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Longitudinal analysis of blood pressure and lipids in childhood nephrotic syndrome

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Abstract

Background

In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that hypertensive BP and dyslipidemia would persist in children with nephrotic syndrome, regardless of steroid treatment response.

Methods

A multi-center longitudinal observational analysis of data obtained from children < 19 years of age with new onset nephrotic syndrome enrolled in the Nephrotic Syndrome Study Network (cNEPTUNE) was conducted. BP and lipid data were examined over time stratified by disease activity and steroid exposure. Generalized estimating equation regressions were used to find determinants of hypertensive BP and dyslipidemia.

Results

Among 122 children, the prevalence of hypertensive BP at any visit ranged from 17.4% to 57.4%, while dyslipidemia prevalence ranged from 40.0% to 96.2% over a median of 30 months of follow-up. Hypertensive BP was found in 46.2% (116/251) of study visits during active disease compared with 31.0% (84/271) of visits while in remission. Dyslipidemia was present in 88.2% (120/136) of study visits during active disease and in 66.0% (101/153) while in remission. Neither dyslipidemia nor hypertensive BP were significantly different with/without medication exposure (steroids and/or CNI). In regression analysis, male sex and urine protein:creatinine ratio (UPC) were significant determinants of hypertensive BP over time, while eGFR was found to be a determinant of dyslipidemia over time.

Conclusions

Results demonstrate persistent hypertensive BPs and unfavorable lipid profiles in the cNEPTUNE cohort regardless of remission status or concurrent steroid or calcineurin inhibitor treatment.

Graphical abstract

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Data availability

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Abbreviations

BP:

Blood pressure

CKD:

Chronic kidney disease

CVD:

Cardiovascular disease

ISKDC:

International Study of Kidney Disease in Children

MCD:

Minimal change disease

FSGS:

Focal segmental glomerulosclerosis

MN:

Membranous nephropathy

NEPTUNE:

Nephrotic Syndrome Study Network

HDL:

High density lipoprotein

LDL:

Low-density lipoprotein

BMI:

Body mass index

eGFR:

estimated Glomerular filtration rate

GEE:

Generalized Estimating Equation

IR:

Infrequently relapsing

FRSD:

Frequently relapsing steroid dependent

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Acknowledgements

We would like to acknowledge the NEPTUNE sites:

Cleveland Clinic, Cleveland, OH: K Dell*, J Sedor**, M Schachere#, J Negrey#

Children’s Hospital, Los Angeles, CA: K Lemley*, J Scott#

Children’s Mercy Hospital, Kansas City, MO: T Srivastava*, S Morrison

Cohen Children’s Hospital, New Hyde Park, NY: C Sethna*, M Pfaiff#

Columbia University, New York, NY: P Canetta*, A Pradhan#

Emory University, Atlanta, GA: L Greenbaum*, C Wang**, E Yun#

Harbor-University of California Los Angeles Medical Center: S Adler*, J LaPage#

John H. Stroger Jr. Hospital of Cook County, Chicago, IL: A Athavale*, M Itteera

Johns Hopkins Medicine, Baltimore, MD: M Atkinson*, T Dell#

Mayo Clinic, Rochester, MN: F Fervenza*, M Hogan**, J Lieske*, G Hill#

Montefiore Medical Center, Bronx, NY: F Kaskel*, M Ross*, P Flynn#

NIDDK Intramural, Bethesda MD: J Kopp*

New York University Medical Center, New York, NY: L Malaga-Dieguez*, O Zhdanova**, F Modersitzki#, L Pehrson#

Stanford University, Stanford, CA: R Lafayette*, B Yeung#

Temple University, Philadelphia, PA: I Lee*, S Quinn-Boyle#

University Health Network Toronto: H Reich *, M Hladunewich**, P Ling#, M Romano#

University of Miami, Miami, FL: A Fornoni*, C Bidot#

University of Michigan, Ann Arbor, MI: M Kretzler*, D Gipson*, A Williams#, C Klida#

University of North Carolina, Chapel Hill, NC: V Derebail*, K Gibson*, A Froment#, F Ochoa-Toro#

University of Pennsylvania, Philadelphia, PA: L Holzman*, K Meyers**, K Kallem#, A Swenson#

University of Texas Southwestern, Dallas, TX: K Sambandam*, K Aleman#, M Rogers#

University of Washington, Seattle, WA: A Jefferson*, S Hingorani**, K Tuttle**§, L Manahan#, E Pao#, A Cooper#§

Wake Forest University Baptist Health, Winston-Salem, NC: JJ Lin*, Stefanie Baker#

Data analysis and coordinating center: M Kretzler*, L Barisoni**, C Gadegbeku**, B Gillespie**, D Gipson**, L Holzman**, L Mariani**, M Sampson**, J Sedor**, J Zee**, G Alter, H Desmond, S Eddy, D Fermin, M Larkina, S Li, S Li, CC Lienczewski, T Mainieri, R Scherr, A Smith, A Szymanski, A Williams.

