Dyslipidemia in children with chronic kidney disease-findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study.

BACKGROUND: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. METHODS: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3-5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. RESULTS: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. CONCLUSIONS: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.

A case of crescentic glomerulonephritis with exacerbation of pre-existing IgA nephropathy after COVID-19.

BACKGROUND: Relapses or new-onset IgA nephropathy (IgAN) have been documented in patients after vaccination against SARS-CoV-2; however, only one adult patient has been reported in whom pre-existing IgAN worsened during coronavirus disease 2019 (COVID-19). CASE: We present the first pediatric case with biopsy-proven IgAN and genetically confirmed Alport syndrome, who developed end-stage kidney disease after an exacerbation of IgAN associated with COVID-19. The patient`s basal serum creatinine was 0.7-0.9 mg/dL before infection. He had not been vaccinated against COVID-19. He was admitted to the hospital with edema, hypertension, an elevated serum creatinine of 4.7 mg/ dL, and massive proteinuria. Three months before admission, he had been admitted to another hospital with COVID -19 and an elevated serum creatinine (1.9 mg/dL), but no biopsy had been performed at that time. The kidney biopsy revealed IgAN with 50% fibrocellular crescents with sclerosed glomeruli, tubular atrophy, and interstitial fibrosis. His serum creatinine did not decrease even after five administrations of pulse steroids, and hemodialysis was initiated. CONCLUSION: In conclusion, COVID -19 may pose a high risk for exacerbation of pre-existing glomerular disease. It is therefore necessary to closely monitor the kidney function of patients with underlying glomerulonephritis during and after COVID-19 and consider an early biopsy if serum creatinine does not return to baseline levels. In addition, this case report highlights the clinical importance of the co-occurence of IgAN and Alport syndrome.

Magnetic resonance imaging based kidney volume assessment for risk stratification in pediatric autosomal dominant polycystic kidney disease.

Introduction: In the pediatric context, most children with autosomal dominant polycystic kidney disease (ADPKD) maintain a normal glomerular filtration rate (GFR) despite underlying structural kidney damage, highlighting the critical need for early intervention and predictive markers. Due to the inverse relationship between kidney volume and kidney function, risk assessments have been presented on the basis of kidney volume. The aim of this study was to use magnetic resonance imaging (MRI)-based kidney volume assessment for risk stratification in pediatric ADPKD and to investigate clinical and genetic differences among risk groups. Methods: This multicenter, cross-sectional, and case-control study included 75 genetically confirmed pediatric ADPKD patients (5-18 years) and 27 controls. Kidney function was assessed by eGFR calculated from serum creatinine and cystatin C using the CKiD-U25 equation. Blood pressure was assessed by both office and 24-hour ambulatory measurements. Kidney volume was calculated from MRI using the stereological method. Total kidney volume was adjusted for the height (htTKV). Patients were stratified from A to E classes according to the Leuven Imaging Classification (LIC) using MRI-derived htTKV. Results: Median (Q1-Q3) age of the patients was 6.0 (2.0-10.0) years, 56% were male. There were no differences in sex, age, height-SDS, or GFR between the patient and control groups. Of the patients, 89% had PKD1 and 11% had PKD2 mutations. Non-missense mutations were 73% in PKD1 and 75% in PKD2. Twenty patients (27%) had hypertension based on ABPM. Median htTKV of the patients was significantly higher than controls (141 vs. 117 ml/m, p = 0.0003). LIC stratification revealed Classes A (38.7%), B (28%), C (24%), and D + E (9.3%). All children in class D + E and 94% in class C had PKD1 variants. Class D + E patients had significantly higher blood pressure values and hypertension compared to other classes (p > 0.05 for all). Discussion: This study distinguishes itself by using MRI-based measurements of kidney volume to stratify pediatric ADPKD patients into specific risk groups. It is important to note that PKD1 mutation and elevated blood pressure were higher in the high-risk groups stratified by age and kidney volume. Our results need to be confirmed in further studies.

Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Due to a lack of evidence, treatment recommendations are based on expert opinion, resulting in variation. The aim of this study was to describe the clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy-proven IgAVN in order to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy-proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analysed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow-up. RESULTS: The median follow-up was 3.7 years (interquartile range 2-6.2). At last follow-up, 29% of patients had an eGFR <90 mL/min/1.73 m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second-line immunosuppressive regimen being superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow-up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly, there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

Spatial Distribution of Macrophage Subtypes Among Rejection Subtypes in Renal Transplant Biopsies by Dual Immunohistochemistry.

We performed dual immunohistochemistry for CD163/CD34 and CD68/CD34 in 108 renal transplant indication biopsies to investigate the presence and distribution of macrophages in various renal compartments. All Banff scores and diagnoses were revised according to the Banff 2019 classification. CD163 and CD68 positive cell counts (CD163pos and CD68pos) were evaluated in the interstitium, glomerular mesangium, and, within glomerular and peritubular capillaries. The diagnosis was antibody-mediated rejection (ABMR) in 38 (35.2%), T-cell mediated rejection (TCMR) in 24 (22.2%), mixed rejection in 30 (27.8%), and no rejection in 16 (14.8%). Banff lesion scores t , i , and ti were correlated with both CD163 and CD68 interstitial inflammation scores ( r > 0.30; P < 0.05). Glomerular total CD163pos was correlated to Banff lesion scores g and cg ( r > 0.30; P < 0.05). Glomerular total, mesangial, and intracapillary CD68pos were correlated with g ( r > 0.30; P < 0.05). Both glomerular total and peritubular capillary CD68pos were correlated with peritubular capillaritis ( r > 0.30; P < 0.05). Glomerular CD163pos were significantly higher in ABMR compared with no rejection, in mixed rejection compared with no rejection and TCMR. CD163pos in peritubular capillaries was significantly higher in mixed rejection compared with no rejection. Glomerular CD68pos was significantly higher in ABMR compared with no rejection. CD68pos per peritubular capillary was higher in mixed rejection, ABMR, and TCMR compared with no rejection. In conclusion, compared with CD68 positive macrophages, localization of CD163 positive macrophages in various renal compartments seems to be different among rejection subtypes and their glomerular infiltration seems to be more specific for the presence of ABMR component.

Clinical and subclinical acute kidney injury in children with mild-to-moderate COVID-19.

BACKGROUND: Our aim was to identify acute kidney injury (AKI) and subacute kidney injury using both KDIGO criteria and urinary biomarkers in children with mild/moderate COVID-19. METHODS: This cross-sectional study included 71 children who were hospitalized with a diagnosis of COVID-19 from 3 centers in Istanbul and 75 healthy children. We used a combination of functional (serum creatinine) and damage (NGAL, KIM-1, and IL-18) markers for the definition of AKI and subclinical AKI. Clinical and laboratory features were evaluated as predictors of AKI and subclinical AKI. RESULTS: Patients had significantly higher levels of urinary biomarkers and urine albumin-creatinine ratio than healthy controls (p < 0.001). Twelve patients (16.9%) developed AKI based on KDIGO criteria, and 22 patients (31%) had subclinical AKI. AKI group had significantly higher values of neutrophil count on admission than both subclinical AKI and non-AKI groups (p < 0.05 for all). Neutrophil count was independently associated with the presence of AKI (p = 0.014). CONCLUSIONS: This study reveals that even children with a mild or moderate disease course are at risk for AKI. Association between neutrophil count and AKI may point out the role of inflammation in the development of AKI. IMPACT: The key message of our article is that not only children with severe disease but also children with mild or moderate disease have an increased risk for kidney injury due to COVID-19. Urinary biomarkers enable the diagnosis of a significant number of patients with subclinical AKI in patients without elevation in serum creatinine. Our findings reveal that patients with high neutrophil count may be more prone to develop AKI and should be followed up carefully. We conclude that even children with mild or moderate COVID-19 disease courses should be evaluated for AKI and subclinical AKI, which may improve patient outcomes.

