Pediatric kidney care experience after the 2023 Turkey/Syria earthquake.

BACKGROUND/AIMS: Two earthquakes on February 6th, 2023 destroyed ten cities in Türkiye. We report our experience with pediatric victims during these catastrophes, with a focus on crush syndrome related-acute kidney injury (Crush-AKI) and death. METHOD: A web-based software was prepared. Patient demographics, time under rubble (TUR), admission laboratory data, dialysis, and kidney and overall outcomes were asked. RESULTS: 903 injured children (median age: 11.62 years) were evaluated. Mean TUR was 13 h (Interquartile range-IQR: 32.5), max 240 h). 31 of 32 patients with a TUR of >120 h survived. The patient who rescued after ten days survived.Two-thirds of the patients were given 50 mEq/L sodium-bicarbonate in 0.45% sodium-chloride solution on admission day. 58% of patients were given intravenous fluid (IVF) at a volume of 2000-3000 mL/m2 body surface area (BSA), 40% of 3000-4000 mL/m2 BSA, and only 2% of >4000 mL/m2 BSA. 425 patients had surgeries, 48 suffered from major bleeding. Amputations were recorded in 96 patients. Eighty-two and 66 patients required ventilator and inotropic support, respectively.Crush-AKI developed in 314 patients (36% of all patients). 189 patients were dialyzed. Age > 15 years, creatine phosphokinase (CK)≥20 950 U/L, TUR≥10 h, and the first-day IVF volume < 3000-4000 mL/m2 BSA were associated with Crush-AKI development. 22 deaths were recorded, 20 of 22 occurred in patients with Crush-AKI and within the first 4 days of admission. All patients admitted after 7 days survived. CONCLUSIONS: This is the most extensive pediatric kidney disaster data after an earthquake. Serum CK level was significantly associated with Crush-AKI at the levels of >20 950 U/L, but not with death. Adolescent age and initial IVF of less than 3000-4000 mL/m2 BSA were also asscoiated with Crush-AKI. Given that mildly injured victims can survive longer periods in the disaster field, we suggest uninterrupted rescue activity for at least 10 days.

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

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN 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 analyzed 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 (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 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 to be 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.

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.

Assessing fatigue and related factors in adolescents with familial Mediterranean fever (FMF): psychometric properties of the PedsQL Multidimensional Fatigue Scale.

BACKGROUND: Fatigue is a common problem in pediatric rheumatic diseases and is associated with poor quality of life. However, no validated methods are available to measure fatigue in adolescents with familial Mediterranean fever (FMF). The aim of the study was to establish validity and reliability for the child self-report PedsQL Multidimensional Fatigue Scale (PedsQL-MFS) and to investigate the effects of physical characteristics, diseaserelated characteristics, sleep quality/duration, and the amount of physical activity on fatigue in adolescents with FMF. METHODS: Seventy-one adolescents with FMF (13-18 years) were included. Children were examined regarding physical- and disease-related characteristics and completed patient-reported outcome measures (PROMs) regarding sleep quality/duration, physical activity levels, and fatigue. PedsQL-MFS was re-completed within the following 7-14 days. RESULTS: PedsQL-MFS demonstrated excellent test-retest reliability (ICC in 95% CI: 0.877-0.958) and internal consistency (Cronbach`s α: 0.928). All items contributed to the total score (item-total correlation > 0.3). PedsQLMFS scores were significantly correlated to fatigue (r: -0.666, p < 0.001), physical activity (r: 0.373, p < 0.001), sleep quality (rs: 0.678, p < 0.001), and sleep duration (r: 0.473, p < 0.001). Being female, having attacks in the last six months, a sleep duration of less than seven hours, and engaging in less physical activity resulted in higher fatigue. CONCLUSIONS: PedsQL-MFS seems to be feasible for assessing fatigue in adolescents with FMF. Sex, recent attacks, sleep, and physical activity should be taken into consideration in the fatigue management of patients with FMF.

