Nephrol Dial Transplant, 2025, 40, 874–883

https://doi.org/10.1093/ndt/gfae289
Advance access publication date: 17 December 2024

Tailored management strategies for IgA nephropathy

REVIEW

based on clinical presentations

Manuel Praga 1 , Fernando Caravaca-Fontán 2
, Iara Da Silva3 , Gema Fernández-Juárez4 , Eduardo Gutiérrez5 , Angel M. Sevillano5
and Hernan Trimarchi6
1
Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain

Downloaded from https://academic.oup.com/ndt/article/40/5/874/7926970 by ERA - Member Access user on 30 April 2025

2
Department of Nephrology, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain
3
Department of Nephrology, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain
4
Department of Nephrology, Hospital Universitario La Paz, Madrid, Spain
5
Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
6
Department of Nephrology, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
Correspondence to: Manuel Praga; E-mail: mpragat@senefro.org

Watch the video of this contribution at https://academic.oup.com/ndt/pages/author_videos

ABSTRACT
The treatment landscape for immunoglobulin A nephropathy is rapidly evolving with the introduction of novel therapies targeting di-
verse disease pathways. Some have already been approved in different countries, while others are under investigation in randomized
controlled trials (RCTs) with encouraging results. However, almost all performed RCTs have included only patients with refractory
non-nephrotic proteinuria and preserved renal function. Other clinical presentations (rapidly progressive forms, malignant hyperten-
sion, thrombotic microangiopathy, nephrotic syndrome) have received less attention and are systematically excluded from RCTs. In
contrast, certain aspects, such as the impact of haematuria or management in special populations (e.g. pregnant patients or trans-
plant recipients), remain underexplored. This review proposes therapeutic algorithms to guide treatment decisions in different clinical
scenarios while highlighting gaps in current research.

Keywords: haematuria, IgA nephropathy, kidney transplant, pregnancy, proteinuria

INTRODUCTION CLINICAL AND HISTOLOGICAL

The treatment landscape for immunoglobulin A nephropathy
PARAMETERS INFLUENCING IgAN
(IgAN) is undergoing a significant transformation with the advent
OUTCOMES
of novel therapies that have shown promising efficacy. However, Numerous studies have consistently shown that the amount
an often-overlooked aspect of IgAN is the variability in its clini- of proteinuria is directly associated with kidney survival [4].
cal presentation. While the majority of cases present with non- Likewise, treatment-induced proteinuria reduction, regardless of
nephrotic proteinuria accompanied by microscopic haematuria, the type of treatment, significantly decreases the decline in esti-
other less common clinical presentations (e.g. rapidly progres- mated glomerular filtration rate (eGFR) and the risk of end-stage
sive forms, malignant hypertension, thrombotic microangiopathy, kidney disease (ESKD), hence proteinuria reduction has been
nephrotic syndrome) have received less attention and are sys- adopted as a surrogate for the treatment effect in most RCTs [5].
tematically excluded from RCTs. Additionally, although episodes Early studies indicated a time-averaged proteinuria (proteinuria
of visible haematuria are often the initial manifestation of the evaluated throughout follow-up) of 1 g/day as the limit below
disease in many patients, their impact on the disease course which most patients had a stable clinical course [4]. However,
remains poorly studied. Furthermore, there is limited informa- more recent studies have shown that lower levels of proteinuria
tion on the management of IgAN during pregnancy and in trans- (>0.5 g/day or even >0.3 g/day) may also be associated with a
plant recipients, highlighting gaps in current understanding and poor prognosis [6–8]. Despite its value as a prognostic marker,
care. proteinuria has certain limitations that must be considered,
In this article we propose a series of therapeutic algorithms tai- as it may reflect chronic irreversible damage sequelae of pre-
lored to the different clinical presentations of IgAN and the di- vious episodes of inflammation rather than active glomerular
verse clinical scenarios in which therapeutic decisions must be lesions.
made. Many of the recommendations we propose are based on Haematuria is one of the distinctive features of IgAN. Although
limited evidence, given the scarcity of available studies in these less intensively studied than proteinuria, several recent studies
areas. It is also important to remark that this article does not aim have shown its strong prognostic influence in the long-term out-
to provide a comprehensive review of IgAN pathogenesis or treat- come of the disease [9–12]. Time-averaged haematuria (average
ment. For those seeking a detailed overview, we refer readers to level over follow-up) is associated with the risk of progressing
several excellent recent reviews [1–3]. to ESKD, with higher levels correlating with increased risk [10].

Received: October 20, 2024; Editorial decision: December 7, 2024

© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.
All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
 M. Praga et al. | 875

Conversely, the resolution of haematuria—whether spontaneous Renin–angiotensin system inhibitors (RASis)

or treatment induced—is often followed by stabilization of kid- Many prospective studies have demonstrated benefits by em-
ney function [9, 11]. However, variability in the methods used to ploying angiotensin-converting enzyme inhibitors (ACEis) or an-
assess haematuria has limited its utility as an inclusion crite- giotensin receptor blockers (ARBs) in IgAN patients, both in Cau-
rion or surrogate marker in most RCTs conducted to date. We casian and Asian subjects, with better kidney survival and reduc-
recommend performing microscopic urinary sediment analysis tions in proteinuria [18, 19]. Based on this accumulated evidence,
to quantify the number of red blood cells per high-power field RASis remain the cornerstone of first-line therapy in IgAN. RASi
(RBC/HPF). However, while microscopic analysis is preferred therapy should be carefully titrated to achieve optimal control
for accuracy, urine dipstick and automated urine analysers of proteinuria and blood pressure (BP) and this optimization may
are also acceptable methods, with studies demonstrating good take >3–6 months.
correlation between these techniques and standard microscopic
evaluation [12]. Sodium–glucose co-transporter 2 inhibitors (SGLT2is)

Downloaded from https://academic.oup.com/ndt/article/40/5/874/7926970 by ERA - Member Access user on 30 April 2025

