Estudio longitudinal del manejo renal del agua en pacientes diagnosticados de hipercalciuria idiopática en la infancia / Longitudinal study of kidney water management in patients diagnosed with idiopathic hypercalciuria in childhood

Existe controversia si la hipercalciuria idiopática (HI) produce alteraciones en el manejo renal del agua. Por primera vez en la literatura, llevamos a cabo un estudio longitudinal del manejo renal del agua (MRA) en pacientes diagnosticados de HI en edad pediátrica y con seguimiento hasta la edad adulta (media de seguimiento de 17,7 ± 1,4 años). MÉTODOS: Veintinueve pacientes (7 M, 22 F) mayores de 24 años (media 28,2 ± 2,9 años, rango: 24,1-35,9) que fueron diagnosticados de HI en la edad pediátrica (media 7,6 ± 3,2 años, rango: 1-14) fueron incluidos. Se determinaron la osmolaridad urinaria máxima (OsU) y/o el volumen urinario ajustado para 100 ml de tasa de filtrado glomerular (V/TFG) en ambos tiempos (pediátrico y adulto). Además, siempre que fue posible, en ambas edades se recogieron los niveles plasmáticos de creatinina, sodio plasmático, ácido úrico, cociente citrato/creatinina y calcio/citrato y, además, se realizó una ecografía renovesical. RESULTADOS: El MRA estuvo alterado en edad pediátrica en 9/29 casos (31%) (4 con OsU máxima reducida y 5 con V/TFG elevado). En la edad adulta, 7/29 (24,1%) presentaron alteración del MRA (6 OsU reducidos y uno con V/TFG elevado). En comparación con el grupo de edad pediátrica, los pacientes adultos mostraron valores reducidos de V/TFG, cociente calcio/creatinina y citrato/creatinina, así como aumento de creatinina plasmática, ácido úrico y del cociente calcio/citrato. No hubo diferencias en la OsU máxima en ambos tiempos. Sin embargo, la OsU en la edad adulta fue significativamente menor en aquellos que tenían cólicos renales comparado con aquellos que no los tuvieron (p = 0,04). CONCLUSIONES: La alteración del MRA ocurrió en aproximadamente un tercio de los pacientes con HI, y no se alteró tras 20 años después de su diagnóstico. Nosotros pensamos que estos resultados pueden ser debido a un cierto cumplimiento de la dieta protectora recomendada y al tratamiento farmacológico administrado en el diagnóstico de HI en la edad pediátrica

INTRODUCTION: There is much debate about whether idiopathic hypercalciuria (IH) affects kidney water management. For the first time in the literature, we carried out a longitudinal study of kidney water management (KWM) in patients diagnosed with IH in childhood and followed-up until adulthood (mean follow-up 17.7 ± 1.4 years). Methods; Twenty-nine patients (7 M, 22 F) over the age of 24 years (mean 28.2 ± 2.9 years, range: 24.1-35.9) who were diagnosed with IH in childhood (mean 7.6 ± 3.2 years, range: 1-14) were included. Maximum urine osmolality (UO) and/or urine volume adjusted for 100ml of glomerular filtration rate (V/GFR) in both age groups (paediatric and adult) were determined. Moreover, whenever possible, in both age groups plasma creatinine levels, plasma sodium levels, uric acid levels, the citrate/creatinine ratio and the calcium/citrate ratio were recorded and a renal and bladder ultrasound was performed. RESULTS: In the paediatric age group, KWM was altered in 9/29 cases (31%) (4 with reduced maximum UO and 5 with elevated V/GFR). In adulthood, KWM was found to be affected in 7/29 cases (24.1%) (6 with reduced UO and one with elevated V/GFR). Compared to the paediatric age group, adult patients had lower V/GFR, calcium/creatinine and citrate/creatinine values, as well as higher plasma creatinine, uric acid and calcium/citrate. There were no differences in the maximum UO in both age groups. However, UO in adulthood was significantly lower in subjects who had renal colic compared to those who did not (P = .04). CONCLUSIONS: KWM was affected in approximately one third of patients with IH, which persisted 20 years after diagnosis. We think that these results may be due to adherence to the recommended protective diet and to the pharmacological treatment administered at the diagnosis of IH during childhood

Longitudinal study of kidney water management in patients diagnosed with idiopathic hypercalciuria in childhood. / Estudio longitudinal del manejo renal del agua en pacientes diagnosticados de hipercalciuria idiopática en la infancia.

INTRODUCTION: There is much debate about whether idiopathic hypercalciuria (IH) affects kidney water management. For the first time in the literature, we carried out a longitudinal study of kidney water management (KWM) in patients diagnosed with IH in childhood and followed-up until adulthood (mean follow-up 17.7±1.4 years). METHODS: Twenty-nine patients (7 M, 22 F) over the age of 24 years (mean 28.2±2.9 years, range: 24.1-35.9) who were diagnosed with IH in childhood (mean 7.6±3.2 years, range: 1-14) were included. Maximum urine osmolality (UO) and/or urine volume adjusted for 100ml of glomerular filtration rate (V/GFR) in both age groups (paediatric and adult) were determined. Moreover, whenever possible, in both age groups plasma creatinine levels, plasma sodium levels, uric acid levels, the citrate/creatinine ratio and the calcium/citrate ratio were recorded and a renal and bladder ultrasound was performed. RESULTS: In the paediatric age group, KWM was altered in 9/29 cases (31%) (4 with reduced maximum UO and 5 with elevated V/GFR). In adulthood, KWM was found to be affected in 7/29 cases (24.1%) (6 with reduced UO and one with elevated V/GFR). Compared to the paediatric age group, adult patients had lower V/GFR, calcium/creatinine and citrate/creatinine values, as well as higher plasma creatinine, uric acid and calcium/citrate. There were no differences in the maximum UO in both age groups. However, UO in adulthood was significantly lower in subjects who had renal colic compared to those who did not (P=.04). CONCLUSIONS: KWM was affected in approximately one third of patients with IH, which persisted 20 years after diagnosis. We think that these results may be due to adherence to the recommended protective diet and to the pharmacological treatment administered at the diagnosis of IH during childhood.

