bluuebunny/crossref_metadata_2025 huggingface dataset:
MO112SYSTEMIC OXALOSIS IN PRIMARY HYPEROXALURIA TYPE 3 – ARE THE PATIENTS AT RISK?
Authors: Hoppe Bernd , Martin Higueras Cristina , Herberg Ulrike , Birtel Johannes , Born Mark
Published: May 2021

Background and Aims

Primary Hyperoxaluria type 3 (PH3) is said to be the less problematic form of PH and with low risk of chronic kidney disease (CKD) and end stage renal disease. However, a recent OxalEurope registry evaluation reported both urine and plasma oxalate levels in a comparable range as in PH1 and PH2 patients. In addition, PH3 patients remain symptomatic with recurrent kidney stones, even in adulthood, and 24% of the 95 patients evaluated were on CKD ≥ 2 at last follow up. Hence, it was speculated, that PH3 patients may also be on risk to develop systemic oxalate deposition.

Method

We retrospectively analyzed the imaging procedures performed so far in patients regularly seen at the German Hyperoxaluria Center, which included: eye exams; x-rays of the hand; bone MRI (3 Thesla of the left knee and proximal tibia); and Speckle tracking echocardiography using 2D Cardiac Performance Analysis VC (TomTec Imaging Systems GmbH, Germany), which measures changes in global longitudinal strain (GLS), an index of left ventricular contractibility. The normal range for GLS is ≤18%. All patients or parents signed an informed consent.

Results

From the 49 PH3 patients registered at the German Hyperoxaluria center, 12 pediatric and 4 adult patients are seen on a regular basis, at least twice a year, and the rest are followed in other centers. All the 16 patients were in stable kidney function and in no less than CKD 2. Eye examination was performed in six patients and was normal in all. Four patients received an x-ray of the left hand, which was normal in 3, but in one patient with a problematic clinical course (multiple stone removal procedures, decline in GFR), tiny sclerosing areas, although no true metaphyseal bands, were seen at caput MCP IV and the thumb. Therefore, MRI of the left knee and proximal tibia was performed in this and another patient, which showed no signs of systemic oxalate deposition. Speckle tracking echocardiography was done in 6 patients and was abnormal in one (GLS – 17.3 and left ventricular hypertrophy) and borderline in the twin sibling (GLS – 18.6). The patient with the abnormal GLS also had salivary stones in the parotid gland, as were also found in his other, older sibling in a routine x-ray of the jaw before orthodontic treatment.

Conclusion

Although this is currently only data of a small cohort of patients, the parameters available so far show, that systemic oxalate deposition may also occur in PH3. Based on our experience on PH1, we regard Speckle tracking echocardiography as the best parameter to detect early systemic calcium-oxalate depositions. Hence the reduction in global longitudinal strain, thus ventricular contractability, is a clear proof of such deposits. Of course, data in more patients are needed to elucidate the true risk of systemic oxalate deposition and we are therefore currently screening all our PH3 patients.
MO121ASSOCIATION BETWEEN BONE MINERAL DENSITY, BODY COMPOSITION AND SERUM SCLEROSTIN IN MALE STONE-FORMERS
Authors: Guedes Rodrigues Fernanda , Pietrobom Igor , Subtil Ormanji Milene , Ligeiro Gonçalves Esper Priscila , Matos Ana Cristina , Ribeiro da Rocha Daniel , Dos Santos Dutra Adriana , De Borst Martin , Pfeferman Heilberg Ita
Published: May 2021

Background and Aims

Reduced bone mineral density (BMD) has been observed in stone-formers (SF). Although obesity is considered a protective factor for bone health due to increased mechanical load, the role of muscle mass (lean) or body fat remains controversial. Sclerostin, an antagonist of the Wnt signaling pathway, is secreted by osteocytes and its actions involve the inhibition of bone formation, FGF23 stimulation, and increased urinary calcium and phosphorus excretion. Recent studies also indicate its association with body composition. The aim of the present study was to evaluate the relationship between BMD and body composition with serum sclerostin levels in male SF.

Method

This is a retrospective study, based on medical records of SF with available data of BMD and body composition, serum and urinary biochemistry and hormonal measurements including sclerostin. BMD had been assessed at lumbar spine (L1-L4), femoral neck (FN) and total femur (TF) and body composition (fat and lean mass) in a dual energy X-ray absorptiometry (DXA).

Results

Fifty-five male SF (37.2 ± 9.3 years) were included. Patients were divided into tertiles according to the percentage of body fat (T1, n = 19, 8.7-20.0 %; T2, n = 20, 20.1-26.0 %; T3, n = 16, 26.1-38.0 %). There was no statistical difference in BMD in any of the sites between these tertiles. Higher urinary sodium and serum sclerostin were observed in T3 versus T1 (280 ± 93 vs 199 ± 75 mEq/day, p <0.05; 33.6 ± 14.7 vs 24.7 ± 8.3 pmol/L, p<0.05, respectively). There was an inverse association between serum sclerostin and lean mass (β= -0.30, p=0.001) and direct association with fat mass (β=0.40, p=0.001), urinary calcium and phosphorus (β=0.29, p=0.02; β=0.32, p=0.01). In a multivariate linear regression model, lean mass was an independent predictor of BMD at L1-L4, FN and TF (β= 0.70, p<0.001; β=0.70, p<0.001; β=0.57, p=0.00, respectively) and at the TF there was also an inverse association between body fat and PTH (β= –0.51, p= 0.03; β= –0.25, p= 0.03).

Conclusion

These data suggest that male SF with a higher percentage of body fat had higher levels of serum sclerostin, which were directly associated with calciuria and phosphaturia but not with BMD. In addition, lean mass was an independent predictor of BMD. Further studies are needed to determine long-term effects of serum sclerostin levels upon bone formation in SF.
MO122SEX DIFFERENCES IN THE RISK OF KIDNEY STONES
Authors: Ferraro Pietro Manuel , Taylor Eric N , Curhan Gary C
Published: May 2021

Background and Aims

Kidney stone disease is a highly prevalent condition. Men are at higher risk of developing stones compared with women, however recent data suggest a changing epidemiology with women being relatively more affected than in the past. The reasons for such differences and changes over time are not clear.

