Creative Arts Therapy Among Children With Cancer: Symptom Assessment Reveals Reduced Anxiety.

BACKGROUND: Symptom distress is related to decreased quality of life (QOL) among children with cancer, with high levels of pain, nausea, and anxiety reported. Creative arts therapy (CAT) has been related to improved QOL and symptoms in pediatric oncology, but the quality of evidence is mixed. OBJECTIVE: This article aims to examine the QOL symptom subscales in relation to CAT over time in children during the first year of cancer treatment. METHODS: A secondary analysis of prospective data was performed with linear mixed modeling on 267 observations with predictors of 2 groups: No CAT (n = 18) vs CAT (n = 65). The covariate of time (6 months) was used to explore the CAT relationship with the Pediatric Quality of Life Inventory (PedsQL) symptom subscales (pain and hurt, nausea, procedural anxiety, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication). RESULTS: Children (n = 83) were between 3 and 17 years old (M = 6), 51.2% female, and 32% minority. All tumor types were represented: liquid (37.3%), solid (24.1%), and central nervous system (38.6%). Reduced child report of procedural anxiety was significantly related to receiving CAT with a medium magnitude of association (adjusted effect size = 0.58, P = .01). CONCLUSION: Creative arts interventions were associated with a longitudinal improvement in anxiety in children with cancer. Further work is needed to target interventions to the appropriate specific burdensome symptoms. IMPLICATION FOR PRACTICE: Pediatric oncology nurses can advocate for CAT as an effective intervention to ameliorate the burdensome procedural anxiety experienced by patients.

A Chinese longitudinal maternity cohort study (2013-2021) on intrahepatic cholestasis phenotypes: Risk associations from environmental exposure to adverse pregnancy outcomes.

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease that occurs during mid-to-late pregnancy and is associated with various adverse pregnancy outcomes, including intrauterine fetal demise. However, since the underlying cause of ICP remains unclear, there is an ongoing debate on the phenotyping criteria used in the diagnostic process. Here, we identified single- and multi-symptomatic ICP (ICP-S and ICP-M) in 104,221 Chinese females from the ZEBRA maternity cohort, with the objective of exploring the risk implications of the two phenotypes on pregnancy outcomes and from environmental exposures. We employed multivariate binary logistic regression to estimate confounder-adjusted odds ratios and found that ICP-M was more strongly associated with preterm birth and low birth weight compared to ICP-S. Throughout pregnancy, incremental exposure to PM2.5, O3, and greenness could alter ICP risks by 17.3%, 12.5%, and -2.3%, respectively, with more substantial associations observed with ICP-M than with ICP-S. The major scientific advancements lie in the elucidation of synergistic risk interactions between pollutants and the protective antagonistic effects of greenness, as well as highlighting the risk impact of preconceptional environmental exposures. Our study, conducted in the context of the "three-child policy" in China, provides epidemiological evidence for policy-making to safeguard maternal and neonatal health.

Radiation Protection Considerations for Cancer Patients with End-stage Renal Disease Receiving 131 I Treatment.

ABSTRACT: Differentiated thyroid cancer (DTC) is commonly treated first with a partial or complete thyroidectomy, followed by radioiodine (RAI) ablative therapy to eliminate remaining cancer cells. In such treatments, physical decay and urinary excretion are the primary means of 131 I. As such, patients with impaired urinary ability clearance, such as patients with end-stage renal disease (ESRD) whose urinary ability is impaired by dysfunction, can retain abnormally high activities of RAI, posing a concern to both the patient and those with whom the patient interacts. Additionally, ESRD patients are commonly administered dialysis therapy, wherein their blood is externally cycled through a dialyzer (hemodialysis) or filtered by instilling a dialysate fluid into the peritoneum (peritoneal dialysis) to filter uremic toxins from their blood that accumulate due to kidney dysfunction. These factors make determining release and dosing for ESRD patients receiving RAI therapy dependent on a plurality of variables. An evaluation of the current patient release guidelines, as given in US Nuclear Regulatory Commission (US NRC) Regulatory Guide 8.39 Rev. 1 for ESRD patients receiving RAI, has yet to be addressed. In this study, a biokinetic model for 131 I in ESRD patients receiving dialysis has been developed, improving on traditional two-compartment models, reflective of kinetics from multi-compartment models with updated transfer coefficients modified to reflect the different physiological functions of compartments. This updated biokinetic model was integrated with Monte Carlo radiation transport calculations using stylized computational hermaphroditic phantoms to calculate dose rate coefficients in exposure scenarios and compared with those of the point source models of NRC Reg Guide 8.39 Rev. 1 (and the proposed verbiage in Rev. 2). Results demonstrated that the baseline models of Rev. 1 and Rev. 2 overestimated the effective dose rate to an exposed individual for the majority of time post-administration, where both models overestimated the total dose to the maximally exposed individual. However, the application of several patient-specific modifying factors to the Rev. 2 model resulted in an overestimation by only a factor of 1.25, and in general, the results produced with the patient-specific modifications provide improved convergence with the dose rate coefficients computed in this study for ESRD patients.