A rare cause of nephrotic syndrome-sphingosine-1-phosphate lyase (SGPL1) deficiency: 6 cases and a review of the literature.

BACKGROUND: Recently, recessive mutations in SGPL1 (sphingosine-1-phosphate lyase), which encodes the final enzyme of sphingolipid metabolism, have been reported to cause steroid-resistant nephrotic syndrome, adrenal insufficiency, and many other organ/system involvements. We aimed to determine the clinical and genetic characteristics, and outcomes in patients with SGPL1 mutations. METHODS: The study included 6 patients with bi-allelic SGPL1 mutation. Clinical, genetic, and laboratory characteristics, and outcomes of the patients were evaluated retrospectively. We also reviewed previously reported patients with SGPL1 mutations and compared them to the presented patients. RESULTS: The median age at kidney presentation was 5 months. Four patients (67%) were diagnosed before age 1 year. Kidney biopsy showed focal segmental glomerulosclerosis in 2 patients and diffuse mesangial sclerosis in one patient. Steroids were given to 3 patients, but they did not respond. All 6 patients progressed to chronic kidney disease; 5 required kidney replacement therapy (KRT) at a median age of 6 months. Deceased kidney transplantation was performed in one patient. All 6 patients had adrenal insufficiency, of which 5 were diagnosed at age < 6 months. Three patients had hypothyroidism, 2 had ichthyosis, 4 had immunodeficiency, 5 had neurological findings, and 2 had genitourinary system anomalies. Four patients died at a median age of 30.5 months. Two patients are being followed up with KRT. One patient had a novel mutation. CONCLUSIONS: Patients with SGPL1 mutations have a poor prognosis, and many types of extrarenal organ/system involvement beyond adrenal insufficiency can be seen. Genetic diagnosis of such patients is important for treatment, genetic counseling, and screening for comorbid conditions. A higher resolution version of the Graphical abstract is available as Supplementary information.

Increased risk for kidney sequelae surrogates in survivors of Wilms tumor.

BACKGROUND: There is evidence of increased risk of hypertension, albuminuria, and development of chronic kidney disease (CKD) in long-term follow-up of survivors of Wilms tumor (WT). However, most studies were conducted in heterogeneous groups, including patients with solitary kidney. In addition, little is known about tubular dysfunction. This study aimed to investigate kidney sequelae, including CKD development, hypertension, and glomerular and tubular damage in WT survivors. METHODS: This cross-sectional, single-center study included 61 patients treated for WT. Surrogates for kidney sequelae were defined as presence of at least one of the following: decrease in GFR for CKD, hypertension detected by ambulatory blood pressure monitoring, albuminuria (albumin-to-creatinine ratio [ACR] > 30 mg/g), or increase in at least one tubular biomarker (beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, kidney injury marker-1, and liver fatty acid-binding protein) in 24-h urine. RESULTS: Median age of patients was 11.7 years, with median follow-up of 8.8 years. Thirty-eight patients (62%) had at least one surrogate for kidney sequelae. Twenty-four patients (39%) had CKD, 14 patients (23%) had albuminuria, 12 patients (21%) had hypertension, and 11 patients (18%) had tubular damage. Urine ACR was significantly higher in patients with advanced tumor stage and patients with nephrotoxic therapy than their counterparts (p < 0.05), but neither eGFR nor tubular biomarkers showed any association with tumor- or treatment-related factors. CONCLUSIONS: A considerable number of patients with WT have kidney sequelae, especially early-stage CKD with a high prevalence. Albuminuria emerges as a marker associated with tumor stages and nephrotoxic treatment. 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".

Elevated Urinary VEGF-A, Transferrin, and Angiotensinogen Levels in Normoalbuminuric Children and Adolescents with Type 1 Diabetes: Can They Be Early Markers of Diabetic Kidney Disease?

