Nephrology Commons^™

Polygenic Risk Scores And Hla Class Ii Variants Are Biomarkers Of Corticosteroid Response In Childhood Nephrotic Syndrome., Tiffany Tu, Alejandro Ochoa, Amika Sood, Ashley Dabrik, Megan Chryst-Stangl, Brandon Lane, Guanghong Wu, Frank Donovan, Ursula Harper, Settara Chandrasekharappa, Christopher Esezobor, Adaobi Solarin, David Hooper, Christine Sethna, Sandra Amaral, Mahmoud Kallash, Michelle Rheault, Priya Verghese, Vikas Dharnidharka, Eloise Salmon, Patricia Weng, Tarak Srivastava, Michael E Seifert, Cozumel Pruette, David Selewski, Keisha Gibson, Tracy Hunley, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arvind Bagga, Aditi Sinha, Nicholas Webb, Larry Greenbaum, Ali Gharavi, Krzysztof Kiryluk, Matthias Kretzler, Lisa Guay-Woodford, Simone Sanna-Cherchi, Agnieszka Bierzynska, Ania Koziell, Gavin Welsh, Moin Saleem, Charles Rotimi, Eileen Chambers, Cliburn Chan, Curegn Consortium, Pnrc Glomerular Disease Group, Cibmtr/Nmdp Consortium, Annette Jackson, Adebowale Adeyemo, Rasheed Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Nephrotic syndrome (NS), a common glomerular disease in children, is classified based on response to corticosteroid therapy as either steroid-sensitive nephrotic syndrome (SSNS), or steroid-resistant nephrotic syndrome (SRNS). However, there are no current reliable predictors of therapy response at initial clinical presentation.

METHODS: To evaluate predictors, we conducted genome-wide association studies, developed polygenic risk scores (PRS) for therapy response and analyzed classical HLA alleles in 1,997 children (994 discovery and 1,003 replication/validation cohorts) previously unstudied children with NS and 3,558 ancestry-matched control individuals.

RESULTS: A significant association with HLA loci defined by variants in HLA-DQB1, HLA-DRB1, and HLA-DQA1 were …

Diabetic Nephropathy Masquerading As Systemic Disease: The Critical Role Of Renal Biopsy In A Young Uninsured Woman With Nephrotic Syndrome, Yolanda V. Gutierrez, Alexis Vargas Del Toro, Cristina Kochi Yamamoto, Jose Loayza Pintado, Andres Suarez-Parraga

School of Medicine Publications

Nephrotic syndrome can have overlapping features across multiple diseases, making diagnosis difficult without tissue confirmation. We describe a 30-year-old uninsured Hispanic woman with type 1 diabetes, hypertension, and CKD3B who presented with nephrotic syndrome, sepsis, and progressive muscle weakness. Her pleural effusions, periorbital changes, elevated free light chains, and dysphagia raised concern for systemic conditions such as amyloidosis or polymyositis, especially given inconsistent outpatient follow-up. Because her management would differ significantly depending on the underlying cause and due to the high risk of loss to follow-up, a renal biopsy was pursued. Serologic studies were unremarkable, and biopsy ultimately confirmed diabetic …

Clinical Decision-Making About Immunosuppressive Treatment In Focal Segmental Glomerulosclerosis., Brooke Blazius, Jonathan P. Troost, Jeffrey B. Kopp, Rulan S. Parekh, Brenda Gillespie, Isabelle Ayoub, Mahmoud Kallash, Rasheed Gbadegesin, Pietro A. Canetta, Tarak Srivastava, Tracy E. Hunley, Katherine E. Twombley, Yonatan A. Peleg, Larry A. Greenbaum, Aftab S. Chishti, Carla M. Nester, Amy K. Mottl, Susan L. Hogan, Virginie Royal, Vivette D. D'Agati, Kimberly J. Reidy, Krzysztof Mucha, Julia Steinke, Simone Sanna-Cherchi, David T. Selewski, Dhruti P. Chen, C John Sperati, Ronald J. Falk, Howard Trachtman, Jason M. Kidd, Cure Glomerulonephropathy (Curegn) Study Consortium

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE & OBJECTIVE: Focal segmental glomerulosclerosis (FSGS) is a heterogeneous disorder with a high risk of progression to kidney failure. There are no approved therapies for FSGS, and futility of treatment is poorly defined. The Cure Glomerulonephropathy (CureGN) study offers the opportunity to describe the characteristics of participants who started immunosuppressive therapy (IST), never received IST, or in whom this treatment was discontinued.

