Complement gene mutations in children with C3 glomerulopathy: do they affect the response to mycophenolate mofetil?

BACKGROUND: C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes. METHODS: Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival. RESULTS: Out of the 60 patients, 17 had mutations. The most common mutation was in the CFH gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years, p = 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%, p = 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group. CONCLUSIONS: This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.

Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study.

BACKGROUND: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. METHODS: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. RESULTS: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). CONCLUSIONS: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study.

BACKGROUND: The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI. METHODS: A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI. RESULTS: Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive. CONCLUSIONS: Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

A broad clinical spectrum of PLCε1-related kidney disease and intrafamilial variability.

BACKGROUND: The phenotypic and genotypic spectrum and kidney outcome of PLCε1-related kidney disease are not well known. We attempted to study 25 genetically confirmed cases of PLCε1-related kidney disease from 11 centers to expand the clinical spectrum and to determine the relationship between phenotypic and genotypic features, kidney outcome, and the impact of treatment on outcome. METHODS: Data regarding demographics, clinical and laboratory characteristics, histopathological and genetic test results, and treatments were evaluated retrospectively. RESULTS: Of 25 patients, 36% presented with isolated proteinuria, 28% with nephrotic syndrome, and 36% with chronic kidney disease stage 5. Twenty patients underwent kidney biopsy, 13 (65%) showed focal segmental glomerulosclerosis (FSGS), and 7 (35%) showed diffuse mesangial sclerosis (DMS). Of the mutations identified, 80% had non-missense, and 20% had missense; ten were novel. No clear genotype-phenotype correlation was observed; however, significant intrafamilial variations were observed in three families. Patients with isolated proteinuria had significantly better kidney survival than patients with nephrotic syndrome at onset (p = 0.0004). Patients with FSGS had significantly better kidney survival than patients with DMS (p = 0.007). Patients who presented with nephrotic syndrome did not respond to any immunosuppressive therapy; however, 4/9 children who presented with isolated proteinuria showed a decrease in proteinuria with steroids and/or calcineurin inhibitors. CONCLUSION: PLCε1-related kidney disease may occur in a wide clinical spectrum, and genetic variations are not associated with clinical presentation or disease course. However, clinical presentation and histopathology appear to be important determinants for prognosis. Immunosuppressive medications in addition to angiotensin-converting enzyme inhibitors may be beneficial for selected patients. "A higher resolution version of the Graphical abstract is available as Supplementary information".

Predictors of poor kidney outcome in children with C3 glomerulopathy.

BACKGROUND: C3 glomerulopathy (C3G) is characterized by heterogeneous clinical presentation, outcome, and predominant C3 accumulation in glomeruli without significant IgG. There is scarce outcome data regarding childhood C3G. We describe clinical and pathological features, treatment and outcomes, and risk factors for progression to chronic kidney disease stage 5 (CKD5) in the largest pediatric series with biopsy-proven C3G. METHODS: Sixty pediatric patients with C3G from 21 referral centers in Turkey were included in this retrospective study. Patients were categorized according to CKD stage at last visit as CKD5 or non-CKD5. Demographic data, clinicopathologic findings, treatment, and outcome data were compared and possible risk factors for CKD5 progression determined using Cox proportional hazards model. RESULTS: Mean age at diagnosis was 10.6 ± 3.0 years and follow-up time 48.3 ± 36.3 months. Almost half the patients had gross hematuria and hypertension at diagnosis. Nephritic-nephrotic syndrome was the commonest presenting feature (41.6%) and 1/5 of patients presented with nephrotic syndrome. Membranoproliferative glomerulonephritis was the leading injury pattern, while 40 patients had only C3 staining. Patients with DDD had significantly lower baseline serum albumin compared with C3GN. Eighteen patients received eculizumab. Clinical remission was achieved in 68.3%. At last follow-up, 10 patients (16.6%) developed CKD5: they had lower baseline eGFR and albumin and higher frequency of nephrotic syndrome and dialysis requirement than non-CKD5 patients. Lower serum albumin and eGFR at diagnosis were independent predictors for CKD5 development. CONCLUSIONS: Children with C3G who have impaired kidney function and hypoalbuminemia at diagnosis should be carefully monitored for risk of progression to CKD5. Graphical abstract.

