Kidney transplant in pediatric gut transplant recipients - Technical challenges and outcomes.

BACKGROUND: There is limited data in the literature about pediatric kidney transplant (KT) following gut transplant (GT). The purpose of this study is to highlight the technical challenges and outcomes of KT in pediatric gut recipients who developed kidney failure (KF). METHODS: A retrospective single-center study of pediatric GT recipients from January 2000 to December 2019 was performed. In total, 14 (7%) out of 206 pediatric GT recipients developed KF and were listed for KT. Ten patients underwent kidney after gut transplant (KAGT), three patients underwent simultaneous kidney and re-do gut transplant (SKAGT), and one patient died on the KT waitlist. RESULTS: 1-, 5-, and 10-year kidney graft survival was 100%, 91%, and 78%, respectively. 1-, 5-, and 10-year GT graft survival was 100%, 77%, and 77%, respectively. 1-, 5-, and 10-year patient survival was 100%, 91%, and 91%, respectively. CONCLUSION: Despite the technical complexity, KAGT and SKAGT for pediatric GT recipients that develop KF can be performed with favorable outcomes.

Investigating the human spirit and spirituality in pediatric patients with kidney disease.

Human spirit is an integral part of the medicinal art and science trifecta: body-mind-spirit, and it is contained in the World Health Organization definition of health. Human spirit is defined as our purpose in life, relationships with all living creatures or "Higher Power", and in general our place on planet Earth. Spirituality is a required part of patient care according to Joint Commission on Accreditation of Health Care Organizations. There is an abundant medical literature that documents discrepancies in the results between studies and populations, and points to the importance of cultural, ethnic, spiritual or religious differences. Validated questionnaires used in research for last several decades demonstrated an association of spirituality with clinical outcomes, coping, and quality of life in different adult chronic diseases. There are also validated scales to measure hope in children based on the premise that children are goal directed and that their goal-related thoughts can be understood, yet their purposefulness, meaning of life and spirit in pediatric nephrology remains mostly unexamined. Although pediatric nephrology has made significant advances in molecular techniques, artificial intelligence, machine learning, and started to address more broad social issues such as racism, health equity, diversity of our work force, etc, it lacks both systematic ways of studying and philosophical approach to fostering human spirit. This mini review examines the place and knowledge gaps in human spirit and spirituality in pediatric nephrology. We review the concept of the human spirit and medical literature pertaining to its role in pediatric nephrology.

Hyponatremia Treatment Guidelines - Have They Gone Too Far?

Hyponatremia is a common electrolyte abnormality affecting hospitalized patients.1 It is an independent predictor for mortality and is associated with increased length of hospital stay and higher costs. The most serious potential complication is hyponatremic encephalopathy, a medical emergency that can result in death or irreversible brain injury if inadequately treated.2 Hypertonic saline is a safe and effective means of correcting hyponatremia.2-4 A rare yet serious complication from excessive correction of chronic hyponatremia is the development of cerebral demyelination.

Balanced Crystalloids versus Normal Saline in Children with Critical Asthma.

There is little known about the impact of maintenance fluid choice in children with critical asthma on clinical outcomes. Our primary study objectives were to determine the differences in the serum chloride and bicarbonate levels based on the receipt of 0.9% saline or a balanced solution. The secondary study objectives included differences in acute kidney injury (AKI) and intensive care unit (ICU)/hospital length of stay (LOS). In this retrospective cohort study, we included 1166 patients admitted to a quaternary children's hospital with critical asthma between 2017 and 2019. The patients were stratified based on if they received 0.9% saline or a balanced solution (Lactated Ringer's or Plasma-lyte) for maintenance therapy. The study outcomes were determined using independent sample t-tests, multivariable logistic regression, and negative binomial regression. The patients who received 0.9% saline maintenance therapy had a significantly higher increase in their serum chloride levels when compared to those who received balanced solutions (0.9% saline: +4 mMol/L, balanced: +2 mMol/L, p = 0.002). There was no difference in the decrease in the serum bicarbonate levels (0.9% saline: -0.4 mMol/L, balanced: -0.5 mMol/L, p = 0.830). After controlling for age, race, sex, and the Pediatric Logistic Organ Dysfunction (PELOD-2) score, there was no association between the type of fluid received and the development of AKI (OR 0.87, 95% CI: 0.46-1.63, p = 0.678). Additionally, there was no association between the type of fluid and hospital or ICU LOS. Thus, despite higher serum chloride levels in the patients that received 0.9% saline, the choice of fluid therapy did not have an impact on the serum bicarbonate values, the development of AKI or hospital and ICU LOS, suggesting there is little difference between 0.9% saline and balanced solutions as maintenance therapy in children with critical asthma.