STUDY DESIGN: An observational cohort.

SETTINGS & PARTICIPANTS: Participants enrolled in CureGN with FSGS and surveyed nephrologists.

INTERVENTIONS: The clinical and laboratory data from participants with FSGS who were enrolled in the CureGN observational cohort were reviewed …

Emerging Role Of Sh3bp2 As Regulator Of Immune And Nonimmune Cells In Nephrotic Syndrome., Tarak Srivastava, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are major forms of nephrotic syndrome that remain difficult to treat. MCD and FSGS have distinct but also overlapping clinical, histological, metabolic, and molecular features. Effective use of immunosuppressive drugs, activated immune cells, altered cytokine profiles, and upregulated signaling pathways suggest a link between immune dysfunction and nephrotic syndrome, but the exact mechanism of immunopathogenesis is unclear. Immune dysfunction is an area of ongoing research for identifying novel molecular targets for treating nephrotic syndrome. However, the available animal models do not directly address the role of immune dysfunction in nephrotic …

A Case Of Occlusive Myocardial Infarction Caused By Nephrotic Syndrome In A 26-Year-Old Type 1 Diabetic, Kyle Admire, Charlotta Jornlid, Chelsea Ryan, Rebecca Pauly

Marshall Journal of Medicine

Nephrotic syndrome is a rare condition distinguished by proteinuria exceeding 3g per day. Other associated characteristics include hematuria, hypoalbuminemia, edema, and hyperlipidemia. There is an array of complications of this syndrome, which are primarily due to the profound losses of protein in the urine. One such complication is thromboembolism, with most documented cases in the form of venous thromboembolism of the extremities which is in part due to urinary loss of antithrombin III and increased synthesis of prothrombotic factors. There are limited available data regarding arterial thrombi and especially few reports about coronary thromboses, which can be life-threatening. In this …

Apolipoprotein E Dyslipidemia And Nephrotic Syndrome: A Rare Connection, Sahana Tito, Avica Atri, Shivaraj Patil, Saima Dean, Sweta Carpenter

Einstein Health Papers

Severe hyperlipidemia warrants an extensive evaluation. We report a case of a 25-year-old man of Chinese descent seen in the cardiology-lipid clinic. He was found to have a serum low-density lipoprotein cholesterol of 12.12 mmol/L (468 mg/dL) and serum triglycerides of 2.29 mmol/L (203 mg/dL) during routine screening. Work-up revealed nephrotic-range proteinuria, and renal biopsy showed dilated glomerular capillary loops with lipid deposits, pathognomonic of lipoprotein glomerulopathy. Genetic studies showed apolipoprotein E3/E4 phenotype. He was treated with a high-intensity statin and fibrate therapy, which resulted in a marked improvement in dyslipidemia and proteinuria.

Tobacco Exposure In Adults And Children With Proteinuric Glomerulopathies: A Neptune Cohort Study., Linda Wang, Bayle Smith-Salzberg, Kevin Ec Meyers, Dorey A. Glenn, Katherine R. Tuttle, Vimal K. Derebail, Tammy M. Brady, Keisha Gibson, Abigail R. Smith, Michelle M. O'Shaughnessy, Tarak Srivastava, Gentzon Hall, Jarcy Zee, Markus Bitzer, Christine B. Sethna

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Tobacco exposure has been recognized as a risk factor for cardiovascular disease (CVD) and progression of kidney disease. Patients with proteinuric glomerulopathies are at increased risk for cardiovascular morbidity and mortality. Multiple studies have linked tobacco exposure to CVD and chronic kidney disease, but the relationships between smoking and proteinuric glomerulopathies in adults and children have not been previously explored.