Method

We analyzed the association between sex and the first symptomatic incident kidney stone using data from three large, longitudinal cohorts. Incidence rates for men and women overall and across categories of age and calendar time were computed and hazard ratios (HRs) and 95% confidence intervals (CIs) generated with age-adjusted Cox proportional hazards regression models. Mediation analysis was performed in order to estimate the amount of excess risk for men explained by established risk factors, including BMI, waist circumference, history of high blood pressure, history of diabetes, use of thiazides, dietary intakes of animal protein, caffeine, fructose, potassium, sodium, oxalate, phytate, dietary and supplemental intakes of calcium, vitamin C and vitamin D, sugar-sweetened beverages and total fluid intake.

Results

The analysis included data from 268,616 participants, contributing 5,876,205 person-years of follow-up, during which 10,303 incident stone events were confirmed. The overall incidence rate of kidney stones was 271 and 158 per 100,000 person-years for men and women, respectively. The age-adjusted HR for men compared with women was 2.32 (95% CI 2.20, 2.45). About 18% of the difference in rates was explained by the risk factors included in the analysis. The risk of stones was consistently higher across categories of age among men compared with women. With regard to calendar time, the risk remained higher among men, but tended to decrease over time while it increased among women, resulting in a relative risk reduction of 38% for after 2009 compared with before 1990.

Conclusion

The risk of kidney stones is higher among men compared with women. This difference is only partly explained by modifiable risk factors.
MO113CALCULATED URINARY CALCIUM-OXALATE SATURATION (ßCAOX) IS NOT SPECIFICALLY ELEVATED IN PATIENTS WITH PRIMARY HYPEROXALURIA
Authors: Hoppe Bernd , Böhm Wolfgang , Martin Higueras Cristina
Published: May 2021

Background and Aims

In the primary hyperoxalurias (PH; types 1-3) recurrent urolithiasis (UL) and/or progressive nephrocalcinosis (NC) are the clinical hallmarks. Three different enzyme defects lead to endogenous oxalate overproduction and to extremely elevated urinary oxalate excretion (UOx). Thus, it seems logical that urine is supersaturated for calcium-oxalate (CaOx). It was, hence, speculated that urinary CaOx saturation (ßCaOx), calculated by computed programs, is significantly higher as compared to that of patients with idiopathic CaOx stones. We now aimed to evaluate and calculate urinary ßCaOx in PH patients according to type, as well as in non-PH patients with UL or NC.

Method

The computed equilibrium program EQUIL2 was used for the calculation of ßCaOx. For this, 24 h urine specimen of 70 patients with non-PH NC (46 male, 24 female, median age 6.06 (range 0.3-31.4 years)), of 149 idiopathic CaOx UL (90/59 m/f, age 8.5 (0.1-68.6)), of 51 PH 1 patients (31/21, age 12.33 (0.8-63.8)), of 5 PH 2 patients (3/2, age

5.41 (4.3-12.9)) and of 14 PH 3 patients (8/6, age 8.5 (2.9-29.3)) were analyzed for all necessary components. All patients were in stable kidney function (eGFR > 45 ml/min).

Results

Uox was higher in the PH patients as compared to the non-PH UL or NC patients (p < 0.05). However, there was no statistical difference between the Uox in PH 1 vs PH 2 or PH 3 patients, although, a clear effect of B6 medication was visible in PH1 patients. Urinary calcium excretion was lower (not significant) in PH patients as compared to NC/UL. There was no difference in ßCaOx when PH were compared to non-PH patients and it mostly remained in the normal range.

Conclusion

Urine ßCaOx is similar in PH and non-PH stone formers. Therefore, calculation of ßCaOx using computed programs is not a reliable parameter to define the definitively extreme CaOx supersaturation of urine from PH patients. This miscalculation is related to a rather lowish urinary calcium excretion in PH as compared to other UL/NC patients. Therefore, we recommend not to use such programs to express the risk of recurrent stone disease or nephrocalcinosis in PH.
MO1156,7-DIHYDROXYCOUMARIN AMELIORATE EXPERIMENTAL NEPHROLITHIASIS BY INHIBITING MLKL PHOSPHORYLATION
Authors: Prajapati Smita , Tomar Bhawna , Srivastava Anjali , Mulay Shrikant Ramesh
Published: May 2021

Background and Aims

Intrarenal deposition of organic and inorganic minerals attributes towards the pathogenesis of nephrolithiasis. Various current studies implicates crystal mineralization involves necroinflammation for the progression of crystal induced chronic kidney diseases (CKD). We hypothesized that 6,7-dihydroxycoumarin (6,7-DHC) inhibits calcium oxalate (CaOx) induced necroptosis and ameliorates nephrolithiasis.

Method

We used an in vitro unbiased high content screening for identifying natural compounds that inhibits CaOx induced necroptosis. Molecular docking and molecular dynamic simulations were done to study the interaction between 6,7-DHC - MLKL. Further, for in vivo studies mice and rats models of nephrolithiasis were used. Renal injuries, CaOx deposition and fibrosis were evaluated using histological analysis. Protein expressions were assessed using immunoblots. Data was analysed using one way ANOVA.

Results

An unbiased in vitro high content screening of a library of 24 natural compounds identified 6,7-DHC as a potential candidate. Further, pretreatment with 6,7-DHC protected human and mouse cells from CaOx crystal mediated necroptosis in vitro. Treatment with 6,7-DHC also protected both mice and rats from nephrolithiasis. Computational modelling have revealed 6,7-DHC interacts with MLKL and inhibits its phosphorylation by ATP which is a key event in necroptosis signaling cascade.

