Nephrology Commons^™

Risk Factors For Short- And Long-Term Outcomes In Children With Stec-Hus/D, Judith Sebestyen Vansickle, Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Background. Hemolytic uremic syndrome (HUS) is one of the common causes for acute kidney injury in childhood. Objective. The goals of our study were to identify risk factors for short-term complications and long-term outcomes of chronic kidney disease (CKD) in Shiga toxin-producing Escherichia coli (STEC)-HUS and other diarrhea positive (D+) HUS. Methods. Retrospective chart review was obtained of 58 pediatric patients treated for STEC-HUS and other D+ HUS between February 2002 and January 2011. Results. Thirty-three patients (56.9%) required dialysis. Dialysis was more likely initiated if a patient was a female (P < .012), oliguric (urine output < 0.5 mL/kg/h, P < .0005), or hemoglobin (HGB) level >10 g/dL …

Mechanotransduction Signaling In Podocytes From Fluid Flow Shear Stress., Tarak Srivastava, Hongying Dai, Daniel P. Heruth, Uri S. Alon, Robert E. Garola, Jianping Zhou, R Scott Duncan, Ashraf El-Meanawy, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Virginia J. Savin, Mukut Sharma

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Recently, we and others have found that hyperfiltration-associated increase in biomechanical forces, namely, tensile stress and fluid flow shear stress (FFSS), can directly and distinctly alter podocyte structure and function. The ultrafiltrate flow over the major processes and cell body generates FFSS to podocytes. Our previous work suggests that the cyclooxygenase-2 (COX-2)-PGE2-PGE2 receptor 2 (EP2) axis plays an important role in mechanoperception of FFSS in podocytes. To address mechanotransduction of the perceived stimulus through EP2, cultured podocytes were exposed to FFSS (2 dyn/cm2) for 2 h. Total RNA from cells at the end of FFSS treatment, 2-h post-FFSS, and 24-h …

Successful Reversal Of Furosemide-Induced Secondary Hyperparathyroidism With Cinacalcet., Tarak Srivastava, Shahryar Jafri, William E. Truog, Judith Sebestyen Vansickle, Winston M. Manimtim, Uri S. Alon

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Secondary hyperparathyroidism (SHPT) is a rare complication of furosemide therapy that can occur in patients treated with the loop diuretic for a long period of time. We report a 6-month-old 28-weeks premature infant treated chronically with furosemide for his bronchopulmonary dysplasia, who developed hypocalcemia and severe SHPT, adversely affecting his bones. Discontinuation of the loop diuretic and the addition of supplemental calcium and calcitriol only partially reversed the SHPT, bringing serum parathyroid hormone level down from 553 to 238 pg/mL. After introduction of the calcimimetic Cinacalcet, we observed a sustained normalization of parathyroid hormone concentration at 27 to 63 pg/mL …

Hyperfiltration-Associated Biomechanical Forces In Glomerular Injury And Response: Potential Role For Eicosanoids., Mukut Sharma, Ram Sharma, Ellen T. Mccarthy, Virginia J. Savin, Tarak Srivastava

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Hyperfiltration is a well-known risk factor in progressive loss of renal function in chronic kidney disease (CKD) secondary to various diseases. A reduced number of functional nephrons due to congenital or acquired cause(s) results in hyperfiltration in the remnant kidney. Hyperfiltration-associated increase in biomechanical forces, namely pressure-induced tensile stress and fluid flow-induced shear stress (FFSS) determine cellular injury and response. We believe the current treatment of CKD yields limited success because it largely attenuates pressure-induced tensile stress changes but not the effect of FFSS on podocytes. Studies on glomerular podocytes, tubular epithelial cells and bone osteocytes provide evidence for a …

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

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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

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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, …