Clinico- Radiological Profile and Outcome of Isolated Paramedian Hemipontine Infarcts.

OBJECTIVE: To study the clinico- radiological profile and outcome of isolated paramedian hemipontine infarcts. MATERIALS AND METHODS: This is a prospective cross- sectional study. 50 consecutive patients admitted between January 2019 and December 2020 with a diagnosis of isolated paramedian hemipontine stroke were included. The locations of the infarcts were classified as follows- caudal; middle; rostral; dorsomedian; caudal and middle; and middle and rostral pons. The clinico- radiological profiles were studied and the outcomes were assessed using NIHSS (National Institutes of Health Stroke Scale) and mRS (modified Rankin score). Data was analysed using SPSS 22 version software. Paired t-test was used as a test of significance to identify the mean differences between the two quantitative variables. RESULTS: Majority of the subjects were 51- 60 years (34 percent). The most common risk factors were hypertension and type 2 diabetes mellitus. The most common clinical features were hemiparesis and speech disturbances. Pure motor hemiparesis (PMH) is the common syndrome seen in paramedian hemipontine strokes with infarcts located in caudal; middle; caudal and middle; and middle and rostral pons. In ataxic hemiparesis, infarcts were located in dorsomedian pons. In dysarthria clumsy hand syndrome, infarcts were located at rostral pons. 44 percent of the subjects had left vertebral artery abnormality. There was a statistically significant difference in the mean NIHSS and mRS when compared at admission/ discharge and at 3 months. CONCLUSION: Isolated paramedian hemipontine stroke syndromes have good topographical correlation with patients usually having a good functional outcome at the end of three months.

Fulminant Vaccine-Induced Immune Thrombotic Thrombocytopenia After ChAdOx1 nCoV-19 (AZD1222) Vaccine Administration in a Woman With Obesity: A Case Report.

Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome, is a rare complication of ChAdOx1 nCoV-19 (AZD1222) vaccine administration. The overall incidence of VITT worldwide is one case per 100 000 exposures. Because of the high mortality rate from VITT, thorough monitoring is crucial to predict the risk of occurrence. The underlying risk factors for VITT are not fully understood. Potential risk factors include sex (female) and young age (less than 50 years), but further research must be conducted to confirm these assumptions. We report the case of a woman with obesity, which is a risk factor for deep vein thrombosis in the legs and for pulmonary embolism, who experienced fulminant VITT after AZD1222 vaccine administration. Keywords: Vaccine-induced immune thrombotic thrombocytopenia, AZ vaccine, Obesity, Risk factor.

Non-Hodgkin's Lymphoma of the Central Nervous System with N-Methyl-D-Aspartate Receptor Antibody Positivity - A Case Report.