Cardiac functions in children with steroid-sensitive nephrotic syndrome.

BACKGROUND: The aim of the present study was to evaluate the presence of cardiac systolic and diastolic dysfunction in pediatric patients with steroid-sensitive nephrotic syndrome (NS). METHODS: The study population consisted of 19 patients with debut-relapse of NS aged 1-18 years and 30 sex and age-matched healthy controls. Blood and urine samples, two M-mode conventional echocardiograms and tissue Doppler velocity imaging were evaluated in both attack and remission periods. RESULTS: With regard to conventional pulse wave Doppler (cPWD), steroid-sensitive NS patients (both in debut / relapse and in remission periods) had a higher peak of late diastolic flow velocities (A peak), and patients in debut / relapse had a lower E/A ratio than the control group, indicating diastolic dysfunction (overall P = 0.003 and P = 0.006, respectively). Based on tissue Doppler velocity imaging echocardiography results, patients in debut/relapse had a higher A' and a lower E'/A' ratio (overall P < 0.001 and P = 0.001, respectively). There was also a significant difference in the cPWD E/TDI E' ratio between the patients showing an increased cPWD E/TDI E' ratio in remission periods compared to in debut/relapse periods (P = 0.09). The albumin levels were positively correlated with E'/A' and E/ E' ratio (r = 0.609; P = 0.007, r = 0.472; P = 0.041 respectively). CONCLUSIONS: Systolic cardiac functions are preserved but diastolic functions are affected in steroid-sensitive NS patients both in debut/relapse and in remission periods in a relatively short time. The persistence of left ventricular (LV) dysfunction during the remission period requires special attention during the follow up for early detection of cardiac abnormalities.

Acoustic Radiation Force Impulse Quantification in the Evaluation of Renal Parenchyma Elasticity in Pediatric Patients With Chronic Kidney Disease: Preliminary Results.

OBJECTIVES: To evaluate renal parenchymal elasticity with acoustic radiation force impulse imaging in pediatric patients with chronic kidney disease (CKD) and compare with healthy volunteers. METHODS: Thirty-eight healthy volunteers and 30 pediatric CKD patients were enrolled in this prospective study. The shear wave velocity (SW) values of both kidneys in CKD patients and healthy volunteers were evaluated. RESULTS: The mean SW in healthy volunteers was 2.21 ± 0.34 m/s, whereas the same value was 1.81 ± 0.49, 1.72 ± 0.63, 1.66 ± 0.29, 1.48 ± 0.37, and 1.23 ± 0.27 for stages 1, 2, 3, 4, and 5 in CKD patients, respectively. The SW was significantly lower for each stage in the CKD patients compared with healthy volunteers. Acoustic radiation force impulse could not predict the different stages of CKD, with the exception of stage 5. The cut-off value for predicting CKD was 1.81 m/s; at this threshold, sensitivity was 76.5% and specificity was 92.1% (area under the curve = 0.870 [95% confidence interval: 0.750-0.990]; P < .001). Interobserver agreement expressed as intraclass coefficient correlation was 0.65 (95% confidence interval: 0.34 to 0.83; P < .001). CONCLUSIONS: Acoustic radiation force impulse may be a potentially useful tool in detecting CKD in pediatric patients.

Evaluation of Renal Parenchyma Elasticity With Acoustic Radiation Force Impulse Quantification in Nutcracker Syndrome and Comparisons With Grayscale Doppler Sonography and Laboratory Findings.

OBJECTIVES: We sought to evaluate renal parenchymal elasticity with Virtual Touch quantification of acoustic radiation force impulse imaging in nutcracker syndrome and to compare shear-wave velocity (SWV) values with grayscale Doppler sonography and laboratory findings. METHODS: Thirty-eight healthy volunteers and forty-three nutcracker syndrome patients were enrolled in this prospective study. SWV values for both kidneys in nutcracker syndrome patients and healthy volunteers were evaluated. Grayscale Doppler ultrasound and laboratory findings were obtained and compared with SWV values in both nutcracker syndrome patients and healthy volunteers. RESULTS: In nutcracker syndrome patients, SWV values for the left kidney were significantly lower than those for the right kidney (n = 43; 1.93 ± 0.43 m/s vs 2.53 ± 0.45 m/s [P < .001]). Healthy volunteers' SWV values for both kidneys had no statistically significant differences. There was a statistically significant difference between nutcracker syndrome patients and healthy volunteers for the SWV values and body mass index values. There was no statistically significant correlation between SWV values of nutcracker syndrome patients and age, gender, glomerular filtration rate, body mass index, vein diameter ratio, peak velocity ratio, or resistive indices. CONCLUSIONS: Acoustic radiation force impulse imaging offers new, additional information on the affected left kidney parenchymal changes in nutcracker syndrome patients.