Studies have shown that patients with both significant pro- SGLT2is reduce glomerular hyperfiltration by inducing vaso-
teinuria and persistent microhaematuria tend to have a worse constriction of the afferent arteriole. The EMPA-KIDNEY
prognosis [9]. In contrast, those with proteinuria without micro- (NCT03594110) and DAPA-CKD (NCT03036150) trials demon-
haematuria or those with isolated microhaematuria have a sig- strated a slower decline in eGFR among IgAN patients treated
nificantly better prognosis [9]. While conclusive studies are lack- with SGLT2i [20, 21]. In a large retrospective cohort study includ-
ing, the presence/absence of haematuria could potentially help ing 192 IgAN patients, SGLT2i treatment was associated with a
distinguish between proteinuria driven by active immunological significant reduction in proteinuria [22]. However, the benefits
and inflammatory processes and residual proteinuria caused by of SGLT2is in slowing eGFR decline has only been demonstrated
chronic damage. in patients with impaired kidney function who were not on
Histological lesions, grouped by the MEST-C score [mesan- immunosuppression. Further studies are needed to evaluate the
gial hypercellularity (M), endocapillary cellularity (E), segmen- effects of SGLT2is in IgAN patients with normal kidney function
tal sclerosis (S), interstitial fibrosis/tubular atrophy (T) and cres- and/or those undergoing immunosuppressive treatments.
cents (C)], have a decisive role on the prognosis [8, 13]. Within
this score, active lesions (mesangial hypercellularity, endocapil- Endothelin receptor antagonists (ERAs)
lary hypercellularity, crescents) may regress with immunosup-
In IgAN, the endothelin and RAS are interactively activated [23],
pressive/immunomodulatory treatments, while chronic lesions
leading to hyperfiltration, inflammation and fibrosis. The PRO-
(segmental glomerulosclerosis, tubular atrophy/interstitial fibro-
TECT trial (NCT03762850) aimed to assess the efficacy and safety
sis) are generally unresponsive to these treatments.
of sparsentan (a dual ERA-ARB blocker) versus irbesartan on
proteinuria and eGFR in 406 IgAN individuals with proteinuria
≥1.0 g/day and an eGFR ≥30 ml/min/1.73 m2 [24, 25]. From base-
TREATMENT STANDARDS IN IgAN AND line to week 110, the change in urinary protein:creatinine ratio
EXPERT OPINION CONSIDERATIONS (UPCR) was −42.8% with sparsentan versus −4.4% with irbesar-
Several key factors should be carefully considered when deter- tan, while the eGFR 2-year total slope was −2.9 ml/min with
mining the appropriate treatment approach for each IgAN pa- sparsentan versus −3.9 ml/min with irbesartan [25]. These results
tient. First, not all patients with IgAN have a progressive course. led to sparsentan being approved by the US Food and Drug Admin-
The long-term prognosis for biopsy-proven IgAN patients who istration and European agencies. A recent interim analysis from a
present with minor urinary abnormalities (proteinuria <0.5 g/day phase 3 RCT demonstrated that atrasentan, a selective endothe-
and microhaematuria) and normal kidney function was re- lin type A receptor antagonist, significantly reduced proteinuria
ported as excellent [14]. Importantly, all patients in this study compared with placebo in patients with IgAN [26].
were Caucasian; different studies have shown a worse outcome
in Asian patients [15]. Second, as demonstrated by the STOP- Mineralocorticoid receptor antagonists (MRAs)
IgAN trial (NCT00554502), a significant proportion of patients A recent meta-analysis showed that finerenone, a mineralocor-
achieve short-term remission with lifestyle measures and non- ticoid antagonist, confers significant antiproteinuric effects in
immunosuppressive treatments [16]. Third, the amount of pro- CKD patients, potentially leading to another approach for IgAN
teinuria has been the main, if not the only, criterion for including [27]. Steroidal mineralocorticoid receptor antagonists (spironolac-
patients in RCTs and for assessing treatment responses. Other key tone, eplerenone) and thiazide-like diuretics (hydrochlorothiazide,
clinical parameters such as haematuria, eGFR slope, histological amiloride, chlortalidone) also have an important antiproteinuric
data or the type of clinical presentation have not been considered effect, although they have not been specifically evaluated in IgAN
in prospective trials. Fourth, it is essential to account for the dis- [28].
tinct mechanisms of action among available therapeutic options.
These can be broadly categorized into lifestyle interventions, non- Immunosuppressive and disease-specific
immunosuppressive treatments and immunosuppressive or im- targeted therapies
munomodulatory drugs.
Systemic corticosteroids
Along with their direct effects on the podocyte cytoskeleton, cor-
Lifestyle measures and non-immunosuppressive ticosteroids have a potent anti-inflammatory effect. The efficacy
treatments of corticosteroids on kidney outcomes in IgAN has been shown
Lifestyle measures (e.g. regular physical exercise, weight manage- in several RCTs and retrospective studies [29, 30]. However, the
ment and smoking cessation) are fundamental in managing IgAN STOP-IgAN trial found more complications and no significant dif-
and should be implemented and closely monitored in all patients ferences in kidney function decline between patients treated with
[17]. corticosteroids and those receiving conservative therapy [16, 31].
876 | Nephrol Dial Transplant, 2025, Vol. 40, No. 5

In the TESTING trial (NCT01560052), corticosteroids significantly Complement inhibitors

reduced kidney function loss and ESKD as compared with placebo, The complement system plays an important role in the pathogen-
both in the first phase of the study and in a second phase in esis of IgAN [47]. Glomerular deposits of C3 and C4d are associated
which corticosteroid dose was reduced (0.4 mg/kg/day, maximum with a significantly worse prognosis, and lesions of thrombotic
32 mg/day, tapered for 6–9 months). Although there was an excess microangiopathy (TMA) are a not uncommon finding in kidney
of corticosteroid-related side effects, the difference from placebo biopsies of IgAN patients [48, 49]. Several complement inhibitors
was smaller than in patients treated with the high-dose regimen targeting different steps of the complement system (iptacopan,
[32, 33]. These data suggest that corticosteroids may offer bene- ravulizumab, cemdisiran) have shown positive results in phase 2
fits for IgAN patients at risk of disease progression, but their use RCTs [50–52]. In an interim efficacy analysis of a phase 3 trial with
must be carefully balanced against their well-documented side iptacopan, a significant decrease in proteinuria as compared with
effects. placebo was found [53].

Mycophenolate mofetil (MMF)

Downloaded from https://academic.oup.com/ndt/article/40/5/874/7926970 by ERA - Member Access user on 30 April 2025