PURPOSE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, among the paraneoplastic syndromes, is a recently characterized autoimmune encephalitis most commonly associated with antibodies against subunits of the NMDAR in the central nervous system. As a paraneoplastic syndrome, anti-NMDAR encephalitis is commonly associated with ovarian teratomas, small cell lung carcinomas and testicular germ cell tumors. To our knowledge, there have been no cases with primary central nervous system lymphoma (PCNSL), a rare type of extranodal non-Hodgkin's lymphoma, without lymph node involvement associated with anti-NMDAR encephalitis. CASE REPORT: A 58-year-old right-handed male patient with complaints of instability in walking for two months, progressively smaller handwriting, hallucinations when falling asleep or waking up, decreased memory, inability to maintain attention was admitted to our hospital for further diagnosis and treatment. Lumbar puncture was performed with the diagnosis of possible encephalitis after many further examinations and CSF studies revealed NMDAR antibody positivity, leading to the initial diagnosis of anti - NMDAR encephalitis. He was treated with high dose methylprednisolone and intravenous immunoglobulin. Due to the continuation of the patient's presenting symptoms and cranial magnetic resonance imaging findings, a stereotactic brain biopsy was performed from the area with contrast enhancement and the diagnosis was revised as PCNSL associated with NMDAR antibody positivity. CONCLUSION: This report emphasizes the importance of anti-NMDAR encephalitis as a paraneoplastic syndrome in previously undiagnosed PCNSL. Therefore, it is crucial to be aware of anti-NMDAR encephalitis as a paraneoplastic neurological syndrome that can present with non-Hodgkin's lymphoma. It is necessary to continually observe the evolution of the disease and perform further diagnostic tests for early identification.

Isolated Bilateral Triceps Weakness in Myasthenia Gravis.

PURPOSE: Myasthenia gravis (MG) is the most common autoimmune disease that affects the neuromuscular junction and can cause weakness in various muscle groups. The most commonly affected muscles are the eye, facial, and neck flexors. Focal or dominant weakness of the triceps muscle is rare. In this case, we aimed to describe a rare form of MG consisting of selective or dominant triceps muscle weakness. CASE REPORT: We present a 45-year-old male patient whose initial complaints were diplopia and ptosis. Acetylcholine receptor antibody was positive. After 10 years of well-being following thymectomy, bilateral triceps weakness was added to his ocular symptoms despite regular medication (pyridostigmine and prednisone). Repetitive nerve stimulation (RNS) showed decremental responses in the right triceps muscles. CONCLUSION: It is important to recognize this type of myasthenia gravis to facilitate diagnosis and appropriate treatment and to avoid unnecessary investigations and treatments.

Loss of PKCδ/Prkcd prevents cartilage degeneration in joints but exacerbates hyperalgesia in an experimental osteoarthritis mouse model.

Pain is the prime symptom of osteoarthritis (OA) that directly affects the quality of life. Protein kinase Cδ (PKCδ/Prkcd) plays a critical role in OA pathogenesis; however, its significance in OA-related pain is not entirely understood. The present study investigated the functional role of PKCδ in OA pain sensation. OA was surgically induced in control (Prkcdfl/fl), global- (Prkcdfl/fl; ROSACreERT2), and sensory neuron-specific conditional knockout (cKO) mice (Prkcdfl/fl; NaV1.8/Scn10aCreERT2) followed by comprehensive analysis of longitudinal behavioral pain, histopathology and immunofluorescence studies. GlobalPrkcd cKO mice prevented cartilage deterioration by inhibiting matrix metalloproteinase-13 (MMP13) in joint tissues but significantly increased OA pain. Sensory neuron-specificdeletion of Prkcd in mice did not protect cartilage from degeneration but worsened OA-associated pain. Exacerbated pain sensitivity observed in global- and sensory neuron-specific cKO of Prkcd was corroborated with markedly increased specific pain mediators in knee synovium and dorsal root ganglia (DRG). These specific pain markers include nerve growth factor (NGF) and vascular endothelial growth factor (VEGF), and their cognate receptors, including tropomyosin receptor kinase A (TrkA) and vascular endothelial growth factor receptor-1 (VEGFR1). The increased levels of NGF/TrkA and VEGF/VEGFR1 were comparable in both global- and sensory neuron-specific cKO groups. These data suggest that the absence of Prkcd gene expression in the sensory neurons is strongly associated with OA hyperalgesia independent of cartilage protection. Thus, inhibition of PKCδ may be beneficial for cartilage homeostasis but could aggravate OA-related pain symptoms.