Role Of Biomechanical Forces In Hyperfiltration-Mediated Glomerular Injury In Congenital Anomalies Of The Kidney And Urinary Tract., Tarak Srivastava, Ganesh Thiagarajan, Uri S. Alon, Ram Sharma, Ashraf El-Meanawy, Ellen T. Mccarthy, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood. The mechanism of maladaptive hyperfiltration that occurs from loss of functional nephrons, including solitary kidney, is not clear. We re-examine the phenomenon of hyperfiltration in the context of biomechanical forces with special reference to glomerular podocytes. Capillary stretch exerts tensile …

Diet And Polycystic Kidney Disease: A Pilot Intervention Study., Jacob M. Taylor, Jill M. Hamilton-Reeves, Debra K. Sullivan, Cheryl A. Gibson, Catherine Creed, Susan E. Carlson, Donald E. Wesson, Jared J. Grantham

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BACKGROUND & AIMS: Dietary sodium, protein, acid precursors, and water have been linked to cyst growth in polycystic kidney disease; yet, no studies in patients have examined the feasibility of using a dietary intervention that controls all of these factors. The aim of this study was to determine if a diet, appropriate for persons of most ages, reduces the excretion of sodium, urea, acid, and decreases mean urine osmolality while gaining acceptance by patients with autosomal dominant polycystic kidney disease (ADPKD).

METHODS: Twelve adults with ADPKD enrolled in a pre-post pilot feasibility study and served as their own controls. Individuals …

Renin-Angiotensin Ii-Aldosterone System Blockers And Time To Renal Replacement Therapy In Children With Ckd., Alison G. Abraham, Aisha Betoko, Jeffrey J. Fadrowski, Christopher Pierce, Susan L. Furth, Bradley A. Warady, Alvaro Muñoz

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BACKGROUND: Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin-angiotensin II-aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD.

METHODS: A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m

RESULTS: There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more …

Assessment Of Dietary Intake Of Children With Chronic Kidney Disease., Wun Fung Hui, Aisha Betoko, Jonathan D. Savant, Alison G. Abraham, Larry A. Greenbaum, Bradley A. Warady, Marva M. Moxey-Mims, Susan L. Furth

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OBJECTIVE: Our aim was to characterize the nutrient intake of children with chronic kidney disease (CKD) relative to recommended intake levels.

METHODS: We conducted a cross-sectional study of dietary intake assessed by Food Frequency Questionnaire (FFQ) in The North American Chronic Kidney Disease in Children (CKiD) prospective cohort study. Nutrient intake was analyzed to estimate the daily consumption levels of various nutrients and compared with national guidelines for intake.

RESULTS: There were 658 FFQs available for analysis; 69.9 % of respondents were boys, with a median age [Interquartile range (IQR)] of 11 years (8-15). Median daily sodium, potassium, and phosphorus …

Genetic Drivers Of Kidney Defects In The Digeorge Syndrome., Esther Lopez-Rivera, Yangfan P. Liu, Miguel Verbitsky, Blair R. Anderson, Valentina P. Capone, Edgar A. Otto, Zhonghai Yan, Adele Mitrotti, Jeremiah Martino, Nicholas J. Steers, David A. Fasel, Katarina Vukojevic, Rong Deng, Silvia E. Racedo, Qingxue Liu, Max Werth, Rik Westland, Asaf Vivante, Gabriel S. Makar, Monica Bodria, Matthew G. Sampson, Christopher E. Gillies, Virginia Vega-Warner, Mariarosa Maiorana, Donald S. Petrey, Barry Honig, Vladimir J. Lozanovski, Rémi Salomon, Laurence Heidet, Wassila Carpentier, Dominique Gaillard, Alba Carrea, Loreto Gesualdo, Daniele Cusi, Claudia Izzi, Francesco Scolari, Joanna A E Van Wijk, Adela Arapovic, Mirna Saraga-Babic, Marijan Saraga, Nenad Kunac, Ali Samii, Donna M. Mcdonald-Mcginn, Terrence B. Crowley, Elaine H. Zackai, Dorota Drozdz, Monika Miklaszewska, Marcin Tkaczyk, Przemyslaw Sikora, Maria Szczepanska, Malgorzata Mizerska-Wasiak, Grazyna Krzemien, Agnieszka Szmigielska, Marcin Zaniew, John M. Darlow, Prem Puri, David Barton, Emilio Casolari, Susan L. Furth, Bradley A. Warady, Zoran Gucev, Hakon Hakonarson, Hana Flogelova, Velibor Tasic, Anna Latos-Bielenska, Anna Materna-Kiryluk, Landino Allegri, Craig S. Wong, Iain A Drummond, Vivette D'Agati, Akira Imamoto, Jonathan M. Barasch, Friedhelm Hildebrandt, Krzysztof Kiryluk, Richard P. Lifton, Bernice E. Morrow, Cecile Jeanpierre, Virginia E. Papaioannou, Gian Marco Ghiggeri, Ali G. Gharavi, Nicholas Katsanis, Simone Sanna-Cherchi

