectomy in IgAN:
  • Tonsillectomy alone or with pulsed glucocorticoids may improve kidney survival and partial or complete remission of hematuria and proteinuria, based on multiple, mostly retrospective studies from Japan
  • (Supplementary Table S536-40).36-38, 40-42
  • Tonsillectomy is recommended in the Japanese Society of Nephrology Guidelines for the treatment of patients with IgAN.
  • Tonsillectomy should not be performed as a treatment for IgAN in non-Japanese patients.

2.3.1.2 Managing glomerular inflammation

Question Title

* Recommendation 2.3.1.2.1: In settings where nefecon is not available, we suggest that patients who are at risk of progressive kidney function loss with IgAN be treated with a limited course of a reduced-dose systemic glucocorticoid regimen combined with antimicrobial prophylaxis after a thorough toxicity risk assessment (2B).

Question Title

* Practice Point 2.3.1.2.1: Reduced-dose systemic glucocorticoid regimen:
  • Methylprednisolone (or equivalent) 0.4 mg/kg per day (maximum: 32 mg/d) for 2 months followed by dose tapering by 4 mg/d each month for a total of 6–9 months.
  • The conversion of methylprednisolone to commonly used forms of systemic glucocorticoids is: 1 mg methylprednisolone equals 1.3 mg of prednisone or prednisolone.
  • Treatment with systemic glucocorticoids should incorporate antimicrobial prophylaxis against Pneumocystis jirovecii and anti-viral prophylaxis in hepatitis B carriers , along with gastroprotection and bone protection according to local guidelines.

Question Title

* Practice Point 2.3.1.2.2: Factors to consider before using systemic glucocorticoids in IgAN:
  • Systemic glucocorticoids are effective anti-inflammatory drugs, but there is no evidence at the doses recommended in this guideline that they reduce the formation of pathogenic forms of IgA or immune complexes at the recommended doses.
  • The dose and duration of systemic glucocorticoid treatment required to manage glomerular inflammation when used in combination with a therapy to reduce pathogenic forms of IgA is not known but should not exceed, and is likely to be much less than, the reduced-dose scheme for systemic glucocorticoids for active lupus nephritis, suggested in Practice Point 10.2.3.1.1 of the KDIGO 2024 Clinical Practice Guideline For The Management Of Lupus Nephritis.45
  • The following patient characteristics are likely to increase the risks of systemic glucocorticoid related toxicity:
    • eGFR <30 ml/min per 1.73 m2,
    • Diabetes and prediabetes,
    • Obesity,
    • Latent infections (e.g., viral hepatitis, tuberculosis),
    • Active peptic ulceration,
    • Uncontrolled psychiatric illness,
    • Osteoporosis, and
    • Cataracts.
  • There is insufficient evidence to support the use of the Oxford Classification MEST-C score in determining when systemic glucocorticoids should be commenced.
  • There are no data to support efficacy or reduced toxicity of alternate-day systemic glucocorticoid regimens.

2.3.4 Managing the responses to IgAN-induced nephron loss

Question Title

* Practice Point 2.3.4.1: Interventions for all patients with IgAN:
  • Control blood pressure to a target of ≤120/70 mm Hg, using a RASi as the first choice drug intervention
  • Lifestyle advice should be given, where appropriate, on smoking cessation, weight reduction, dietary sodium restriction (<2 g/d) and regular exercise.
  • A cardiovascular risk assessment should be undertaken and interventions commenced as per local guidelines.

Question Title

* Recommendation 2.3.4.1: We recommend all patients who are at risk of progressive kidney function loss with IgAN be treated with an optimized maximally tolerated dose of either an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) (1B).

Question Title

* Recommendation 2.3.4.2: We suggest that patients who are at risk of progressive kidney function loss with IgAN be treated with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) (2B).

Question Title

* Practice Point 2.3.4.2: Factors to consider before using an SGLT2i in patients with IgAN:
  • There was no requirement for patients with IgAN to be on an optimized maximally tolerated dose of RASi for a minimum of 3 months for inclusion in The Study of Heart and Kidney Protection With Empagliflozin (EMPA-KIDNEY) and Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trials.
  • IgAN patients included in EMPA-KIDNEY and DAPA-CKD likely had longstanding disease, based on the age and eGFR at randomization; therefore, there is uncertainty over the value of SGLT2i in patients with IgAN and a relatively preserved eGFR (>60 ml/min per 1.73 m2) (see Table 2).