Conclusion

All together our studies indicates that 6,7-DHC owns a novel pharmacological inhibitory property towards MLKL and it could serve as a lead molecule for further development of novel coumarin based MLKL inhibitors. Moreover, our findings also suggests that 6,7-DHC could be used as a therapeutic strategy for combating nephrolithiasis.
MO116COMPARISON OF THE CHARACTERISTICS BETWEEN UNILATERAL AND BILATERAL RENAL STONES AND THEIR ASSOCIATION WITH KIDNEY INJURY IN CHINESE POPULATION
Authors: Fan Xiaohong , Ye Wenling , Ma Jie , Wang Liang , Li Xuemei
Published: May 2021

Background and Aims

Urinary stone disease (USD) has been associated with increased risk for chronic kidney disease (CKD) and end-stage renal disease (ESRD) in Western populations. However, the comparison of metabolic disorders between unilateral and bilateral renal stones and their association with CKD have not been fully examined. It is also unclear whether there is an increased risk for kidney tubular injury makers such as N-acetyl-ß-D-glucosaminidase (NAG) and alpha-1-microglobulin (α1-MG) in different stone formers.

Method

We performed a cross-sectional study of 10,281 participants in rural China in 2014. All subjects underwent a renal ultrasound to detect USD; stone formers were grouped into one or two sides of USD by ultrasound exams. CKD was defined as a decreased estimated glomerular filtration rate (eGFR, <60mL/min/1.73m2) and/or albuminuria (ACR≥30mg/g). Increased urine NAG and α1-MG were defined as the values of NAG and α1-MG above the 75th percentile of the sample distribution.

Results

The mean age of the study population was 55.4±10.0 years; 47.1% were males. Among all participants, 4.9% (n=507) had unilateral renal stone, and 0.7% had bilateral renal stones. The proportion of CKD in non-stone formers, unilateral and bilateral renal stones were 11.0%, 19.2%, and 29.7%, respectively (p for trend<0.001). Bilateral renal stone formers tend to have a higher proportion of hypertension and diabetes. In multivariate analyses after adjustment for multiple confounders, bilateral renal stones were significantly associated with an increased risk of decreased eGFR (OR 3.38; 95% CI 1.05-10.90), albuminuria (OR 3.01; 95% CI 1.76-5.13), CKD (OR 3.18; 95% CI 1.88-5.36), increased NAG (OR 1.95; 95% CI 1.21-3.16) and α1-MG (OR 2.54; 95% CI 1.56-4.12) compared with non-stone formers.

Conclusion

In the present study, bilateral renal stone formers tend to have a higher proportion of metabolic disorders and are also associated with a higher risk of CKD and kidney tubular injury. Further studies are needed to confirm the increased risk for ESRD.
MO118ROLE OF DUAL ENERGY COMPUTED TOMOGRAPHY IN PREDICTING THE CHEMICAL COMPOSITION OF STONES
Authors: Bhat Dr Sanjay , Kaul Anupma
Published: May 2021

Background and Aims

Dual-energy CT (DECT) has shown excellent outcomes in differentiating the chemical composition of the urinary stones with a great accuracy. A reliable determination of the chemical type of the stone help the clinician to better satisfy treatment options for the patient- medical versus surgery We used the DECT in our study to assess the accuracy of non-invasive differentiation of renal stones using the 3rd generation dual-source computed tomography (CT) scanner in determining the chemical composition of renal stones and to determine appropriate management based on DECT determined chemical composition of stones.

Method

This prospective study was conducted in the Department of surgery and radiodiagnosis and Imaging, Era Medical College and RML institute of Medical Sciences , Lucknow over the study period, i.e., November 2016 to May 2018 . The patients were those referred for non-contrast/contrast CT for the diagnosis/evaluation of urolithiasis from the department of Surgery admitted for PCNL/ESWL/therapeutic ureterorenoscopy. DECT ratios of the various stones were noted and compared with the post extraction analysis of stones for composition. A total of 100 patients were included in the study, and their DECT results were compared with the post-extraction analysis (by infrared spectroscopy as the standard comparative method).

Results

Mean age of patients was 41.15+/- 10.08 years with 64% being males. DECT was highly sensitive and specific in the diagnosis of various types of calculi based on their dual-energy ratio. It was found to be 100% sensitivity and 97.2% specificity for differentiating UA stones with level of agreement between chemical and DECT was almost perfect (k= .951) .However for hydroxyapatite stones was substantial (k=.889). Most of the stones belonged to non-UA category (72%), and only 28% were UA calculi. The sensitivity and specificity in differentiating a calcium oxalate from non-calcium oxalate calculus was 94.1% and 95.5%, respectively.

Conclusion

DECT highly sensitive and effective in characterizing chemical composition of the urinary stones and can help in determining the management plan and reduce the unnecessary burden of surgical interventions.
MO1004IMBALANCE IN URINARY PROTEOGLYCANS AND THE INSULIN GROWTH FACTOR (IGF) AXIS IN CHILDREN WITH NEPHROLITHIASIS*
Authors: Kovacevic Larisa , Kovacevic Natalija , Lakshmanan Yegappan
Published: May 2021

Background and Aims

In vitro experiments have shown that exposure of renal epithelial cells to calcium oxalate crystals leads to synthesis of proteins involved in extracellular matrix (ECM) production. Cell proliferation and accumulation of ECM proteins have been reported in animal models and kidney biopsies from patients with stones. Based on the role of ECM in the Randall plaque formation, we aimed to identify and quantify ECM proteins in the urine of children with nephrolithiasis (RS) using a proteomic approach.