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.

Predictors of febrile urinary tract infection caused by extended-spectrum beta-lactamase-producing bacteria.

BACKGROUND: We aimed to evaluate the predictability of extended-spectrum beta-lactamase (ESBL)-producing bacteria (PB) with inflammation markers and hemogram parameters as neutrophil-lymphocyte-ratio (NLR), platelets-lymphocyte-ratio (PLR) and mean-platelet-volume (MPV) in infants with febrile urinary tract infection until the urine cultures are resulted. METHODS: Infants between 2-24 months hospitalized for the first febrile urinary tract infections were grouped as those infected with ESBL-PB and non-ESBL-PB. The demographic and laboratory data (inflammation markers and hemogram parameters) and the ultrasonographical findings were compared between the two groups. RESULTS: A total of 232 patients were included in the study. The mean age was 8.82 ± 5.68 (2-23) months and 114 (49%) of them were female. Escherichia coli was the most common isolated bacteria (79%) followed by Klebsiella pneumoniae (15.5%) in urine cultures. There were 88 patients in ESBL-PB infected group and 144 patients in the non-ESBL-PB group. The hematologic parameters such as white blood cell count (WBC) count, NLR, PLR, MPV and procalcitonin (PCT) were similar between the two groups. Only the rate of ultrasonographic abnormalities was significantly higher in infants infected with ESBL-PB (p=0.012). The risk of ESBL-PB positivity in urine cultures increased with age (OR 1.068, 95% CI 1.002-1.139, p=0.045), PCT (OR 1.094, 95% CI 1.011-1.184, p=0.025), and ultrasonographic abnormalities (OR 3.981, 95% CI 1.792-8.845, p=0.001). CONCLUSIONS: Platelet counts, WBC, MPV, NLR, PLR, and PCT were not reliable markers, however having an ultrasonographic abnormality is the most important independent risk factor for prediction of infection with ESBL-PB.

A rare endocrinological complication of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) may lead to increase in serum levels of peptide hormones as a result of changes in peripheral metabolism. The pathogenesis of uremic hyperprolactinemia in CKD is not fully understood. Plasma prolactin levels are elevated in women, pubertal girls, and also in men with chronic kidney disease. But this is not comon in prepubertal boys. Also in prepubertal children and postmenopausal women, hyperprolactinemia rarely results in galactorrhea. We aimed to discuss hyperprolactinemia and galactorrhea in a 12-year-old male with CKD. CASE: A twelve-year-old boy with chronic kidney disease (CKD) suffered from bilateral galactorrhea. He was on follow-up at Pediatric Nephrology Department from the age of two due to bilateral dysplastic kidney. On physical examination, his weight was - 0.59 SDS, height was -2.82 SDS, Blood pressure was 115 / 72 (75p), stretched penis length was 6 cm, testicular volume was 3mL / 3mL, pubic hair was Tanner Stage 1, breast examination did not reveal plaque on bilateral breast. He was receiving recombinant erythropoietin, sodium bicarbonate, polystyrene sulfonate, calcium acetate, and calcitriol treatments. Glomerular filtration rate was 23ml/min/1.73 m2 (CKD stage IV). Serum prolactin (PRL) was > 200 µg/L (N, 2.64-13.13). The pituitary adenoma was excluded with pituitary and cranial magnetic resonance imaging (gadolinium). Cabergoline (0.5 mg/ twice weekly) was initiated to decrease PRL levels and reduce galactorrhea. In the second week of treatment, serum PRL level was suppressed (0.4 µg/L) and galactorrhea was completely resolved. CONCLUSIONS: Although uremic hyperprolactinemia is very rarely seen in childhood, it is important to evaluate, and initiate an appropriate treatment since it is associated with delayed puberty and infertility in adulthood in many cases.

Effects of ambulatory blood pressure monitoring parameters on left ventricular mass index in hypertensive children.