Secondary Trigeminal Neuralgia Caused by Cerebellopontine Angle Arachnoid Cyst in A 27-Year-Old Female: A Case Report.

PURPOSE: Secondary (TN) caused by an arachnoid cyst in the (CPA) region is a rare finding. Based on the reported literature, there are only 5 cases of secondary trigeminal neuralgia caused by an arachnoid cyst in the cerebellopontine angle region. CASE REPORT: A 27-year-old female presented to our neurosurgery clinic with a 2-year history of brief episodes of paroxysm pain in the left cheek. The pain was described as an electric shock-like pain triggered by simple stimuli. The magnetic resonance imaging (MRI) showed a well-confined cystic lesion in the left CPA, which compresses the left pons and the cisternal segment of the left trigeminal nerve. The patient was managed operatively to fenestrate the cyst and decompress the trigeminal nerve. The histopathological result of the cyst wall was consistent with an arachnoid cyst. Six months after surgery, the patient is in good health condition and symptom-free without medication. CONCLUSION: Arachnoid cyst in the CPA region is one of the rare causes of secondary TN. Preoperative imaging with MRI is important to provide better results to differentiate the pathology. Surgical treatment to fenestrate the arachnoid cyst and decompress the trigeminal nerve have a good result and can improve the patient's quality of life.

HSP90ß regulates EAAT2 expression and participates in ischemia­reperfusion injury in rats.

Cerebrovascular diseases (CVDs) have become a global public health problem and ischemia­reperfusion injury, the major cause of neurological impairment exacerbation, is closely related to excitotoxicity. The present study aimed to investigate the effects of changes in heat shock protein (HSP)90ß expression and verify whether HSP90ß regulates EAAT2 expression in a cerebral ischemia­reperfusion injury model. Healthy adult Sprague­Dawley (SD) male rats were used to establish a control group, sham­operated group, middle cerebral artery occlusion (MCAO) group, empty virus group and lentivirus group. A model of cerebral ischemia­reperfusion was established using the MCAO method. Lentivirus construction and injection were used to interfere with the expression of HSP90ß. The modified neurological severity score was used to assess neurological deficits. Triphenyltetrazolium chloride staining was used to detect infarct areas. Immunofluorescence was used to detect HSP90ß expression localization and the expression levels of HSP90ß and EAAT2 were determined using western blotting and reverse transcription­quantitative PCR. An MCAO model was successfully established and it was found that HSP90ß, but not HSP90α, was upregulated after MCAO. HSP90ß expression coincided with astrocyte markers in the ischemic penumbra area, while no expression was observed in microglia. Inhibition of HSP90ß expression improved neurological deficits and alleviated brain injury by increasing EAAT2 expression. These results suggested that HSP90ß is involved in the process of cerebral ischemia­reperfusion injury in rats and that inhibition of HSP90ß expression increases EAAT2 levels, conferring a neuroprotective effect in MCAO model rats.

Hypertension in Wilms tumor.

Wilms tumor (WT) represents over 90% of all pediatric kidney tumors. Children with WT often present acutely with hypertension which resolves in the short term after nephrectomy. However, WT survivors have increased long-term risk of hypertension, primarily due to decreased nephron mass after nephrectomy, with additional insults from possible exposure to abdominal radiation and nephrotoxic therapies. The diagnosis of hypertension may be improved by ambulatory blood pressure monitoring (ABPM), as several recent single-center studies have shown a substantial proportion of WT survivors with masked hypertension. Current gaps in knowledge include determining which WT patients may benefit from routine screening with ABPM, correlation of casual and ABPM parameters with cardiac abnormalities, and longitudinal assessment of cardiovascular and kidney parameters in relation to appropriate treatment of hypertension. This review aims to summarize the most recent literature on hypertension presentation and management at the time of WT diagnosis as well as the long-term hypertension risk and impact on kidney and cardiovascular outcomes in WT survivors.

Chronic kidney disease-associated pruritus: what is known and its application in children.

