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.

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.

Pantoprazole Induced Acute Interstitial Nephritis in a Patient with Diabetic Ketoacidosis.

Childhood-onset type 1 diabetes mellitus (DM) is a common chronic metabolic disease associated with life-threatening complications. Diabetic ketoacidosis (DKA) is an acute complication of type 1 DM that has significant mortality mostly due to cerebral edema. Other putative complications of DKA include hypokalemia, hypophosphatemia, hypoglycemia, intracerebral and peripheral venous thrombosis, rhabdomyolysis, acute pancreatitis, and acute kidney injury (AKI) (Murdoch IA et al., Acta Paediatr 1993; 82:498-500).

Long-term renal survival of paediatric patients with lupus nephritis.

BACKGROUND: Childhood-onset systemic lupus erythematosus (SLE) is more severe than adult-onset disease, including more frequent kidney involvement. This study aimed to investigate baseline clinical features, treatment modalities and short- and long-term renal outcomes of paediatric patients with lupus nephritis (LN). MATERIALS AND METHODS: This study enrolled 53 LN patients out of 102 childhood-onset SLE patients followed at Hacettepe University between 2000 and 2020. The demographic and clinical data were reviewed retrospectively from the medical charts and electronic records. All SLE patients with renal involvement underwent renal biopsy either at the time of diagnosis or during follow-up. RESULTS: The median age at onset of SLE was 13.3 years [interquartile range (IQR) 10.4-15.8]. The median follow-up duration was 43.1 months (IQR 24.3-69.3). Of the 102 SLE patients, 53 (52%) had LN. The most frequent histopathological class was Class IV LN (54.7%), followed by Class III (22.6%). The proportion of patients who achieved either complete or partial remission was 77.3% and 73% at 6 and 12 months, respectively. In the overall LN cohort, 5- and 10-year renal survival rates were 92% and 85.7%, respectively. The remission rate at Month 6 was significantly higher in mycophenolate mofetil (MMF)- and cyclophosphamide (CYC)-treated groups than other combination therapies (P = 0.02). Although no difference was found between the CYC and MMF response rates (P = 0.57) in proliferative LN (Classes III and IV), the majority of Class IV patients (79%) received CYC as induction therapy. There was no difference between the response rates in any treatment regimens at Month 12 (P = 0.56). In the multivariate analysis, male gender, requiring dialysis at the time of LN diagnosis and failure to achieve remission at 6 and 12 months were found to be associated with poor renal outcome. CONCLUSIONS: Our study demonstrated that male gender, failure to achieve remission at 6 and 12 months and requiring dialysis at the time of diagnosis were the best predictors of poor renal outcome. Therefore appropriate and aggressive management of paediatric LN is essential to achieve and maintain remission.

Hemophagocytic Lymphohistiocytosis Associated With Hemolytic Uremic Syndrome in a Child: A Case Report and Systematic Literature Review.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder resulting from excessive activation and nonmalignant proliferation of T-lymphocytes and macrophages. Hemolytic uremic syndrome (HUS) is a disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Reports pertaining to the association between HLH and HUS are rarely published; however, we report on a 4-year-old boy who was diagnosed with both conditions and treated successfully with high-dose steroid and intravenous immunoglobulin. Differentiating HUS from HLH can be challenging because of their clinical similarities. Therefore, prompt diagnosis and immunosuppressive treatment are essential and life-saving to these patients.

The effect of antidiuretic hormone on urine and serum electrolyte levelsin children with primary monosymptomatic nocturnal enuresis

Background/aim: The data concerning the effects of desmopressin on water/electrolyte disturbances of children with primary monosymptomatic nocturnal enuresis (PMNE) are limited. In the present study we aimed to evaluate the effect and tolerability of desmopressin on blood and urine electrolytes and osmolality in PMNE.Materials and methods: Thirty-five children with PMNE between the ages of 5 and 15 participated in the study. Patients collected urine during the daytime and acknowledged the night time fluid restriction before starting to use the desmopressin tablets. The medication was taken orally at least 1 h before bedtime. Blood and urine samples were collected before the introduction of the treatment (day 0) and on the third and seventh days of the administration of desmopressin to determine osmolality and electrolyte levels.Results: Thirty-five patients participated in the study. Twenty-one patients (60%) were male and 14 (40%) were female. The mean age was 9.6 - 2.7 years. There were no significant changes in serum osmolality, urine osmolality, and serum sodium concentration. Mean urine calcium/creatinine ratio was 0.03 - 0.01 mg/mg at the beginning, 0.06 - 0.02 mg/mg on the third day, and 0.04 - 0.01 mg/mg on the seventh day of the study. No significant changes were seen in urine calcium/creatinine ratio before and after treatment.Conclusion: Desmopressin appeared to be a well-tolerated drug and provided a safe and effective treatment for children who were following fluid intake restriction for PMNE.

Evaluation of Tubular Dysfunction Using Urine Biomarkers in Children with COVID-19.

OBJECTIVE: The coronavirus disease pandemic is a major problem that the world has been facing since December 2019. It mainly affects the respiratory system; however, the disease can affect the kidneys to different degrees. This study aimed to determine the changes in tubular dysfunction and inflammation parameters in children with coronavirus disease using urine biomarkers. MATERIALS AND METHODS: We included 36 children who tested positive for severe acute respiratory syndrome coronavirus 2 on real-time reverse transcriptase-polymerase chain reaction using respiratory specimens. Coronavirus disease-positive and -negative period parameters were evaluated. For measurement of interleukin-1ß, interleukin-6, and urine ß2 microglobulin levels, patients' urine samples were collected at diagnosis and 1 month after discharge. Additionally, routine urine and hematological parameters were evaluated concurrently. RESULTS: For all patients, the median urine ß2 microglobulin, serum urea, and lactate dehydrogenase levels were significantly higher in the coronavirus disease-positive period than in the coronavirus disease-negative period (P < .05). Further, serum platelet count was significantly lower in the coronavirus disease-positive period than in the coronavirus disease-negative period (P < .05). However, there was no difference in serum creatinine, interleukin-6, or interleukin-1ß levels between the 2 periods (P > .05). CONCLUSION: Our results suggest kidney involvement and tubular dysfunction in patients with asymptomatic, mild, and moderate infections. Furthermore, interleukin-1ß and interleukin-6 levels were high in the urine, even in non-critically ill patients. We believe that these findings contribute to the accumulation of evidence on continued inflammation in the kidney.