OBJECTIVE: We aimed to evaluate the effects of blood pressure (BP) values obtained by 24-h ambulatory BP monitoring (ABPM) of hypertensive children and adolescents on left ventricular mass index (LVMI). METHODS: Patients diagnosed with HT with BP measurements confirmed with ABPM and evaluated with echocardiography for LVMI were included. The patients were divided into two groups according to their BMI as obese and nonobese. SDSs of ABPM parameters were compared between the groups. RESULTS: A total of 158 children with HT were included in the study. Ninety of these patients were obese. In obese and nonobese cases, mean SDS levels were similar in ABPM parameters, whereas LVMI was significantly higher in obese patients ( P = 0.049). There was a significant correlation between LVMI and 24-h SBP SDS, daytime SBP SDS, 24-h SBP load and daytime BP load. In obese cases, there was a statistically significant correlation between LVMI and 24-h SBP SDS, daytime SBP SDS, 24-h SBP load, daytime SBP load as well as nighttime SBP SDS and nighttime SBP load. When the whole group was evaluated, 24-h SBP SDS was the most effective parameter influencing LVMI ( P = 0.001). Similarly, the most effective ABPM parameter on LVMI in obese patients was 24-h SBP SDS ( P = 0.001). CONCLUSION: A significantly higher rate of LVMI in obese patients suggests that obesity itself is an effective factor on LVMI. In addition, systolic hypertension is more effective on cardiac functions compared with DBP measurements and systolic-DBP dipping ratios.

COVID-19 in pediatric nephrology centers in Turkey.

BACKGROUND: There is limited data on COVID-19 disease in children with kidney disease. We aimed to investigate the characteristics and prognosis of COVID-19 in pediatric nephrology patients in Turkey. METHODS: This was a national, multicenter, retrospective cohort study based on an online survey evaluating the data between 11th March 2020 and 11th March 2021 as an initial step of a detailed pediatric nephrology COVID-19 registry. RESULTS: Two hundred and three patients (89 girls and 114 boys) were diagnosed with COVID-19. One-third of these patients (36.9%) were between 10-15 years old. Half of the patients were on kidney replacement therapy: kidney transplant (KTx) recipients (n = 56, 27.5%), patients receiving chronic hemodialysis (n = 33, 16.3%) and those on peritoneal dialysis (PD) (n = 18, 8.9%). Fifty-four (26.6%) children were asymptomatic. Eighty-two (40.3%) patients were hospitalized and 23 (28%) needed intensive care unit admission. Fifty-five percent of the patients were not treated, while the remaining was given favipiravir (20.7%), steroid (16.3%), and hydroxychloroquine (11.3%). Acute kidney injury developed in 19.5% of hospitalized patients. Five (2.4%) had MIS-C. Eighty-three percent of the patients were discharged without any apparent sequelae, while 7 (3.4%) died. One hundred and eight health care staff were infected during the study period. DISCUSSION: COVID-19 was most commonly seen in patients who underwent KTx and received HD. The combined immunosuppressive therapy and frequent exposure to the hospital setting may increase these patients' susceptibility. Staff infections before vaccination era were alarming, various precautions should be taken for infection control, particularly optimal vaccination coverage.

A new recommendation for febrile urinary tract infection in children aged 2-24 months: Tepecik UTI Guideline-2.