Digital pathology committee: Carmen Avila-Casado (University Health Network, Toronto), Serena Bagnasco (Johns Hopkins University), Joseph Gaut (Washington University in St Louis), Stephen Hewitt (National Cancer Institute), Jeff Hodgin (University of Michigan), Kevin Lemley (Children’s Hospital of Los Angeles), Laura Mariani (University of Michigan), Matthew Palmer (University of Pennsylvania), Avi Rosenberg (Johns Hopkins University), Virginie Royal (University of Montreal), David Thomas (University of Miami), Jarcy Zee (University of Pennsylvania) Co-Chairs: Laura Barisoni (Duke University) and Cynthia Nast (Cedar Sinai).

*Principal Investigator; **Co-investigator; #Study Coordinator

§Providence Medical Research Center, Spokane, WA

Funding

The Nephrotic Syndrome Study Network (NEPTUNE) is part of the Rare Diseases Clinical Research Network (RDCRN), which is funded by the National Institutes of Health (NIH) and led by the National Center for Advancing Translational Sciences (NCATS) through its Division of Rare Diseases Research Innovation (DRDRI). NEPTUNE is funded under grant number U54DK083912 as a collaboration between NCATS and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Additional funding and/or programmatic support is provided by the University of Michigan, NephCure Kidney International and the Halpin Foundation. RDCRN consortia are supported by the RDCRN Data Management and Coordinating Center (DMCC), funded by NCATS and the National Institute of Neurological Disorders and Stroke (NINDS) under U2CTR002818. Dr. Sethna is supported by NIH/NHLBI 1R01HL162912-01A1 and NIH/NIDDK R01DK131091. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Role of funder/sponsor: All funders had no role in the design and conduct of the study.

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics, Cohen Children’s Medical Center of NY, New Hyde Park, NY, USA

    Johnathon Carboni & Christine B. Sethna

  2. Division of Nephrology, Department of Pediatrics, Dell Children’s Medical Center, University of Texas, Austin, TX, USA

    Elizabeth Thomas

  3. Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA

    Debbie S. Gipson & Howard Trachtman

  4. Division of Nephrology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Tammy M. Brady

  5. Section of Nephrology, Children’s Mercy Hospital and University of Missouri, Kansas City, MO, USA

    Tarak Srivastava

  6. Division of Pediatric Nephrology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA

    David T. Selewski

  7. Division of Nephrology, Department of Pediatrics, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA

    Larry A. Greenbaum & Chia-shi Wang

  8. Center for Pediatric Nephrology and Hypertension, Cleveland Clinic Children’s, Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA

    Katherine M. Dell

  9. Division of Nephrology, Department of Pediatrics, Children’s Hospital at Montefiore, Bronx, NY, USA

    Frederick Kaskel & Kimberly Reidy

  10. Division of Nephrology, Department of Pediatrics, Levine Children’s Hospital, Charlotte, NC, USA

    Susan Massengill

  11. Division of Pediatric Nephrology, Department of Pediatrics and Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA

    Cheryl L. Tran

  12. Division of Nephrology, Department of Pediatrics, Stanford University, Palo Alto, CA, USA

    Richard Lafayette

  13. Division of Nephrology, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Salem Almaani

  14. Division of Nephrology, Department of Pediatrics, University of Washington, Seattle, WA, USA

    Sangeeta Hingorani

  15. Department of Pediatrics, Division of Nephrology, Duke University Medical Center, Durham, NC, USA

    Rasheed Gbadegesin

  16. Division of Pediatric Nephrology, UNC Kidney Center, Chapel Hill, North Carolina, USA

    Keisha L. Gibson

Authors
  1. Johnathon Carboni
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  2. Elizabeth Thomas
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  3. Debbie S. Gipson
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  4. Tammy M. Brady
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  5. Tarak Srivastava
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  6. David T. Selewski
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  7. Larry A. Greenbaum
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  8. Chia-shi Wang
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  9. Katherine M. Dell
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  10. Frederick Kaskel
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  11. Susan Massengill
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  12. Kimberly Reidy
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  13. Cheryl L. Tran
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  14. Howard Trachtman
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  15. Richard Lafayette
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  16. Salem Almaani
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  17. Sangeeta Hingorani
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  18. Rasheed Gbadegesin
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  19. Keisha L. Gibson
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  20. Christine B. Sethna
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Consortia