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BACKGROUND: The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown.

METHODS: We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice.

RESULTS: We identified heterozygous deletions of 22q11.2 in 1.1% …

Newborn Sequencing In Genomic Medicine And Public Health., Jonathan S. Berg, Pankaj B. Agrawal, Donald B. Bailey, Alan H. Beggs, Steven E. Brenner, Amy M. Brower, Julie A. Cakici, Ozge Ceyhan-Birsoy, Kee Chan, Flavia Chen, Robert J. Currier, Dmitry Dukhovny, Robert C. Green, Julie Harris-Wai, Ingrid A. Holm, Brenda Iglesias, Galen Joseph, Stephen F. Kingsmore, Barbara A. Koenig, Pui-Yan Kwok, John Lantos, J Steven Leeder, Megan A. Lewis, Amy L. Mcguire, Laura V. Milko, Sean D. Mooney, Richard B. Parad, Stacey Pereira, Josh E. Petrikin, Bradford C. Powell, Cynthia M. Powell, Jennifer M. Puck, Heidi L. Rehm, Neil Risch, Myra Roche, Joseph T. Shieh, Narayanan Veeraraghavan, Michael S. Watson, Laurel K. Willig, Timothy W. Yu, Tiina Urv, Anastasia L. Wise

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The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing …

Cystatin C And Cardiac Measures In Children And Adolescents With Ckd., Tammy M. Brady, Kelly Townsend, Michael F. Schneider, Christopher Cox, Thomas Kimball, Peace Madueme, Bradley A. Warady, Susan Furth, Mark Mitsnefes

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BACKGROUND: Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. …

Ambulatory Blood Pressure, Left Ventricular Hypertrophy, And Allograft Function In Children And Young Adults After Kidney Transplantation., Gilad Hamdani, Edward J. Nehus, Coral D. Hanevold, Judith Sebestyen Van Sickle, Robert Woroniecki, Scott E. Wenderfer, David K. Hooper, Douglas Blowey, Amy Wilson, Bradley A. Warady, Mark M. Mitsnefes

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BACKGROUND: Hypertension is a common complication and is an important risk factor for graft loss and adverse cardiovascular outcomes in pediatric kidney transplantation. Ambulatory blood pressure monitoring (ABPM) is the preferred method to characterize blood pressure status.

METHODS: We conducted a retrospective review of a large cohort of children and young adults with kidney transplant to estimate the prevalence of abnormal ambulatory blood pressure (ABP), assess factors associated with abnormal ABP, and examine whether ambulatory hypertension is associated with worse allograft function and left ventricular hypertrophy (LVH).

RESULTS: Two hundred twenty-one patients had ABPM, and 142 patients had echocardiographic results …

Role Of Fgf23 In Pediatric Hypercalciuria., Maria Goretti Moreira Guimarães Penido, Marcelo De Sousa Tavares, Uri S. Alon

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Background: This study explored the possible role of FGF23 in pediatric hypercalciuria.