Reference values of renal tubular function tests are dependent on age and kidney function.

Electrolyte disorders due to tubular disorders are rare, and knowledge about validated clinical diagnostic tools such as tubular function tests is sparse. Reference values for tubular function tests are based on studies with small sample size in young healthy volunteers. Patients with tubular disorders, however, frequently are older and can have a compromised renal function. We therefore evaluated four tubular function tests in individuals with different ages and renal function. We performed furosemide, thiazide, furosemide-fludrocortisone, and desmopressin tests in healthy individuals aged 18-50 years, healthy individuals aged more than 50 years and individuals with compromised renal function. For each tubular function test we included 10 individuals per group. The responses in young healthy individuals were in line with previously reported values in literature. The maximal increase in fractional chloride excretion after furosemide was below the lower limit of young healthy individuals in 5/10 older subjects and in 2/10 patients with compromised renal function. The maximal increase in fractional chloride excretion after thiazide was below the lower limit of young healthy individuals in 6/10 older subjects and in 7/10 patients with compromised renal function. Median maximal urine osmolality after desmopressin was 1002 mosmol/kg H2O in young healthy individuals, 820 mosmol/kg H2O in older subjects and 624 mosmol/kg H2O in patients with compromised renal function. Reference values for tubular function tests obtained in young healthy adults thus cannot simply be extrapolated to older patients or patients with compromised kidney function. Larger validation studies are needed to define true reference values in these patient categories.

Determination of doping peptides via solid-phase microelution and accurate-mass quadrupole time-of-flight LC-MS.

A complete analytical protocol for the determination of 25 doping-related peptidic drugs and 3 metabolites in urine was developed by means of accurate-mass quadrupole time-of-flight (Q-TOF) LC-MS analysis following solid-phase extraction (SPE) on microplates and conventional SPE pre-treatment for initial testing and confirmation, respectively. These substances included growth hormone releasing factors, gonadotropin releasing factors and anti-diuretic hormones, with molecular weights ranging from 540 to 1320Da. Optimal experimental conditions were stablished after investigation of different parameters concerning sample preparation and instrumental analysis. Weak cation exchange SPE followed by C18 HPLC chromatography and accurate mass detection provided the required sensitivity and selectivity for all the target peptides under study. 2mg SPE on 96-well microplates can be used in combination with full scan MS detection for the initial testing, thus providing a fast, cost-effective and high-throughput protocol for the processing of a large batch of samples simultaneously. On the other hand, extraction on 30mg SPE cartridges and subsequent target MS/MS determination was the protocol of choice for confirmatory purposes. The methodology was validated in terms of selectivity, recovery, matrix effect, precision, sensitivity (limit of detection, LOD), cross contamination, carryover, robustness and stability. Recoveries ranged from 6 to 70% (microplates) and 17-95% (cartridges), with LODs from 0.1 to 1ng/mL. The suitability of the method was assessed by analyzing different spiked or excreted urines containing some of the target substances.

[Osmoregulating effect of vasopressin with prolonged action on Brattleboro rats with hypothalamic diabetes insipidus].

The particularities of urine osmotic concentration depending on hormonal background of vasopressin were studied in rats. It was found that WAG and Brattleboro lines of rats characterized respectively by normal level and absence of endogenous vasopressin, possess interline correlation of urine osmolality (p = 0.86) in various conditions between the extreme hydrating and dehydratation. Concentrating level of WAG rats varies from 747 +/- 94 to 2936 +/- 128 mOsm/kg, but that of Brattleboro rats changes more within the 160 +/- 9 being twice lower as isotonicity to 1305 +/- 142 mOcm/kg. Urine concentrating goes up to 1391 +/- 76 mOcm/kg in Brattleboro rats already on the day of the action of exogenous vasopressin secreted from ALZET minipump, however, in spite of constant work of this minipump during 4 hrs a week, further increasing of urine osmolality was not observed in Brattleboro rats.

Effects of angiotensin II and C-type natriuretic peptide on the in situ perfused trunk preparation of the dogfish, Scyliorhinus canicula.

The renal roles of physiologically relevant doses of angiotensin II (Ang II) and C-type natriuretic peptide (CNP) were investigated in the dogfish, Scyliorhinus canicula, using an in situ perfused trunk preparation. Perfusion with 10(-9) M Ang II resulted in a glomerular antidiuresis and decreases in perfusate flow rate, transport maxima for glucose and the proportion of filtering glomeruli. In addition, the renal clearances and excretion of urea, sodium, and chloride were significantly reduced, whereas the relative clearances of these parameters remained unchanged. In contrast, perfusion of 10(-9) M CNP caused a glomerular diuresis, an increase in transport maxima for glucose, but no significant change in the proportion of filtering glomeruli. In addition, the renal clearances of urea, sodium, and chloride were significantly increased but there was no effect on the relative clearances of urea, sodium, or chloride. Perfusion with 10(-10) M Ang II or CNP had no significant renal effects. Our results suggest that these hormones act at the level of the glomeruli rather than at a tubular level.