Evidence map›Paper›PMID 41781699›Full record

ArticlePediatric nephrology (Berlin, Germany)2026

Clinical course of proteinuria due to cubilin variants: a large multicenter pediatric cohort.

Neslihan Cicek, Ceren Alavanda, Ayse Seda Pınarbası, Aylin Inal, Bahriye Atmıs, Secil Kezer, Mehtap Akbalik Kara, Okan Akaci, Serim Pul, Sevcan Hatipoglu and 12 more

Abstract readMulticenter Study
In one paragraph

Article in Pediatric nephrology (Berlin, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Neslihan CicekDepartment of Pediatric Nephrology, Marmara University School of Medicine, Fevzi Çakmak Mahallesi Muhsin Yazıcıoğlu Caddesi No:10, Ust Kaynarca, Pendik, Istanbul, Türkiye. drneslihancicek@yahoo.com.ORCID http://orcid.org/0000-0002-5859-4177
Ceren AlavandaDepartment of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye.ORCID http://orcid.org/0000-0002-7327-3849
Ayse Seda PınarbasıDepartment of Pediatric Nephrology, Diyarbakir Childrens' Hospital, Diyarbakır, Türkiye.ORCID http://orcid.org/0000-0002-2443-4378
Aylin InalDepartment of Pediatric Nephrology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.ORCID http://orcid.org/0000-0002-1164-734X
Bahriye AtmısDepartment of Pediatric Nephrology, Faculty of Medicine, Cukurova University, Adana, Türkiye.ORCID http://orcid.org/0000-0002-1133-4845
Secil KezerDepartment of Pediatric Nephrology, Bagcılar Training and Research Hospital, Istanbul, Türkiye.ORCID http://orcid.org/0000-0002-5828-331X
Mehtap Akbalik KaraDepartment of Pediatric Nephrology, Faculty of Medicine, Gaziantep University, Gaziantep, Türkiye.ORCID http://orcid.org/0000-0003-0790-323X
Okan AkaciDepartment of Pediatric Nephrology, University of Health Sciences, Bursa Yuksek Ihtisas Training and Reseach Hospital, Bursa, Türkiye.ORCID http://orcid.org/0000-0002-2148-1160
Serim PulDepartment of Pediatric Nephrology, Umraniye Training and Research Hospital, Istanbul, Türkiye.ORCID http://orcid.org/0000-0001-6896-404X
Sevcan HatipogluDepartment of Pediatric Nephrology, Faculty of Medicine, Dokuz Eylül University, Izmir, Türkiye.ORCID http://orcid.org/0000-0002-6438-2015
Zeynep Nagehan Yuruk YildirimDepartment of Pediatric Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye.ORCID http://orcid.org/0000-0003-2891-2231
Ayse AgbasDepartment of Pediatric Nephrology, Cerrahpaşa Faculty of Medicine, Istanbul University, Istanbul, Türkiye.ORCID http://orcid.org/0000-0002-3658-8622
Emre LeventogluDepartment of Pediatric Nephrology, Konya City Hospital, Konya, Türkiye.ORCID http://orcid.org/0000-0002-0504-7911
Ilknur GirisgenDepartment of Pediatric Nephrology, Faculty of Medicine, Pamukkale University, Denizli, Türkiye.ORCID http://orcid.org/0000-0003-2617-4466
Mehtap KayaDepartment of Pediatric Nephrology, University of Health Sciences Kartal Dr. Lutfi Kırdar City Hospital, Istanbul, Türkiye.ORCID http://orcid.org/0000-0002-6750-5172
Nimet Sasmaz NurdagDepartment of Pediatric Nephrology, Faculty of Medicine, Cukurova University, Adana, Türkiye.ORCID http://orcid.org/0000-0002-8162-3677
Sercin GuvenDepartment of Pediatric Nephrology, Marmara University School of Medicine, Fevzi Çakmak Mahallesi Muhsin Yazıcıoğlu Caddesi No:10, Ust Kaynarca, Pendik, Istanbul, Türkiye.ORCID http://orcid.org/0000-0003-3284-9204
Ozde Nisa TurkkanDepartment of Pediatric Nephrology, Marmara University School of Medicine, Fevzi Çakmak Mahallesi Muhsin Yazıcıoğlu Caddesi No:10, Ust Kaynarca, Pendik, Istanbul, Türkiye.ORCID http://orcid.org/0000-0003-2928-9031
Nurdan YildizDepartment of Pediatric Nephrology, Marmara University School of Medicine, Fevzi Çakmak Mahallesi Muhsin Yazıcıoğlu Caddesi No:10, Ust Kaynarca, Pendik, Istanbul, Türkiye.ORCID http://orcid.org/0000-0001-6805-5313
Pinar AtaDepartment of Medical Genetics, Marmara University School of Medicine, Istanbul, Turkey.ORCID http://orcid.org/0000-0002-6688-2347
Ismail DursunDepartment of Pediatric Nephrology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye.ORCID http://orcid.org/0000-0002-0191-4344
Ibrahim GokceDepartment of Pediatric Nephrology, Marmara University School of Medicine, Fevzi Çakmak Mahallesi Muhsin Yazıcıoğlu Caddesi No:10, Ust Kaynarca, Pendik, Istanbul, Türkiye.ORCID http://orcid.org/0000-0002-6896-5162

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionWe aimed to evaluate the clinical and genetic characteristics and clinical course of children with persistent proteinuria associated with CUBN variants.

methodsForty-eight children with CUBN variants from 15 pediatric nephrology centers were included. Patients' characteristics, serum creatinine, albumin, hemoglobin, vitamin B12 levels, urinalysis, spot urine protein/creatinine (uPCR), microalbumin/creatinine (uACR), beta-2 microglobulin/creatinine (uBMCR) ratios, estimated glomerular filtration rates (eGFRs), treatments, kidney biopsies, and genetic findings were evaluated.

resultsAll patients had normal serum albumin and creatinine and preserved eGFR. There was no significant change in eGFR between the first and last visits (p = 0.15), whereas uPCR was lower at the last visit (p = 0.001). Kidney biopsy was performed in 13 (27%); light microscopy was normal in all except one patient with focal segmental glomerulosclerosis (FSGS). Thirty-five patients (72.9%) had ACEi/ARB therapy, which was discontinued in 21 patients without subsequent worsening of proteinuria. Overall, 26 distinct CUBN variants were identified, predominantly in the C-terminal region. The most frequent variant was c.10102A > G (p.Met3368Val). Variant types included 15 (57.7%) missense, 7 (27%) nonsense, 3 (11.5%) splicing, and 1 (3.8%) frameshift variants.

conclusionsIn this multicenter, large pediatric cohort, proteinuria associated with CUBN variants generally followed a benign course over short to mid-term follow-up even without sustained ACEi/ARB therapy. Embedding targeted CUBN testing into the evaluation of children with asymptomatic proteinuria and normal kidney function may reduce unnecessary kidney biopsies and prolonged medication, while improving family counseling. We outline a stepwise care pathway → early genetic screening → conservative monitoring with periodic eGFR and proteinuria assessment → consideration of ACEi/ARB discontinuation and recommend prospective validation and cost-effectiveness studies.

Indexed as

ProteinuriaReceptors, Cell SurfaceAdolescentBiopsyChildChild, PreschoolFemaleGlomerular Filtration RateHumansInfantKidneyMaleintrinsic factor-cobalamin receptorReceptors, Cell SurfaceChildrenCubilinCUBNProteinuria

Identifiers

PMID41781699
PMCPMC13197286

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.