Chronic kidney disease-associated pruritus (CKD-aP) or uremic pruritus (UP) is a frequent symptom in patients with kidney failure receiving kidney replacement therapy. Severe chronic kidney disease-associated pruritus correlates with poor outcome in patients on dialysis. It is multifactorial in etiology and has a significant impact on quality of life. There is, however, limited data for children. This review summarizes current epidemiology, clinical characteristics, pruritus scoring systems, and available therapeutic options for pruritus in patients with chronic kidney disease and those receiving dialysis. Optimal care requires proper awareness of the severity of symptoms, the impact on quality of life, and the possible long-term outcomes. Optimizing dialysis prescription and correcting electrolyte abnormalities are important treatment targets. A wide range of therapeutic options is also available although none are well-studied in children. An earlier recognition of this debilitating symptom in children and treatment is imperative. A higher resolution version of the Graphical abstract is available as Supplementary information.

Long-term treatment of chronic kidney disease patients with anemia using hypoxia-inducible factor prolyl hydroxylase inhibitors: potential concerns.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been approved in several countries as a supplement or even an alternative to the clinical treatment of anemia in patients with chronic kidney disease (CKD). Activation of HIF by HIF-PHIs effectively increases hemoglobin (Hb) level in CKD patients by inducing multiple HIF downstream signaling pathways. This indicates that HIF-PHIs have effects beyond erythropoietin, while their potential benefits and risks should be necessarily assessed. Multiple clinical trials have largely demonstrated the efficacy and safety of HIF-PHIs in the short-term treatment of anemia. However, in terms of long-term administration, especially over 1 year, the benefits and risks of HIF-PHIs still need to be assessed. Particular attention should be paid to the risk of kidney disease progression, cardiovascular events, retinal diseases, and tumor risk. This review aims to summarize the current potential risks and benefits of HIF-PHIs in CKD patients with anemia and further discuss the mechanism of action and pharmacological properties of HIF-PHIs, in order to provide direction and theoretical support for future studies.

Incremental dialysis: review of the literature with pediatric perspective.

Drivers towards initiation of kidney replacement therapy in advanced chronic kidney disease include metabolic and fluid derangements, growth, and nutritional status with focus on health optimization. Once initiated, prescription of dialysis is often uniform despite variability in patient characteristics and etiology of kidney failure. Preservation of residual kidney function has been associated with improved outcomes in patients with advanced chronic kidney disease on dialysis. Incremental dialysis is the approach of reducing the dialysis dose by reduction in treatment time, days, or efficiency of clearance. Incremental dialysis has been described in adults at initiation of kidney replacement therapy, to better preserve residual kidney function and meet the individual needs of the patient. Consideration of incremental dialysis in pediatrics may be reasonable in a subset of children with continued emphasis on promotion of growth and development.

Predictive ability of 2-h serum neutrophil gelatinase-associated lipocalin for perinatal asphyxia-induced acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common cause of mortality and morbidity in asphyxiated newborns. Recent research suggests serum neutrophil gelatinase-associated lipocalin (sNGAL) as an early biomarker of AKI in newborns with perinatal asphyxia. The prospect of sNGAL is yet to be studied in Nigeria, with a huge burden of asphyxia-related neonatal deaths. METHODS: A cross-sectional analytic study was conducted on 53 asphyxiated term newborns and 53 healthy babies at the newborn unit of the Wesley Guild Hospital Ilesa, Nigeria. sNGAL was assessed in all neonates with perinatal asphyxia at baseline (within 30 min of delivery), 2 h, and 48 h of life. RESULTS: Mean sNGAL was significantly higher in asphyxiated newborns than in the control group, 81.4 (45.9) vs. 53.7 (29.2), p < 0.001. However, the mean 2-h sNGAL levels were similar in asphyxiated babies with and without AKI 100.5 (36.7) ng/ml vs. 85.3 (31.4) ng/ml, p = 0.115. The 2-h sNGAL with an AUC of 0.61 at an 83.0 ng/ml cut-off had an acceptable discriminating capability of predicting AKI. The sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 51.5%, 50%, and 81%, respectively. CONCLUSION: This study shows that sNGAL levels were significantly elevated in newborns with perinatal asphyxia compared to healthy neonates, but the 2-h sNGAL is less predictive of AKI in newborns with perinatal asphyxia. The negative predictive value is high, and this may find some relevance in the attempts at early exclusion of asphyxiated babies prone to AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Mild hypophosphatasia may be twice as prevalent as previously estimated: an effective clinical algorithm to detect undiagnosed cases.

