Bone mineral density in adolescent urinary stone formers: is sex important?
Bone; children; disease; fracture; health; inflammation; kidney-stones; nephrolithiasis; osteoporosis; Pediatrics; risk; Sex; Urolithiasis; Urolithiasis
Urinary stone disease (USD) is affecting a greater number of children and low bone mineral density (BMD) and increased skeletal fractures have been demonstrated in stone patients; however, the mechanism(s) driving bone disease remain unclear. This pilot study was undertaken to assess an adolescent kidney stone cohort's BMD and evaluate for an inverse correlation between BMD and urine concentration of lithogenic minerals and/or inflammatory levels. Prospective case-control study was carried out at a large pediatric center. 15 participants with USD (12-18 years of age, 8 female) were matched by age, sex, and body mass index to 15 controls. Lumbar and total body BMD z-score did not differ between groups. When stone formers were separated by sex, there was a significant difference between male stone formers vs. controls total body BMD z-score (Fig. 1). BMD z-score did not significantly correlate with urine calcium, oxalate, citrate or magnesium. Higher urine IL-13 did significantly correlate with higher total body BMD z-score (r = 0.677, p = 0.018). Total body BMD z-score did significantly correlate with body mass index (BMI) as expected for the control group (r = 0.6321, p = 0.0133). However, this relationship was not present in the USD group (r = - 0.1629, p = 0.5619). This is a small but hypothesis-generating study which demonstrates novel evidence of male-specific low BMD in adolescent stone formers. Furthermore, we demonstrated a positive association between urine
Kusumi Kirsten; Schwaderer Andrew L; Clark Curtis; Budge Kevin; Hussein Nazar; Raina Rupesh; Denburg Michelle; Safadi Fayez F
Urolithiasis
2020
2020-03-31
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1007/s00240-020-01183-w" target="_blank" rel="noreferrer noopener">10.1007/s00240-020-01183-w</a>
The Role of Endothelin and Endothelin Antagonists in Chronic Kidney Disease.
Focal segmental glomerulosclerosis; Diabetic nephropathy; Endothelin; Endothelin antagonists; Hypertensive nephropathy
Background: Endothelins (ET) are a family of peptides that act as potent vasoconstrictors and pro-fibrotic growth factors. ET-1 is integral to renal and cardiovascular pathophysiology and exerts effects via autocrine, paracrine and endocrine signaling pathways tied to regulation of aldosterone, catecholamines, and angiotensin. In the kidney, ET-1 is critical to maintaining renal perfusion and controls glomerular arteriole tone and hemodynamics. It is hypothesized that
Raina Rupesh; Chauvin Abigail; Chakraborty Ronith; Nair Nikhil; Shah Haikoo; Krishnappa Vinod; Kusumi Kirsten
Kidney diseases (Basel, Switzerland)
2020
2020-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1159/000504623" target="_blank" rel="noreferrer noopener">10.1159/000504623</a>
Overview of Monogenic or Mendelian Forms of Hypertension
aldosteronism; apparent mineralocorticoid excess; congenital adrenal hyperplasia; disease; familial; familial hyperaldosteronism; features; genes; Gordon syndrome; hyperaldosteronism; Liddle syndrome; Liddle syndrome; mineralocorticoid excess; monogenic hypertension; mutations; Pediatrics; prevalence; stroke; update
Monogenic or Mendelian forms of hypertension are described as a group of conditions characterized by insults to the normal regulation of blood pressure by the kidney and adrenal gland. These alterations stem from single mutations that lead to maladaptive overabsorption of electrolytes with fluid shift into the vasculature, and consequent hypertension. Knowledge of these various conditions is essential in diagnosing pediatric or early-onset adult hypertension as they directly affect treatment strategies. Precise diagnosis with specific treatment regimens aimed at the underlying physiologic derangement can restore normotension and prevent the severe sequelae of chronic hypertension.
Raina Rupesh; Krishnappa Vinod; Das Abhijit; Amin Harshesh; Radhakrishnan Yeshwanter; Nair Nikhil R; Kusumi Kirsten
Frontiers in Pediatrics
2019
1905-07
<a href="http://doi.org/10.3389/fped.2019.00263" target="_blank" rel="noreferrer noopener">10.3389/fped.2019.00263</a>
Adolescents with urinary stones have elevated urine levels of inflammatory mediators
Biomarker; Cytokine; Innate immunity; Interleukin
Urinary stones are increasing in children, primarily during adolescence. Although urinary stones are often viewed in the context of intermittent stone events, increasing evidence indicates that stones are a metabolic process associated with chronic kidney disease and cardiovascular disease. These aforementioned stone-associated conditions may have pediatric origins. To compare urine inflammatory markers in otherwise healthy stone forming children versus matched controls. Urine samples were collected from 12 adolescents with urinary stones along with 15 controls. The levels of 30 urine cytokines were measured using a Mesoscale 30-Plex Human Cytokine panel and normalized to urine creatinine levels. Macrophage inflammatory protein 1β and interleukin 13 levels were significantly elevated in the urine of the stone forming adolescents compared to controls. Interleukin 17A was elevated in the urine of controls. This study indicates that urine levels of cytokines involved in chronic inflammation and fibrosis are elevated in urinary stone formers as early as adolescence. Because stone formers are at risk for chronic kidney disease, macrophage inflammatory protein 1β and interleukin 13 represent investigative targets.