Hydroxychloroquine
MMF and mycophenolic acid analogues (MPAAs) are potent im- Hydroxychloroquine is an antimalarial drug with immunomodu-
munosuppressive agents that inhibit lymphocyte proliferation. latory effects through Toll-like receptors inhibition. A small RCT
Additionally, they have anti-inflammatory and anti-fibrotic ef- conducted in China reported an important proteinuria reduction
fects and inhibit the proliferation of mesangial cells [34]. Al- after 6 months of treatment in IgAN patients at risk of progression
though negative results were reported in Caucasian patients [54], and other reports have corroborated this effect.
[35], studies conducted in China have shown beneficial effects
of MMF in monotherapy or with reduced-dose regimens of
corticosteroids [36, 37]. Patients with active disease—indicated TREATMENT ALGORITHMS: EXPERT
by the presence of haematuria—are more likely to respond OPINION PROPOSALS
to MMF. In RCTs conducted in China, all participants pre- Patients presenting with proteinuria/haematuria,
sented with microscopic haematuria at baseline, leading to with or without declining kidney function (Fig. 1)
positive outcomes [36, 37]. In contrast, studies that did not Optimized conservative treatment (OCT) (lifestyle measures) to-
include haematuria as an inclusion criterion yielded nega- gether with RASi are mandatory in patients presenting with sta-
tive results [35]. The Kidney Disease: Improving Global Out- ble kidney function and proteinuria >0.3 g/day. Aims of treatment
comes guidelines recommend MMF only for Chinese patients are systolic BP <120–130 mmHg and proteinuria <0.3 g/day. RASi
[17], but positive results have been reported in Caucasian should be up-titrated gradually to achieve these objectives and
patients [38–40]. the addition of MRA or thiazide diuretics can help in controlling
BP and reducing proteinuria [28].
Targeted-release budesonide (Nefecon)
We recommend adding SGLT2i if proteinuria is still >0.3 g/day
Nefecon is specifically designed to deliver budesonide to the distal after 3–6 months of OCT + RASi [22, 55]. SGLT2i-induced pro-
ileum, a region abundant in lymphoid tissues with a high produc- teinuria reduction is relatively rapid, so the patient should be re-
tion of pathogenic IgA [41]. In the NefIgArd trial (NCT03643965) evaluated after 2–3 months of its onset. In the case of significant
[42, 43], 364 patients who maintained proteinuria >1 g/day de- proteinuria despite OCT + RASi + SGLT2i, two options can be con-
spite RASi were randomized to Nefecon 16 mg or placebo. At sidered, mainly based on the absence/presence of significant and
9 months, proteinuria was reduced by 50% with Nefecon and kid- persistent haematuria (>20 RBC/HPF):
ney function remained stable, in contrast to a marked loss of
kidney function in the placebo group. The proportion of patients • When important proteinuria persists without accompanying
without microscopic haematuria during the follow-up was signif- significant haematuria, we suggest the addition of sparsen-
icantly higher in the Nefecon group and patients with haematuria tan [25], given its strong antiproteinuric effect. RASi should
at baseline were more likely to benefit from treatment [43]. After be discontinued since sparsentan also blocks angiotensin II
Nefecon discontinuation, an increase in proteinuria toward base- receptors.
line values was observed and eGFR continued to fall in parallel • In patients with significant proteinuria and haematuria,
with placebo, suggesting that longer treatment or repeated cycles especially if active lesions were found in kidney biopsy,
may be necessary. we recommend one of the following immunosuppressive/
immunomodulatory treatments:
APRIL/BAFF inhibitors • corticosteroids + MMF [36, 37], Nefecon [41, 43] or corti-
APRIL (a proliferation-inducing ligand) and BAFF (B cell activat- costeroids in monotherapy [32, 33, 56]. MMF in monother-
ing factor) are factors that stimulate B cell proliferation and apy [37, 38] could be a good option for patients at risk for
increased APRIL levels have been reported in IgAN. A phase 2 corticosteroid-induced side effects.
study with sibeprenlimab, an antibody that neutralizes APRIL,
showed a significant reduction in proteinuria accompanied by No studies have compared these different treatments, so the
eGFR stabilization, remission of haematuria in a large propor- decision should be based on individual patient’s characteristics.
tion of patients and an important reduction in galactose-deficient MMF has demonstrated its efficacy in RCTs performed in China
IgA1 level, along with a good safety profile [44]. Phase 1/2 tri- [36, 37]. However, in our experience and that of others, this drug
als with other APRIL inhibitors and dual inhibitors of APRIL (or its equivalent in mycophenolic acid) is also effective in Cau-
and BAFF have shown preliminary positive results [45]. If these casian patients with refractory proteinuria, haematuria, active
preliminary results are confirmed, APRIL/BAFF inhibitors will histological lesions and rapid decline of kidney function [38–40,
likely become a first-line treatment in IgAN patients. These pos- 57]. In contrast, the combination with MMF allows a reduction in
itive reports contrast with the negative results of a trial with the doses and duration of corticosteroids [36]. Corticosteroids in
rituximab [46]. monotherapy (preferably using the reduced-dose protocol of the
 M. Praga et al. | 877

Downloaded from https://academic.oup.com/ndt/article/40/5/874/7926970 by ERA - Member Access user on 30 April 2025

Figure 1: Treatment algorithm for patients presenting with proteinuria/hematuria, with or without declining kidney function.

TESTING trial) [33] could be considered for young, non-obese pa- with immunosuppressive treatments. We recommend using RASi
tients with no predisposition to diabetes. On the other hand, since at BP-controlling doses, without additional treatment, for these
corticosteroid-like side effects are less common and severe with patients due to their favourable prognosis [9, 14]. However, regu-
Nefecon [42, 43], this drug seems a preferable option in older or lar follow-up is advised to monitor for any potential increase in
obese patients and in general in those with a profile prone to side proteinuria.
effects of corticosteroids.
A decline of kidney function in a patient with proteinuria and
haematuria should prompt immediate treatment with one of the Patients presenting with macroscopic
above-mentioned immunosuppressive/immunomodulatory op- haematuria (Fig. 2)
tions [39, 40, 57]. Likewise, we suggest rapidly initiating one of Up to 40–50% of IgAN patients refer an episode of gross haema-
these treatments in patients with nephrotic syndrome accompa- turia as the first manifestation of the disease [59], although its
nied by intense haematuria and active lesions on kidney biopsy prognostic significance remains uncertain. Typically, episodes of
even though kidney function is stable. This latter presentation is gross haematuria last between 2 and 5 days, although they can
more frequent in children and good results have been reported persist for several weeks in some cases.
with corticosteroids in monotherapy or combined with another We recommend repeating the laboratory workup if gross
immunosuppressant [58]. haematuria persists for >5 days and consider kidney biopsy (in
The different treatment pathways we propose do not nec- non-diagnosed patients) if visible haematuria persists >1 week.
essarily mean that sparsentan cannot be effective in patients The patient should be re-evaluated once macroscopic haematuria
with haematuria and active lesions or that immunosuppressive has disappeared. A kidney biopsy is generally indicated when sig-
agents cannot benefit patients with refractory proteinuria with- nificant proteinuria and microscopic haematuria persist after the
out haematuria. However, we think that our treatment algorithm episode.
better differentiates the main mechanisms of action of these Some patients present an acute kidney injury (AKI) of variable
drugs: counteracting glomerular hyperfiltration and proteinuria- severity coincidental with a gross haematuria outbreak [60–62].
induced tubulointerstitial damage (RASi, SGLT2i, ERA) on the one A kidney biopsy is required to rule out other diagnostic possi-
hand or decreasing the immunologic activity of the disease (cor- bilities. When IgAN is confirmed, intratubular RBC casts are the
ticosteroids, MMF, Nefecon). most relevant histological lesion. Tubular damage, induced by the
In aggressive cases that are refractory to the immunosuppres- haemoglobin released by intratubular erythrocytes, is thought to
sive treatments mentioned above, we recommend considering en- be the cause of AKI [60–62].
rolment in clinical trials for new therapies or initiate treatment A complete recovery of kidney function after visible haema-
with an anti-APRIL/BAFF drug or a complement blocker [44, 45, turia disappearance is observed in many patients, especially in
50–53]. the youngest [60]. However, a significant proportion of cases (up
Finally, some patients show persistent isolated microhaema- to 25% in some studies) show incomplete or no recovery of kidney
turia without accompanying significant proteinuria, either as an function [61]. Age >50 years, duration of haematuria >10 days,
initial presentation of the disease or after proteinuria resolution severity of tubular necrosis and the existence of CKD before the
878 | Nephrol Dial Transplant, 2025, Vol. 40, No. 5