Method

Prospective, controlled, pilot study of pooled urine from RS (N=30, 24 females, mean age 12.95±4.03 years) versus age- and gender-matched healthy controls (HC), using liquid chromatography-mass spectrometry (LC-MS/MS). Patient inclusion criteria consisted of age 5-18 years, history of clinically (typical renal colic) and radiographically (ultrasound or CT) proven renal stone, at least two 24-hour satisfactory urine collections (urinary creatinine more than 15 mg/kg/day), absence of hematuria or pyuria, and normal renal function. Children who were not toilet trained, or those with bladder stones, nephrocalcinosis, neuropathic bladder, major congenital bladder abnormality, active urinary tract infection, presence of blood in urine, chronic kidney disease, previous major reconstructive bladder surgery requiring catheterization, and significant cardiac, pulmonary, gastro-intestinal, and neurological problems were excluded. Relative protein abundance was estimated using spectral counting. The criteria for protein selection were: 1) patient/control abundance ratios of >5 or <0.2 as a threshold to be well above observed technical variations in MS experiments; and 2) ≤0.05 p-value for the Fisher’s Exact Test. Results were confirmed by ELISA testing. Statistical analyses were conducted with IBM SPSS® version 20.

Results

We found 36 (15.7%) ECM proteins out of 229 proteins that met the above criteria. Significant differences between RS and HC were found among two proteoglycans and four insulin growth factor (IGF) proteins (Table). Significant increase in the urinary excretion of IGFBP4 in RS (37.00 ± 37.68 ng/mg creatinine ) versus HC (19.04 ± 20.32 ng/mg creatinine) was confirmed by ELISA (p=0.049). Statistically significant correlation was found between urinary IGFBP4 concentration and 24-hour urinary calcium excretion (p<0.001).

Conclusion

Alteration in proteoglycans and the IGF axis appears to have a significant role in the mechanism of nephrolithiasis, likely by modulating ECM biosynthesis. Further understanding of their roles in nephrolithiasis may aid in generation of novel therapeutic approaches.
MO1013RETROSPECTIVE ANALYSIS OF THROMBOTIC COMPLICATIONS IN SHIGA-TOXIN ASSOCIATED HEMOLYTIC UREMIC SYNDROME IN CHILDREN
Authors: Emirova Khadizha , Tolstova Evgeniya , Orlova Olga , Muzurov Alexandr , Mstislavskaya Sofya , Pankratenko Tatiana , Abaseeva Tatiana , Generalova Galina
Published: May 2021

Background and Aims

Shiga-toxin associated hemolytic-uremic syndrome (STEC-HUS) is a thrombotic microangiopathy (TMA) followed by intestinal infection caused by shiga-toxin-producing E. coli. Endothelium damage of the microvasculature leads to the formation of platelet-fibrin thrombi and occlusion of small vessels. The aim of our study was a retrospective analysis of thrombotic complications in children with STEC-HUS.

Method

We retrospectively analyzed the case histories of patients in the dialysis department of St. Vladimir's Children's City Clinical Hospital from 2009 to 2019. The study included patients with STEC-HUS with the development of thrombotic complications.

Results

Among 410 patients with STEC-HUS, 16 patients with thrombotic complications were identified. Equally boys and girls, mean age 3.5 ± 2.4 g. Respiratory support was required in 6 cases. The duration of anuria was 9.9 +/- 6.2 days, in 2 cases only oliguria was noted. In all patients blood transfusion, fresh frozen plasma were needed, antibiotics were used. In all cases, continuous venovenous hemodiafiltration (CVVHDF) was performed with 2-way catheters, usually in the femoral vein. Thrombotic complications in all cases were associated with therapy. In 11 children, thrombosis was localized in the femoral, iliac veins and vena cava inferior. Clinical manifestations in the form of limb edema, cyanosis were noted in 4 patients, in other cases the diagnosis was made by ultrasound. 3 patients with thrombosis of the branches of the central retinal vein, vena cava superior, mesenteric thrombosis. 1 patient was diagnosed with dissecting femoral vein aneurysm. In 3 cases, CVVGDF had to be stopped due to catheter thrombosis. Before the current thrombosis, these children were not prescribed anicoagulants. Coagulation tests indices indicated hypercoagulability and were characterized by higher thrombin time, increased levels of D-dimer, and increased fibrinolysis time.

Conclusion

Large vessel thrombosis in children with STEC-HUS is a rare complication. The provoking factor for the implementation of thrombotic events in all cases was femoral vein catheterization. When managing patients with STEC-HUS monitoring of coagulation status is needed for the purpose of timely administration of anticoagulants.
MO1014PROSPECTIVE STUDY OF SAFETY AND EFFECTIVENESS OF OFATUMUMAB AS A TREATMENT IN REFRACTORY NEPHROTIC SYNDROME (CORTICODEPENDENT AND CORTICORRESISTANT)
Authors: Hernández Zúñiga Lina Catherine , Vinuesa Jaca Ana , Arango Sancho Pedro , Calzada Baños Yolanda , Codina Sampera Elena , López Baez Víctor , Madrid Aris Álvaro
Published: May 2021

Background and Aims

Ofatumumab (OFA) is an anti-CD-20 monoclonal antibody useful in nephrotic syndrome refractory to conventional treatments and rituximab (RTX). Our objective is to evaluate the response and safety in patients with nephrotic syndrome (NS) treated with Ofatumumab.

Method

A prospective descriptive study of 2 years duration (2017-2019) in children with NS refractory to first-line therapies who received treatment with anti-CD20 monoclonal antibodies. To do this, we divided the cohort into 3 groups: Patients with corticodependent NS (CDNS) without response or with adverse effects associated with first-line treatment that preclude its use (Group 1); Corticosteroid-resistant SN (CRNS) (Group 2) and SN with post-transplant recurrence (Group 3). In them, the results of safety and remission rate were evaluated.