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* Recommendation 2.3.4.3: We suggest that patients who are at risk of progressive kidney function loss with IgAN be treated with sparsentan (2B).

Question Title

* Practice Point 2.3.4.3: Factors to consider before using sparsentan in patients with IgAN
  • Sparsentan is a dual endothelin angiotensin receptor antagonist (DEARA) and should not be prescribed together with a RASi.
  • The approval status, labelled indication and availability vary globally.

2.4 Special situations

Question Title

* Practice Point 2.4.1: IgAN with nephrotic syndrome:
  • Rarely, patients with IgAN present with nephrotic syndrome (including edema and both hypoalbuminemia and nephrotic-range proteinuria >3.5 g/d).
  • In these cases, mesangial IgA deposition can be associated with light and electron microscopy features otherwise consistent with a podocytopathy resembling minimal change disease (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 in Chapter 5 of the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases.12
  • Peoples with nephrotic syndrome whose kidney biopsy has coexistent features of a mesangioproliferative glomerulonephritis (MPGN) should be managed in the same way as those patients who are at risk of progressive kidney function loss from IgAN.
  • Nephrotic-range proteinuria without nephrotic syndrome may also be seen in IgAN, and this commonly reflects coexistent secondary focal segmental glomerulosclerosis (FSGS) (e.g., obesity, uncontrolled hypertension) or development of extensive glomerulosclerosis and tubulointerstitial fibrosis.

Question Title

* Practice Point 2.4.2: IgAN with AKI:
  • AKI can occur in people with IgAN in the context of severe visible hematuria, 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 hematuria. Immediate management of AKI with visible hematuria should focus on supportive care for AKI.
  • IgAN may also present with AKI either de novo or during its natural history due to a rapidly progressive glomerulonephritis (RPGN), often with extensive crescent formation, commonly in the absence of visible hematuria. In the absence of visible hematuria and when other causes of an RPGN (e.g., antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis [AAV], anti-glomerular basement membrane [GBM] disease) and reversible causes (e.g., drug toxicity, common pre- and post-kidney causes) have been excluded, a kidney biopsy should be performed as soon as possible.

Question Title

* Practice Point 2.4.3: IgAN with RPGN:
  • Rapidly progressive IgAN is defined as a ≥50% decline in eGFR over ≤3 months, where other causes of an RPGN (e.g., AAV, anti-GBM disease) and reversible causes (e.g., 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 (SCr) 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 systemic glucocorticoids in accordance with the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis.44
  • Prophylactic measures that should accompany immunosuppression are discussed in Chapter 1 of the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases.12
  • There is insufficient evidence to support the use of rituximab for the treatment of rapidly progressive IgAN.

Question Title

* Practice Point 2.4.4: 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 RASi, SGLT2i, sparsentan, and nefecon. Blood pressure control should be optimized with alternative antihypertensive medications prior to conception.
  • In those women at risk of progressive loss of kidney function, a trial of treatments to optimally suppress production of pathogenic forms of IgA and IgA immune complexes and glomerular inflammation prior to conception may be preferable to initiation of these treatments during pregnancy.
  • RASi, SGLT2i, and sparsentan must not be used during pregnancy and breastfeeding.
  • The evidence to date suggests that first trimester systemic glucocorticoid use may confer a small increase in the odds of cleft lip with or without cleft palate, although data are conflicting and it is unknown to what extent the underlying maternal disease may contribute. Systemic glucocorticoid use in pregnancy does not increase the risks of preterm birth, low birth weight, or preeclampsia.
  • The use of nefecon in pregnancy is not advised, however, studies examining the use of budesonide by pregnant women with inflammatory bowel disease have not identified any harmful effects. Budesonide has a Food and Drug Administration (FDA) Pregnancy Category C Risk designation, so risk cannot be ruled out.