Downloaded from https://academic.oup.com/ndt/article/40/5/874/7926970 by ERA - Member Access user on 30 April 2025

Figure 2: Recommendations for the management of patients presenting with macroscopic hematuria.

episode of haematuria are risk factors for this poor outcome [61]. 5 years after diagnosis [67]. It is important to differentiate RPI-
The prognosis is particularly catastrophic in elderly IgAN patients gAN from gross haematuria–induced AKI. In the latter, the most
[63]. remarkable histological findings are intratubular RBC casts with
For the management of gross haematuria–associated AKI, we acute tubular necrosis; crescents can be occasionally found, but
recommend supportive treatment. It is important to determine if in <30% of the glomeruli [60, 61].
the patient is receiving anticoagulant treatment, since IgAN is the Some patients with complete nephrotic syndrome (nephrotic-
most frequent underlying kidney pathology in anticoagulation- range proteinuria together with hypoalbuminaemia) exhibit pre-
related AKI [64]. In such cases, anticoagulation withdrawal should dominant or exclusive deposits of IgA on kidney biopsy, without
be considered on a case-by-case basis. Those patients in whom accompanying C3 deposits and with little or no mesangial prolifer-
gross haematuria persists for >2–3 weeks without kidney function ation. Electron microscopy shows extensive fusion of the podocyte
recovery pose a difficult therapeutic dilemma. Immunosuppres- foot processes. The response to corticosteroids and subsequent
sive treatment (corticosteroids, corticosteroids plus MMF) could disease course in these patients resemble those seen in minimal
be tried in young patients (especially if active glomerular lesions change disease. It is crucial to distinguish these individuals from
predominate in the kidney biopsy), although there is no published those who present with nephrotic syndrome accompanied by pro-
evidence in this regard. On the contrary, a retrospective study nounced haematuria and active lesions (M1, E1) in the kidney
showed no differences in the outcome of patients >50 years of biopsy.
age with haematuria-induced AKI who received conservative or Malignant hypertension (severe hypertension with haemor-
immunosuppressive treatments [65]. Patient and kidney survival rhages and exudates on funduscopic examination) is another rare
were remarkably poor in both groups and complications were presentation of IgAN [68]. IgAN accounted for 10% of patients
more common among the latter. in a large cohort of patients with malignant hypertension [69].
The prognosis is very poor, with most patients reaching ESKD
despite good BP control, and immunosuppression does not sig-
Atypical presentations (Fig. 3) nificantly alter this unfavourable outcome [68, 69]. Thrombotic
Rapidly progressive/crescentic IgAN (RPIgAN) is defined by a de- microangiopathy (TMA) lesions are found in most of these pa-
crease in eGFR >50% within 3 months alongside the presence of tients, although haematologic TMA (microangiopathic haemolytic
crescents in >30% of glomeruli. Patients with RPIgAN have sys- anaemia, thrombocytopaenia) is rare [68]. On the other hand, the
tematically been excluded from clinical trials, resulting in limited finding of TMA lesions (not included in the MEST-C score) ranges
treatment evidence. However, observational studies suggest that from 2 to 50% of kidney biopsies and confers a poor prognosis [49,
treatment with methylprednisolone pulses, followed by oral pred- 70, 71]. As in other types of TMA, evidence suggests a pathogenic
nisone and oral or intravenous cyclophosphamide, may be bene- role of complement dysregulation: intense deposits of comple-
ficial [66]. In cases of rapid kidney function decline that do not ment factors (C4d, C3d, C5b-9) and pathogenic variants in comple-
precisely meet the criteria for RPIgAN, favourable effects of corti- ment genes have been reported [72]. Intensive antihypertensive
costeroids and MMF have been reported [39, 40]. Nevertheless, the treatment (mainly based on RASi) is mandatory. Some reports sug-
prognosis of RPIgAN is poor, with >70% of patients reaching ESKD gest a beneficial effect of short courses of complement blockers
 M. Praga et al. | 879

Downloaded from https://academic.oup.com/ndt/article/40/5/874/7926970 by ERA - Member Access user on 30 April 2025

Figure 3: Atypical presentations of IgA nephropathy.

Figure 4: IgA nephropathy and pregnancy.

[73], but controlled studies are lacking. The effect of immunosup- patient [77]. Other authors prefer to stop RASis only when preg-
pressive or immunomodulatory treatments remains unknown. nancy is confirmed [76]. SGLT2i should be discontinued, as well as
sparsentan.
Pregnancy does not increase the risk of IgAN progression, at
IgAN and pregnancy (Fig. 4) least in early CKD stages [74]. Conversely, there is an increased risk
Proteinuria >1 g/day before or early in pregnancy is associated of pre-eclampsia and other adverse pregnancy outcomes (preterm
with worse pregnancy outcomes [74–76]. Therefore, it is advisable birth, small for gestational age newborn) [74, 76]. Low-dose aspirin
to plan pregnancies when the disease is in clinical remission. should be prescribed for pre-eclampsia prevention [76].
Most IgAN women are receiving RASis, drugs that should be If a significant increase in proteinuria is observed during preg-
avoided during pregnancy. We prefer to gradually discontinue nancy, it is essential to thoroughly evaluate potential causes
them before conception in order to assess proteinuria and BP af- (e.g. withdrawal of RASi at the onset of pregnancy, pregnancy-
ter RASi discontinuation. If proteinuria increases significantly, the associated hyperfiltration, weight gain). The soluble FMS-like
possible risks of pregnancy should be carefully discussed with the tyrosine kinase-1:placental growth factor ratio can be helpful for
880 | Nephrol Dial Transplant, 2025, Vol. 40, No. 5

