Effects of the pandemic on adolescent and caregiver attitudes towards telemedicine use.

BACKGROUND: Telemedicine use increased during the COVID-19 pandemic. We compared both adolescent/caregiver attitudes towards telemedicine pre- and intra-pandemic. MATERIALS AND METHODS: In a tertiary care setting with a large remote catchment area, we conducted qualitative analysis of structured interviews with dyads of 11 to 18-year-old patients and their caregivers using NVivo during the pandemic and compared the findings to our previous research [1]. RESULTS: We enrolled 14 dyads (35 ± 27 in-person visits and 4 ± 3 telemedicine visits per participant) and compared these with 11 dyads before the pandemic. Adolescents' mean age was 15.2 ± 2.1 years (range 11.2 - 18.2). The median distance to our medical center was 184.8 km (range 3.9 - 1,214 km, 6 dyads > 100 km). While the preferred ratio of telemedicine to in-person visits was 2 : 1 in caregivers (like pre-pandemic), many emphasized telemedicine as the safer option. Interestingly, adolescents preferred more in-person visits during the pandemic (1 : 1 ratio) compared to pre-pandemic (2 : 1 ratio). Qualitative analysis identified two main themes: consultation-specific factors and contextual factors. Consultation-specific factors were more valued during in-person visits, especially by adolescents. Consultation-specific factors remained the same pre- and post-pandemic, however, adolescents more often emphasized comfort, communication, and personal connection for in-person visits during the pandemic. Contextual factors were valued for telemedicine by adolescents and caregivers, and telemedicine was identified as the norm during the pandemic. Interestingly, the two main contextual themes pre-pandemic: frustration with technological aspects of telemedicine and adolescents not taking telemedicine seriously, disappeared during the pandemic. No disadvantages for telemedicine in the contextual factors were identified during the pandemic. CONCLUSION: The COVID-19 pandemic changed the user-expressed attitudes (especially among adolescents) on the transfer to telemedicine for chronic care.

Growth hormone therapy in HHRH.

Background: Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) (SLC34A3 gene, OMIM 241530) is an autosomal recessive disorder that results in a loss of function of the sodium-phosphate NPT2c channel at the proximal tubule. Phosphate supplementation rarely improves serum phosphate, hypercalciuria, nephrocalcinosis, 1,25(OH)2 vitamin D (1,25(OH)2D) levels or short stature. Methods: We describe 23Na MRI and the successful use of recombinant human growth hormone (rhGH) and Fluconazole to improve growth (possibly confounded by puberty) and hypercalciuria in a now 12-year-old male with HHRH (novel homozygous SLC34A3 mutation, c.835_846 + 10del.T). Results: The patient had chronic bone pain, hypophosphatemia (0.65 mmol/L[reference interval 1.1-1.9]), pathological fractures and medullary nephrocalcinosis/hypercalciuria (urinary calcium/creatinine ratio 1.66 mol/mmol[<0.6]). TmP/GFR was 0.65 mmol/L[0.97-1.64]; 1,25(OH)2D was >480 pmol/L[60-208]. Rickets Severity Score was 4. Treatment with 65 mg/kg/day of sodium phosphate and potassium citrate 10 mmol TID failed to correct the abnormalities.Adding rhGH at 0.35 mg/kg/week to the phosphate therapy, improved bone pain, height z-score from -2.09 to -1.42 over 6 months, without a sustained effect on TmP/GFR. Fluconazole was titrated to 100 mg once daily, resulting for the first time in a reduction of the 1,25(OH)2D to 462 and 426 pmol/L; serum phosphate 0.87 mmol/L, and calcium/creatinine ratio of 0.73.23Na MRI showed normal skin (z-score + 0.68) and triceps surae muscle (z-score + 1.5) Na+ levels; despite a defect in a sodium transporter, hence providing a rationale for a low sodium diet to improve hypercalciuria. Conclusions: The addition of rhGH, Fluconazole and salt restriction to phosphate/potassium supplementation improved the conventional therapy. Larger studies are needed to confirm our findings.

Animal, Human, and 23Na MRI Imaging Evidence for the Negative Impact of High Dietary Salt in Children.

PURPOSE OF THE REVIEW: Conditions typically prevalent in adults such as hypertension, kidney stones, osteoporosis, and chronic kidney disease are increasing among adolescents and young adults (AYA). The purpose of this review is to describe the association of these conditions to a high salt diet among pediatric patients. RECENT FINDINGS: We present animal, human, and 23Na MRI evidence associated with the negative impact of high dietary salt in children. Special focus is placed on novel 23Na MRI imaging which reveals the important concept of a third compartment for sodium storage in soft tissue. Finally, we make recommendations on who should not be on a low salt diet. SUMMARY: A high salt intake predisposes children and AYA to considerable morbidity. We exhort the reader to engage in advocacy efforts to curve the incidence and prevalence of high salt-related life-limiting conditions.