Question Title

* Practice Point 2.4.5: IgAN in children:

General considerations for children with IgAN
  • A more extensive review of the management of IgAN in children can be found in the 2024 International Pediatric Nephrology Association Guidelines for the Management of IgA nephropathy and IgA vasculitis (submitted)
  • In this guideline, we define children as those aged <18 years, but it is acknowledged that post-pubertal children in some respects may have a similar course and response to treatment as adults with IgAN. However, there are insufficient data currently to recommend that they be managed as adults with IgAN.
  • Visible hematuria is more frequent in children than in adults, and this may account for earlier diagnosis in children.56
  • Children generally have higher eGFR, lower urine protein excretion, and more hematuria than adults at diagnosis.55

Question Title

* Practice Point 2.4.5: IgAN in children (continued):

Kidney biopsy in children with IgAN
  • A kidney biopsy is usually performed at presentation of symptoms (hematuria, proteinuria, normal C3) to confirm the diagnosis (and rule out other diagnoses) and assess the degree of inflammation/presence of necrosis.
  • In particular, a kidney biopsy should be performed promptly in children with persistent (>2-3 weeks) or recurrent hematuria and nephrotic-range proteinuria and/or reduced eGFR.88
  • A kidney biopsy should also be performed in children with persistent or recurrent hematuria and PCR >500 mg/g (50 mg/mmol) in ≥2 measurements on clear urine 1–2 weeks apart.88
  • In children with persistent or recurrent hematuria and PCR between 200–500 mg/g (20-50 mg/mmol) in ≥3 measurements on clear urine 1–2 weeks apart, performing a kidney biopsy should be considered.88
  • Inflammation, mesangial, and endocapillary hypercellularity tend to be more prevalent in kidney biopsies of IgAN in children than in those of adults.89-92

Question Title

* Practice Point 2.4.5: IgAN in children (continued):

Treatment of children with IgAN
  • There is strong evidence suggesting a benefit of RAS blockade in children.132 All children with IgAN and proteinuria >200 mg/d or PCR >200 mg/g (>20 mg/mmol) should receive RAS blockade, advice on moderating dietary salt intake below 3–5 g/d, and optimal lifestyle and blood pressure control (systolic blood pressure [SBP] <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 systemic glucocorticoids. However, RCTs and specific expert consensus-driven indications are lacking.89, 91-96
  • Evidence derived mostly from retrospective studies suggests that treatment with systemic glucocorticoids (plus second-line immunosuppression) leads to improved kidney survival.56, 97
  • The risk-benefit balance of glucocorticoid side effects must be considered. Systemic oral glucocorticoids are used in selected settings, in children with clinical risk of progression (i.e., a) PCR 500–1000 mg/g (50–100 mg/mmol) despite 3–6 months of RASB or b) PCR >1000 mg/g (>100 mg/mmol) despite 4 weeks of RAS, or c) active MEST-C scores [≥1 of the following scores: M1, E1, S1 with podocyte lesions, C1], and/or PCR consistently [i.e., persisting over 2–3 weeks in ≥2 measurements 1–2 weeks apart, >1000 mg/g (100 mg/mmol) in addition to RAS blockade].
    • Duration of treatment is not established, but usually 2 mg/kg per day (max 60 mg/m2 per day) of oral prednisone/prednisolone [or equivalent] for a maximum of 4 weeks followed by alternate-day dosing tapered over 5–6 months are given.
    • Further extension of the duration may be useful in some cases. Lower doses as those emerging from the adult TESTING trial (0.4 mg/kg per day of prednisone/prednisolone [or equivalent] for 2 months, tapering over 6 months) should be considered.

Question Title

* Practice Point 2.4.5: IgAN in children (continued):