Downloaded from https://academic.oup.com/ndt/article/40/5/874/7926970 by ERA - Member Access user on 30 April 2025

Figure 5: IgAN and kidney trasplantation.

differential diagnosis with pre-eclampsia after the 20th week of although clinical experience with this drug in transplant recipi-
pregnancy [78]. ents is currently lacking. Conversely, for patients with persistent
The risk of IgAN relapse during pregnancy is rare [76, 79]. In proteinuria ≥0.5–1 g/day, significant haematuria and/or active le-
patients with a clear suspicion of IgAN flare (glomerular haema- sions on kidney biopsy, we recommend a more aggressive thera-
turia, significant increase in proteinuria), short courses of cor- peutic approach. Potential options include high-dose intravenous
ticosteroids or azathioprine may be considered [76]. Tacrolimus pulses of corticosteroids (e.g. 0.5–1 g/day for 1–3 days), although
could be useful in primarily proteinuric relapses [80]. Hydroxy- the efficacy and safety of additional corticosteroid dosing remain
chloroquine [54] can be used in pregnancy, although there are no uncertain. The addition of Nefecon may represent a promising al-
specific reports in this context. ternative to consider. These therapies can be combined with up-
titration of MMF. Moreover, complement blockade—either with ip-
tacopan [50, 53] or anti-C5 therapy [51, 84]—may be particularly
IgAN and kidney transplantation (Fig. 5) appropriate in cases with concomitant TMA lesions.
Reported recurrence rates after kidney transplantation vary
widely in IgAN, from 9 to 61% [81]. This variability is likely influ-
enced by differences in follow-up length and institutional prac- CONCLUSION
tices related to allograft biopsy [82].
The treatment landscape for IgAN is undergoing a transformative
We advocate for close monitoring of IgAN patients following
shift, with novel therapies targeting diverse pathways involved in
kidney transplantation to facilitate early detection of potential
its complex pathogenesis. However, it is important to recognize
recurrence. Regular evaluation of urinary sediment at each visit
that IgAN presents in varied forms, many of which are underrep-
is particularly useful for detecting glomerular haematuria. When
resented in most clinical trials. While proteinuria levels are key to
proteinuria and haematuria are detected, a graft biopsy is needed
guiding therapeutic decisions, other factors such as the presence
to confirm recurrent IgAN. Likewise, if a graft biopsy is performed
and degree of haematuria, histological findings categorized by the
for any other indication in patients with IgAN in their native kid-
MEST-C score and the progression of kidney function should also
neys, we advise routine IF staining for IgA. If recurrent disease is
be considered in designing optimal treatment plans. Likewise, the
confirmed, the MEST-C score should be used for further assess-
mechanisms of action of currently available drugs must be care-
ment [13, 83].
fully evaluated to select the most appropriate treatments or ef-
Regarding treatment strategies, initial management should fo-
fective drug combinations. In this article we propose a set of ther-
cus on OCT alongside RASi up to the maximum tolerated doses.
apeutic algorithms tailored to the diverse clinical presentations of
For patients with persistent proteinuria ≥0.3 g/day, SGLT2i should
IgAN, grounded in these principles.
be added to prevent disease progression [20, 55]. For patients with
persistent proteinuria ≥0.5–1 g/day without significant haema-
turia or deteriorating kidney function, we suggest sparsentan [25],
 M. Praga et al. | 881

FUNDING docapillary hypercellularity, crescent score and renal out-

comes in immunoglobulin A nephropathy. Nephrol Dial Transplant
None declared.
2021;36:840–7. https://doi.org/10.1093/ndt/gfz267
11. Yu G-Z, Guo L, Dong J-F et al. Persistent hematuria and kidney
AUTHORS’ CONTRIBUTIONS disease progression in IgA nephropathy: a cohort study. Am J Kid-
ney Dis 2020;76:90–9. https://doi.org/10.1053/j.ajkd.2019.11.008
M.P. carried out the design and general coordination of the re- 12. Zand L, Fervenza FC, Coppo R. Microscopic hematuria as a risk
view. M.P. and F.C. designed the figures. All authors participated factor for IgAN progression: considering this biomarker in se-
in the discussions about treatment algorithms, developed at least lecting and monitoring patients. Clin Kidney J 2023;16:ii19–27.
one section of the manuscript, including the literature review, and https://doi.org/10.1093/ckj/sfad232
approved and signed the final document. 13. Trimarchi H, Barratt J, Cattran DC et al. Oxford classification
of IgA nephropathy 2016: an update from the IgA Nephropa-

Downloaded from https://academic.oup.com/ndt/article/40/5/874/7926970 by ERA - Member Access user on 30 April 2025