Results

Thirty-three patients (21 with SNCD, 11 with SNCR, and 1 with SN recurrence in transplantation) were included and administered anti-CD20. The male / female ratio was 2: 1 and the mean age at diagnosis was 5.2 years. 100% of the children (33) received RTX and 18.2% (6) OFA. The RTX achieved complete remission in 87.9% (29) and 48.3% of these did not present new relapses after 70 months of follow-up. 100% of Group 1 presented complete remission after RTX, although 52.4% (11) presented at least 1 relapse after 22.9 months (mean 2.5 relapses). In group 2, 72.72% (8) complete remission and 27.2% (3) partial, with persistent proteinuria. 36.4% (4) presented relapse after 17 months of treatment (mean 1 relapse). Of the 6 who received OFA, 83.3% presented complete remission (1 SNCR and 4 SNCD) and 1 patient (SNCD) presented relapse at 24 months (mean follow-up 1 year). The other case, a 13-year-old girl with recurrence of focal segmental glomerulosclerosis (FSGS) in kidney transplantation, presented partial remission after one year of treatment in association with immunoadsorption sessions. Regarding safety, adverse reactions occurred in 6% (2): allergic reaction with 2nd dose of RTX and cytokine release syndrome with 1st dose of OFA.

Conclusion

Ofatumumab in our series has proven to be an effective and safe drug in difficult-to-manage NS, achieving complete remission in 5 patients who had not previously responded to Rituximab
MO1015EARLY URINARY SYSTEM COMPLICATIONS IN CHILDREN WITH HEMATOPOETIC STEM CELL TRANSPLANTATION
Authors: Gurbanov Anar , Gülhan Bora , Kuşkonmaz Barış , Okur Fatma Visal , Uçkan Çetinkaya Duygu , Ozdemir Gulsah , Taş Nesrin , Çelegen Kübra , Ozaltin Fatih , Duzova Ali , Topaloglu Rezan
Published: May 2021

Background and Aims

Urinary system complications after hematopoietic stem cell transplantation (HSCT) cause severe morbidity and mortality. The aim of the study is to investigate the incidence and risk factors of urinary system complications in patients who had HSCT during their childhood.

Method

Patients who had HSCT between January 2010-2019 with a minimum follow-up period of 6 months were included in the study. Data regarding urinary system complications were collected from the medical records of the patients. pRIFLE and KDIGO classification systems were used for the definition of acute kidney injury (AKI).

Results

167 patients (108 males and 59 females) with allogeneic (n=165) and autologous (n=2) HSCT were investigated for renal complications. In cohort, HSCT was performed in 41 patients (%24.6) secondary to malignant diseases and in 126 patients secondary to non-malignant diseases. Hemorrhagic cystitis (HC) developed in 28 patients (16.8%) after HSCT. The mean age of the patients with and without HC was 14.6±5.6 years and 10.5±6 years, respectively (p=0.044). Among patients with HC, 17 had concomitant viral infection. Presence of viral infection, gender, disease group, history conditioning regime, total body irradiation, acute graft-versus-host disease and veno-occlusive disease (VOD) did not have any effect on the development of HC in logistic regression analysis. In cohort, 126 patients (75.4%) developed AKI according to KDIGO classification (stage 1; 55 patients, stage 2; 36 patients, stage 3; 35 patients). The mean period of development of AKI after HSCT was 34±22 days. The risk of AKI (according to KDIGO) was higher in patients who had HSCT secondary to malignant diseases and/or who developed viral infections after HSCT (p=0.034 and p=0.013, respectively). Among patients, 71 patients (%42.5) developed AKI according to pRIFLE classification. The risk of AKI (according to pRIFLE) was higher in patients who had HSCT secondary to malignant diseases, who developed viral infections and/or who developed VOD during follow-up (p=0.043, p=0.001 and p=0.006, respectively). One patient developed thrombotic microangiopathy after HSCT. None of the patients had nephrotic syndrome during follow-up period.

Conclusion

Patients who had HSCT secondary to malignant disease, viral infections and/or VOD had higher risk of AKI and should be closely monitored.
MO1017PSYCHOSOCIAL REPERCUSSIONS AND QUALITY OF LIFE OF CHILDREN UNDERGOING HEMODIALYSIS IN A DEVELOPING COUNTRY
Authors: Naouaoui Salma , Ahtitich Kamal , Chettati Meriem , Fadili Wafaa , Laouad Inass
Published: May 2021

Background and Aims

Despite major advances in the provision of renal replacement therapy, children and adolescents on dialysis frequently have compromised daily life activities and a worse quality of life compared with healthy peers. While these aspects have been studied extensively in affluent countries, data from developing regions are scant. The aim of our study was assessing the psychosocial repercussions and the quality of life (QoL) of children with end stage renal disease (ESRD) undergoing hemodialysis in a Moroccan tertiary care hospital and comparing them with healthy controls.

Methods

We performed a cross-sectional investigation, at Mohammed VI university hospital of Marrakesh, using parent/child reports of generic module for QoL assessment: PedsQLTM Inventory version 4 for both cases and controls. Disease-specific module: PedsQLTM ESRD version 3 was used for ESRD cases. Twenty-two children on maintenance hemodialysis and 50 controls were enrolled in our study.

Results

The mean age of the ESRD cases was 11.6 ± 4.7 years (range 4– 18 years) with female predominance (58%). Controls were age- and sex-matched. A statistically significant difference was observed between ESRD cases and controls regarding all aspects of QoL. The total QOL mean score was 51.2 ± 13.6 and 82.8 ± 11.2 among cases and controls, respectively. All individual QoL domains were significantly worse in ESRD cases.

Conclusion

Our findings showed that the quality of life of children undergoing hemodialysis may be dramatically affected especially in limited-resources countries. And this raises the need to introduce quality of life assessment as a part of pediatric ESRD management.
MO1018IS LOW NORMAL BLOOD PRESSURE LEVEL IN PATIENTS WITH X-LINKED ALPORT SYNDROME OUR GOAL?
Authors: Aksenova Marina , Tutelman Konstantin , Konkova Natalia
Published: May 2021

Background and Aims

The mean blood pressure <50th percentile for age, gender and height is recommended in children with chronic kidney disease, especially in case of proteinuria. The aim was to define the influence of low normal mean blood pressure level on the progression of renal disease in children with X-linked Alport syndrome (XLAS).