OBJECTIVES: Since the prevalence of hypophosphatasia (HPP), a rare genetic disease, seems to be underestimated in clinical practice, in this study, a new diagnostic algorithm to identify missed cases of HPP was developed and implemented. METHODS: Analytical determinations recorded in the Clinical Analysis Unit of the Hospital Universitario Clínico San Cecilio in the period June 2018 - December 2020 were reviewed. A new clinical algorithm to detect HPP-misdiagnosed cases was used including the following steps: confirmation of persistent hypophosphatasemia, exclusion of secondary causes of hypophosphatasemia, determination of serum pyridoxal-5'-phosphate (PLP) and genetic study of ALPL gene. RESULTS: Twenty-four subjects were selected to participate in the study and genetic testing was carried out in 20 of them following clinical algorithm criteria. Eighty percent of patients was misdiagnosed with HPP following the current standard clinical practice. Extrapolating these results to the current Spanish population means that there could be up to 27,177 cases of undiagnosed HPP in Spain. In addition, we found a substantial proportion of HPP patients affected by other comorbidities, such as autoimmune diseases (∼40 %). CONCLUSIONS: This new algorithm was effective in detecting previously undiagnosed cases of HPP, which appears to be twice as prevalent as previously estimated for the European population. In the near future, our algorithm could be globally applied routinely in clinical practice to minimize the underdiagnosis of HPP. Additionally, some relevant findings, such as the high prevalence of autoimmune diseases in HPP-affected patients, should be investigated to better characterize this disorder.

Antihypertensive medication nonadherence and target organ damage in children with chronic kidney disease.

BACKGROUND: Nonadherence is common in children with chronic kidney disease (CKD). This may contribute to inadequate blood pressure control and adverse outcomes. This study examined associations between antihypertensive medication nonadherence, ambulatory blood pressure monitoring (ABPM) parameters, kidney function, and cardiac structure among children with CKD. METHODS: We performed secondary analyses of data from the CKD in Children (CKiD) study, including participants with treated hypertension who underwent ABPM, laboratory testing, and echocardiography biannually. Nonadherence was defined by self-report of any missed antihypertensive medication 7 days prior to the study visit. Linear regression and mixed-effects models were used to assess the association of nonadherence with baseline and time-updated ABPM profiles, estimated glomerular filtration rate (eGFR), urine protein to creatinine ratio (UPCR), and left ventricular mass index (LVMI). RESULTS: Five-hundred and eight participants met inclusion criteria, followed for a median of 2.9 years; 212 (42%) were female, with median age 13 years (IQR 10-16), median baseline eGFR 49 (33-64) ml/min/1.73 m2 and median UPCR 0.4 (0.1-1.0) g/g. Nonadherence occurred in 71 (14%) participants. Baseline nonadherence was not significantly associated with baseline 24-h ABPM parameters (for example, mean 24-h SBP [ß - 0.1, 95% CI - 2.7, 2.5]), eGFR (ß 1.0, 95% CI - 0.9, 1.2), UCPR (ß 1.1, 95% CI - 0.8, 1.5), or LVMI (ß 0.6, 95% CI - 1.6, 2.9). Similarly, there were no associations between baseline nonadherence and time-updated outcome measures. CONCLUSIONS: Self-reported antihypertensive medication nonadherence occurred in 1 in 7 children with CKD. We found no associations between nonadherence and kidney function or cardiac structure over time. A higher resolution version of the Graphical abstract is available as Supplementary information.

Hyporeninemic hypoaldosteronism in RMND1-related mitochondrial disease.