Treatment of children with IgAN (continued)
  • Regimens including intravenous methylprednisolone are also used on an individual basis in patients with higher clinical and histological risk for progression, such as a) children with acute onset of IgAN and worsening of kidney function (eGFR <90 ml/min per 1.73 m2) and/or PCR >1000 mg/g (100 mg/mmol) with active severe MEST-C scores (≥2 of the following scores: M1, E1, S1 with podocyte lesions, C1) or b) children with crescentic forms of IgAN (C2).
    • In cases with C1 or C2 in the absence of any other MEST-C score >0 the level of proteinuria must be considered.55, 89, 91, 98
    • In cases with C2, irrespective of proteinuria, treatment of rapidly progressive IgAN is suggested (see below). Dosing regimens may be as follows: 3 methylprednisolone intravenous pulses given at the dose of 15 mg/kg per day each (maximum dose: 500 mg/dose) on 3 consecutive or alternate days followed by oral prednisone/prednisolone as indicated above.
      • Alternatively, the intravenous pulses can be repeated 3 times at 2-month intervals, with oral prednisone/prednisolone given at 0.5 mg/kg per day for 2 months between pulse cycles, for a total of 6 months.99, 100
  • Children with IgAN not benefiting from adequate diet, RAS blockade, and glucocorticoids alone, should, whenever possible, be enrolled in clinical trials. Another potential approach is the use of immunosuppressants (e.g., calcineurin inhibitors, cyclophosphamide, mizoribine where available, mycophenolate mofetil or rituximab) in addition to glucocorticoids in these children.
  • As for adults, IgAN with MCD may be found, and it should be treated as steroid-sensitive nephrotic syndrome (SSNS; Chapter 4).
  • As in adults, children with rapidly progressive IgAN have a poor outcome, and despite limited evidence, this subgroup should be offered treatment with systemic glucocorticoids (usually as methylprednisolone pulses) and cyclophosphamide.53, 89, 91

Question Title

* Practice Point 2.4.5: IgAN in children (continued):

Follow-up of children with IgAN
  • Aim for proteinuria ≤200 mg/d (≤400 mg/1.73 m2 per d) or PCR ≤200 mg/g (≤0.2 g/g [≤20 mg/mmol]).
  • Aim for SBP at <90th percentile for age, sex, and height.
  • Continue to follow patients after complete remission, as they can relapse even after many years.101 In particular, yearly monitoring of blood pressure and urinalysis for patients with a history of pediatric IgAN is necessary.

2.5 Global implementation of the updated IgAN KDIGO Guideline

Question Title

* 2.5 Comments Only

2.6 Horizon scanning for future new drug approvals and updates to the Guideline

Question Title

* 2.6 Comments Only

IMMUNOGLOBULIN A VASCULITIS
2.7. Diagnosis

Question Title

* Practice Point 2.7.1: Considerations for the diagnosis of immunoglobulin A vasculitis associated nephritis (IgAVN):
  • There are no internationally agreed upon criteria for the diagnosis of IgAV in adults
  • In children, a clinical diagnosis of IgAV can be made based on international criteria.102-104
  • A diagnosis of IgAVN can only be made with a kidney biopsy
  • A kidney biopsy should be performed in adults with suspected IgAV if there are signs of significant end organ tissue damage: proteinuria ≥0.5 g/d persistent for >4 weeks, kidney function impairment or an RPGN.
  • Assess all adult patients with IgAV and IgAVN for secondary causes and for malignancy, with age- and sex-appropriate screening tests.

2.8. Prognosis

Question Title

* Practice Point 2.8.1: Considerations regarding the prognosis of IgAVN:
  • 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.105-107
  • The utility of the Oxford MEST-C classification has recently been studied.108 This showed that in patients treated with immunosuppression E1 lesions were strongly associated with initial improvement followed by progressive decline in kidney function.
  • The International IgAN Prediction Tool9 is not designed for determining prognosis of IgAVN.

2.9. Treatment
2.9.1. Prevention of nephritis in IgAV

Question Title

* Recommendation 2.9.1.1: We recommend not using systemic glucocorticoids to prevent nephritis in patients with isolated extrarenal IgAV (1B).