thy Classification Working Group. Kidney Int 2017;91:1014–21.
DATA AVAILABILITY STATEMENT
https://doi.org/10.1016/j.kint.2017.02.003
No new data were generated or analysed in support of this 14. Gutiérrez E, Zamora I, Ballarín JA et al. Long-term outcomes of
research. IgA nephropathy presenting with minimal or no proteinuria.
J Am Soc Nephrol 2012;23:1753–60. https://doi.org/10.1681/ASN.
2012010063
CONFLICT OF INTEREST STATEMENT 15. Li PKT, Ho KKL, Szeto CC et al. Prognostic indicators of IgA
M.P. reports fees from Alexion, Apellis, Vifor, GSK, Novartis, nephropathy in the Chinese—clinical and pathological perspec-
Otsuka, STADA and Travere and royalties from UpToDate. F.C.-F. tives. Nephrol Dial Transplant 2002;17:64–9. https://doi.org/10.
reports fees from Novartis and Apellis. H.T. reports fees from Cal- 1093/ndt/17.1.64
liditas, Travere, Chinook, Novartis, Otsuka, Hi-Bio, Vera, BioCryst, 16. Rauen T, Eitner F, Fitzner C et al. Intensive supportive care
Alpine-Vertex, Takeda, Sanofi, Alexion, Bayer, Dimerix and As- plus immunosuppression in IgA nephropathy. N Engl J Med
traZeneca. The remaining authors declare no conflicts of interest. 2015;373:2225–36. https://doi.org/10.1056/NEJMoa1415463
17. Rovin BH, Adler SG, Barratt J et al. Executive summary of the
KDIGO 2021 guideline for the management of glomerular dis-
REFERENCES eases. Kidney Int 2021;100:753–79. https://doi.org/10.1016/j.kint.
1. Floege J, Rauen T, Tang SCW. Current treatment of IgA 2021.05.015
nephropathy. Semin Immunopathol 2021;43:717–28. https://doi. 18. Praga M, Gutiérrez E, González E et al. Treatment of IgA
org/10.1007/s00281-021-00888-3 nephropathy with ACE inhibitors. J Am Soc Nephrol 2003;14:1578–
2. Cattran DC, Floege J, Coppo R. Evaluating progression risk in 83. https://doi.org/10.1097/01.ASN.0000068460.37369.DC
patients with immunoglobulin A nephropathy. Kidney Int Rep 19. Coppo R, Peruzzi L, Amore A et al. IgACE. J Am Soc Nephrol
2023;8:2515–28. https://doi.org/10.1016/j.ekir.2023.09.020 2007;18:1880–8. https://doi.org/10.1681/ASN.2006040347
3. El Karoui K, Fervenza FC, De Vriese AS. Treatment of 20. EMPA-KIDNEY Collaborative Group. Empagliflozin in patients
IgA nephropathy: a rapidly evolving field. J Am Soc Nephrol with chronic kidney disease. N Engl J Med 2023;388:117–27.
2024;35:103–16. https://doi.org/10.1681/ASN.0000000000000242 https://doi.org/10.1056/NEJMoa2204233
4. Reich HN, Troyanov S, Scholey JW et al. Remission of pro- 21. Heerspink HJL, Stefánsson BV, Correa-Rotter R et al. Da-
teinuria improves prognosis in IgA nephropathy. J Am pagliflozin in patients with chronic kidney disease. N Engl J Med
Soc Nephrol 2007;18:3177–83. https://doi.org/10.1681/ASN. 2020;383:1436–46. https://doi.org/10.1056/NEJMoa2024816
2007050526 22. Caravaca-Fontán F, Stevens K, Padrón M et al. Sodium-glucose
5. Inker LA, Heerspink HJL, Tighiouart H et al. Association of cotransporter 2 inhibition in primary and secondary glomeru-
treatment effects on early change in urine protein and treat- lonephritis. Nephrol Dial Transplant 2024;39:328–40. https://doi.
ment effects on GFR slope in IgA nephropathy: an individ- org/10.1093/ndt/gfad175
ual participant meta-analysis. Am J Kidney Dis 2021;78:340–9.e1. 23. Kohan DE, Barratt J, Heerspink HJL et al. Targeting the endothelin
https://doi.org/10.1053/j.ajkd.2021.03.007 A receptor in IgA nephropathy. Kidney Int Rep 2023;8:2198–210.
6. Pitcher D, Braddon F, Hendry B et al. Long-term outcomes in IgA https://doi.org/10.1016/j.ekir.2023.07.023
nephropathy. Clin J Am Soc Nephrol 2023;18:727–38. https://doi. 24. Heerspink HJL, Radhakrishnan J, Alpers CE et al. Sparsentan in
org/10.2215/CJN.0000000000000135 patients with IgA nephropathy: a prespecified interim analysis
7. Barbour SJ, Cattran DC, Espino-Hernandez G et al. Identifying from a randomised, double-blind, active-controlled clinical trial.
the ideal metric of proteinuria as a predictor of renal outcome Lancet 2023;401:1584–94. https://doi.org/10.1016/S0140-6736(23)
in idiopathic glomerulonephritis. Kidney Int 2015;88:1392–401. 00569-X
https://doi.org/10.1038/ki.2015.241 25. Rovin BH, Barratt J, Heerspink HJL et al. Efficacy and safety of
8. Coppo R, Troyanov S, Bellur S et al. Validation of the Oxford clas- sparsentan versus irbesartan in patients with IgA nephropathy
sification of IgA nephropathy in cohorts with different presenta- (PROTECT): 2-year results from a randomised, active-controlled,
tions and treatments. Kidney Int 2014;86:828–36. https://doi.org/ phase 3 trial. Lancet 2023;402:2077–90. https://doi.org/10.1016/
10.1038/ki.2014.63 S0140-6736(23)02302-4
9. Sevillano AM, Gutiérrez E, Yuste C et al. Remission of 26. Heerspink HJL, Jardine M, Kohan DE et al. Atrasentan in patients
hematuria improves renal survival in IgA nephropathy. with IgA nephropathy. N Engl J Med 2025;392:544–54. https://doi.
J Am Soc Nephrol 2017;28:3089–99. https://doi.org/10.1681/ASN. org/10.1056/NEJMoa2409415
2017010108 27. Yasmin F, Aamir M, Najeeb H et al. Efficacy and safety
10. Bobart SA, Alexander MP, Shawwa K et al. The associa- of finerenone in chronic kidney disease and type 2 di-
tion of microhematuria with mesangial hypercellularity, en- abetes patients: a systematic review and meta-analysis.
882 | Nephrol Dial Transplant, 2025, Vol. 40, No. 5

Ann Med Surg 2023;85:4973–80. https://doi.org/10.1097/MS9. 43. Lafayette R, Kristensen J, Stone A et al. Efficacy and safety of
0000000000001180 a targeted-release formulation of budesonide in patients with
28. Trujillo H, Caravaca-Fontán F, Caro J et al. The forgotten an- primary IgA nephropathy (NefIgArd): 2-year results from a ran-
tiproteinuric properties of diuretics. Am J Nephrol 2021;52: domised phase 3 trial. Lancet 2023;402:859–70. https://doi.org/
435–49. https://doi.org/10.1159/000517020 10.1016/S0140-6736(23)01554-4
29. Pozzi C, Bolasco P, Fogazzi G et al. Corticosteroids in 44. Mathur M, Barratt J, Chacko B et al. A phase 2 trial of
IgA nephropathy: a randomised controlled trial. Lancet sibeprenlimab in patients with IgA nephropathy. N Engl J Med
1999;353:883–7. https://doi.org/10.1016/S0140-6736(98)03563-6 2024;390:20–31. https://doi.org/10.1056/NEJMoa2305635
30. Tesar V, Troyanov S, Bellur S et al. Corticosteroids in IgA 45. Lafayette R, Barbour S, Israni R et al. A phase 2b, random-
nephropathy. J Am Soc Nephrol 2015;26:2248–58. https://doi.org/ ized, double-blind, placebo-controlled, clinical trial of atacicept
10.1681/ASN.2014070697 for treatment of IgA nephropathy. Kidney Int 2024;105:1306–15.
31. Rauen T, Wied S, Fitzner C et al. After ten years of follow-up, https://doi.org/10.1016/j.kint.2024.03.012