OBJECTIVE: We hypothesized that diabetic kidney disease (DKD) begins early, before albuminuria occurs. We therefore aimed to assess potential early urinary biomarkers of DKD in normoalbuminuric and normotensive children and adolescents with type 1 diabetes (T1D) to evaluate the relationship between these markers and clinical and laboratory risk factors for DKD. METHODS: This cross-sectional study included 75 children and adolescents with T1D (62% females, mean age 13.9 ± 3.2 years) with normoalbuminuria (an albumin/creatinine ratio [ACR] below 30 mg/g creatinine). Fifty-five age- and sex-matched healthy children and adolescents served as controls. For the assessment of early DKD, urinary levels of angiotensinogen (AGT), transferrin, nephrin, vascular endothelial growth factor-A (VEGF-A), and kidney injury molecule-1 (KIM-1) were measured in adequately collected 24-h urine samples using enzyme-linked immunoassays. RESULTS: The mean disease duration was 7.3 ± 3.2 (range 2.1-15.7) years, and the mean HbA1c level was 8.8 ± 1.4%. The median levels of urine VEGF-A/Cr, AGT/Cr, and transferrin/Cr were significantly higher in normoalbuminuric patients with T1D, compared with those of controls (p < 0.001, p = 0.02, and p = 0.001, respectively), but there was no difference in nephrin/Cr and KIM-1/Cr between the 2 groups. Although none of the patients had albuminuria, the median level of urine ACR was significantly higher in the patient group than the control group (p = 0.003). The ACR was positively correlated with glomerular filtration rate (GFR). Urinary transferrin/Cr, AGT/Cr, and VEGF-A/Cr were significantly correlated with ACR, but not with either GFR or diabetic risk factors including HbA1c or disease duration. CONCLUSION: Normoalbuminuric and normotensive children and adolescents with T1D have elevated urinary VEGF, AGT, and transferrin levels, which may indicate the development of DKD before albuminuria occurs.

Hemodiafiltration Is Associated With Reduced Inflammation and Increased Bone Formation Compared With Conventional Hemodialysis in Children: The HDF, Hearts and Heights (3H) Study.

BACKGROUND: Patients on dialysis have a high burden of bone-related comorbidities, including fractures. We report a post hoc analysis of the prospective cohort study HDF, Hearts and Heights (3H) to determine the prevalence and risk factors for chronic kidney disease-related bone disease in children on hemodiafiltration (HDF) and conventional hemodialysis (HD). METHODS: The baseline cross-sectional analysis included 144 children, of which 103 (61 HD, 42 HDF) completed 12-month follow-up. Circulating biomarkers of bone formation and resorption, inflammatory markers, fibroblast growth factor-23, and klotho were measured. RESULTS: Inflammatory markers interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein were lower in HDF than in HD cohorts at baseline and at 12 months (P < .001). Concentrations of bone formation (bone-specific alkaline phosphatase) and resorption (tartrate-resistant acid phosphatase 5b) markers were comparable between cohorts at baseline, but after 12-months the bone-specific alkaline phosphatase/tartrate-resistant acid phosphatase 5b ratio increased in HDF (P = .004) and was unchanged in HD (P = .44). On adjusted analysis, the bone-specific alkaline phosphatase/tartrate-resistant acid phosphatase 5b ratio was 2.66-fold lower (95% confidence interval, -3.91 to -1.41; P < .0001) in HD compared with HDF. Fibroblast growth factor-23 was comparable between groups at baseline (P = .52) but increased in HD (P < .0001) and remained unchanged in HDF (P = .34) at 12 months. Klotho levels were similar between groups and unchanged during follow-up. The fibroblast growth factor-23/klotho ratio was 3.86-fold higher (95% confidence interval, 2.15-6.93; P < .0001) after 12 months of HD compared with HDF. CONCLUSION: Children on HDF have an attenuated inflammatory profile, increased bone formation, and lower fibroblast growth factor-23/klotho ratios compared with those on HD. Long-term studies are required to determine the effects of an improved bone biomarker profile on fracture risk and cardiovascular health.

Transient minimal hydronephrosis on contralateral kidney in infants with unilateral hydronephrosis: Is it an early sign of worsening of the affected kidney?