METHODS: Data from the Nephrotic Syndrome Study Network (NEPTUNE), a multi-center prospective observational study of participants with proteinuric glomerulopathies, was analyzed. 371 adults and 192 children enrolled in NEPTUNE were included in the analysis. Self-reported tobacco exposure was classified …

Thsd7a Associated Membranous Nephropathy Leading To Metastatic Neuroendocrine Carcinoma, Angel Juarez, Lidice Galindo, Maryam Gondal

South Atlantic Division GME Research Day 2023

No abstract provided.

Gluten-Free Diet In Childhood Difficult-To-Treat Nephrotic Syndrome: A Pilot Feasibility Study., Tarak Srivastava, Katherine M. Dell, Kevin V. Lemley, Debbie S. Gipson, Frederick J. Kaskel, Kevin Edward Meyers, Christian Faul, Ayelet Goldhaber, Laurajane Pehrson, Howard Trachtman

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Minimal change disease in childhood can follow a frequently relapsing or steroid-dependent course in up to 40% of cases. Second-line immunosuppressive medications that are used to manage these patients are associated with significant adverse effects. There is a need for safer alternative treatments for difficult-to-treat nephrotic syndrome. Therefore, we conducted an open-label feasibility study to assess the safety and efficacy of a gluten-free diet as treatment for pediatric patients with difficult-to-treat nephrotic syndrome. As a second aim, we sought to determine if the plasma zonulin concentration can identify those who are more likely to respond to this intervention.

METHODS: …

Urinary Epidermal Growth Factor As A Marker Of Disease Progression In Children With Nephrotic Syndrome., Debbie S. Gipson, Howard Trachtman, Anne Waldo, Keisha L. Gibson, Sean Eddy, Katherine M. Dell, Tarak Srivastava, Kevin V. Lemley, Larry A. Greenbaum, Sangeeta Hingorani, Kevin E. Meyers, Frederick J. Kaskel, Kimberly J. Reidy, Christine B. Sethna, Cheryl L. Tran, Chia-Shi Wang, Katherine R. Tuttle, Gia Oh, Alicia M. Neu, Elizabeth Brown, Jen-Jar Lin, Jennifer Lai Yee, Therese M M. Roth, Jonathan P. Troost, Brenda W. Gillespie, Matthew G. Sampson, Matthias Kretzler, Wenjun Ju

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Childhood-onset nephrotic syndrome has a variable clinical course. Improved predictive markers of long-term outcomes in children with nephrotic syndrome are needed. This study tests the association between baseline urinary epidermal growth factor (uEGF) excretion and longitudinal kidney function in children with nephrotic syndrome.

Methods: The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. uEGF was measured at baseline for all participants and normalized by the urine …

Remarks About The Study On Infection-Associated Relapses In Children With Nephrotic Syndrome: A Short-Term Outcome Study, Akbar Shoukat Ali, Raheel Allana, Rahim Jandani

Department of Medicine

No abstract provided.

Pediatric Immunization Practices In Nephrotic Syndrome: An Assessment Of Provider And Parental Knowledge, Cheryl L Tran, David T Selewski, Gia J Oh, Jonathan P Troost, Susan F Massengill, Samhar I Al-Akash, Shefali Mahesh, Rasheda Amin, Isa F Ashoor, Rahul Chanchlani, Mahmoud Kallash, Robert P Woroniecki, Debbie S Gipson

Faculty, Staff and Student Publications

Background: Children with nephrotic syndrome (NS) are at high risk for vaccine-preventable infections due to the immunological effects from the disease and concurrent treatment with immunosuppressive medications. Immunizations in these patients may be deferred due to their immunosuppressive treatment which may increase the risk for vaccine-preventable infections. Immunization practices in children with NS continue to vary among pediatric nephrologists. This raises the question of whether children with NS are receiving the recommended vaccinations at appropriate times. Therefore, it is critical to understand the practices and patient education provided by physicians to patients on the topic of vaccinations.