Downloaded from https://academic.oup.com/ndt/article/40/5/874/7926970 by ERA - Member Access user on 30 April 2025

no difference between supportive care plus immunosuppres- 46. Lafayette RA, Canetta PA, Rovin BH et al. A randomized, con-
sion and supportive care alone in IgA nephropathy. Kidney Int trolled trial of rituximab in IgA nephropathy with protein-
2020;98:1044–52. https://doi.org/10.1016/j.kint.2020.04.046 uria and renal dysfunction. J Am Soc Nephrol 2017;28:1306–13.
32. Lv J, Zhang H, Wong MG et al. Effect of oral methylprednisolone https://doi.org/10.1681/ASN.2016060640
on clinical outcomes in patients with IgA nephropathy. JAMA 47. Caravaca-Fontán F, Gutiérrez E, Sevillano ÁM et al. Targeting
2017;318:432–42. https://doi.org/10.1001/jama.2017.9362 complement in IgA nephropathy. Clin Kidney J 2023;16:ii28–39.
33. Lv J, Wong MG, Hladunewich MA et al. Effect of oral methyl- https://doi.org/10.1093/ckj/sfad198
prednisolone on decline in kidney function or kidney fail- 48. Espinosa M, Ortega R, Sánchez M et al. Association of C4d depo-
ure in patients with IgA nephropathy. JAMA 2022;327:1888–98. sition with clinical outcomes in IgA nephropathy. Clin J Am Soc
https://doi.org/10.1001/jama.2022.5368 Nephrol 2014;9:897–904. https://doi.org/10.2215/CJN.09710913
34. Dell’Oglio MP, Zaza G, Rossini M et al. The anti-fibrotic ef- 49. El Karoui K, Hill GS, Karras A et al. A clinicopathologic
fect of mycophenolic acid-induced neutral endopeptidase. study of thrombotic microangiopathy in IgA nephropathy.
J Am Soc Nephrol 2010;21:2157–68. https://doi.org/10.1681/ASN. J Am Soc Nephrol 2012;23:137–48. https://doi.org/10.1681/ASN.
2010020181 2010111130
35. Maes BD, Oyen R, Claes K et al. Mycophenolate mofetil in IgA 50. Zhang H, Rizk DV, Perkovic V et al. Results of a randomized
nephropathy: results of a 3-year prospective placebo-controlled double-blind placebo-controlled phase 2 study propose ipta-
randomized study. Kidney Int 2004;65:1842–9. https://doi.org/10. copan as an alternative complement pathway inhibitor for
1111/j.1523-1755.2004.00588.x IgA nephropathy. Kidney Int 2024;105:189–99. https://doi.org/10.
36. Hou J-H, Le W-B, Chen N et al. Mycophenolate mofetil combined 1016/j.kint.2023.09.027
with prednisone versus full-dose prednisone in IgA nephropa- 51. Lafayette R, Tumlin J, Fenoglio R et al. Efficacy and safety of
thy with active proliferative lesions: a randomized controlled ravulizumab in IgA nephropathy. A phase 2 randomized double-
trial. Am J Kidney Dis 2017;69:788–95. https://doi.org/10.1053/j. blind placebo-controlled trial. J Am Soc Nephrol 2024. https://doi.
ajkd.2016.11.027 org/10.1681/ASN.0000000534
37. Hou FF, Xie D, Wang J et al. Effectiveness of mycophenolate 52. Barratt J, Liew A, Yeo SC et al. Phase 2 trial of cemdisiran in
mofetil among patients with progressive IgA nephropathy: a adult patients with IgA nephropathy: a randomized controlled
randomized clinical trial. JAMA Netw Open 2023;6:e2254054. trial. Clin J Am Soc Nephrol 2024;19:452–62. https://doi.org/10.
https://doi.org/10.1001/jamanetworkopen.2022. 2215/CJN.0000000000000384
54054 53. Perkovic V, Barratt J, Rovin B et al. Alternative complement path-
38. Beckwith H, Medjeral-Thomas N, Galliford J et al. Mycophenolate way inhibition with iptacopan in IgA nephropathy. N Engl J Med
mofetil therapy in immunoglobulin A nephropathy: histological 2025;392:531–43. https://doi.org/10.1056/NEJMoa2410316.
changes after treatment. Nephrol Dial Transplant 2017;32:i123–8. 54. Liu L-J, Yang Y-Z, Shi S-F et al. Effects of hydroxychloroquine
https://doi.org/10.1093/ndt/gfw326 on proteinuria in IgA nephropathy: a randomized controlled
39. Miao J, Duriseti P, Radhakrishnan Y et al. Mycophenolate mofetil trial. Am J Kidney Dis 2019;74:15–22. https://doi.org/10.1053/j.
and steroid for treatment of patients with IgA nephropathy. Kid- ajkd.2019.01.026
ney Int Rep 2024;9:182–5. https://doi.org/10.1016/j.ekir.2023.10. 55. Wheeler DC, Toto RD, Stefánsson BV et al. A pre-specified anal-
015 ysis of the DAPA-CKD trial demonstrates the effects of da-
40. Huerta A, Mérida E, Medina L et al. Corticosteroids and mycophe- pagliflozin on major adverse kidney events in patients with
nolic acid analogues in immunoglobulin A nephropathy with IgA nephropathy. Kidney Int 2021;100:215–24. https://doi.org/10.
progressive decline in kidney function. Clin Kidney J 2022;15:771– 1016/j.kint.2021.03.033
7. https://doi.org/10.1093/ckj/sfab244 56. Tesar V, Troyanov S, Bellur S et al. Corticosteroids in IgA
41. Fellström BC, Barratt J, Cook H et al. Targeted-release budesonide nephropathy: a retrospective analysis from the VALIGA study.
versus placebo in patients with IgA nephropathy (NEFIGAN): J Am Soc Nephrol 2015;26:2248–58. https://doi.org/10.1681/ASN.
a double-blind, randomised, placebo-controlled phase 2b trial. 2014070697
Lancet 2017;389:2117–27. https://doi.org/10.1016/S0140-6736(17) 57. Chen Y, Li Y, Yang S et al. Efficacy and safety of mycophenolate
30550-0 mofetil treatment in IgA nephropathy: a systematic review. BMC
42. Barratt J, Lafayette R, Kristensen J et al. Results from part A of Nephrol 2014;15:193. https://doi.org/10.1186/1471-2369-15-193
the multi-center, double-blind, randomized, placebo-controlled 58. Shima Y, Nakanishi K, Sato M et al. IgA nephropathy with presen-
NefIgArd trial, which evaluated targeted-release formulation tation of nephrotic syndrome at onset in children. Pediatr Nephrol
of budesonide for the treatment of primary immunoglobulin 2017;32:457–65. https://doi.org/10.1007/s00467-016-3502-6
A nephropathy. Kidney Int 2023;103:391–402. https://doi.org/10. 59. Lai KN, Tang SCW, Schena FP et al. IgA nephropathy. Nat Rev Dis
1016/j.kint.2022.09.017 Prim 2016;2:16001. https://doi.org/10.1038/nrdp.2016.1
 M. Praga et al. | 883