Method

mean day blood pressure normalized for sex, age, height (MBP), urine protein (mg/m2/day) and eGFR were assessed in retrospective single center study.

Results

The children with XLAS (n=69, 47M, age 9.49±4.18 years, eGFR=109±17.36 ml/min/1,73m2) were divided into 3 groups according the MBP level during follow up (4[3;5] years): (1) MBP<50‰ (n=27, 13М), (2) MBP 50-90‰ (n=33, 25M), (3) MBP≥90‰ (9М). The decline of eGFR (ml/min/1,73m2/year) was higher in male (-3[-0.8;-4.7] vs 0.2[-0.4;2]; χ2= 21.15587, p = 0.0067), in children with MBP ≥90‰ (0.65[-2.65;2] vs -2.3[-6;2.3] vs -3[-7.5;-1.8] in 1st, 2nd and 3 groups, respectively; р1,3=0.0091) and in patients with proteinuria (-2.5[-7;0.5] vs 0.2[-4;3]; p=0.0018). The risk of achieving eGFR<60 ml/min/1,73m2 was higher in pts of 3 group (OR=5.33, 95% CI 1.75;16.22) especially in the presence of proteinuria (OR=7.08, 95% CI 2.46;20.39). The multivariate analysis of predictive factors for eGFR reduction showed that the proteinuria (χ2=12.554, p=0.0019), the male gender (χ2=7.107, p=0.0077) and not MBP (χ2=5.4, p=0.07) were independent risk factors for eGFR decline.

Conclusion

The male gender and proteinuria are independent risk factors for renal disease progression in children with XLSA. We assumed that the goal of treatment, at least in XLAS’ patients with normal blood pressure, is to decrease proteinuria.
MO1019ASSOCIATION OF VEGF ANF TGF1 GENES POLYMORPHISMS WITH SERUM CONCENTRATION OF GENE PRODUCTS IN CHILDREN WITH LUPUS NEPHRITIS
Authors: Kazyra Ina , Sukalo Alexandr , Bialkevich Hanna , Krylova-Alefirenko Anna , Nikitchenko Natallia , Goncharova Roza
Published: May 2021

Background and Aims

Previously it was shown that significantly elevated serum concentration of vascular-endothelial growth factor (VEGF) and transforming growth factor β (TGF-β1) is observed in Lupus Nephritis (LN) patients, especially in those with disease exacerbation. In this study we investigated the association of selected single nucleotide polymorphisms (SNP) in TGF-β1 and VEGF genes with serum concentration of the gene product in children with LN.

Method

We enrolled 22 children with LN (m:f 2/20) aged 10 to 17 years. Blood samples were taken twice in every child – in remission and during exacerbation of the disease. Serum concentration of VEGF and TGF-β1 was measured using R&D Systems Quantikine ELISA “Human TGF-β1” and “VEGF” kits. DNA was analyzed by polymerase chain reaction for identification of selected SNPs – VEGF rs699947 (A/C), rs2010963 (G/C), TGF-β1 rs1800469 (G/A).

Results

We didn’t find any association of serum concentration of TGF-β1 with rs1800469 polymorphism in individuals with LN in exacerbation and in remission either (p>0,05).

Concentration of VEGF was associated with genotypes of VEGF gene. It was significantly higher in LN patients harboring AA genotype for rs699947 comparing with those with CC+CA group of genotypes (ie carrying at least one minor allele A). This association was observed in exacerbation period (p<0,001), but not in remission (p>0,05).

We compared major genotype GG and group of genotypes GC+CC (ie patients with at least one minor allele C) of VEGF gene (rs2010963). It was found that statistically significant elevation of gene product was found in individuals with group of genotypes GC+CC in exacerbation period (p=0,036). In remission concentration of the gene product didn't differ in patients with GG and GC+CC genotypes (p=0,97).

VEGF gene genotypes rs699947 and rs2010963 are in high linkage disequilibrium (LD). Having analyzed combined genotypes we found that association with the gene product was the same as in rs699947 alone analysis. This may suggest functional importance of this SNP. Rs2010963 more likely to show association with the gene product due to linkage with rs699947.

Conclusion

There is an association between VEGF gene genotypes (rs699947 and rs2010963) and gene product serum concentration in LN pediatric patients in exacerbation period. Among two investigated loci of VEGF gene rs699947 might be considered more relevant risk marker of VEGF disfunction. No statistically significant association was found in our study for TGF-β1 gene genotypes (rs1800469) and its' product serum concentration.
MO1022CENTRAL VENOUS CATHETERS FIRST - THE ACHILLES’ HEEL IN PEDIATRIC HEMODIALYSIS VASCULAR ACCESS
Authors: Domingos Ana , Teixeira Ana , Matos Paula , Rocha Liliana , Almeida Paulo , Costa Teresa , Faria Maria do Sameiro , Mota Maria Conceição
Published: May 2021

Background and Aims

Management of children with end-stage kidney disease (ESKD) requiring dialysis is always challenging and particular concerns exists regarding vascular access. International reports through the years are not satisfactory, with a high rate of central venous catheter (CVC), when “Fistula First” is the goal in Hemodialysis (HD). Suggested reasons for this phenomenon include, for example, age-related anatomical limitations, shorter awaiting times for or “scheduled” transplantation, pain and anxiety related to punctures or lack of pediatric/surgical expertise. Here we present the results of the last 13 years of experience in pediatric HD vascular access from a reference center in northern Portugal.

Method

A retrospective descriptive study of patients admitted to our pediatric HD Unit between January 2007 and December 2020. Clinical data was collected from medical records.