Administration of 3% Sodium Chloride and Local Infusion Reactions.

Three-percent sodium chloride (3% NaCl) is a hyperosmolar agent used to treat hyponatremic encephalopathy or other cases of increased intracranial pressure. A barrier to the use of 3% NaCl is the perceived risk of local infusion reactions when administered through a peripheral vein. We sought to evaluate reports of local infusion reactions associated with 3% NaCl over a 10-year period throughout a large healthcare system. A query was conducted through the Risk Master database to determine if there were any local infusion reactions associated with peripheral 3% NaCl administration throughout the entire UPMC health system, which consists of 40 hospitals with 8400 licensed beds, over a 10-year time period from 14 May 2010 to 14 May 2020. Search terms included infiltrations, extravasations, phlebitis, IV site issues, and IV solutions. There were 23,714 non-chemotherapeutic and non-contrast-associated intravenous events, of which 4678 (19.7%) were at UPMC Children's Hospital. A total of 2306 patients received 3% NaCl, of whom 836 (35.8%) were at UPMC Children's Hospital. There were no reported local infusion reactions with 3% NaCl. There were no reported local infusion reaction events associated with 3% NaCl in a large healthcare system over a 10-year period. This suggests that 3% NaCl can be safely administered through a peripheral IV or central venous catheter.

Infantile Primary Hyperoxaluria Type 1 Treated With Lumasiran in Twin Males.

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that results in oxalate overproduction leading to nephrolithiasis (NL), nephrocalcinosis (NC), kidney failure, and systemic oxalosis. Infantile PH1 is its most severe form, and it may require intensive hemodialysis followed by a liver-kidney transplant. Lumasiran is an RNA interference (RNAi) therapeutic agent that reduces hepatic oxalate production, which has been recently approved for the treatment of PH1. In this report, we present a case of twin males with infantile PH1 and bilateral NL and NC who were treated with lumasiran at 12 months of age. Their symptoms abated after therapy was started without disease progression. To the best of our knowledge, this is the first report of PH1 occurring in twins and the first report on using lumasiran to treat infantile PH1 outside of a clinical trial. Lumasiran appears to be a successful therapeutic option for infantile PH1.

Association of early hyponatremia and the development of acute kidney injury in critically ill children.

BACKGROUND: Hyponatremia is an independent prognostic factor for mortality; however, the reason for this remains unclear. An observed relationship between hyponatremia and the development of acute kidney injury (AKI) has been reported in certain disease states, but hyponatremia has not been evaluated as a predictor of AKI in critically ill patients or children. METHODS: This is a single-center retrospective cohort study of critically ill children admitted to a tertiary care center. We performed regression analysis to assess the association between hyponatremia at ICU admission and the development of new or worsening stage 2 or 3 (severe) AKI on days 2-3 following ICU admission. RESULTS: Among the 5057 children included in the study, early hyponatremia was present in 13.3% of children. Severe AKI occurred in 9.2% of children with hyponatremia compared to 4.5% of children with normonatremia. Following covariate adjustment, hyponatremia at ICU admission was associated with a 75% increase in the odds of developing severe AKI when compared to critically ill children with normonatremia (aOR 1.75, 95% CI 1.28-2.39). Evaluating sodium levels continuously, for every 1 mEq/L decrease in serum sodium level, there was a 0.05% increase in the odds of developing severe AKI (aOR 1.05, 95% CI 1.02-1.08). Hyponatremic children who developed severe AKI had a higher frequency of kidney replacement therapy, AKI or acute kidney disease at hospital discharge, and hospital mortality when compared to those without. CONCLUSIONS: Hyponatremia at ICU admission is associated with the development of new or worsening AKI in critically ill children. A higher resolution version of the Graphical abstract is available as Supplementary information.

A Survey of Hospital Pharmacy Guidelines for the Administration of 3% Sodium Chloride in Children.

Three percent sodium chloride (3% NaCl) is the treatment of choice for symptomatic hyponatremia. A barrier to the use of 3% NaCl is the perceived risk of both local infusion reactions and neurologic complications from overcorrection. We examine whether children's hospital pharmacies have policies or practice guidelines for the administration of 3% NaCl and whether these pharmacies have restrictions on the administration of 3% NaCl in terms of rate, route, volume and setting. An Internet survey was distributed to the pharmacy directors of 43 children's hospitals participating in the Children's Hospital Association (CHA) network. The response rate was 65% (28/43). Ninety-three percent (26/28) of pharmacy directors reported a restriction for the administration of 3% NaCl, with 57% restricting its use through a peripheral vein or in a non-intensive care unit setting, 68% restricting the rate of administration and 54% restricting the volume of administration. Seventy-one percent (20/28) reported having written policy or practice guidelines. Only 32% of hospital pharmacies allowed 3% NaCl to be administered through a peripheral IV in a non-intensive care unit setting. The majority of children's hospital pharmacies have restrictions on the administration of 3% NaCl. These restrictions could prevent the timely administration of 3% NaCl in children with symptomatic hyponatremia.