Management of severe polyuria in idiopathic Fanconi syndrome.

BACKGROUND: Polyuria is a common problem in patients with tubular diseases, especially for those with CKD and high-output Fanconi syndrome. There are currently no guidelines on how to treat debilitating polyuria, in children or adults, and vasopressin is usually not effective. CASE-DIAGNOSIS/TREATMENT: A 13-year-old female with idiopathic Fanconi syndrome and an eGFR of 69 mL/min/1.73 m2 was severely affected by polyuria of 5 L per day (voiding at least 11 times during the day and up to 8 times at night), impacting her mood (measured by the RCADS-child) and academic performance at school. In the absence of guidelines and with literature discouraging the use of indomethacin in this condition, we attempted indomethacin treatment at a dose of 2 mg/kg divided in two doses with substantial success. Urine output dropped to 2.5L and this was accompanied by a substantial decrease of her sodium wasting from 24.6 to 7.7 mmol/kg/day. Over the course of 18 months, the patient's eGFR dropped temporarily to 60 mL/min/1.73 m2 and was 68 mL/min/1.73 m2 at last follow-up. However, a sodium-23 (23Na) MRI of her thigh revealed ongoing moderate sodium decrease in her skin and substantial Na+ decrease in her muscle when compared to age-matched peers with normal kidney function. CONCLUSIONS: Indomethacin may be a safe and effective treatment option for polyuria in idiopathic Fanconi syndrome.

Adolescent and caregiver attitudes towards telemedicine use in pediatric nephrology.

BACKGROUND: Telemedicine is increasingly utilized as an alternative to in person consultation. Current pandemic conditions are providing additional impetus to virtual care delivery. We compared both adolescent and caregiver (parent or guardian) attitudes towards telemedicine (here as tertiary center to remote health care location) as a crucial determinant of longer-term effectiveness. METHODS: This qualitative research study analyzed transcribed structured telephone interviews with both 11-18 year-old pediatric nephrology patients and their caregivers and performed a quantitative analysis of patient demographics, disease factors and distance to tertiary center vs. telemedicine center. RESULTS: The study was conducted in a medium-sized tertiary pediatric nephrology centre with a large catchment area of over 0.5 million square kilometers and 629,000 children and adolescents under 18 years of age. Eleven dyads of adolescents and caregivers were enrolled. Five adolescents were male. The mean age of the adolescents was 14.4 ± 2.5 years (range 11.2-18.0). The median distance to our tertiary center was 191 km (range 110-1378 km). Four adolescents lived more than 500 km from our tertiary center. The 11 adolescents had a total of 334 in person visits (mean 30 ± 25) and 86 telemedicine visits (mean 8 ± 7). A ratio of 2:1 telemedicine to in-person visits was favored; with caregivers more in favor of remote care than adolescents. Qualitative analysis found that experiences with telemedicine were distinguished by consultation-specific factors and contextual factors. Contextual factors (travel/cost savings) were valued for telemedicine by adolescents and caregivers. Consultation-specific factors, such as the ability to show the doctor physical symptoms, were more valued during in-person consultations, especially by adolescents. The overall visit type preference was related to the nature of the consultation. For regular check-ups, and for adolescents with less complex needs, participants felt that telemedicine offered a comparable experience to in-person visits. Adolescents with more complex conditions preferred in-person visits. CONCLUSIONS: Indiscriminate transfer to chronic care predicated on mainly telemedicine approach is not compatible with user expressed attitudes (especially among adolescents). Accurately mapping models of care to these attitudes is an essential determinant of effective management and longer-term engagement with potentially life-long health challenges.

Principles responsible for trace element concentrations in chronic kidney disease.

Derangements of trace elements often occur in patients with renal failure and play a crucial role in chronic kidney disease. The natural history of trace element deposition with worsening chronic kidney disease has been poorly described. Some essential trace elements may get wasted (e.g., selenium, zinc, and manganese) while other trace elements accumulate (e.g., cobalt, lead, molybdenum, and vanadium). Data are most readily available relating to hemodialysis patients. Continuous renal replacement therapies (for the treatment of acute kidney injury) and chronic kidney disease patients without need for renal replacement therapy remain largely unstudied. We have synthesized all available data on mode of absorption and elimination, volume of distribution, plasma protein binding, and proteinuria to summarize the existing literature, identify future areas of research and to allow some prediction of the fate of individual trace elements in clinical scenarios where no direct observational data are available. More prospective studies evaluating the impact of abnormal trace elements and the possible therapeutic value of intervention are required to improve how robust the current international guideline recommendations (KDOQI) are with respect to trace element monitoring.

Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD.

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in patients with CKD. In the past decade, intestinal dysbiosis and altered gut epithelial barrier function are increasingly recognized in CKD. Uremic patients have slow intestinal transit time, impaired protein assimilation, and decreased consumption of dietary fiber. The use of multiple medications also may contribute to the proliferation of dysbiotic bacteria, which affect the barrier function of intestinal epithelium. In addition, fluid overload and uremic toxins per se directly reduce the gut barrier function. The major consequence of these alterations, the translocation of bacterial fragments from bowel lumen to systemic circulation, can lead to diverse biologic effects and probably represents an important nontraditional CVD risk factor in CKD. Among all bacterial fragments, endotoxin is the most well studied. Plasma endotoxin levels are markedly elevated in both patients with CKD and those on dialysis, and are associated with the systemic inflammatory state, accelerated atherosclerosis, and clinical CVD in patients on dialysis. Optimization of BP control and the use of ultrapure dialysate can reduce plasma endotoxin levels, with probable metabolic and cardiovascular benefits. The benefit of synbiotic therapy is not confirmed, although results from animal studies are impressive. The biologic effects and clinical relevance of other bacterial fragments, such as bacterial DNA fragments, are less well defined. Further studies are needed to delineate the pathogenic relation between circulating bacterial fragments and CVD, and to define the role of the plasma bacterial fragment level as a prognostic indicator of CKD.

Inflammation and Peritoneal Dialysis.

Inflammation is one of the well-recognized nontraditional risk factors that contributes to the excessive cardiovascular mortality in peritoneal dialysis (PD) patients. Serum C-reactive protein and interleukin-6 levels are common surrogate markers used to measure inflammatory burden and predict adverse clinical outcomes in PD patients. Causes of inflammation are complex and can be categorized into factors related to a decrease in renal function and factors related to dialysis. They interact with each other and finally result in systemic and intraperitoneal inflammation. This review discusses the various causes and clinical implications of inflammation in PD patients. More importantly, potential therapeutic options that target the underlying pathogenic mechanisms are explored.

Why Is Your Patient Still Short of Breath? Understanding the Complex Pathophysiology of Dyspnea in Chronic Kidney Disease.

Dyspnea is one of the most common symptoms associated with CKD. It has a profound influence on the quality of life of CKD patients, and its underlying causes are often associated with a negative prognosis. However, its pathophysiology is poorly understood. While hemodialysis may address fluid overload, it often does not significantly improve breathlessness, suggesting multiple and co-existing alternative issues exist. The aim of this article is to discuss the main pathophysiologic mechanisms and the most important putative etiologies underlying dyspnea in CKD patients. Congestive heart failure, unrecognized chronic lung disease, pulmonary hypertension, lung fibrosis, air microembolism, dialyzer bio-incompatibility, anemia, sodium, and fluid overload are potential frequent causes of breathing disorders in this population. However, the relative contributions in any one given patient are poorly understood. Systemic inflammation is a common theme and contributes to the development of endothelial dysfunction, lung fibrosis, anemia, malnutrition, and muscle wasting. The introduction of novel multimodal imaging techniques, including pulmonary functional magnetic resonance imaging with inhaled contrast agents, could provide new insights into the pathophysiology of dyspnea in CKD patients and ultimately contribute to improving our clinical management of this symptom.

Characterising haemodynamic stress during haemodialysis using the extrema points analysis model.

BACKGROUND AND AIMS: It is becoming recognised that the process of haemodialysis (HD) itself induces circulatory stress that could be implicated in the observed higher rate of end-organ damage. We aimed to study the haemodynamic performance during HD using the extrema points (EP) analysis model, and to examine the determinants of the model and its relation to circulatory stress. METHODS: 63 incident HD patients were studied. Mean arterial blood pressure (MAP) EP frequencies and baroreflex sensitivity during HD were computed for continuous non-invasive haemodynamic monitoring. Pulse-wave velocity as a measure of arterial stiffness was performed. High-sensitivity troponin-T was also measured. RESULTS: The time of each dialysis session was divided into four quarters. Repeated measures ANOVA of the MAP EP frequencies for all subjects during HD demonstrated a gradual significant increase reaching peak levels at the third quarter of dialysis time and remaining at that peak during the fourth quarter (F(3,171228) = 392.06, p < 0.001). In multivariate regression, lower baroreflex sensitivity was the only independent predictor of higher MAP EP frequencies (ß = -0.642, p = 0.001, adjusted R(2) for the whole model = 0.385). In linear regression analysis, higher MAP EP frequencies were associated with higher troponin-T levels (ß = 0.442, p = 0.002, R(2) = 0.19, B = 103.29, 95% CI 38.88-167.70). CONCLUSION: The EP analysis model using MAP is a novel functional haemodynamic measure that can represent and quantify circulatory stress during HD. This measure seems to be determined by the integrity of the autonomic function in HD and could represent the link between circulatory stress and end-organ damage in HD patients.

