Diagnóstico y tratamiento de pacientes con vejiga neurogénica en la Unidad Técnica de Cirugía Pediátrica / Diagnosis and treatment of patients with Neurogenic bladder in the Surgery Technical Unit Pediatric

El presente trabajo toma como base el documento: "Manejo Urológico del Mielomeningocele" de las Guías de Atención Pediátrica, del Hospital De Pediatría "Juan P. Garrahan" de la ciudad de Buenos Aires - Argentina; de los autores: Dra. Carol Burek y Dra. Liliana Campmany. En la Unidad Técnica de Cirugía Pediátrica del Hospital de Especialidades Carlos Andrade Marín, se atienden por mes unos 50 a 70 pacientes afectos de vejiga neurogénica desde el nacimiento hasta la adolescencia. Es una enfermedad crónica que requiere un diagnóstico correcto con estudios de imagen y función de la vía urinaria además de un posterior manejo diario por parte de los padres con la guía del médico especialista.

This work is based on the document: "Urological Management of Myelomeningocele" from the Pediatric Care Guidelines of the Hospital De Pediatría "Juan P. Garrahan" of the city of Buenos Aires - Argentina; by the authors: Dr. Carol Burek and Dr. Liliana Campmany. In the Pediatric Surgery Technical Unit of the Carlos Andrade Marín Specialties Hospital, 50 to 70 patients affected by neurogenic bladder from birth to adolescence are treated every month. It is a chronic disease that requires a correct diagnosis with imaging and urinary tract function studies, as well as subsequent daily management by the parents under the guidance of the specialist.

A New Understanding of Potassium's Influence Upon Human Health and Renal Physiology.

Potassium channels are expressed in virtually all cell types, and their activity is the dominant determinant of cellular membrane potential. As such, potassium flux is a key regulator of many cellular processes including the regulation of action potentials in excitable cells. Subtle changes in extracellular potassium can initiate signaling processes vital for survival (insulin signaling) while more extreme and chronic changes may lead to pathological states (acid-base disturbances and cardiac arrhythmia). While many factors acutely influence extracellular potassium levels, it is principally the role of the kidneys to maintain potassium balance by matching urinary excretion with dietary intake. When this balance is disrupted, human health is negatively impacted. In this review, we discuss evolving views of dietary potassium intake as means of preventing and mitigating diseases. We also provide an update on a molecular pathway called the potassium switch, a mechanism by which extracellular potassium regulates distal nephron sodium reabsorption. Finally, we review recent literature describing how several popular therapeutics influence potassium homeostasis.

Race-Based Equations Delayed Black Patients From Getting Onto Kidney Transplant Lists-An Unprecedented New Policy Seeks to Undo the Damage.

This Medical News article is an interview about new policy from the US Organ Procurement and Transplantation Network to address the harms of race-based kidney function estimation.

Redressing the Harms of Race-Based Kidney Function Estimation.

This Viewpoint emphasizes the urgency of abolishing race-based medical practices and explains how they have unjustly contributed to racial inequities in clinical care and health outcomes.

CNN-assisted SERS enables ultra-sensitive and simultaneous detection of Scr and BUN for rapid kidney function assessment.

Kidney disease is highly prevalent and may result in severe clinical outcomes. Serum creatinine (Scr) and blood urea nitrogen (BUN) are the most widely used biomarkers for kidney function assessment, yet when measured alone, the result can be affected by a variety of parameters such as age, gender, protein consumption, etc. Measuring Scr and BUN simultaneously can eliminate most of the external influences and greatly improve the assessment of kidney function. In this study, a real-time kidney function assessment system based on dual biomarker detection was proposed. Scr and BUN were determined using surface-enhanced Raman scattering (SERS) within the concentration range of 10-1 to 10-6 M and 0.28 to 100 mg dl-1, respectively. A one-dimensional convolutional neural network (1D-CNN) model was employed to quantitatively analyze the concentration of biomarkers from the SERS spectral measurements. Moreover, we simulated a variety of kidney health conditions with 16 groups of mixed Scr and BUN in serum. The proposed CNN-assisted SERS method was used to quantify both biomarkers and provide diagnostic results. The Au core-Ag shell nanoprobes provided ultra-sensitive SERS detection and the CNN model achieved excellent regression results with an R2 of 0.9871 in the testing dataset. The system demonstrated a rapid and robust evaluation for the assessment of kidney function, providing a promising idea for medical diagnosis with the help of spectroscopy and deep learning methods.

Metabolomic Profiling Identifies New Endogenous Markers of Tubular Secretory Clearance.