Eculizumab therapy in a patient with dense-deposit disease associated with partial lipodystropy.

BACKGROUND: Dense deposit disease (DDD) (also known as membranoproliferative glomerulonephritis type II) in childhood is a rare glomerulonephritis with frequent progression to end-stage renal disease (ESRD) and a high recurrence after kidney transplantation. The pathophysiologic basis of DDD is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade. CASE-DIAGNOSIS/TREATMENT: A 14-year-old girl presented with edema and nephrotic range proteinuria. Blood tests showed hypoalbuminemia, nephrotic range proteinuria, normal renal function, and a low C3 level. Renal biopsy confirmed the diagnosis of crescentic DDD. Complement analysis revealed strong AP activation (low C3), positive C3 nephritic factor (C3NeF), and a decreased complement factor H (CFH) levels with CFH polymorphisms. Therapy with eculizumab was considered after the failure of corticosteroid and plasmapheresis to modulate the ongoing massive proteinuria and persistence of low serum C3 levels. There was a marked clinical and biochemical response following the administration of eculizumab. CONCLUSIONS: Our case emphasizes the efficacy of eculizumab in the management of crescentic DDD in a patient with a normal renal function, in a short follow-up period. Considering previously reported cases, it appears that eculizumab represents a promising new approach which may prevent progression to ESRD in a subset of patients with DDD.

Is N-terminal pro-brain natriuretic peptide a reliable marker for body fluid status in children with chronic kidney disease?

INTRODUCTION: Brain natriuretic peptides, released in response to left ventricular stress, have a strong prognostic value in dialysis patients. However, their role in detecting abnormalities of fluid status is under debate; the relationship between volume status and brain natriuretic peptides (BNPs) differs among various studies. The aim of our study was to evaluate the clinical utility of N-terminal proBNP in the assessment of fluid status and cardiovascular risk in this setting. MATERIAL AND METHODS: The study included 65 children: 10 pre-dialysis, 13 hemodialysis, 12 peritoneal dialysis patients and 30 healthy controls. Volume status was determined by multifrequency bioimpedance and NT-pro-BNP, as well as echocardiography to estimate the left ventricle structure and function. RESULTS: The median log NT-proBNP values of hemodialysis and peritoneal dialysis patients were 3.66 (2.05-4.90) and 3.57 (2.51-4.13) pg/ml, respectively, and significantly higher compared with the control group (p < 0.001, p < 0.001). On simple correlation, NT-proBNP was correlated with markers of volume overload and cardiac dysfunction. On multivariate regression analysis, only left ventricle mass index (ß = 0.402, p = 0.003) and left atrium diameter (ß = 0.263, p = 0.018) were independently associated with NT-proBNP (adjusted R 2 of the model: 0.707, p < 0.001). CONCLUSIONS: Our research suggested that NT-proBNP, which was correlated with LV systolic and diastolic dysfunction and fluid overload as assessed by bioimpedance, can be used to evaluate cardiovascular states in a chronic kidney disease (CKD) population. From the early stages of CKD, periodic monitoring of NT-proBNP levels may be essential for early detection of patients with high risk of cardiovascular events, and for taking preventive intervention as soon as possible.

Quantitative Assessment of Muscular Stiffness in Children With Chronic Kidney Disease Using Acoustic Radiation Force Impulse Ultrasound Elastography.