Methods: Plasma FGF23 was measured in 29 controls and 58 children and adolescents with hypercalciuria: 24 before treatment (Pre-Treated) and 34 after 6 months of treatment (Treated). Hypercalciuric patients also measured serum PTH hormone, 25(OH)vitD, phosphate, calcium, creatinine, and 24 h urine calcium, phosphate, and creatinine.

Results: There were no differences in age, gender, ethnicity, or body mass index either between controls and patients, or between Pre-Treated and Treated patients. Median plasma FGF23 in controls was 72 compared with all patients, 58 RU/mL (p = 0.0019). However, …

Multiple Targets For Novel Therapy Of Fsgs Associated With Circulating Permeability Factor., Virginia J. Savin, Mukut Sharma, Jianping Zhou, David Genochi, Ram Sharma, Tarak Srivastava, Amna Ilahe, Pooja Budhiraja, Aditi Gupta, Ellen T. Mccarthy

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A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression. Agents that may prevent the synthesis of the permeability factor include cytotoxic agents or aggressive chemotherapy. Extracorporeal therapies include plasmapheresis, immunoadsorption with protein A …

Life-Threatening Hypercalcemia During Prodrome Of Pneumocystis Jiroveci Pneumonia In An Immunocompetent Infant, Judith Sebestyen Vansickle, Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Severe hypercalcemia in infants is usually attributed to genetic etiologies and less commonly to acquired ones. An 8-week-old girl presented with failure to thrive, mild respiratory distress, and life-threatening hypercalcemia (23.5 mg/dL). Serum 1,25(OH)2-D) level was elevated and parathyroid hormone undetectable. Evaluation for genetic mutations and malignant etiologies of hypercalcemia was negative. Treatment with intravenous hydration, loop diuretic, and calcitonin failed to correct the hypercalcemia, which was subsequently controlled with bisphosphonate therapy. Due to progressive respiratory deterioration, a bronchopulmonary lavage was done on day 17 of her hospitalization disclosing Pneumocystis jiroveci infection. The subsequent immunological investigation showed no abnormalities. She …

Cardiovascular Disease Risk Factors And Left Ventricular Hypertrophy In Girls And Boys With Ckd., Rebecca L. Ruebner, Derek Ng, Mark Mitsnefes, Bethany J. Foster, Kevin Meyers, Bradley A. Warady, Susan L. Furth

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Background and objectives: Prior studies suggested that women with CKD have higher risk for cardiovascular disease (CVD) and mortality than men, although putative mechanisms for this higher risk have not been identified. We assessed sex differences in (1) CVD risk factors and left ventricular hypertrophy (LVH), and (2) the relationship of left ventricular mass (LVM) with different measures of body size in children with CKD.

Design, setting, participants, and measurements: The study population comprised 681 children with CKD from the Chronic Kidney Disease in Children cohort, contributing 1330 visits. CVD risk factors were compared cross-sectionally by sex. LVH was defined …

Toxic Environmental Exposures And Kidney Health In Children., Darcy K. Weidemann, Virginia M. Weaver, Jeffrey J. Fadrowski

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High-level exposures to a number of agents are known to have direct nephrotoxic effects in children. A growing body of literature supports the hypothesis that chronic, relatively low-level exposure to various nephrotoxicants may also increase the risk for chronic kidney disease (CKD) or accelerate its progression. In this review we highlight several environmental nephrotoxicants and their association with CKD in children and adolescents. We also discuss unique epidemiological challenges in the use of kidney biomarkers in environmental nephrotoxicology.