BACKGROUND: The proximal tubules eliminate protein-bound toxins and drugs through secretion. Measurements or estimates of GFR do not necessarily reflect the physiologically distinct process of secretion. Clinical assessment of this important intrinsic kidney function requires endogenous markers that are highly specific for secretory transport. METHODS: We used metabolomics profiling to identify candidate markers of tubular secretory clearance in 50 participants from a kidney pharmacokinetics study. We measured metabolites in three sequential plasma samples and a concurrent 10-hour timed urine sample using hydrophilic interaction liquid chromatography/high-resolution mass spectrometry. We quantified the association between estimated kidney clearance and normalized plasma peak height of each candidate solute to the clearance of administered furosemide, a protein-bound, avidly secreted medication. RESULTS: We identified 528 metabolites present in plasma and urine, excluding pharmaceuticals. We found seven highly (>50%) protein-bound and 49 poorly bound solutes with clearances significantly associated with furosemide clearance and 18 solute clearances favoring an association with furosemide clearance by the 90th percentile compared with GFR. We also found four highly bound and 42 poorly bound plasma levels that were significantly associated with furosemide clearance. CONCLUSIONS: We found several candidate metabolites whose kidney clearances or relative plasma levels are highly associated with furosemide clearance, an avidly secreted tracer medication of the organic anion transporters, highlighting their potential as endogenous markers of proximal tubular secretory clearance.

Niño de 5 años con macrohematuria ¿Sabríamos ante qué glomerulopatía estamos? / Five-year-old with macrohematuria... Would we know what glomerulopathy we’re dealing with?

Presentamos el caso de un escolar de 5 años que consulta en nuestro servicio por macrohematuria. Tras confirmarse el origen glomerular de la misma se sospecha glomerulonefritis aguda postestreptocócica debido al antecedente de infección faringoamigdalar, sin embargo el complemento es normal. Presenta deterioro rápido y progresivo de función renal, por lo que es diagnosticado de glomerulonefritis aguda rápidamente progresiva. Se realiza biopsia renal, donde se evidencia semilunas en un 81% de los glomérulos y depósitos de C3, compatible con glomerulonefritis aguda postinfecciosa. Inmediatamente después, se inicia tratamiento corticoideo presentando una evolución excelente y con recuperación completa de la función renal. Solo el 10-20% de la glomerulonefritis aguda postinfecciosas cursan con niveles de complemento normal, y solo el 0,5% de los casos se manifiesta como una glomerulonefritis rápidamente progresiva. La macrohematuria en niños puede suponer un reto diagnóstico. En ocasiones las manifestaciones son muy variable y superponibles a diferentes causa y hasta la biopsia no podemos llegar a un diagnóstico fiable.(AU)

We present the case of a 5-year-old school boy who consulted our department for asymptomatic macrohematuria. After confirming the glomerular origin, poststreptococcal acute glomerulonephritis was suspected due to a history of pharyngotonsillar infection, however the complement is normal. He presents rapid and progressive deterioration of kidney function, which is why he is diagnosed with rapidly progressive acute glomerulonephritis. A renal biopsy was performed, showing crescents in 81% of the glomeruli and C3 deposits, compatible with acute post-infectious glomerulonephritis. Immediately afterwards, corticosteroid treatment was started, with excellent progress and complete recovery of kidney function. Only 10-20% of acute post-infectious glomerulonephritis present with normal complement levels, and only 0.5% of cases manifest as rapidly progressive glomerulonephritis. Macrohematuria in children can be a diagnostic challenge. Sometimes the manifestations are very variable and can be attributed to different causes and until the biopsy we cannot reach a reliable diagnosis.(AU)

Hematuria persistente en Pediatría: ¿cuándo hacer algo más que observar? / Persistent hematuria in Pediatrics: When to do more than observe?

El objetivo principal del estudio diagnóstico de la hematuria persistente es descartar la presencia de patología renal potencialmente grave. La asociación de proteinuria requiere llevar a cabo controles periódicos de función renal, tensión arterial y cuantificación de proteinuria ante la sospecha de glomerulopatía subyacente. La biopsia renal, ante la persistencia de hematuria y proteinuria, nos dará en la mayoría de ocasiones el diagnóstico definitivo. Presentamos el caso de una niña con hematuria controlada en consulta de nefrología infantil durante años sin deterioro del filtrado glomerular en la que se decide realizar biopsia renal, que nos da el diagnóstico definitivo. La nefropatía IgA es la enfermedad glomerular primaria más frecuente en el mundo y requiere seguimiento durante toda la vida por el posible deterioro de la función renal a largo plazo. En la actualidad no existen protocolos específicos de tratamiento para niños, y los más empleados siguen las guías KDIGO 2021, dirigidas a adultos.(AU)

The main goal of the diagnostic study of persistent hematuria is to rule out the presence of potentially serious renal pathology. The association with proteinuria requires periodic monitoring of renal function, blood pressure, and quantification of proteinuria in cases of suspected underlying glomerulopathy. The kidney biopsy, in the presence of persistent hematuria and proteinuria, will often provide a definitive diagnosis. We present a girl with hematuria monitored in pediatric nephrology department for years without deterioration of glomerular filtration in whom it was decided to perform a kidney biopsy, which gave us the definitive diagnosis. IgA nephropathy is the most common primary glomerular disease worldwide and requires lifelong monitoring due to possible long-term deterioration of kidney function. Currently, there are no specific treatment protocols for children, and the most commonly used ones follow the KDIGO 2021 guidelines, which are directed at adults.(AU)

Ropinirole involved in a fatal case: blood and urinary concentrations.