Hyponatremia, Inflammation at Admission, and Mortality in Hospitalized COVID-19 Patients: A Prospective Cohort Study.

Background: Systemic inflammation has been associated with severe coronavirus disease 2019 (COVID-19) disease and mortality. Hyponatremia can result from inflammation due to non-osmotic stimuli for vasopressin production. Methods: We prospectively studied 799 patients hospitalized with COVID-19 between March 7 and November 7, 2020, at Hospital Posadas in Buenos Aires, Argentina in order to evaluate the association between hyponatremia, inflammation, and its impact on clinical outcomes. Admission biochemistries, high-sensitivity C-reactive protein (hsCRP), ferritin, patient demographics, and outcome data were recorded. Outcomes (within 30 days after symptoms) evaluated included ICU admission, mechanical ventilation, dialysis-requiring acute kidney injury (AKI), and in-hospital mortality. Length of hospital stay (in days) were evaluated using comprehensive data from the EHR. Results: Hyponatremia (median Na = 133 mmol/L) was present on admission in 366 (45.8%). Hyponatremic patients had higher hsCRP (median 10.3 [IR 4.8-18.4] mg/dl vs. 6.6 [IR 1.6-14.0] mg/dl, p < 0.01) and ferritin levels (median 649 [IQR 492-1,168] ng/dl vs. 393 [IQR 156-1,440] ng/dl, p = 0.02) than normonatremic patients. Hyponatremia was associated with higher odds of an abnormal hsCRP (unadjusted OR 5.03, 95%CI: 2.52-10.03), and remained significant after adjustment for potential confounders (adjusted OR 4.70 [95%CI: 2.33-9.49], p < 0.01). Hyponatremic patients had increased mortality on unadjusted (HR 3.05, 95%CI: 2.14-4.34) and adjusted (HR 2.76, 95%CI:1.88-4.06) in Cox proportional hazard models. Crude 30-day survival was lower for patients with hyponatremia at admission (mean [SD] survival 22.1 [0.70] days) compared with patients who were normonatremic (mean [SD] survival 27.2 [0.40] days, p < 0.01). Conclusion: Mild hyponatremia on admission is common, is associated with systemic inflammation and is an independent risk factor for hospital mortality. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04493268.

Primary Hyperoxaluria Type 1 Disease Manifestations and Healthcare Utilization: A Multi-Country, Online, Chart Review Study.

Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that can result in irreversible damage to the kidneys and, eventually, extrarenal organs. While kidney failure is a known consequence of PH1, few studies to date have characterized clinical consequences of PH1 prior to kidney failure, and data on healthcare resource use outcomes across different stages of disease severity in PH1 are also limited. To help fill this knowledge gap, this study characterized the clinical and healthcare resource use (HRU) burden in patients with PH1 with varying stages of kidney disease. Methods: Nephrologists in the United States, Canada, United Kingdom, France, Germany, and Italy abstracted chart data from patients with PH1 under their care via an online questionnaire. Eligible patients had confirmed PH1 and ≥2 office visits from 2016 to 2019. Results: A total of 120 patients were analyzed (median age at diagnosis, 17.4 years old, median age at index 19.5 years old, median eGFR at index 45 ml/min/1.73 m2; median follow-up 1.7 years). During follow-up, the most common PH1 manifestations were kidney stones and urinary tract infections (UTIs, both 56.8%), and the most common symptoms were fatigue/weakness (71.7%) and pain (64.6%). With regard to HRU during follow-up, 37.4% required lithotripsy, 31.3% required ureteroscopy, and 9.6% required nephrolithotomy. PH1-related hospitalizations and emergency/urgent care visits were noted for 84.0 and 81.6% of patients, respectively. Conclusions: The current study demonstrated that patients with PH1 across various stages of kidney disease exhibited a substantial clinical burden, including kidney stones, UTIs, fatigue/weakness, and pain, and required frequent HRU, including kidney stone procedures, hospitalizations, and emergency visits. These findings highlight the significant morbidity and HRU burden in patients with PH1.

Transient Hyperphosphatasemia Following Pediatric Kidney Transplant.

