Renal citrate metabolism and urinary citrate excretion in the infant rat

Renal citrate metabolism and urinary citrate excretion in the infant rat.BackgroundAlthough hypercalciuria has the same prevalence in children as adults, children rarely develop renal stones. This may be explained by a greater urinary citrate excretion in infants compared with adults. The present study examines the renal excretion of citrate and renal cortical citrate metabolism in infant and adult rats.MethodsAdult male and newly weaned infant rats were acclimated to metabolic cages and fed synthetic diets. Urine was collected after two days, and renal cortical citrate metabolism was assayed.ResultsInfant rats had a lower plasma [HCO3-] and higher plasma [K+] and had a fourfold higher urinary citrate:creatinine ratio and a twofold higher concentration of citrate in their urine compared with adult rats. This higher urinary citrate excretion was not due to a difference in renal proximal tubular Na/citrate cotransporter activity, nor renal cortical citrate synthase or ATP citrate lyase activities in infants as compared with adults. However, infant rat kidneys had significantly lower mitochondrial aconitase (m-aconitase) activity. Renal cortical citrate concentrations were comparable in infant and adult rats. Manipulation of plasma [K+] to adult levels did not affect the higher urinary citrate excretion in infant rats.ConclusionsUrinary citrate excretion in infant rats is greater than in adults but does not parallel tissue [citrate]. Thus, this higher urinary citrate is likely due to maturational differences in the proximal tubule, other than Na/citrate cotransport, that directly affect citrate transport

Renal citrate metabolism and urinary citrate excretion in the infant rat

Renal citrate metabolism and urinary citrate excretion in the infant rat.BackgroundAlthough hypercalciuria has the same prevalence in children as adults, children rarely develop renal stones. This may be explained by a greater urinary citrate excretion in infants compared with adults. The present study examines the renal excretion of citrate and renal cortical citrate metabolism in infant and adult rats.MethodsAdult male and newly weaned infant rats were acclimated to metabolic cages and fed synthetic diets. Urine was collected after two days, and renal cortical citrate metabolism was assayed.ResultsInfant rats had a lower plasma [HCO3-] and higher plasma [K+] and had a fourfold higher urinary citrate:creatinine ratio and a twofold higher concentration of citrate in their urine compared with adult rats. This higher urinary citrate excretion was not due to a difference in renal proximal tubular Na/citrate cotransporter activity, nor renal cortical citrate synthase or ATP citrate lyase activities in infants as compared with adults. However, infant rat kidneys had significantly lower mitochondrial aconitase (m-aconitase) activity. Renal cortical citrate concentrations were comparable in infant and adult rats. Manipulation of plasma [K+] to adult levels did not affect the higher urinary citrate excretion in infant rats.ConclusionsUrinary citrate excretion in infant rats is greater than in adults but does not parallel tissue [citrate]. Thus, this higher urinary citrate is likely due to maturational differences in the proximal tubule, other than Na/citrate cotransport, that directly affect citrate transport

Renal cortical mitochondrial aconitase is regulated in hypo- and hypercitraturia

Renal cortical mitochondrial aconitase is regulated in hypo- and hypercitraturia.BackgroundChronic metabolic acidosis and K+ deficiency increase, while alkali feeding decreases proximal tubule citrate absorption and metabolism. The present studies examined the regulation of mitochondrial aconitase (m-aconitase), the first step in mitochondrial citrate metabolism, in these conditions.MethodsRats were fed appropriate diets, and m-aconitase activity and protein abundance measured.ResultsIn chronic metabolic acidosis and chronic K+ deficiency, renal cortical m-aconitase activity was increased 17% and 43%, respectively. This was associated with respective 90% and 221% increases in renal cortical m-aconitase protein abundance. With chronic alkali feeding, there was a 12% decrease in renal cortical m-aconitase activity, associated with a 35% decrease in m-aconitase protein abundance. Hepatic m-aconitase activity was not regulated in a similar manner. There was no regulation of citrate synthase, the enzyme responsible for mitochondrial citrate synthesis.ConclusionsThese studies demonstrate tissue specific chronic regulation of renal cortical m-aconitase activity and protein abundance, which likely contributes to the hypocitraturia and hypercitraturia seen in these conditions. As m-aconitase is the only step in citrate transport and metabolism found to be regulated in alkali feeding, its regulation likely plays a significant role in mediating the hypercitraturia seen in this condition

Role of Cytolethal Distending Toxin in Altered Stool Form and Bowel Phenotypes in a Rat Model of Post-infectious Irritable Bowel Syndrome.