ABSTRACT: The aim of this study was to evaluate the feasibility of quantitative analysis of muscle stiffness in the rectus femoris muscle (RFM) by acoustic radiation force impulse (ARFI) ultrasound elastography in children with chronic kidney disease (CKD). Twenty-three children with CKD and 22 healthy children participated in the study in our radiology department. The strength of each CKD group and healthy group participants' tight extensors was assessed by a physiatrist using a handheld dynamometer. Acoustic radiation force impulse was used to measure the shear wave velocities (SWVs) of the RFM. The mean SWV value of the RFM correlated with the strengths of the tight extensors in the CKD and healthy groups. The mean ± SD SWV values of the RFM in the CKD group for the right (n = 23) and left sides (n = 21) were 1.23 ± 0.25 and 1.26 ± 0.30 m/s, respectively. The mean ± SD SWV values of the RFM in the healthy group for the right (n = 23) and left sides (n = 21) were 1.62 ± 0.33 and 1.65 ± 0.35 m/s, respectively. The SWV of the RFM significantly decreased in the patients with CKD when compared with controls (P < 0.001). The SWV values were not correlated to the handheld dynamometry. The interobserver agreement expressed as the interclass correlation coefficient was 0.65 (95% confidence interval, 0.33-0.84; P < 0.001). The acoustic radiation force impulse demonstrates a difference in RFM muscle stiffness between the CKD and healthy groups. This method is a feasible imaging method for the noninvasive assessment of muscle weakness in children with CKD.

Nutcracker Syndrome in Children: Role of Doppler Ultrasonographic Indices in Detecting the Pattern of Symptoms.

The purpose of this study was to evaluate the clinical characteristics of 44 pediatric patients who were diagnosed as having nutcracker syndrome (NCS). We also investigated the left renal vein Doppler ultrasonography (DUS) results, to determine whether or not there was an association between clinical symptoms and DUS findings among these patients. The clinical data from 44 pediatric patients who were diagnosed as having NCS from January 2008 to December 2015 were retrospectively reviewed. We grouped the patients according to the presenting symptoms as symptomatic (loin pain; macroscopic hematuria or both) and non-symptomatic (microscopic hematuria and proteinuria were detected incidentally) and evaluated the left renal vein DUS indices in these two groups separately. Asymptomatic NCS was found in 27 (61.4%) patients; 21 (47.7%) of whom were admitted for the evaluation of proteinuria. The most frequent presenting symptoms were left flank pain (20.5%) and macroscopic hematuria (13.6%); and 2 (4.5%) patients presented with a combination of left flank pain and macroscopic hematuria. The mean ratio of the diameter of the hilar portion of the left renal vein (LRV) to that of the aortomesenteric portion was 4.36 ± 1.55. The mean ratio of the peak velocity (PV) between the two sites of the LRV was 7.32 ± 2.68 (3.1⁻15.6). The differences in the ratio of the diameters were statistically significant between the two groups and significantly higher in children with asymptomatic NCS (p = 0.025). The PV ratios of the LRV (p = 0.035) were significantly higher in asymptomatic children with NCS than in the symptomatic group. Our study identifies that increased compression ratio of the LRV entrapment is most observed in orthostatic proteinuria and microscopic hematuria.

The role of bioelectrical impedance analysis, NT-ProBNP and inferior vena cava sonography in the assessment of body fluid volume in children with nephrotic syndrome.

BACKGROUND: Assessment of volume status and differentiating "underfill" and "overfill" edema is essential in the management of patients with nephrotic syndrome (NS). OBJECTIVES: Our aim was to evaluate the volume status of NS patients by using different methods and to investigate the utility of bioelectrical impedance analysis (BIA) in children with NS. METHODS: The hydration status of 19 patients with NS (before treatment of NS and at remission) and 25 healthy controls was assessed by multifrequency BIA, serum N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels, inferior vena cava (IVC) diameter, left atrium diameter (LAD) and vasoactive hormones. RESULTS: Renin, aldosterone levels, IVC diameter and LAD were not statistically different between the groups. NT-proBNP values were statistically higher in the attack period compared to remission and the control group (p=0.005 for each). Total body water (TBW), overhydration (OH) and extracellular water (ECW) estimated by the BIA measurement in the attack group was significantly higher than that of the remission group and controls. There were no significant correlations among volume indicators in group I and group II. However, significant correlations were observed between NT-proBNP and TBW/BSA (p=0.008), ECW/BSA (p=0.003) and ECW/ICW (p=0.023) in the healthy group. TBW was found to be higher in patients with NS in association with increased ECW but without any change in ICW. NT-proBNP values were higher in patients during acute attack than during remission. CONCLUSIONS: Our findings support the lack of hypovolaemia in NS during acute attack. In addition, BIA is an easy-to-perform method for use in routine clinical practice to determine hydration status in patients with NS.