Introduction Transient hyperphosphatasemia (TH) is a rare benign condition of elevated serum alkaline phosphatase (AP) levels seen in healthy children. TH has been reported to occur in pediatric solid organ transplants, including kidney transplant patients. Little is known about TH in pediatric kidney transplant patients. Objective To evaluate the incidence and natural history of TH in pediatric kidney transplant patients. Methods A retrospective chart review of patients < 18 years of age who underwent kidney transplantation at the University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between 2008 and 2019 was performed to identify patients with TH, defined as an AP level greater than 1,000 IU/L. Exclusion criteria included repeat kidney transplants or kidney transplant as part of a multiorgan transplant. Results One hundred seventy-six patients underwent a solitary kidney transplant, of which 87 were less than 12 years of age. Eleven patients (6.5%) were found to have TH, all of whom were < 12 years of age (12.8%) (median age: 5 years; range: 1 - 11 years). The median AP level prior to transplant was 183 IU/L (range: 104 - 309 IU/L) and the median peak AP was > 2,300 IU/L (range: 1,227 - 4,912 IU/L). The median time from a kidney transplant to the diagnosis of TH was 0.6 years (range: 0.3 to 7.7 years). The median length of time that TH persisted was 0.5 years (range: 0.2 to 0.9 years). The median estimated glomerular filtration rate (GFR) at the time of diagnosis of TH was 84 mL/min/1.73m2 per the bedside Schwartz equation (range: 45 to 152 mL/min/1.73m2). One patient had variable AP levels over nine months prior to resolution; the other 10 patients had a solitary peak of AP prior to resolution. No patient required treatment of elevated AP levels and the TH resolved spontaneously without intervention. No patients had significant abnormalities of markers of metabolic bone disease or were on active vitamin D, calcium, or phosphorus supplements. Two patients reported bone pain, and one patient was found to have avascular necrosis of the hip. Conclusions TH is a relatively common finding following a pediatric kidney transplant in pre-pubertal children less than 12 years of age. It primarily occurs in the first year following a kidney transplant and usually resolves without recurrence within one year of onset.

Prostatic cyst in a pediatric patient with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inheritable form of renal cystic disease and is associated with cysts in other organs. Prostatic cysts are rare though and have not been reported in the paediatric population. Reported is the presence of a prostatic cyst that was incidentally noted on routine sonogram in a 15 year old with ADPKD.

Chronicity of Uncorrected Hyponatremia and Clinical Outcomes in Older Patients Undergoing Hip Fracture Repair.

Background: Chronic hyponatremia is a risk factor for hip fracture but remains uncorrected in most patients. This study evaluated if preoperative chronicity of uncorrected hyponatremia influences outcomes after hip fracture repair. Materials and Methods: Evaluated were older patients hospitalized for hip fracture repair between 2007 and 2012 with plasma sodium measured at admission and ≥1 preadmission outpatient measurement. Patients were classified as being normonatremic (NN; plasma sodium 135-145 mmol/L), chronic prolonged hyponatremia (CPH; ≥2 consecutive plasma sodium values <135 mmol/L over >90 days), or recent hyponatremia (one plasma sodium <135 mmol/L within 30 days before admission with previously normal plasma sodium). Length of hospital stay, in-hospital death, post-operative complications, 30-day readmission, and long-term mortality were the evaluated outcomes. Multivariable Cox regression was used to evaluate the association of hyponatremia status with outcomes. Results: Among 1,571 eligible patients, 76.7% were NN, 14% had CPH, and 9.1% had RH. Compared with NN patients, CHN patients were older and had more prior heart failure, alcoholism, and anticonvulsant drug use. In multivariable analyses, neither CPH or RH was associated with hospital length of stay, in-hospital or 30-day death, or 30-day readmission, while RH was associated with post-operative sepsis [adjusted odds ratio (aOR) 1.84, 95% CI: 1.01-3.35). Only CPH was independently associated with long-term all-cause death (OR 1.53, 95% CI: 1.12-2.09). Conclusions: Hyponatremia affects nearly 25% of patients undergoing hip fracture repair. Preoperative chronic untreated hyponatremia is associated with increased post-operative mortality following surgical repair of a hip fracture in older patients. Future studies should evaluate if correction of hyponatremia could decrease long-term mortality after hip fracture repair.

Use of C-Reactive Protein and Ferritin Biomarkers in Daily Pediatric Practice.