Background/aimsCampylobacter jejuni infection is a leading cause of acute gastroenteritis, which is a trigger for post-infectious irritable bowel syndrome (PI-IBS). Cytolethal distending toxin (CDT) is expressed by enteric pathogens that cause PI-IBS. We used a rat model of PI-IBS to investigate the role of CDT in long-term altered stool form and bowel phenotypes.MethodsAdult Sprague-Dawley rats were gavaged with wildtype C. jejuni (C+), a C. jejunicdtB knockout (CDT-) or saline vehicle (controls). Four months after gavage, stool from 3 consecutive days was assessed for stool form and percent wet weight. Rectal tissue was analyzed for intraepithelial lymphocytes, and small intestinal tissue was stained with anti-c-kit for deep muscular plexus interstitial cells of Cajal (DMP-ICC).ResultsAll 3 groups showed similar colonization and clearance parameters. Average 3-day stool dry weights were similar in all 3 groups, but day-to-day variability in stool form and stool dry weight were significantly different in the C+ group vs both controls (P < 0.01) and the CDT- roup (P < 0.01), but were not different in the CDT- vs controls. Similarly, rectal lymphocytes were significantly higher after C. jejuni (C+) infection vs both controls (P < 0.01) and CDT-exposed rats (P < 0.05). The counts in the latter 2 groups were not significantly different. Finally, c-kit staining revealed that DMP-ICC were reduced only in rats exposed to wildtype C. jejuni.ConclusionsIn this rat model of PI-IBS, CDT appears to play a role in the development of chronic altered bowel patterns, mild chronic rectal inflammation and reduction in DMP-ICC

Access to primary care is associated with better autoimmune hepatitis outcomes in an urban county hospital

BACKGROUND: Autoimmune hepatitis causes chronic hepatitis and often leads to cirrhosis and death without treatment. We wanted to see if having access to primary care or insurance prior to diagnosis is associated with better outcomes for patients in an urban, public hospital with mostly socioeconomically disadvantaged Hispanic patients. METHODS: We did a retrospective study at our institution. Kaplan Meier survival analysis was done looking at transplant-free overall survival for patients diagnosed at our institution. The log-rank test was done to compare survival between patients with and without prior access to primary care, and between patients with and without insurance at diagnosis. RESULTS: Overall 5- and 10-year transplant-free overall survival was 91 % (95 % CI, 83-100 %) and 75 % (95 % CI, 50-99 %), respectively. Patients with primary care prior to diagnosis had significantly better transplant-free overall survival than those without (log rank test p = 0.019). Patients with primary care also had better clinical markers at diagnosis. Having insurance at diagnosis was not associated with better outcomes. CONCLUSIONS: Outcomes of autoimmune hepatitis are poor in our setting but access to primary care prior to diagnosis was associated with better outcomes. This is likely due to the important role that primary care plays in detecting disease and initiating treatment earlier. With the expansion of access to healthcare that the Affordable Care Act provides, future patients are likely to do better with even rare diseases like autoimmune hepatitis

Two-Year Utilization and Expenditures for Children After a Firearm Injury

INTRODUCTION: Firearm injuries are a leading cause of morbidity among children, but data on healthcare utilization and expenditures after injury are limited. This study sought to analyze healthcare encounters and expenditures for 2 years after a nonfatal firearm injury. METHODS: A retrospective cohort study was conducted between 2020 and 2022 of children aged 0-18 years with International Classification of Diseases, Ninth Revision/ICD-10 diagnosis codes for firearm injury from 2010 to 2016 in the Medicaid MarketScan claims database. Outcomes included the difference in healthcare encounters and expenditures, including mental health. Descriptive statistics characterized patient demographics and healthcare utilization. Changes in health expenditures were evaluated with Wilcoxon sign rank tests. RESULTS: Among 911 children, there were 12,757 total healthcare encounters in the year before the index firearm injury, 15,548 1 encounters in the year after (p\u3c0.001), and 10,228 total encounters in the second year (p\u3c0.001). Concomitantly, there was an overall increase of $14.4 million in health expenditures ($11,415 per patient) 1 year after (p\u3c0.001) and a $0.8 million decrease 2 years after the firearm injury (p=0.001). The children with low previous expenditures (majority of sample) had sustained increases throughout the second year after injury. There was a 31% and 37% absolute decrease in mental health utilization and expenditures, respectively, among children 2 years after the firearm injury. CONCLUSIONS: Children who experience nonfatal firearm injury have an increased number of healthcare encounters and healthcare expenditures in the year after firearm injury, which is not sustained for a second year. Mental health utilization and expenditures remain decreased up to 2 years after a firearm injury. More longitudinal research on the morbidity associated with nonfatal firearm injuries is needed