Results

40 patients were enrolled, mainly boys (n=22, 55%), mean age at admission 10.9±5.3 years (1-17 years), 63% weighing more than 30 kg (n =25) and 15% less than 15kg (n=6). More than half were incident patients starting on HD (n=22, 55%), 42.5% were transferred from peritoneal dialysis (PD) and one patient had a previous kidney transplant (KT). Regarding CKD etiology, 52.5% (n=21) were mainly due to congenital anomalies of the kidney and urinary tract; chronic glomerulonephritis was responsible for 20% of cases (n=8). Most patients initiated HD with a CVC (n=35, 87.5%), including two patients with an arteriovenous fistula (AVF) who required a temporary CVC until fistula maturation. At the end of follow-up, about 45% of the patients ended up with an AVF (comparing to 17.5% at the beginning) and, not unexpectedly, 88.9% (n=16) of them weighed more than 30kg and only one child less than 15 kg. The mean duration of dialysis was 1.2±1.8 years (1 month-8 years); 24 patients were submitted to KT (60%), 6 transferred to PD (15%) and only 4 remain on HD. Average waiting times for KT are quite longer in patients with AFV (1.7±2 years), in comparison to CVC (0.4±0.3 years).

Conclusion

CVC is by far the most used access in incident patients starting on HD. In our center it seems justified by the anatomical limitations of younger and smaller patients, as wells as expected shorter awaiting time for KT. Infectious and mechanical complications must be weighed when using CVC, mainly considering the probable need for different renal replacing techniques over the years. Although our data is quite similar to several international reports and other center experiences, we still aim for the best, with an expected improvement of these results within the coming years. For now, a notable increase in AVF placement at the end of the follow-up is already an encouraging fact.
MO1005ADPEDKD: A GLOBAL ONLINE PLATFORM TO EXPLORE THE CHILDHOOD PHENOTYPE OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE*
Authors: Dachy Angélique , De Rechter Stéphanie , Guay-Woodford Lisa , Mallett Andrew John , Harris Tess , Bockenhauer Detlef , Schaefer Franz , Liebau Max , Mekahli Djalila
Published: May 2021

Background and Aims

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the 4th common cause of renal replacement therapy worldwide. As the disorder has been historically considered an adult-onset disease, there is a lack of longitudinal data from large pediatric cohorts. However, evidence is growing that first manifestations of ADPKD may be detected in childhood and children represent a specific target population for future treatment, allowing a better chance of preserving long term kidney function. To better define the pediatric spectrum of the disease, a global multicenter observational study on childhood-diagnosed ADPKD was launched in 2017.

Method

The ADPedKD registry is a worldwide web-based database, including both retrospective and prospective longitudinal data from young ADPKD patients (≤19 years). Australia, North-America and the United Kingdom joined the initiative with their source databases, namely the KidGen Collaborative (KidGen), NIH-funded Hepato-Renal Fibrocystic Disease (HRFD) and National Registry of Rare Kidney Diseases (RaDaR). Under informed consent, de-identified patient data, including genetics, radiological and laboratory findings, treatments and follow-up were enrolled in the database accessible via https://www.ADPedKd.org/.

Results

1019 ADPKD children (from 89 centers and 33 countries) are enrolled in the registry of which 167 patients from RaDaR, 17 from KidGen, 11 from HRFD and 824 from ADPedKD (401 male/ 423 female) with a mean (± SD) age at diagnosis of 6.3 ± 5.2 years. 81 children (9.8%) were diagnosed prenatally at a mean gestational age of 26.8 ± 7.8 weeks. Reasons for initial visit were: family screening in 325 (39.4%), postnatal incidental finding in 223 (27.0%), presenting features (such as hematuria, hypertension, urinary tract infections and flank or back pain) in 150 (18.2%) or unknown/not available in 126 (15.3%). Genetic testing was performed in 42.8% of the population, with the following results: PKD1 mutation (85.4%), PKD2 mutation (11.7%) and others (6.0%).

Conclusion

The ADPedKD registry is a unique source of clinical observational data that will provide deep phenotyping of children with ADPKD and will allow to define unified diagnostic, treatment and follow-up recommendations.
MO1024CLOSTRIDIUM SEPTICUM INFECTION COMPLICATING HEMOLYTIC UREMIC SYNDROME: A CASE REPORT AND LITERATURE REVIEW
Authors: Cirillo Luigi , Becherucci Francesca , Guzzi Francesco , Errichiello Carmela , Buti Elisa , Roperto Rosa Maria , Materassi Marco , Romagnani Paola
Published: May 2021

Background and Aims

C.septicum is an anaerobic bacterium that resides in the gastrointestinal tract of herbivores. Its presence in human fecal flora is still debated, being found in only 2.8% of healthy adults. Transmitted by oral-fecal route, it reaches the systemic circulation, causing bacteremia, myonecrosis, bowel necrosis, intracranial abscesses/encephalitis. Shiga-toxin producing E. Coli related hemolytic uremic syndrome (STEC-HUS) is a thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia and kidney damage, related to STEC infection. Severe presentation includes gastrointestinal and neurologic involvement. Microangiopathic lesions in the colonic mucosa can facilitate the colonization of systemic circulation by C.septicum, spreading the superinfection. 

Since the first report in 1988, very few cases of STEC-HUS complicated by C.septicum superinfection have been described in literature and thus the factors predicting clinical outcome are not clear.

Method

We describe the case of a 5-years-old girl admitted for anemia, AKI, thrombocytopenia and diarrhea. Previous history was unremarkable. STEC-HUS diagnosis was made. Despite prompt conservative treatment, 12h later her clinical condition worsened, showing ESKD needing dialysis, abdominal pain, progressive hyporesponsiveness. The brain CT scan showed pneumocephalus and encephalitis; blood cultures were drawn and broad-spectrum antibiotic therapy was set (Tab.1). Cardiovascular instability prevented surgical treatment of pneumocephalus to be done. The patient died shortly after because of  septic shock. Post-mortem stool and blood cultures confirmed STEC infection complicated by C.Septicum.