Recent pediatric clinical research has begun to focus on risk stratification tools using multibiomarker models. C-reactive protein (CRP) and ferriti biomarkers are widely available and used to varying degrees in daily practice, but there is no single source examining the evidence behind their use.We set out to summarize the evidence behind the use of CRP and ferritin biomarkers in pediatric practice and to begin development of a consensus for their future use for pediatricians.All the literature involving CRP and ferritin in pediatrics available on PubMed was surveyed. Research applicable to daily pediatric practice was summarized in the body of the article. Pediatric clinicians of various subspecialties contributed to the summary of the use of CRP and ferritin biomarkers in clinical practice in various disease processes. A clinical decision pathway is described, and evidence is summarized.CRP and ferritin biomarkers have diverse uses with various cutoff values in the literature, making their use in daily practice difficult. Elevation of these markers coincides with their significant elevation in uncontrolled inflammation.CRP and ferritin biomarkers are widely used in pediatrics. This review provides a resource summarizing evidence into a single source. There is sufficient evidence to indicate that these biomarkers of inflammation can be useful in guiding clinical decision making in specific clinical scenarios; however, further work is needed to improve their use in clinical practice.

Fragility fractures and reversible osteopaenia due to chronic hyponatraemia in an adolescent male.

Fragility fractures are common in older adults and rare in children. Recent studies have demonstrated that hyponatraemia is a novel risk factor for the development of osteoporosis and hip fractures in older people. Animal studies suggest that hyponatraemia can lead to decreased bone mineral density by stimulating osteoclastic activity in order to mobilise sodium from the bone. Reported is a 16-year-old man with intractable epilepsy and an 11-year history of chronic hyponatraemia (126-135 mEq/L) due to valproic acid induced syndrome of inappropriate antidiuresis who sustained low-impact fragility fractures and had evidence of osteopaenia on both X-ray and dual energy X-ray absorptiometry (DEXA). Hyponatraemia resolved following the discontinuation of valproic acid and bone mineral density normalised on a repeat DEXA 19 months later. This case provides evidence supporting the contention that chronic hyponatraemia contributes to osteopaenia and fragility fractures and that the bone abnormalities are potentially reversible following the correction of hyponatraemia.

Misconceptions and Barriers to the Use of Hypertonic Saline to Treat Hyponatremic Encephalopathy.

Hyponatremic encephalopathy is a potentially life-threatening condition with a high associated morbidity and mortality. It can be difficult to diagnose as the presenting symptoms can be non-specific and do not always correlate with the degree of hyponatremia. It can rapidly progress leading to death from transtentorial herniation. Hypertonic saline is the recommended treatment for hyponatremic encephalopathy, whether acute or chronic, yet it is infrequently used. We believe that the main barriers to its use is the perception that hypertonic saline is associated with a significant risk for cerebral demyelination, that it can't be administered through a peripheral IV and that it requires monitoring in the ICU. Two illustrative cases are presented followed by a discussion of how intermittent bolus's of 100-150 ml of 3% NaCl in rapid succession to acutely increase the plasma sodium by 4-6 mEq/L is a safe and effective way to treat hyponatremic encephalopathy, that can be administered through a peripheral IV in a non-ICU setting.

How Salty Are Your Fluids? Pediatric Maintenance IV Fluid Prescribing Practices Among Hospitalists.

Objective: The primary goal of this study was to assess current maintenance intravenous fluid (mIVF) prescribing practices of pediatric hospitalists after the release of the American Academy of Pediatrics Clinical Practice Guideline (AAP CPG), specifically assessing the rates of various isotonic vs. hypotonic solutions used in discrete age groups and in common clinical scenarios associated with anti-diuretic hormone (ADH) excess and hyponatremia. We hypothesized that isotonic fluids would be selected in most cases outside of the neonatal period. Methods: A voluntary and anonymous survey was distributed to the LISTSERV® for the AAP Section on Hospital Medicine. Results: There were 402 total responses (10.1% response rate) with the majority of respondents being pediatric hospitalists. Isotonic solutions were preferred by respondents in older children compared to younger age groups, at 87.8% for the 1-18 years age group compared to 66.3% for the 28 days to 1 year age group and 10.6% for the younger than 28 days age group (all p values <0.0001). When presented with disease states associated with ADH excess, isotonic fluids were preferred in higher percentages in all age groups except in children younger than 28 days when 0.45% sodium chloride was preferred; 0.2% sodium chloride was rarely chosen. Conclusions: Overall, based on survey responses, pediatric hospitalists are following the 2018 AAP CPG on mIVF and are more likely to choose isotonic fluids as their primary mIVF in pediatric patients outside of the neonatal period, including in scenarios of excess ADH. Isotonic fluids use seems to be higher with increasing age and hypotonic fluids are more commonly chosen in the neonatal period.