BACKGROUND: RMND1 is a nuclear gene needed for proper function of mitochondria. A pathogenic gene will cause multiple oxidative phosphorylation defects. A renal phenotype consisting of hyponatremia, hyperkalemia, and acidosis is frequently reported, previously considered to be due to aldosterone insensitivity. METHODS: Clinical features and pathophysiology of three patients will be reported. DNA of these patients was subjected to exome screening. RESULTS: In the first family, one pathogenic heterozygous and one highly probable heterozygous mutation were detected. In the second family, a homozygous pathogenic mutation was present. The electrolyte disbalance was not due to aldosterone insensitivity but to low plasma aldosterone concentration, a consequence of low plasma renin activity. This disbalance can be treated. In all three patients, the kidney function declined. In the first family, both children suffered from an unexplained arterial thrombosis with dire consequences. CONCLUSIONS: Hyporeninemic hypoaldosteronism is the mechanism causing the electrolyte disbalance reported in patients with RMND1 mutations, and can be treated.

Natural history of urine and plasma oxalate in children with primary hyperoxaluria type 1.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare, severe genetic disease causing increased hepatic oxalate production resulting in urinary stone disease, nephrocalcinosis, and often progressive chronic kidney disease. Little is known about the natural history of urine and plasma oxalate values over time in children with PH1. METHODS: For this retrospective observational study, we analyzed data from genetically confirmed PH1 patients enrolled in the Rare Kidney Stone Consortium PH Registry between 2003 and 2018 who had at least 2 measurements before age 18 years of urine oxalate-to-creatinine ratio (Uox:cr), 24-h urine oxalate excretion normalized to body surface area (24-h Uox), or plasma oxalate concentration (Pox). We compared values among 3 groups: homozygous G170R, heterozygous G170R, and non-G170R AGXT variants both before and after initiating pyridoxine (B6). RESULTS: Of 403 patients with PH1 in the registry, 83 met the inclusion criteria. Uox:cr decreased rapidly over the first 5 years of life. Both before and after B6 initiation, patients with non-G170R had the highest Uox:cr, 24-h Uox, and Pox. Patients with heterozygous G170R had similar Uox:cr to homozygous G170R prior to B6. Patients with homozygous G170R had the lowest 24-h Uox and Uox:cr after B6. Urinary oxalate excretion and Pox tend to decrease over time during childhood. eGFR over time was not different among groups. CONCLUSIONS: Children with PH1 under 5 years old have relatively higher urinary oxalate excretion which may put them at greater risk for nephrocalcinosis and kidney failure than older PH1 patients. Those with homozygous G170R variants may have milder disease. A higher resolution version of the Graphical abstract is available as Supplementary information.

Response to oral iron therapy in children with anemia of chronic kidney disease.

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD) and oral iron is recommended as initial therapy. However, response to iron therapy in children with non-dialysis CKD has not been formally assessed. METHODS: We reviewed medical records of pediatric patients with stages II-IV CKD followed in two New York metropolitan area medical centers between 2010 and 2020 and identified subjects who received oral iron therapy. Response to therapy at follow-up visits was assessed by improvement of hemoglobin, resolution of anemia by the 2012 KDIGO definition, and changes in iron status. Potential predictors of response were examined using regression analyses (adjusted for age, sex, eGFR, and center). RESULTS: Study criteria were met by 65 children (median age 12 years, 35 males) with a median time between visits of 81 days. Median eGFR was 44 mL/min/1.73 m2, and 40.7% had glomerular CKD etiology. Following iron therapy, hemoglobin improved from 10.2 to 10.8 g/dL (p < 0.001), hematocrit from 31.3 to 32.8% (p < 0.001), serum iron from 49 to 66 mcg/dL (p < 0.001), and transferrin saturation from 16 to 21.4% (p < 0.001). There was no significant change in serum ferritin (55.0 to 44.9 ng/mL). Anemia (defined according to KDIGO) resolved in 29.3% of children. No improvement in hemoglobin/hematocrit was seen in 35% of children, and no transferrin saturation improvement in 26.9%. There was no correlation between changes in hemoglobin and changes in transferrin saturation/serum iron, but there was an inverse correlation between changes in hemoglobin and changes in ferritin. The severity of anemia and alkaline phosphatase at baseline inversely correlated with treatment response. CONCLUSIONS: Anemia was resistant to 3 months of oral iron therapy in ~ 30% of children with CKD. Children with more severe anemia at baseline had better treatment response, calling for additional studies to refine approaches to iron therapy in children with anemia of CKD and to identify additional predictors of treatment response.