Background/aim: The criteria for surgical management of ureteropelvic junction obstruction are not well-defined, and there is a risk for loss of renal function before the operation. In this context, certain changes in contralateral kidney had been investigated in order to increase the sensitivity of diagnosis. In this study, we aimed to investigate whether contralateral transient minimal hydronephrosis (CTMH) can be considered as an "early alarm" sign for worsening of the affected kidney in infants with hydronephrosis. Materials and methods: A total of 182 infants (92 surgically treated and 90 conservatively followed-up) with unilateral hydronephrosis were retrospectively analyzed. Ultrasonography and renal scan findings were evaluated. Correlation between the appearance of CTMH, contralateral compensatory hypertrophy (CCH) on ultrasonography, and prognosis of the affected kidney were evaluated. Results: Among the surgically treated patients, 18 (19.6%) patients developed CTMH on average 7 months (0­13 months) before surgery. Among these 18 patients with CTMH, 12 patients (66.6%) had loss of renal function preoperatively, while this ratio was 29.7% on their counterparts (p = 0049). CCH was observed in 31 (33.7%) individuals in surgically treated patient group including all 18 patients with CTMH, while none of the conservatively followed-up patients developed CCH and/or CTMH. In the multiple logistic regression analysis, among the variables investigated, CTMH was found as an independent predictor of the deterioration in the affected kidney and of the poor prognosis (p = 0.011 and p = 0.0004, respectively). Conclusion: In our study, among the variables investigated, CTMH was found as an independent predictor of the deterioration in the affected kidney and poor prognosis in infants followed-up with isolated unilateral hydronephrosis. Additionally, CTMH can be considered as an "early alarm" sign for worsening of the affected kidney and the need for surgical intervention.

Distintos enfoques adoptados por los médicos para tratar la nefrolitiasis en pediatría: estudio basado en una encuesta / Different approaches among physicians to treat pediatric stone disease: a survey-based study

Introducción. Los pediatras, cirujanos y subespecialistas, como urólogos y nefrólogos pediátricos, participan en el diagnóstico y tratamiento de la nefrolitiasis pediátrica. El objetivo fue determinar los enfoques de distintas disciplinas y evaluar las diferencias en sus protocolos de diagnóstico y tratamiento habituales.Población y métodos. Cuestionario administrado a participantes de sesiones sobre nefrolitiasis en congresos nacionales en 2017 para evaluar las rutinas de diagnóstico y tratamiento de la nefrolitiasis entre distintas especialidades (cirujanos y pediatras) y subespecialidades (nefrólogos pediátricos y urólogos pediátricos).Resultados. Se analizaron 324 cuestionarios de 88 pediatras, 121 urólogos, 23 cirujanos pediátricos, 54 nefrólogos pediátricos y 38 urólogos pediátricos. Ambos grupos coincidieron en la necesidad de una evaluación metabólica. Para los cálculos ureterales distales ≥6 mm, los cirujanos preferían una ureteroscopía; los pediatras, una litotricia por ondas de choque (LOC) (p < 0,001); y los subespecialistas, una ureteroscopía (p = 0,636). Para los cálculos en la parte inferior de los cálices renales < 1 cm, los cirujanos y los subespecialistas preferían la LOC y los pediatras, la hidratación (p < 0,001; p = 0,371). Para los cálculos de entre 1,1 cm y 2 cm, los cirujanos preferían la cirugía retrógrada intrarrenal (CRIR) y la LOC, y los pediatras, la LOC (p = 0,001). Para los cálculos más grandes, los cirujanos y subespecialistas preferían la nefrolitotomía percutánea (NLP) y los pediatras, la LOC (p = 0,458; p = 0,001).Conclusión. Existen diferencias entre las disciplinas que participan activamente en el diagnóstico y tratamiento de la nefrolitiasis