AIM: Urinary tract infections (UTIs) represent a common febrile illness in infancy. The study compared two UTI guidelines in terms of number of imaging studies, presence of parenchymal damage and radiation exposure in patients with the first febrile UTI between 2 and 24 months of age. METHOD: The results of Tepecik UTI Guideline-1 used until 2012 (Group 1, n = 105) were retrospectively compared with Tepecik UTI Guideline-2 (Group 2) used after 2013. In Group 1, urinary tract ultrasonography (US), dimercaptosuccinic acid (DMSA) and voiding cystourethrography (VCUG) were made in all patients. In Group 2, if the US result was abnormal, patients were evaluated with VCUG and DMSA. If the US was normal, only DMSA was performed. If the DMSA was abnormal, the VCUG was undergone (n: 43, 40.9%). RESULTS: The abnormal VCUG detection rate was 69.2% in Group 1 and 30.8% in Group 2 (p = 0.09). Sensitivity and specificity of US in the diagnosis of vesicoureteral reflux (VUR) was 15.9% and 96.7% in Group 1 and 61.5% and 70.5% in Group 2, respectively. Abnormal DMSA findings were observed among 33.3% (Groups 1) and 66.7% (Groups 2) subjects, respectively (p > 0.05). The median radiation exposure (500 mrem) of patients in Group 1 was statistically significantly higher than those in Group 2 (200 mrem) (p < 0.001). CONCLUSION: The VCUG should not be the first examination to be considered in such patients. We think that Tepecik UTI Guideline-2 reduces unnecessary invasive procedure and radiation exposure and not missed VUR in the management of children with UTI at 2-24 months. Needs prospective follow-up studies before considering this recommendation.

Are we losing awareness of other infections due to the fear of coronavirus disease-2019 and MIS-C?

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a rarely seen severe complication of coronavirus disease-2019 (COVID-19). Although fever is one of the indispensable symptoms, other infections should be considered in the differential diagnosis during the pandemic. CASE REPORT: An 8-year-old and a 16-year-old female patient were admitted with fever, vomiting, headache. Both had fulfilled the criteria and were diagnosed with MIS-C. However, they both had remarkable persistent costovertebral angle tenderness, which was unexpected in MIS-C. In Case-1, urine analysis showed microscopic hematuria without pyuria, and urine culture showed no bacterial growth. Case-2 had microscopic hematuria and pyuria with Escherichia coli growth in urine culture. Contrast-enhanced computed tomography showed wedge-shaped hypodense multiple lesions in bilateral kidneys for Case-1, in the right kidney for Case-2. They diagnosed acute focal bacterial nephritis (AFBN). CONCLUSIONS: The diagnostic criteria of MIS-C can overlap with the symptoms of other severe septic infections such as AFBN, which is a rare urinary tract infection, diagnosed by imaging of localized renal inflammatory mass-like or wedge-shaped lesion. A detailed anamnesis and careful physical examination may help differential diagnosis.

A partial response to abatacept in a patient with steroid resistant focal segmental glomerulosclerosis.

BACKGROUND: Herein we present our experience with abatacept in a patient diagnosed with primary focal segmental glomerulosclerosis (FSGS) and resistant to steroid and other immunosuppressives. CASE: A 17-year-old girl was diagnosed with idiopathic nephrotic syndrome (NS) at the age of 8 years. Kidney biopsy was performed when she did not respond to 6-weeks of steroid (2mg/kg) therapy followed by three doses of pulse methylprednisolone (PMP) and considered as steroid resistant NS. The biopsy revealed focal segmental glomerulosclerosis (FSGS) and cyclophosphamide was added to the steroid treatment but the patient had no response. The genetic analysis revealed G34G/A318A compound homozygous synonym aminoacid variation in NPHS2 gene, thus all immunosuppressive regimes were stopped and she was put on supportive treatment. Throughout this period, she had nephrotic range of proteinuria, however serum albumin levels were > 3g/dl. At the end of two years, the patient had NS with severe edema and hypoalbuminemia. When the genetic analysis was interpreted again, it was found to be consistent with a polymorphism rather than a mutation. Following 3 doses of PMP, oral steroid treatment was resumed and cyclosporine (CsA) was added to the treatment at the fifth year of follow up. However, she was unresponsive to CsA at the end of the first year as well as mycophenolate mofetil used for 12 months and rituximab used for 6 months, respectively. Then abatacept was instituted and proteinuria decreased below 1 gr/day and serum albumin levels increased to 3 g/dl at the end of 6 doses. Serum albumin levels remained stable in the following 7 months. CONCLUSION: Partial remission including the decrease in proteinuria and increase in albumin levels achieved in our patient encourages the usage of abatacept in patients who do not respond to multiple immunosuppressive therapies.

