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.

Pediatric kidney care experience after the 2023 Türkiye earthquake.

BACKGROUND: Two earthquakes on 6 February 2023 destroyed 10 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: Web-based software was prepared. Patient demographics, time under rubble (TUR), admission laboratory data, dialysis, and kidney and overall outcomes were recorded. RESULTS: A total of 903 injured children (median age 11.62 years) were evaluated. Mean TUR was 13 h (interquartile range 32.5, max 240 h). Thirty-one of 32 patients with a TUR of >120 h survived. The patient who was rescued after 10 days survived. Two-thirds of the patients were given 50 mEq/L sodium bicarbonate in 0.45% sodium chloride solution on admission day. Fifty-eight percent of patients were given intravenous fluid (IVF) at a volume of 2000-3000 mL/m2 body surface area (BSA), 40% at 3000-4000 mL/m2 BSA and only 2% at >4000 mL/m2 BSA. A total of 425 patients had surgeries, and 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). In all, 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. Twenty-two deaths were recorded, 20 of 22 occurring in patients with Crush-AKI and within the first 4 days of admission. All patients admitted after 7 days survived. CONCLUSIONS: These are the most extensive pediatric kidney disaster data obtained 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 associated 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.

Renal Ultrasonographic Abnormalities at Initial Presentation of Children Diagnosed with Acute Lymphoblastic Leukemia and Long-Term Renal Functions and Prognosis in Survivors.

Objectives: The kidney is a vulnerable organ for acute lymphoblastic leukemia (ALL), by the disease, and various associated clinical pictures. This retrospective study aims to document renal ultrasound abnormalities in children with newly diagnosed ALL as well as to investigate the correlation between renal findings and clinical/laboratory/survival data. Methods: All children (age <18 years) with ALL were included in the study. An increase in size/nephromegaly (NM) or hyperechogenicity (HE) of the kidneys at first admission was accepted as a pathological renal abnormality. The clinical/laboratory findings, survival, and long-term renal functions were compared between patients with and without NM/HE. Results: The incidence of NM±HE was 12% in 163 patients. Enlargement of spleen, liver, or both and, hypercreatininemia was independently correlated with the presence of NM/HE. After the induction therapy, ultrasound findings were resolved in all patients, and NM/HE did not influence ALL prognosis. All survivors had normal renal functions in long term. Conclusion: The renal ultrasound abnormalities are not uncommon in children with leukemia at admission, without a negative impact on leukemia prognosis and on long-term renal functions.

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".

Sudden Cardiac Arrest and Malignant Ventricular Tachycardia in an 8-Year-Old Pediatric Patient Who Has Hemolytic Uremic Syndrome Associated with Shiga Toxin-Producing Escherichia coli.

Gastrointestinal, neurological, pancreatic, hepatic, and cardiac dysfunction are extrarenal manifestations of hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli (STEC-HUS). The most frequent cause of death for STEC-HUS is related to the central nervous system and cardiovascular system. Cardiac-origin deaths are predominantly related to thrombotic microangiopathy-induced ischemia and the immediate development of circulatory collapse. STEC-HUS cardiac related deaths in children are rare with only sporadic cases reported. In our literature search, we did not come across any pediatric case report about STEC-HUS causing sudden cardiac arrest and malignant ventricular tachycardia (VT). Herein, we report the case of an 8-year-old female child with a typical clinical manifestation of STEC-HUS. On the seventh day of pediatric intensive care unit admission, the patient had a sudden cardiac arrest, requiring resuscitation for 10 minutes. The patient had return of spontaneous circulation with severe monomorphic pulsed malignant VT. Intravenous treatment with lidocaine, amiodarone and magnesium sulfate were promptly initiated, and we administered multiple synchronized cardioversions, but VT persisted. Furthermore, we were not able to ameliorate her refractory circulation insufficiency by advanced cardiopulmonary resuscitation. Thus, inevitably, the patient lost her life. This case illustrates the need for aggressive management and the dilemma that pediatric critical care specialists, cardiologists, and nephrologists have to face when dealing with STEC-HUS that is worsened by a sudden cardiac arrest accompanied with VT.

The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis.

BACKGROUND AND OBJECTIVES: Infantile nephropathic cystinosis is a severe disease that occurs due to mutations in the cystinosis gene, and it is characterized by progressive dysfunction of multiple organs; >100 cystinosis gene mutations have been identified in multiple populations. Our study aimed to identify the clinical characteristics and spectrum of cystinosis gene mutations in Turkish pediatric patients with cystinosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified the clinical characteristics and spectrum of cystinosis gene mutations in Turkish patients with cystinosis in a multicenter registry that was established for data collection. The data were extracted from this registry and analyzed. RESULTS: In total, 136 patients (75 men and 61 women) were enrolled in the study. The most common clinical findings were growth retardation, polyuria, and loss of appetite. None of the patients had the 57-kb deletion, but seven novel mutations were identified. The most common mutations identified were c.681G>A (p.Glu227Glu; 31%), c.1015G>A (p.Gly339Arg; 22%), and c.18_21 del (p.Thr7Phefs*7; 14%). These mutations were associated with earlier age of disease onset than the other mutations. To understand the effects of these allelic variants on clinical progression, the mutations were categorized into two major groups (missense versus deletion/duplication/splice site). Although patients with missense mutations had a better eGFR at the last follow-up visit, the difference was not significant. Patients in whom treatment began at age <2 years old had later onset of ESRD (P=0.02). Time to ESRD did not differ between the patients with group 1 and group 2 mutations. CONCLUSIONS: The most common cystinosis gene mutations identified in Turkey were c.681G>A (p.Glu227Glu), c.1015G>A (p.Gly339Arg), and c.18_21 del (p.Thr7Phefs*7). Patients with less severe cystinosis gene mutations tend to have better kidney outcome.

Serum gastrin levels and gastroduodenal lesions in children with chronic renal failure on continuous ambulatory peritoneal dialysis: a single-center experience.

OBJECTIVE: The aim of this study was to determine serum gastrin levels and gastroduodenal lesions in children with chronic renal failure (CRF) on continuous ambulatory peritoneal dialysis (CAPD). METHODS: A total of 19 patients (mean age: 11.7±3.9 years, M/F: 1.37) with CRF on CAPD and 20 age-matched and sex-matched patients (mean age: 10.2±1.4 years, M/F: 1.5) with peptic ulcers were included in the study. Serum gastrin, creatinine, phosphate, and parathormone levels were determined. Upper gastrointestinal endoscopy was performed in all patients. RESULTS: The basal gastrin concentrations of CAPD patients were significantly higher than those of patients with peptic ulcer disease without CRF (124.2±59.1 and 53.0±9.4 pg/ml, respectively) (P<0.001). A significant correlation was found between age, duration of uremia, and serum gastrin levels (r=0.59, P<0.01; r=0.60, P<0.01, respectively). No correlation was found between the duration of CAPD and serum gastrin levels in the patient group. Of the patients, 73.6% had abnormal upper gastrointestinal endoscopic findings. The gastroduodenal lesion observed was hemorrhagic gastritis (31.5%), followed by hemorrhagic gastroduodenitis (26.3%), gastric nodular gastritis (10.5%), and polyps (10.5%). CONCLUSION: On the basis of our findings, such as higher serum gastrin levels in patients with CRF than those of the control group and the frequent endoscopic findings of gastroduodenal lesions in most of the patients, we recommend that an endoscopic examination should be considered for all the children with CRF on CAPD awaiting renal transplantation even if they are asymptomatic.