PURPOSE: Ropinirole is an antiparkinsonian  drug and has recently been suggested to be effective in amyotrophic lateral sclerosis. It is expected that ropinirole prescriptions will increase in the near future. However, the fatal concentration in blood is unclear at this time. Therefore, we report a fatal case involving ropinirole intoxication and discuss the fatal concentrations with reference to several autopsy cases involving ropinirole. METHODS: Ropinirole was quantified in femoral vein blood, cardiac blood, and urine from five autopsy cases in which ropinirole was detected by drug screening in our laboratory. One is a ropinirole intoxication case (this report) and the others  were non-intoxication cases. Their ropinirole concentrations were compared and discussed. RESULTS: The ropinirole concentration in this case was 100 ng/mL in femoral blood, 160 ng/mL in cardiac blood, and 1840 ng/mL in urine. The ropinirole concentrations in the four non-ropinirole poisoning cases were 7-35 ng/mL (mean: 24 ng/mL) in femoral blood, 13-100 ng/mL (mean: 60 ng/mL) in cardiac blood, and 140-1090 ng/mL (mean: 640 ng/mL) in urine. Cardiac/peripheral ratios were in the range of 1.6-2.1 (mean 1.8). CONCLUSIONS: There were no obvious signs of overdose, and the high cardiac/peripheral blood ratio suggested that postmortem redistribution may have occurred, but the  peripheral blood ropinirole concentration (100 ng/mL) was obviously higher than that reported in the previous fatal case of ropinirole poisoning (64 ng/mL). Based on these results, the cause of death in this case was considered to be shock and fatal arrhythmia due to ropinirole poisoning. This case provides important data on postmortem blood and urinary levels of ropinirole poisoning.

Mathematical modeling of the lower urinary tract: A review.

AIMS: Understand what progress has been made toward a functionally predictive lower urinary tract (LUT) model, identify knowledge gaps, and develop from them a path forward. METHODS: We surveyed prominent mathematical models of the basic LUT components (bladder, urethra, and their neural control) and categorized the common modeling strategies and theoretical assumptions associated with each component. Given that LUT function emerges from the interaction of these components, we emphasized attempts to model their connections, and highlighted unmodeled aspects of LUT function. RESULTS: There is currently no satisfactory model of the LUT in its entirety that can predict its function in response to disease, treatment, or other perturbations. In particular, there is a lack of physiologically based mathematical descriptions of the neural control of the LUT. CONCLUSIONS: Based on our survey of the work to date, a potential path to a predictive LUT model is a modular effort in which models are initially built of individual tissue-level components using methods that are extensible and interoperable, allowing them to be connected and tested in a common framework. A modular approach will allow the larger goal of a comprehensive LUT model to be in sight while keeping individual efforts manageable, ensure new models can straightforwardly build on prior research, respect potential interactions between components, and incentivize efforts to model absent components. Using a modular framework and developing models based on physiological principles, to create a functionally predictive model is a challenge that the field is ready to undertake.

Alzheimer's disease amyloidogenesis is linked to altered lower urinary tract physiology.

AIMS: While most Alzheimer's disease (AD) research emphasizes cognitive and behavioral abnormalities, lower urinary tract symptoms (LUTS) are observed in a third of AD patients, contributing to morbidity, poor quality of life, and need for institutionalization. Alzheimer's disease-associated urinary dysfunction (ADUD) has been assumed to be due to cognitive decline alone. While mouse studies have suggested that bladder innervation and voiding behavior may be altered in AD models, technical challenges precluded voiding reflex assessments. This study seeks to establish a mouse model of ADUD, and it seeks to characterize the noncognitive sequelae involved in AD-pathology associated alterations in the voiding reflex. METHODS: Having developed techniques permitting the assessment of bladder volume, pressure, and flow in mice, we now provide evidence of alterations in involuntary bladder control and increased response heterogeneity in a transgenic amyloidosis mouse model of AD using cystometry and tissue pharmacomyography. Tg-APP/PS1DE9 (PA) mice and their wild-type (WT) littermates (n = 6-8 per group) were used before plaque onset in the PA mice (4-6 months) and after plaque accumulation in the PA mice (8-10 months) in comparison to their WT control littermates. RESULTS: Novel findings include data suggestive of sphincteric discoordination, with pharmacological evidence of altered adrenergic mechanisms. CONCLUSIONS: Together, these data highlight the importance of addressing noncognitive sequelae of AD and offer novel translational insights into the debilitating impact of AD on LUTS and incontinence.