Recurrent debilitating calf pain associated with fasciitis in Familial Mediterranean fever and response to canacinumab.

BACKGROUND: Myalgia is one of the presenting symptoms of Familial Mediterranean Fever (FMF), which is reported at a rate of 27-39.6%. Recurrent fasciitis in those cases are extremely rare. We aimed to present a case with FMF having radiologically proven fasciitis. CASE: An 11-year-old male patient with a diagnosis of FMF and M694V homozygote mutation, using colchicine regularly at a dose of 2 mg/day (0.08 mg/kg/day) for 4 years; was admitted to the hospital with severe pain and tenderness on the right calf. There were no accompanying symptoms like fever or abdominal pain. He described three similar episodes with pain and tenderness in left and right calves, which were not accompanied by fever in the last 6 months. The erythrocyte sedimentation rate and C-reactive protein levels were high and serum creatinine kinase was normal. The day after initiation of non-steroidal anti-inflammatory drug (NSAID), his complaints regressed. However, after a week, he again had a severe calf pain. Lower extremity arterial and venous doppler ultrasonography was normal. Increased peripheral signal intensity and fasciitis around the soleus muscle was defined in MRI. With NSAIDs, myalgia disappeared in a few days and acute phase reactants decreased within a week. In the follow up, canakinumab was prescribed due to febrile attacks as frequent as once a month and calf pain observed almost weekly. Thereafter, both febrile attacks and recurrent debilitating calf pain were completely ceased. CONCLUSION: There are three cases in the literature with fasciitis related myalgia. With this case, we wanted to emphasize fasciitis as a cause of FMF associated myalgia on MRI. In such cases MRI may be helpful to demonstrate fascial involvement.

Calyceal diverticulum of the kidney in pediatric patients - Is it as rare as you might think?

OBJECTIVE: Calyceal diverticulum (CD) is rarely diagnosed in children. It mimics other cystic lesions of the kidney and may be very difficult to identify. Displaying the communication of these fluid-filled cavities with the collecting system of the kidney via imaging methods is the key diagnostic method. The purpose of this study is to determine the presence of calyceal diverticulum in pediatric patients followed up due to simple renal cyst and/or parapelvic cyst. MATERIAL, AND METHOD: Patients who were newly diagnosed or being followed up with the ultrasonographic diagnosis of simple cyst(s) or parapelvic cyst(s) in the Department of Pediatric Nephrology of Izmir University of Health Sciences Tepecik Training and Research Hospital between December 2015 and July 2018 were included in the study. Age, gender, admission symptoms, recurrent urinary tract infections, stone disease, trauma history, accompanying urinary system and systemic anomalies, localization, and size of the cyst(s) at admission and during follow-up, treatment type and developing complications were noted. Contrast MR urography was applied to all patients. RESULTS: A total of 43 patients [mean age:132 ± 54.9 (12-228) months] including 25 girls were enrolled in the study. The mean follow-up period was 36. 74 ± 19 (1-90) months. The cysts were located mostly in the right kidney and also in the upper pole of the kidney. The mean cyst size was 20.4 ± 11 (8-58) mm at admission, and comparably 20.3 ± 8.6 (10-45) mm at the end of the follow-up. In contrast MR urography, a total of 16 cases were observed at first glance to be associated with pelvicalyceal system. However, in the postcontrast images taken at the 5th minute it was determined that 9 of them were compatible with calyceal diverticulum. CONCLUSION: Although it is thought that well-circumscribed solitary renal fluid collections may be thought to be a simple renal cyst at first glance, the differential diagnosis of calyceal diverticulum (CD) should be absolutely kept in mind. Contrast studies and late-phase postcontrast images are needed for the diagnosis of CD. Although the standard management of CDs in children is conservative, surgical intervention may be rarely required.