Association Of Blood Pressure Variability And Neurocognition In Children With Chronic Kidney Disease., Marc B. Lande, Susan R. Mendley, Matthew B. Matheson, Shlomo Shinnar, Arlene C. Gerson, Joshua A. Samuels, Bradley A. Warady, Susan L. Furth, Stephen R. Hooper

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BACKGROUND: Children with chronic kidney disease (CKD) and hypertension have increased blood pressure variability (BPV), which has been associated with lower neurocognitive test scores in adults. Children with CKD are at risk for decreased neurocognitive function. Our objective was to determine whether children with CKD and increased BPV had worse performance on neurocognitive testing compared with children with CKD and lower BPV.

METHODS: This was a cross-sectional and longitudinal analysis of the relation between BPV and neurocognitive test performance in children ≥6 years enrolled in the Chronic Kidney Disease in Children (CKiD) study. Visit-to-visit BPV was assessed by the standard …

Racial Differences In Renal Replacement Therapy Initiation Among Children With A Nonglomerular Cause Of Chronic Kidney Disease., Derek K. Ng, Marva Moxey-Mims, Bradley A. Warady, Susan L. Furth, Alvaro Muñoz

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PURPOSE: African American (AA) adults with chronic kidney disease (CKD) have a faster progression to end-stage renal disease and are less likely to receive a kidney transplant. It is unclear whether AA children experience renal replacement therapy (RRT) for end-stage renal disease sooner than non-AA children after accounting for socioeconomic status (SES).

METHODS: Among children with nonglomerular CKD in the Chronic Kidney Disease in Children study, we investigated time to RRT (i.e., first dialysis or transplant) after CKD onset using parametric survival models and accounted for SES differences by inverse probability weights.

RESULTS: Of 110 AA and 493 non-AA children …

Magic Study: Aims, Design And Methods Using Systemchange™ To Improve Immunosuppressive Medication Adherence In Adult Kidney Transplant Recipients., Cynthia L. Russell, Shirley Moore, Donna Hathaway, An-Lin Cheng, Guoqing Chen, Kathy Goggin

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BACKGROUND: Among adult kidney transplant recipients, non-adherence to immunosuppressive medications is the leading predictor of poor outcomes, including rejection, kidney loss, and death. An alarming one-third of kidney transplant patients experience medication non-adherence even though the problem is preventable. Existing adherence interventions have proven marginally effective for those with acute and chronic illnesses and ineffective for adult kidney transplant recipients. Our purpose is to describe the design and methods of the MAGIC (Medication Adherence Given Individual SystemCHANGE™) trial

METHODS/DESIGN: We report the design of a randomized controlled trial with an attention-control group to test an innovative 6-month SystemCHANGE™ intervention designed …

Kidney Disease Progression In Autosomal Recessive Polycystic Kidney Disease., Katherine M. Dell, Matthew Matheson, Erum A. Hartung, Bradley A. Warady, Susan L. Furth

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OBJECTIVE: To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort.

STUDY DESIGN: GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test.

RESULTS: Annualized GFR change in subjects …

Techniques And Approaches To Genetic Analyses In Nephrological Disorders., Laurel K. Willig

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Inherited renal disease is a leading cause of morbidity and mortality in pediatric nephrology. High throughput advancements in genomics have led to greater understanding of the biologic underpinnings of these diseases. However, the underlying genetic changes explain only part of the molecular biology that contributes to disease manifestation and progression. Other omics technologies will provide a more complete picture of these cellular processes. This review discusses these omics technologies in the context of pediatric renal disease.

Fracture Burden And Risk Factors In Childhood Ckd: Results From The Ckid Cohort Study., Michelle R. Denburg, Juhi Kumar, Thomas Jemielita, Ellen R. Brooks, Amy Skversky, Anthony A. Portale, Isidro B. Salusky, Bradley A. Warady, Susan L. Furth, Mary B. Leonard

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Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence …

Genetic Loci Associated With Renal Function Measures And Chronic Kidney Disease In Children: The Pediatric Investigation For Genetic Factors Linked With Renal Progression Consortium., Matthias Wuttke, Craig S. Wong, Elke Wühl, Daniel Epting, Li Luo, Anselm Hoppmann, Anke Doyon, Yong Li, Gkdgen Consortium, Betül Sözeri, Daniela Thurn, Martin Helmstädter, Tobias B. Huber, Tom D. Blydt-Hansen, Albrecht Kramer-Zucker, Otto Mehls, Anette Melk, Uwe Querfeld, Susan L. Furth, Bradley A. Warady, Franz Schaefer, Anna Köttgen

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BACKGROUND: Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown.