Methods: After informed …

Text Messaging For Disease Monitoring In Childhood Nephrotic Syndrome., Chia-Shi Wang, Jonathan P. Troost, Larry A. Greenbaum, Tarak Srivastava, Kimberly Reidy, Keisha Gibson, Howard Trachtman, John D. Piette, Christine B. Sethna, Kevin Meyers, Katherine M. Dell, Cheryl L. Tran, Suzanne Vento, Krishna Kallem, Emily Herreshoff, Sangeeta Hingorani, Kevin Lemley, Gia Oh, Elizabeth Brown, Jen-Jar Lin, Frederick Kaskel, Debbie S. Gipson

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: There is limited information on effective disease monitoring for prompt interventions in childhood nephrotic syndrome. We examined the feasibility and effectiveness of a novel text messaging system (SMS) for disease monitoring in a multicenter, prospective study.

Methods: A total of 127 patientsresults, symptoms, and medication adherence were sent to a designated caregiver (n = 116) or adolescent patient (n = 3). Participants responded by texting. Feasibility of SMS was assessed by SMS adoption, retention, and engagement, and concordance between participant-reported results and laboratory/clinician assessments. The number of disease relapses and time-to-remission data captured by SMS were compared …

Recurrence Of Nephrotic Syndrome Following Kidney Transplantation Is Associated With Initial Native Kidney Biopsy Findings., Jonathan H. Pelletier, Karan R. Kumar, Rachel Engen, Adam Bensimhon, Jennifer D. Varner, Michelle N. Rheault, Tarak Srivastava, Caroline Straatmann, Cynthia Silva, T Keefe Davis, Scott E. Wenderfer, Keisha Gibson, David Selewski, John Barcia, Patricia Weng, Christoph Licht, Natasha Jawa, Mahmoud Kallash, John W. Foreman, Delbert R. Wigfall, Annabelle N. Chua, Eileen Chambers, Christoph P. Hornik, Eileen D. Brewer, Shashi K. Nagaraj, Larry A. Greenbaum, Rasheed A. Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence.

METHODS: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were …

An Eqtl Landscape Of Kidney Tissue In Human Nephrotic Syndrome., Christopher E. Gillies, Rosemary Putler, Rajasree Menon, Edgar Otto, Kalyn Yasutake, Viji Nair, Paul Hoover, David Lieb, Shuqiang Li, Sean Eddy, Damian Fermin, Michelle T. Mcnulty, Nephrotic Syndrome Study Network (Neptune), Nir Hacohen, Krzysztof Kiryluk, Matthias Kretzler, Xiaoquan Wen, Matthew G. Sampson, Tarak Srivastava

Manuscripts, Articles, Book Chapters and Other Papers

Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian "Deterministic Approximation of Posteriors" (DAP) to fine-map …

Hla-Dqa1 And Apol1 As Risk Loci For Childhood-Onset Steroid-Sensitive And Steroid-Resistant Nephrotic Syndrome., Adebowale Adeyemo, Christopher Esezobor, Adaobi Solarin, Asiri Abeyagunawardena, Jameela A. Kari, Sherif El Desoky, Larry A. Greenbaum, Margret Kamel, Mahmoud Kallash, Cynthia Silva, Alex Young, Tracey E. Hunley, Nilka De Jesus-Gonzalez, Tarak Srivastava, Rasheed Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

Background: Few data exist for the genetic variants underlying the risk for steroid-sensitive nephrotic syndrome (SSNS) in children. The objectives of this study were to evaluate HLA-DQA1 and APOL1 variants as risk factors for SSNS in African American children and use classic HLA antigen types and amino acid inference to refine the HLA-DQA1 association.

Study design: Case-control study.

Setting & participants: African American children with SSNS or steroid-resistant nephrotic syndrome (SRNS) were enrolled from Duke University and centers participating in the Midwest Pediatric Nephrology Consortium.