Kusumi Kirsten; Ketz John; Saxena Vijay; Spencer John David; Safadi Fayez; Schwaderer Andrew
Urolithiasis
2019
2019-04
<a href="http://doi.org/10.1007/s00240-019-01133-1" target="_blank" rel="noreferrer noopener">10.1007/s00240-019-01133-1</a>
Comparison of Risk Factors for Pediatric Kidney Stone Formation: The Effects of Sex.
pediatrics; age; sex; kidney stones; urolithiasis
Background: Urinary stones are affecting more children, and pediatric stone formers have unique pathophysiology compared to adults. While adult stone formers are most frequently male, children have an age dependent sex prevalence. Under 10 years, a majority of stone formers are boys; adolescent stone formers are mostly female. Previous adult studies have shown that stone composition is influenced by the sex and age of the stone former. Thus, we hypothesize that female and male stone forming children will also have sex and age specific stone phenotypes. Methods: Retrospective chart review of a large pediatric center's stone forming children 6/1/2009 to 6/1/2016. Patients were identified by ICD 9 codes: N20, N20.1, and N20.9. Charts were reviewed for radiographic evidence of stones or documented visualized stone passage. Results: One hundred and thirty six subjects: 54 males and 82 females. Females were older, median age 14 years [interquartile range (IQR): 11, 15] vs. males' median age 12 years (IQR: 11, 14) (p < 0.01). Females had lower height z-scores, median 0.2 (IQR: -0.8, 0.8) vs. males' median 0.8 (IQR: -0.2, 1.8) (p < 0.01). Presenting symptoms were similar except flank pain affecting 39% of females vs. 22% of males (p = 0.04). Leukocyte esterase was positive in more females than males (33 vs. 4%) (p < 0.001). Males had a higher BUN/Cr ratio, mean +/- standard deviation of 19.8 +/- 6.3 vs. 16.6 +/- 6.5 in females (p = 0.01). Glomerular hyperfiltration was present in 9% of patients while 35% of patients had estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m(2). Treatment strategies and clinical course were similar except females were told to increase dietary citrate more frequently than males (21 vs. 4%) (p < 0.01). Conclusion: We have provided a novel analysis and demonstrated that low height z-score and pyuria are more common in female stone formers. We have also shown that 9% of pediatric stone formers have labs consistent with hyperfiltration. Whether high protein intake and/or chronic dehydration are associated with hyperfiltration and long-term renal function in children with kidney stones will be an area for future research.
Schwaderer Andrew L; Raina Rupesh; Khare Anshika; Safadi Fayez; Moe Sharon M; Kusumi Kirsten
Frontiers in pediatrics
2019
2019
<a href="http://doi.org/10.3389/fped.2019.00032" target="_blank" rel="noreferrer noopener">10.3389/fped.2019.00032</a>
Renal Calcium Oxalate Deposits Induce a Pro-Atherosclerotic and Pro-Osteoporotic Response in Mice.
*CARDIOVASCULAR DISEASE; *Gene Expression Regulation; *KIDNEY STONES; *METABOLIC BONE DISEASE; *MURINE MODEL; Animal; Animals; Atherosclerosis/*metabolism/pathology; Calcium Oxalate/*metabolism; Disease Models; Kidney/*metabolism/pathology; Mice; Osteoporosis/*metabolism/pathology; Urinary Calculi/*metabolism/pathology
Urinary stone disease (USD) is increasing in adult and pediatric populations. Adult and pediatric studies have demonstrated decreased bone mineral density and increased fracture rates. USD has also been independently linked to increased rates of myocardial infarction and cerebral vascular accidents. Although USD is a multisystem disorder involving the kidneys, bone, and vasculature, the molecular mechanisms linking these three organs remain unknown. Calcium oxalate nephropathy was induced in C57BL/6J mice with intra-peritoneal (ip) injection of sodium glyoxolate. Half of each kidney underwent Pizzalato staining and half was snap frozen for RNA extraction. RT(2) Profiler Mouse Atherosclerosis, Osteoporosis, and Calcium Signaling PCR Arrays (Qiagen) were performed. Only results that passed quality checks in PCR array reproducibility and genomic DNA contamination were included. Genes had to show at least fourfold differential expression and P \textless 0.01 to be considered significant. Atherosclerosis array showed upregulation of 19 genes by fourfold, 10 of which were \textgreater/=10-fold. All 19 had P 10-fold increase. All 10 have P /=10-fold. All 10 have P
Kusumi Kirsten; Barr-Beare Evan; Saxena Vijay; Safedi Fayez; Schwaderer Andrew
Journal of cellular biochemistry
2017
2017-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jcb.25924" target="_blank" rel="noreferrer noopener">10.1002/jcb.25924</a>