Featured research (6)

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.
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.
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".
Recessive mutations in the genes encoding the four subunits of the tRNA splicing endonuclease complex (TSEN54, TSEN34, TSEN15, and TSEN2) cause various forms of pontocerebellar hypoplasia, a disorder characterized by hypoplasia of the cerebellum and the pons, microcephaly, dysmorphisms, and other variable clinical features. Here, we report an intronic recessive founder variant in the gene TSEN2 that results in abnormal splicing of the mRNA of this gene, in six individuals from four consanguineous families affected with microcephaly, multiple craniofacial malformations, radiological abnormalities of the central nervous system, and cognitive retardation of variable severity. Remarkably, unlike patients with previously described mutations in the components of the TSEN complex, all the individuals that we report developed atypical hemolytic uremic syndrome (aHUS) with thrombotic microangiopathy, microangiopathic hemolytic anemia, thrombocytopenia, proteinuria, severe hypertension, and end-stage kidney disease (ESKD) early in life. Bulk RNA sequencing of peripheral blood cells of four affected individuals revealed abnormal tRNA transcripts, indicating an alteration of the tRNA biogenesis. Morpholino-mediated skipping of exon 10 of tsen2 in zebrafish produced phenotypes similar to human patients. Thus, we have identified a novel syndrome accompanied by aHUS suggesting the existence of a link between tRNA biology and vascular endothelium homeostasis, which we propose to name with the acronym TRACK syndrome (TSEN2 Related Atypical hemolytic uremic syndrome, Craniofacial malformations, Kidney failure). This article is protected by copyright. All rights reserved.

Lab head

Salim Caliskan
Department
  • Department of Pediatric Nephrology

Members (3)

Nur Canpolat
  • Istanbul University-Cerrahpaşa Cerrahpaşa Faculty of Medicine
Ayşe Ağbaş
  • Istanbul University-Cerrahpasa
Seha Saygili
  • Istanbul University-Cerrahpasa
Esra Karabag Yilmaz
Esra Karabag Yilmaz
  • Not confirmed yet
Ebru Burcu Demirgan
Ebru Burcu Demirgan
  • Not confirmed yet