on behalf of the Nephrotic Syndrome Study Network (NEPTUNE)*

  • K. Dell
  • , J. Sedor
  • , M. Schachere
  • , J. Negrey
  • , K. Lemley
  • , J. Scott
  • , T. Srivastava
  • , S. Morrison
  • , C. Sethna
  • , M. Pfaiff
  • , P. Canetta
  • , A. Pradhan
  • , L. Greenbaum
  • , C. Wang
  • , E. Yun
  • , S. Adler
  • , J. LaPage
  • , A. Athavale
  • , M. Itteera
  • , M. Atkinson
  • , T. Dell
  • , F. Fervenza
  • , M. Hogan
  • , J. Lieske
  • , G. Hill
  • , F. Kaskel
  • , M. Ross
  • , P. Flynn
  • , J. Kopp
  • , L. Malaga-Dieguez
  • , O. Zhdanova
  • , F. Modersitzki
  • , L. Pehrson
  • , R. Lafayette
  • , B. Yeung
  • , I. Lee
  • , S. Quinn-Boyle
  • , H. Reich
  • , M. Hladunewich
  • , P. Ling
  • , M. Romano
  • , A. Fornoni
  • , C. Bidot
  • , M. Kretzler
  • , D. Gipson
  • , A. Williams
  • , C. Klida
  • , V. Derebail
  • , K. Gibson
  • , A. Froment
  • , F. Ochoa-Toro
  • , L. Holzman
  • , K. Meyers
  • , K. Kallem
  • , A. Swenson
  • , K. Sambandam
  • , K. Aleman
  • , M. Rogers
  • , A. Jefferson
  • , S. Hingorani
  • , K. Tuttle
  • , L. Manahan
  • , E. Pao
  • , A. Cooper
  • , J. J. Lin
  • , Stefanie Baker
  • , M. Kretzler
  • , L. Barisoni
  • , C. Gadegbeku
  • , B. Gillespie
  • , D. Gipson
  • , L. Holzman
  • , L. Mariani
  • , M. Sampson
  • , J. Sedor
  • , J. Zee
  • , G. Alter
  • , H. Desmond
  • , S. Eddy
  • , D. Fermin
  • , M. Larkina
  • , S. Li
  • , C. C. Lienczewski
  • , T. Mainieri
  • , R. Scherr
  • , A. Smith
  • , A. Szymanski
  • , A. Williams
  • , Carmen Avila-Casado
  • , Serena Bagnasco
  • , Joseph Gaut
  • , Stephen Hewitt
  • , Jeff Hodgin
  • , Kevin Lemley
  • , Laura Mariani
  • , Matthew Palmer
  • , Avi Rosenberg
  • , Virginie Royal
  • , David Thomas
  • , Jarcy Zee
  • , Laura Barisoni
  •  & Cynthia Nast

Contributions

Dr Christine Sethna and Johnathon Carboni conceptualized and designed the study, collected data, carried out the data analysis/interpretation and statistical analysis, drafted the initial manuscript, and critically reviewed and revised the manuscript. Drs Elizabeth Thomas, Debbie S. Gipson, Tammy M. Brady, Tarak Srivastava, David T Selewski, Larry A. Greenbaum, Chia-shi Wang, Katherine M Dell, Frederick Kaskel, Susan Massengill, Kimberly Reidy, Cheryl L. Tran, Howard Trachtman, Richard Lafayette, Salem Almaani, Sangeeta Hingorani, Rasheed Gbadegesin, Keisha L. Gibson conceptualized and designed the study, collected data, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Christine B. Sethna.

Ethics declarations

Ethics approval

NEPTUNE was approved by the Institutional Review Board at each participating site and written informed consent/assent was obtained from each participant. This study protocol was reviewed and approved by University of Michigan Medical School (IRBMED), approval number HUM00158219.

Conflicts of interest

Christine Sethna has been on an advisory board for Travere Therapeutics. Larry Greenbaum receives research support from Alexion, Advicenne, Abbvie, Apelis, Aurinia, Reata Pharmaceuticals, Vertex, Roche, and Otsuka; Larry Greenbaum provides consulting for Novartis, Alexion, Roche, Aurinia, and Otsuka. Chia-shi Wang receives research support from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under Award Number K23DK118189, NephCure Kidney International (NKI), Boehringer-Ingelheim, and IQVIA outside the submitted work. Richard Lafayette provides consulting for Alexion, GSK, Aurinia, Calliditas, Chinook, Vera, Novartis, Omeros, Chemocentryx, Travere; Richard Lafayette receives research support from Alexion, Calliditas, Chinook, Vera, Novartis, Omeros, Chemocentryx, Travere, Roche, and Pfizer. Tarak Srivastava has received research funding from Roche, Apellis Pharmaceuticals, and Travere Therapeutics. The other authors have no relevant conflicts to disclose.

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Carboni, J., Thomas, E., Gipson, D.S. et al. Longitudinal analysis of blood pressure and lipids in childhood nephrotic syndrome. Pediatr Nephrol 39, 2161–2170 (2024). https://doi.org/10.1007/s00467-024-06301-z

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