Previous literature on this specific clinical picture has been reviewed and summarized.

Results

Eleven additional cases (7 males) have been previously described. Mean age of presentation was 2.9 years. A; abdominal symptoms (commonly distention and pain) were reported in all cases, while ESRD was present in 10 cases. Six patients presented fever. Central nervous system presentation as pneumocephalus was associated with poor prognosis, while surgical treatment availability of brain lesions to survival. In one case the infection caused myonecrosis (Tab. 1).

The mortality rate was about 60%. In 7 cases, clinical conditions worsened in less than 24h and this was in all cases related to poor outcome.

Conclusion

C.septicum superinfection complicating STEC-HUS is a rare but fearsome complication to be aware of. Rapid diagnosis and surgical treatment are essential for the successful management of this particular condition.
MO1025SCREENING FOR CELIAC DISEASE AMONG PEDIATRIC PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Ibrahim Magid A Abd El Fattah , Hamdy Ahmed M , Anwar Doha , Ragia M Said
Published: May 2021

Background and Aims

Chronic kidney diseases (CKD) in children are a group of diseases that not only affects the kidneys but also all systems of the body particularly causing anemia, bone diseases and failure to thrive in that age group. Gastrointestinal tract (GIT) manifestations are not thoroughly highlighted in those patients although they definitely have repercussions on their growth and development. GIT diseases such as celiac disease (CD) has been long linked to renal manifestations either through increasing risk of kidney diseases or as a proved association. The aim of this study was screening for celiac disease and GIT symptoms among pediatric patients with chronic kidney disease.

Method

A case-control study included 90 CKD patients from Nephrology unit, Children’s Hospital, Ain Shams University, who has been diagnosed for at least 3 months and not receiving steroids or immunosuppressive therapy: 60 patients with end stage renal disease (ESRD) on regular hemodialysis (HD) & 30 with CKD on conservative treatment. Their ages ranged between 2-13 years old, 47 males, 43 females. 200 controls were also enrolled in the study (for GIT manifestations): healthy children with ages ranging from 2-13 years old, 77 males, 123 females within a period of 12 months. All patients & controls were interviewed about GIT manifestations they regularly experience and any GIT troubles they have. All CKD patients were screened for CD by Anti Tissue transglutaminase IgG and IgA blood testing.

Results

Reviewing the most significant GIT symptoms among patients, we found that 86.7% had mucoid diarrhea, 77.8% had abdominal distension, 75.6% had anorexia, 64.4% had epigastric pain, 51.1% had watery diarrhea, 30% had nausea, 30% had vomiting, and 25.6% had constipation. None suffered from hematemesis, melena or bloody diarrhea. GIT symptoms were significantly more pronounced in CKD patients compared to controls and even more in ESRD patients than CKD patients. All patients were negative for CD screening by Anti Tissue transglutaminase IgG and IgA. No significant correlations were seen between Anti Tissue transglutaminase IgG and IgA and age, sex, anthropometric measures (except for BMI), biochemical results (except for s. ferritin) or eitiology of renal disease were observed.

Conclusion

GIT troubles are more pronounced in children with CKD compared to age and sex matched healthy controls. CD is not particularly prevalent among CKD pediatric patients compared to the known percentage among this age population.
MO1028EFFECTIVENESS AND KIDNEY PROGNOSIS IN THE TREATMENT OF CORTICORRESISTANT NEPHROTIC SYNDROME IN PEDIATRICS
Authors: Vinuesa Jaca Ana , Hernández Zúñiga Lina Catherine , Arango Sancho Pedro , Codina Sampera Elena , Calzada Baños Yolanda , López Baez Víctor , Madrid Aris Álvaro
Published: May 2021

Background and Aims

To report the response to different treatments and the renal prognosis in a cohort of patients with corticosteroid-resistant nephrotic syndrome (CRNS).

Method

Retrospective observational study in patients with CRNS. For this, the results of the histology, the different treatment guidelines used in each case and the evolution of renal function were collected, determining the results in terms of remission and renal survival in the different groups.

Results

Of the initial cohort of 37 patients, 33 were included, excluding 4 patients with Finnish-type genetic CRNS. The mean age at diagnosis was 6.1 years. 54.5% were women. Regarding the initial biopsy, 45.5% corresponded to minimal changes (15 patients), 27.3% (9) focal and segmental glomerulosclerosis, 15.1% (5) diffuse mesangial proliferation and 12.1% (4) others. The mean follow-up was 53 months (3-115 months). 27 patients (84.4%) received cyclosporine (CyA), 66.7% (18) of them presented complete remission and 22.2% (6) partial response. Of the patients in complete remission, 33% had at least one relapse after 17 months of treatment (7–27 months). Rituximab was administered in 12 patients (37.5%), of which 7 had not previously responded to immunosuppressants. 100% of frequent relapsers presented complete remission after administration of Rituximab, although 3 had subsequent relapses (60%) after 21 months of treatment (12-34 months). 57% of the patients who did not respond to immunosuppressants did not respond to Rituximab either, with Ofatumumab allowing complete remission in one of them. When relating the results with the histology, we saw how the remission in minimal changes and diffuse mesangial proliferation was 100% and 80%, respectively, although it was 33.3% in focal and segmental glomerulosclerosis. Similarly, renal failure was more frequent in patients with focal segmental glomerulosclerosis (77.7%). Of the remissions (24; 72.7%), 3 were partial (9.1%) and 6 (18.2%) did not respond to any immunosuppressive treatment, with the need for kidney transplantation in 2 of them (6%) and with 1 deceased due to an infectious cause (3%).

Conclusion

Histology and, especially, focal and segmental glomerulosclerosis, play a prognostic role in the CRNS with a lower remission rate and a greater deterioration in renal function and the need for associated kidney transplantation.