Question Title

* Practice Point 2.9.1.1: Considerations for the management of all patients with IgAV-associated nephritis (IgAVN) who are at risk of progressive kidney function decline and do not have a rapidly progressive glomerulonephritis:
  • Proteinuria ≥0.5 per day (while on or off treatment for IgAVN) identifies a patient with IgAVN at increased risk of progressive loss of kidney function.
  • The aspiration for the management of IgAVN, like IgAN, should be to simultaneously
    • Prevent or reduce IgA immune complex formation, mesangial deposition, and immune complex mediated glomerular injury.
    • In parallel, manage the consequences of existing IgAVN-induced nephron loss.
  • Unlike IgAN, there are no treatments proven to prevent/reduce IgA immune complex formation in IgAVN.
  • Prevention of immune complex-mediated injury should incorporate treatments with proven anti-inflammatory effects, and ideally should be used in combination with, and not as a replacement for, treatments that prevent/reduce IgA immune complex formation.
    • In all patients in whom systemic glucocorticoids are being considered, a detailed discussion of the risks and benefits of each drug should be undertaken with the patient.
    • In those patients who wish to try systemic glucocorticoids, a reduced-dose regimen as described for IgAN should be employed with antimicrobial prophylaxis.
  • Management of the consequences of IgAVN-induced nephron loss should include:
    • Lifestyle advice, including information on dietary sodium restriction, smoking cessation, weight control, and exercise, as appropriate,
    • Control blood pressure to a target of ≤120/70 mm Hg, using a RASi as the first choice drug intervention
    • Measures to reduce glomerular hyperfiltration and the impact of proteinuria on the tubulointerstitium, using singly or in combination, RASi and SGLT2i, and
    • A thorough cardiovascular risk assessment and commencement of appropriate interventions as necessary.
  • Offer participation in a clinical trial if one is available.
  • There is insufficient evidence to support the use of the Oxford Classification MEST-C score in determining which drug should be commenced in IgAVN.
  • There is insufficient evidence to base treatment decisions on the presence and number of crescents in the kidney biopsy.
  • The International IgAN Prediction Tool 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.

2.10 Special situations

Question Title

* Practice Point 2.10.1: 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 KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis.44
  • IgAVN with RPGN, as well as other presentations of 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.115

2.10.1 IgAV-associated nephritis in children

Question Title

* Practice Point 2.10.1.1: In this guideline, we define children as those aged <18 years, but it is acknowledged that post-pubertal children in some respects may have a similar course and response to treatment as adults with IgAN. However, there are insufficient data currently to recommend that they be managed as adults with IgAN.

Question Title

* Practice Point 2.10.1.2: A more extensive review of the management of IgAVN in children can be found in the 2024 International Pediatric Nephrology Association Guidelines for the Management of IgA nephropathy and IgA vasculitis (submitted).

Briefly:
  • The majority of children who will develop nephritis do so within 3 months of presentation. Urinary monitoring is necessary at onset of vasculitis and then at least monthly for ≥6 months from initial presentation of systemic disease.
  • A kidney biopsy should be promptly performed in children with nephrotic-range proteinuria or impaired GFR (<90 ml/min per 1.73 m2).
  • In children with IgAV and moderate proteinuria (PCR 1000–2000 mg/g or 100-200 mg/mmol) for 2–4 weeks or mild proteinuria (PCR 200-500 mg/g or 20–50 mg/mmol) for >4 weeks a kidney biopsy should be considered.
  • In children with confirmed IgAVN, a pediatric nephrologist should be consulted.
  • In children with IgAVN and persistent proteinuria for >3 months, ACEi or ARB treatment should be considered.
  • There are no data supporting the use of glucocorticoids to prevent nephritis in children with IgAV and absent evidence of kidney involvement or with isolated microhematuria.116, 117
  • Oral prednisone/prednisolone for 3–6 months or pulsed intravenous methylprednisolone should be considered in children with IgAVN and nephrotic-range proteinuria (PCR >2000 mg/g or 200 mg/mmol) or RPGN and histological risk for progression (International Study of Kidney Disease in Children [ISKDC] ≥II).
  • Other immunosuppressive agents in addition to glucocorticoids (e.g., calcineurin inhibitors, cyclophosphamide, mizoribine where available, mycophenolate mofetil or rituximab) should be considered in the following indications: to reduce the glucocorticoid dose and/or if PCR >2000 mg/g (200 mg/mmol) and/or insufficient response to glucocorticoids.
  • Children with IgAVN with nephrotic syndrome and/or rapidly deteriorating kidney function are treated in the same way as those with rapidly progressive IgAN.
  • Monitoring children with IgAVN with evaluation of urinalysis, eGFR, and blood pressure should be considered for ≥5 years after the initial episode. Lifelong monitoring, individualized according to the severity and response to treatment, appears prudent for children who received therapy for their IgAVN.

Question Title

* IgAN and IgAV Guideline Comments

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