Introduction. Pediatricians, surgeons and subspecialties as pediatric urology and nephrology are involved in the diagnosis and treatment of pediatric renal stone disease (RSD). The aim of this study was to determine diagnostic and treatment approaches, of different disciplines, and to assess differences in their routine diagnostic and treatment protocols.Population and methods. A questionnaire was designed and administered to the participants of the RSD sessions in national congresses of all disciplines in 2017 to evaluate the diagnostic and treatment routines of specialties (surgeons and pediatricians) and subspecialties (pediatric nephrologists and pediatric urologists) for RSD. Results. A total, of 324 questionnaires were analyzed, from 88 pediatricians (27 %), 121 urologists (37 %), 23 pediatric surgeons (7 %), 54 pediatric nephrologists (17 %), and 38 pediatric urologists (12 %). Both groups agreed on the necessity of metabolic evaluation. For distal ureter stones that were ≥ 6 mm; surgeons preferred ureteroscopy (URS), pediatricians preferred shock wave lithotripsy (SWL) (p < 0.001) and subspecialties preferred URS for the treatment (p = 0.636). For lower calix stones less than 1 cm surgeons and subspecialists preferred SWL, while pediatricians preferred hydration (p < 0.001, p = 0.371). For the stone between 1.1 and 2 cm, surgeons preferred intrarenal surgery (RIRS) and SWL, pediatricians preferred SWL (p = 0.001). For larger stones, surgeons and subspecialists preferred percutaneous nephrolithotomy (PCNL), and pediatricians preferred SWL (p = 0.458 p = 0.001). Pediatric urologist chose low-dose computerized tomography as a diagnostic radiologic evaluation (p = 0.029).Conclusion. There are differences between the disciplines who take an active role in diagnosis and treatment of RSD.

Different approaches among physicians to treat pediatric stone disease: a survey-based study. / Distintos enfoques adoptados por los médicos para tratar la nefrolitiasis en pediatría: estudio basado en una encuesta.

INTRODUCTION: Pediatricians, surgeons and subspecialties as pediatric urology and nephrology are involved in the diagnosis and treatment of pediatric renal stone disease (RSD). The aim of this study was to determine diagnostic and treatment approaches, of different disciplines, and to assess differences in their routine diagnostic and treatment protocols. POPULATION AND METHODS: A questionnaire was designed and administered to the participants of the RSD sessions in national congresses of all disciplines in 2017 to evaluate the diagnostic and treatment routines of specialties (surgeons and pediatricians) and subspecialties (pediatric nephrologists and pediatric urologists) for RSD. RESULTS: A total, of 324 questionnaires were analyzed, from 88 pediatricians (27 %), 121 urologists (37 %), 23 pediatric surgeons (7 %), 54 pediatric nephrologists (17 %), and 38 pediatric urologists (12 %). Both groups agreed on the necessity of metabolic evaluation. For distal ureter stones that were ≥ 6 mm; surgeons preferred ureteroscopy (URS), pediatricians preferred shock wave lithotripsy (SWL) (p < 0.001) and subspecialties preferred URS for the treatment (p = 0.636). For lower calix stones less than 1 cm surgeons and subspecialists preferred SWL, while pediatricians preferred hydration (p < 0.001, p = 0.371). For the stone between 1.1 and 2 cm, surgeons preferred intrarenal surgery (RIRS) and SWL, pediatricians preferred SWL (p = 0.001). For larger stones, surgeons and subspecialists preferred percutaneous nephrolithotomy (PCNL), and pediatricians preferred SWL (p = 0.458 p = 0.001). Pediatric urologist chose low-dose computerized tomography as a diagnostic radiologic evaluation (p = 0.029). CONCLUSION: There are differences between the disciplines who take an active role in diagnosis and treatment of RSD.