The role of bioelectrical impedance analysis, NT-ProBNP and inferior vena cava sonography in the assessment of body fluid volume in children with nephrotic syndrome / El papel del análisis de impedancia bioeléctrica, la NT-proBNP y la ecografía de vena cava inferior en la evaluación del volumen de líquidos corporales en niños con síndrome nefrótico

Background: Assessment of volume status and differentiating ’underfill ’ and ’overfill ’ edema is essential in the management of patients with nephrotic syndrome (NS). Objectives: Our aim was to evaluate the volume status of NS patients by using different methods and to investigate the utility of bioelectrical impedance analysis (BIA) in children with NS. Methods: The hydration status of 19 patients with NS (before treatment of NS and at remission) and 25 healthy controls was assessed by multifrequency BIA, serum N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels, inferior vena cava (IVC) diameter, left atrium diameter (LAD) and vasoactive hormones. Results: Renin, aldosterone levels, IVC diameter and LAD were not statistically different between the groups. NT-proBNP values were statistically higher in the attack period compared to remission and the control group (p=0.005 for each). Total body water (TBW), overhydration (OH) and extracellular water (ECW) estimated by the BIA measurement in the attack group was significantly higher than that of the remission group and controls. There were no significant correlations among volume indicators in group I and group II. However, significant correlations were observed between NT-proBNP and TBW/BSA (p=0.008), ECW/BSA (p=0.003) and ECW/ICW (p=0.023) in the healthy group. TBW was found to be higher in patients with NS in association with increased ECW but without any change in ICW. NT-proBNP values were higher in patients during acute attack than during remission. Conclusions: Our findings support the lack of hypovolaemia in NS during acute attack. In addition, BIA is an easy-to-perform method for use in routine clinical practice to determine hydration status in patients with NS (AU)

Antecedentes: La evaluación del estado volumétrico y la diferenciación entre edema «por sobrellenado» y «por infrallenado» es fundamental en el manejo de los pacientes con síndrome nefrótico (SN). Objetivos: Nuestro objetivo fue evaluar el estado volumétrico de los pacientes con SN mediante el uso de diversos métodos y estudiar la utilidad del análisis de impedancia bioeléctrica (BIA) en niños con SN. Métodos: Se evaluó el estado de hidratación de 19 pacientes con SN (antes del tratamiento y en la remisión) y de 25 controles sanos mediante BIA multifrecuencia, valores plasmáticos de la fracción N-terminal del péptido natriurético cerebral (NT-proBNP), diámetro de la vena cava inferior, diámetro de la aurícula izquierda y hormonas vasoactivas. Resultados: La renina, los niveles de aldosterona, el diámetro de la vena cava inferior y el de la aurícula izquierda no fueron estadísticamente diferentes entre los grupos. Los valores de la NT-proBNP fueron estadísticamente más altos en el período de crisis que en el momento de remisión y que en el grupo de control (p=0,005 en cada uno). El agua total corporal (TBW), la hiperhidratación y el agua extracelular (ECW) estimada mediante la medición del BIA en el grupo de crisis fue considerablemente mayor que la del grupo de remisión y los controles. No hubo correlaciones importantes entre los indicadores de volumen en el grupo I y en el grupo II. Sin embargo, se observaron correlaciones considerables entre NT-proBNP y TBW/BSA (p=0,008), ECW/BSA (p=0,003) y ECW/ICW (p=0,023) en el grupo sano. Se encontró que TBW fue mayor en los pacientes con SN relacionado con el aumento de ECW, pero sin ningún cambio en ICW. Los valores de la NT-proBNP fueron más altos en los pacientes durante la crisis aguda que durante la remisión. Conclusiones: Nuestros hallazgos apoyan la falta de hipovolemia en el SN durante la crisis aguda. Además, BIA es un método fácil de utilizar en la práctica clínica habitual para determinar el estado de hidratación en pacientes con SN (AU)