60. Praga M, Gutierrez-Millet V, Navas JJ et al. Acute worsening of 73. Nakamura H, Anayama M, Makino M et al. Atypical hemolytic
renal function during episodes of macroscopic hematuria in IgA uremic syndrome associated with complement factor H muta-
nephropathy. Kidney Int 1985;28:69–74. https://doi.org/10.1038/ tion and IgA nephropathy: a case report successfully treated
ki.1985.120 with eculizumab. Nephron 2018;138:324–7. https://doi.org/10.
61. Gutiérrez E, González E, Hernández E et al. Factors that 1159/000485194
determine an incomplete recovery of renal function in 74. Piccoli GB, Kooij IA, Attini R et al. A systematic review
macrohematuria-induced acute renal failure of IgA nephropa- on materno-foetal outcomes in pregnant women with IgA
thy. Clin J Am Soc Nephrol 2007;2:51–7. nephropathy: a case of “late-maternal” preeclampsia? J Clin Med
62. Moreno JA, Martín-Cleary C, Gutiérrez E et al. AKI associated 2018;7:212. https://doi.org/10.3390/jcm7080212
with macroscopic glomerular hematuria: clinical and patho- 75. Oh HJ, Han SH, Yoo DE et al. Reduced pre-pregnancy protein-
physiologic consequences. Clin J Am Soc Nephrol 2012;7:175–84. uria is associated with improving postnatal maternal renal out-
https://doi.org/10.2215/CJN.01970211 comes in IgA nephropathy women. Clin Nephrol 2011;76:447–54.

Downloaded from https://academic.oup.com/ndt/article/40/5/874/7926970 by ERA - Member Access user on 30 April 2025

63. Sevillano AM, Diaz M, Caravaca-Fontán F et al. IgA nephropathy https://doi.org/10.5414/CN107208
in elderly patients. Clin J Am Soc Nephrol 2019;14:1183–92. https: 76. Fakhouri F, Schwotzer N, Cabiddu G et al. Glomerular diseases
//doi.org/10.2215/CJN.13251118 in pregnancy: pragmatic recommendations for clinical manage-
64. Trujillo H, Sandino J, Cavero T et al. IgA nephropathy is the most ment. Kidney Int 2023;103:264–81. https://doi.org/10.1016/j.kint.
common underlying disease in patients with anticoagulant- 2022.10.029
related nephropathy. Kidney Int Rep 2022;7:831–40. https://doi. 77. Da Silva I, Orozco-Guillén A, Longhitano E et al. Pre-gestational
org/10.1016/j.ekir.2022.01.1048 counselling for women living with CKD: starting from the bright
65. Sevillano AM, Caravaca-Fontán F, Cordero Garcia-Galan L et al. side. Clin Kidney J 2024;17:sfae084. https://doi.org/10.1093/ckj/
Effect of immunosuppressive treatments on kidney outcomes sfae084
after gross hematuria-related acute kidney injury in older pa- 78. Rolfo A, Attini R, Tavassoli E et al. Is it possible to differen-
tients with IgA nephropathy. Kidney Int Rep 2023;8:1596–604. tiate chronic kidney disease and preeclampsia by means of
https://doi.org/10.1016/j.ekir.2023.05.027 new and old biomarkers? A prospective study. Dis Markers
66. Tumlin JA, Lohavichan V, Hennigar R. Crescentic, proliferative 2015;2015:127083. https://doi.org/10.1155/2015/127083
IgA nephropathy: clinical and histological response to methyl- 79. Isaacs JD, Evans DJ, Pusey CD. Mesangial IgA disease with
prednisolone and intravenous cyclophosphamide. Nephrol Dial crescent formation during pregnancy: postpartum treatment
Transplant 2003;18:1321–9. https://doi.org/10.1093/ndt/gfg081 with immunosuppression. Nephrol Dial Transplant 1990;5:619–22.
67. Lv J, Yang Y, Zhang H et al. Prediction of outcomes in crescentic https://doi.org/10.1093/ndt/5.8.619
IgA nephropathy in a multicenter cohort study. J Am Soc Nephrol 80. Hu T, Liu Q, Xu Q et al. Tacrolimus decreases protein-
2013;24:2118–25. https://doi.org/10.1681/ASN.2012101017 uria in patients with refractory IgA nephropathy. Medicine
68. Sevillano ÁM, Cabrera J, Gutiérrez E et al. Malignant hyperten- (Baltimore) 2018;97:e0610. https://doi.org/10.1097/MD.00000000
sion: a type of IgA nephropathy manifestation with poor prog- 00010610
nosis. Nefrologia 2015;35:42–9. 81. Uffing A, Pérez-Saéz MJ, Jouve T et al. Recurrence of IgA
69. Cavero T, Auñón P, Caravaca-Fontán F et al. Thrombotic nephropathy after kidney transplantation in adults. Clin J
microangiopathy in patients with malignant hypertension. Am Soc Nephrol 2021;16:1247–55. https://doi.org/10.2215/CJN.
Nephrol Dial Transplant 2023;38:1217–26. https://doi.org/10.1093/ 00910121
ndt/gfac248 82. Cosio FG, Cattran DC. Recent advances in our understanding of
70. Cai Q, Shi S, Wang S et al. Microangiopathic lesions in IgA recurrent primary glomerulonephritis after kidney transplan-
nephropathy: a cohort study. Am J Kidney Dis 2019;74:629–39. tation. Kidney Int 2017;91:304–14. https://doi.org/10.1016/j.kint.
https://doi.org/10.1053/j.ajkd.2019.03.416 2016.08.030
71. Trimarchi H, Coppo R. Glomerular endothelial activation, C4d 83. Park S, Go H, Baek CH et al. Clinical importance of the updated
deposits and microangiopathy in immunoglobulin A nephropa- Oxford classification in allograft IgA nephropathy. Am J Trans-
thy. Nephrol Dial Transplant 2021;36:581–6. https://doi.org/10. plant 2019;19:2855–64. https://doi.org/10.1111/ajt.15400
1093/ndt/gfz241 84. Duval A, Olagne J, Obrecht A et al. Eculizumab as a therapeu-
72. Li J, Guo L, Shi S et al. The role of complement in microangio- tic approach for severe crescentic recurrence of immunoglobu-
pathic lesions of IgA nephropathy. Kidney Int Rep 2022;7:1219–28. lin A nephropathy after kidney transplantation. Am J Transplant
https://doi.org/10.1016/j.ekir.2022.03.028 2023;23:1626–30. https://doi.org/10.1016/j.ajt.2023.05.031

Received: October 20, 2024; Editorial decision: December 7, 2024

© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.
All rights reserved. For permissions, please e-mail: journals.permissions@oup.com