Introducción. Los pediatras, cirujanos y subespecialistas, como urólogos y nefrólogos pediátricos, participan en el diagnóstico y tratamiento de la nefrolitiasis pediátrica. El objetivo fue determinar los enfoques de distintas disciplinas y evaluar las diferencias en sus protocolos de diagnóstico y tratamiento habituales. Población y métodos. Cuestionario administrado a participantes de sesiones sobre nefrolitiasis en congresos nacionales en 2017 para evaluar las rutinas de diagnóstico y tratamiento de la nefrolitiasis entre distintas especialidades (cirujanos y pediatras) y subespecialidades (nefrólogos pediátricos y urólogos pediátricos). Resultados. Se analizaron 324 cuestionarios de 88 pediatras, 121 urólogos, 23 cirujanos pediátricos, 54 nefrólogos pediátricos y 38 urólogos pediátricos. Ambos grupos coincidieron en la necesidad de una evaluación metabólica. Para los cálculos ureterales distales ≥6 mm, los cirujanos preferían una ureteroscopía; los pediatras, una litotricia por ondas de choque (LOC) (p < 0,001); y los subespecialistas, una ureteroscopía (p = 0,636). Para los cálculos en la parte inferior de los cálices renales < 1 cm, los cirujanos y los subespecialistas preferían la LOC y los pediatras, la hidratación (p < 0,001; p = 0,371). Para los cálculos de entre 1,1 cm y 2 cm, los cirujanos preferían la cirugía retrógrada intrarrenal (CRIR) y la LOC, y los pediatras, la LOC (p = 0,001). Para los cálculos más grandes, los cirujanos y subespecialistas preferían la nefrolitotomía percutánea (NLP) y los pediatras, la LOC (p = 0,458; p = 0,001). Conclusión. Existen diferencias entre las disciplinas que participan activamente en el diagnóstico y tratamiento de la nefrolitiasis.

Natural history of patients with infantile nephrolithiasis: what are the predictors of surgical intervention?

BACKGROUND: We evaluated the risk factors for the requirement of surgical intervention in infants with nephrolithiasis. METHODS: The medical records of 122 (156 kidney units (KU)) infants were reviewed. The clinical features, stone characteristics, changes in stone status, and treatment protocols were noted. The stone status of the KU was categorized into 3 groups according to the change in size between the first and last ultrasound: resolution, unchanged, and growth. RESULTS: The median age was 8 months (r: 2-12). The median length of follow-up was 16 months (r: 10-36). Resolution was detected in 94 KUs (60%). Stone growth was detected in 39 KUs (25%), and stone size was unchanged in 23 KUs (15%). Surgical intervention was required in 26 patients (17%). A history of intensive care unit (ICU) follow-up and a stone size > 5 mm at time of diagnosis were defined as independent risk factors for stone growth (p = 0.005, < 0.001, respectively). The surgical intervention rate was higher in stones > 5 mm and stones with pelvic localization (p = 0.018, 0.021, respectively). Stone resolution was higher in patients with stone size ≤ 5 mm (p = 0.018). CONCLUSION: A stone size > 5 mm at the time of diagnosis and a history of ICU follow-up are independent risk factors for stone growth. Pelvic localization of stones and stones > 5 mm are associated with an increased risk of surgical intervention.

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.

Telemedicine Applications in a Tertiary Pediatric Hospital in Turkey During COVID-19 Pandemic.

Background: A novel type of Coronavirus emerged at Wuhan in late 2019 involving preferentially the respiratory system. Owing to the rapid spread, almost 22 million people became infected and 700,000 died. Similar to other countries, the need for additional hospital beds and intensive care units required diversion of health care resources toward the care for those with COVID-19 in Turkey. Telemedicine appeared as a safe and low-cost alternative for the maintainability of pediatric health services during the pandemics. Within this context, we aimed to deliver the health services through telemedicine during the follow-up of chronic childhood diseases. Materials and Methods: This prospective study included five pediatric subspecialties, including allergy immunology, hematology and oncology, nephrology, rheumatology, and inborn metabolic disorders. After the interview, patients and involved physicians were requested to fill out a questionnaire designed to measure the level of satisfaction and the quality of the service we offered. Results: Of the 263 interviews, overall patient and physician satisfaction was 99% and 87%, respectively. As results of the interviews, 250 routine visits were performed, 181 acute complaints were assessed, drug changes were made in 118 patients, 9 patients were determined to be unable to get their drugs, and 12 who misused their drugs. The main advantage of the telemedicine declared by the patients was "not to waste time for transportation." The main concerns of the participants were inability to perform physical and laboratory examinations. Conclusion: Consequently, we considered telemedicine as a feasible alternative not only during pandemics but also in daily practice in Turkey.