METHODS: The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular …

Depressive Symptoms In Children With Chronic Kidney Disease., Amy J. Kogon, Matthew B. Matheson, Joseph T. Flynn, Arlene C. Gerson, Bradley A. Warady, Susan L. Furth, Stephen R. Hooper, Chronic Kidney Disease In Children (Ckid) Study Group

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OBJECTIVE: To assess depression in children with chronic kidney disease and to determine associations with patient characteristics, intellectual and educational levels, and health-related quality of life (HRQoL).

STUDY DESIGN: Subjects aged 6-17 years from the Chronic Kidney Disease in Children cohort study completed the Children's Depression Inventory (CDI), Wechsler Abbreviated Scales of Intelligence, Wechsler Individual Achievement Test-II-Abbreviated, and the Pediatric Inventory of Quality of Life Core Scales 4.0. Regression analyses determined associations of CDI score and depression status with subject characteristics, intellectual and educational levels, and HRQoL. A joint linear mixed model and Weibull model were used to determine the …

Renal And Cardiovascular Morbidities Associated With Apol1 Status Among African-American And Non-African-American Children With Focal Segmental Glomerulosclerosis., Robert P. Woroniecki, Derek K. Ng, Sophie Limou, Cheryl A. Winkler, Kimberly J. Reidy, Mark Mitsnefes, Matthew G. Sampson, Craig S. Wong, Bradley A. Warady, Susan L. Furth, Jeffrey B. Kopp, Frederick J. Kaskel

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BACKGROUND AND OBJECTIVES: African-American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression, and cardiovascular morbidity in children.

DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease.

RESULTS: A total of 140 AA children in the CKiD study were genotyped. High …

Serum Glomerular Albumin Permeability Activity: Association With Rapid Progression To End-Stage Renal Disease In Focal Segmental Glomerulosclerosis., Sudhindra Pudur, Tarak Srivastava, Mukut Sharma, Ram Sharma, Sergey Tarima, Hongying Dai, Ellen T. Mccarthy, Virginia J. Savin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a major cause of renal failure. Sera of some FSGS patients increase glomerular albumin permeability (Palb) during in vitro testing and cause proteinuria in experimental animals.

OBJECTIVES: To determine whether permeability activity of FSGS serum (Palb activity) is associated with rate of progression to renal replacement therapy (RRT).

DESIGN: This is an observational study based on medical and demographic information and Palb activity testing.

SETTING: Studies were performed at Medical College of Wisconsin.

PATIENTS: Serum was submitted by patients' nephrologists for measurement of Palb activity. Each patient had had a biopsy diagnosis of FSGS, …

Can Office Blood Pressure Readings Predict Masked Hypertension?, Mark M. Mitsnefes, Chris Pierce, Joseph Flynn, Joshua Samuels, Janis Dionne, Susan Furth, Bradley A. Warady, Ckid Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Studies in children with chronic kidney disease indicate a high prevalence of masked hypertension detected by ambulatory blood pressure monitoring (ABPM). However, it is not well known if the frequency of masked hypertension is related to the level of normal casual blood pressure (BP).

METHODS/RESULTS: We hypothesized that lower levels of normal casual BP are associated with a lower prevalence of masked hypertension. Data from the chronic kidney disease (CKiD) cohort were analyzed cross-sectionally across multiple visits. The majority of children with normal casual BP also had normal wake and sleep ABP (60 %), even at the highest percentiles …