Exploring haemodynamics of haemodialysis using extrema points analysis model.

BACKGROUND: Haemodialysis is a form of renal replacement therapy used to treat patients with end stage renal failure. It is becoming more appreciated that haemodialysis patients exhibit higher rates of multiple end organ damage compared to the general population. There is also a strong emerging evidence that haemodialysis itself causes circulatory stress. We aimed at examining haemodynamic patterns during haemodialysis using a new model and test that model against a normal control. METHODS: We hypothesised that blood pressures generated by each heart beat constantly vary between local peaks and troughs (local extrema), the frequency and amplitude of which is regulated to maintain optimal organ perfusion. We also hypothesised that such model could reveal multiple haemodynamic aberrations during HD. Using a non-invasive cardiac output monitoring device (Finometer®) we compared various haemodynamic parameters using the above model between a haemodialysis patient during a dialysis session and an exercised normal control after comparison at rest. RESULTS: Measurements yielded 29,751 data points for each haemodynamic parameter. Extrema points frequency of mean arterial blood pressure was higher in the HD subject compared to the normal control (0.761Hz IQR 0.5-0.818 vs 0.468Hz IQR 0.223-0.872, P < 0.0001). Similarly, extrema points frequency of systolic blood pressure was significantly higher in haemodialysis compared to normal. In contrary, the frequency of extrema points for TPR was higher in the normal control compared to HD (0.947 IQR 0.520-1.512 vs 0.845 IQR 0.730-1.569, P < 0.0001) with significantly higher amplitudes. CONCLUSION: Haemodialysis patients potentially exhibit an aberrant haemodynamic behaviour characterised by higher extrema frequencies of mean arterial blood pressure and lower extrema frequencies of total peripheral resistance. This, in theory, could lead to higher variation in organ perfusion and may be detrimental to vulnerable vascular beds.

Rationale and design of a multi-centre randomised controlled trial of individualised cooled dialysate to prevent left ventricular systolic dysfunction in haemodialysis patients.

BACKGROUND: The main hypothesis of this study is that patients having regular conventional haemodialysis (HD) will have a smaller decline in cardiac systolic function by using cooler dialysate. Cooler dialysate may also be beneficial for brain function. METHODS/DESIGN: The trial is a multicentre, prospective, randomised, un-blinded, controlled trial. Patients will be randomised 1:1 to use a dialysate temperature of 37°C for 12 months or an individualised cooled dialysate. The latter will be set at 0.5°C less than the patient's own temperature, determined from the mean of 6 prior treatment sessions with a tympanic thermometer, up to a maximum of 36°C. Protocol adherence will be regularly checked. Inclusion criteria are incident adult HD patients within 180 days of commencing in-centre treatment 3 times per week with capacity to consent for the trial and without contra-indications for magnetic resonance imaging. Exclusion criteria include not meeting inclusion criteria, inability to tolerate magnetic resonance imaging and New York Heart Association Grade IV heart failure. During the study period, resting cardiac and cerebral magnetic resonance imaging will be performed at baseline and 12 months on an inter-dialytic day. Cardiovascular performance during HD will also be assessed by continuous cardiac output monitors, intra-dialytic echocardiography and biomarkers at baseline and 12 months. The primary outcome measure is a 5% between-group difference in left ventricular ejection fraction measured by cardiac magnetic resonance imaging at 12 months compared to baseline. Analysis will be by intention-to-treat. Secondary outcome measures will include changes in cerebral microstructure and changes in cardiovascular performance during HD. A total of 73 patients have been recruited into the trial from four UK centres. The trial is funded by a Research for Patient Benefit Grant from the National Institute of Healthcare Research. AO is funded by a British Heart Foundation Clinical Research Training Fellowship Grant. The funders had no role in the design of the study. DISCUSSION: This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysate temperature for preserving cardiac and cerebral function in HD patients. TRIAL REGISTRATION: ISRCTN00206012 and UKCRN ID 7422.