Factor: Genetic variants in HLA-DQA1 (C34Y [rs1129740]; F41S [rs1071630]) and APOL1 high-risk alleles.

Outcomes: SSNS …

Blood Pressure And Visit-To-Visit Blood Pressure Variability Among Individuals With Primary Proteinuric Glomerulopathies., Christine B. Sethna, Kevin E C Meyers, Laura H. Mariani, Kevin J. Psoter, Crystal A. Gadegbeku, Keisha L. Gibson, Tarak Srivastava, Matthias Kretzler, Tammy M. Brady

Manuscripts, Articles, Book Chapters and Other Papers

Hypertension and blood pressure variability (BPV; SD and average real variability) in primary proteinuric glomerulopathies are not well described. Data were from 433 participants in the NEPTUNE (Nephrotic Syndrome Study Network). Hypertensive BP status was defined as previous history of hypertension or BP ≥140/90 mm Hg for adults/≥95th percentile for children at baseline. BPV was measured in participants with ≥3 visits in the first year. Two-hundred ninety-six adults (43 years [interquartile range, 32-57.8 years], 61.5% male) and 147 children (11 years [interquartile range, 5-14 years], 57.8% male) were evaluated. At baseline, 64.8% of adults and 46.9% of children were hypertensive. …

Efficacy And Safety Of Sparsentan Compared With Irbesartan In Patients With Primary Focal Segmental Glomerulosclerosis: Randomized, Controlled Trial Design (Duet)., Radko Komers, Debbie S. Gipson, Peter Nelson, Sharon Adler, Tarak Srivastava, Vimal K. Derebail, Kevin E. Meyers, Pablo Pergola, Meghan E. Macnally, Jennifer L. Hunt, Alvin Shih, Howard Trachtman

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Primary focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome and end-stage renal disease. There are no US Food and Drug Administration-approved therapies for FSGS, and treatment often fails to reduce proteinuria. Endothelin is an important factor in the pathophysiology of podocyte disorders, including FSGS. Sparsentan is a first-in-class, orally active, dual-acting angiotensin receptor blocker (ARB) and highly selective endothelin Type A receptor antagonist. This study is designed to evaluate whether sparsentan lowers proteinuria compared with an ARB alone and has a favorable safety profile in patients with FSGS.

Methods: DUET is a phase 2, randomized, active-control, …

Hla-Dqa1 And Plcg2 Are Candidate Risk Loci For Childhood-Onset Steroid-Sensitive Nephrotic Syndrome., Rasheed A. Gbadegesin, Adebowale Adeyemo, Nicholas J A Webb, Larry A A. Greenbaum, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arundhati Kale, Debbie Gipson, Tarak Srivastava, Jen-Jar Lin, Deepa Chand, Tracy E. Hunley, Patrick D. Brophy, Arvind Bagga, Aditi Sinha, Michelle N. Rheault, Joanna Ghali, Kathy Nicholls, Elizabeth Abraham, Halima S. Janjua, Abiodun Omoloja, Gina-Marie Barletta, Yi Cai, David D. Milford, Catherine O'Brien, Atif Awan, Vladimir Belostotsky, William E. Smoyer, Alison Homstad, Gentzon Hall, Guanghong Wu, Shashi Nagaraj, Delbert Wigfall, John Foreman, Michelle P. Winn, Mid-West Pediatric Nephrology Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were …

Secondary Membranous Nephropathy Associated With Guillain-Barré Syndrome., Edward J Filippone, Mitul Kanzaria, Rodney Bell, Eric Newman, John L Farber

Department of Medicine Faculty Papers

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome (NS) in adults. It may be primary, usually mediated by IgG4 anti-phospholipase A2 autoantibodies or secondary to various other conditions. Guillain- Barré syndrome (GBS) has been associated with MN, but a cause and effect relation has not been proven. We present a case of concurrent development of GBS and severe NS, with renal biopsy demonstrating MN. IgG4 stain was negative, indicating that most likely, the MN was secondary and probably caused by the underlying GBS.