Renal Biopsy Prognostic Findings in Children With Atypical Hemolytic Uremic Syndrome.

BACKGROUND: The aim of this study was to investigate the histopathological findings in kidney biopsies in children with atypical hemolytic uremic syndrome (aHUS) and to determine whether specific pathological findings in aHUS have a prognostic value. METHODS: Renal biopsy specimens of 29 patients who were recorded in the national Turkish aHUS registry database were available for review. Histopathological findings were compared with the clinical and laboratory features at the presentation and the final outcome. RESULTS: The mean age at presentation and follow-up period was 4.9 ± 3.9 and 3.9 ± 3.0 years, respectively. The median time interval from the first symptom to biopsy was 10 days. Vascular thrombosis and interstitial fibrosis were significantly related to chronic kidney disease (CKD) requiring dialysis or kidney transplantation during follow-up (5.6-fold, for both). Glomerular necrosis, cortical necrosis, and glomerular sclerosis were markedly associated with CKD without dialysis (6.2-fold, 13.3-fold, and 8.8-fold, respectively). However, presence of endothelial swelling, subendothelial widening, and fragmented erythrocytes was found to be correlated with a favorable final outcome. CONCLUSIONS: Presence of vascular thrombosis, cortical necrosis, and glomerular sclerosis in histopathological evaluation correlated with developing CKD. Chronic changes in the interstitial compartment were also related to poor prognosis, a finding that has been shown for the first time in pediatric aHUS cases.

A 9.5-year-old boy with recurrent neurological manifestations and severe hypertension, treated initially for polyarteritis nodosa, was subsequently diagnosed with adenosine deaminase type 2 deficiency (DADA2) which responded to anti-TNF-α.

A 9.5-year-old boy was referred with a 2-year history of recurrent fever, myalgia, abdominal pain and various neurological manifestations associated with increased acute phase reactants and IgG level. During the recent episode, severe hypertension and right-sided hemiparesis developed and angiography demonstrated irregularities and stenosis in renal and mesenteric artery branches. Although these manifestations were consistent with polyarteritis nodosa (PAN), the consanguinity of his parents, a cousin with similar clinical features and early disease onset led to suspicion of deficiency of adenosine deaminase type 2 (DADA2) diseases. DADA2 was established by demonstration of decreased ADA2 enzyme activity and a homozygous G47R mutation in the CECR1 gene. The diagnosis of DADA2 is challenging because of the overlapping manifestations with PAN and other periodic fever syndromes. DADA2 should be considered in the differential diagnosis of PAN. Raised IgG levels (usually low in DADA2) should be sought in future cases.Abbreviations: CECR1, cat eye syndrome chromosome region candidate 1; DADA2, deficiency of adenosine deaminase type 2; MEFV, Mediterranean fever; PAN, polyarteritis nodosa.

Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease.

BACKGROUND: Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Serum levels of gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiac comorbidities in adult CKD patients. METHODS: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured by high-performance liquid chromatography in serum of children participating in the Cardiovascular Comorbidity in Children with CKD (4C) Study. Results were correlated with measurements of the carotid intima-media thickness (cIMT), central pulse wave velocity (PWV), and left ventricular mass index (LVMI) in children aged 6-17 years with initial eGFR of 10-60 ml/min per 1.73 m2. RESULTS: The median serum levels of total IS and of pCS, measured in 609 patients, were 5.3 µmol/l (8.7) and 17.0 µmol/l (21.6), respectively. In a multivariable regression model, IS and pCS showed significant positive associations with urea and negative associations with eGFR and uric acid. Furthermore, positive associations of pCS with age, serum albumin, and non-Mediterranean residency and a negative association with glomerular disease were observed. By multivariable regression analysis, only IS was significantly associated with a higher cIMT SDS at baseline and progression of PWV SDS within 12 months, independent of other risk factors. CONCLUSIONS: Serum levels of gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. Only IS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort.