Ambulatory blood pressure parameters and their association with albuminuria in adolescents with type 1 diabetes mellitus.

BACKGROUND: This study aimed to evaluate the blood pressure (BP) status, including arterial stiffness parameters, hemodynamic indicators, circadian profile, and its association with albuminuria in adolescents with type 1 diabetes mellitus (DM1). METHODS: The analysis included 46 patients, with diabetes duration of 7.38 ± 3.48 years. Ambulatory blood pressure monitoring (ABPM) was conducted using an oscillometric device, the Mobil-O-Graph, which is a Pulse Wave Analysis Monitor. RESULTS: Hypertension (HT) was diagnosed in 31 adolescents (67% of patients), primarily due to isolated nocturnal BP (21 cases, 68% of HT cases). The HT group exhibited significantly increased diastolic load (DL). Pulse wave velocity (PWV, a measure of arterial stiffness) values showed a strong correlation with both peripheral systolic BP (r = 0.954) and central systolic BP (r = 0.838). Additionally, non-dipping status was found in 61% of the HT group. Urinary albumin excretion (UAE) was positively correlated with diastolic BP (particularly nocturnal) peripheral and central BP, DL, heart rate, augmentation index (AIx@75), and nocturnal total vascular resistance (TVR). Diastolic non-dippers exhibited a significant increase in UAE. CONCLUSIONS: Hypertension is a common complication in adolescents with type 1 diabetes mellitus, primarily caused by elevated nocturnal diastolic BP. Albuminuria is mainly associated with diastolic BP, especially during the nocturnal period and in cases of diastolic non-dipping status. The association of UAE with AIx@75 and nocturnal TVR suggests the presence of early-stage vascular disease in diabetic adolescents.

Acute kidney injury and diabetic kidney disease in children with acute complications of diabetes.

BACKGROUND: Diabetic ketoacidosis (DKA) and hyperglycaemia without ketoacidosis are common acute complications of diabetes. Their association with acute kidney injury (AKI) and diabetic kidney disease (DKD) was studied. METHODS: The study group consisted of 197 children with type 1 diabetes with average diabetes duration of 8.08 ± 2.32 years. The medical history of the patients was retrospectively reviewed. The number of children with severe hyperglycaemia, DKA and AKI was assessed. The association with the risk of chronic kidney disease (CKD) was analysed. RESULTS: AKI was found in 14% of cases hospitalised for DKA and 8% of cases hospitalised for hyperglycaemia. Patients with AKI showed a significantly increased corrected sodium (141.23 ± 5.09 mmol/L, p = 0.035). Patients with AKI in DKA showed a significant increase in WBC (20.73 ± 8.71 × 103/µL, p = 0.0009). Follow-up analysis after a minimum of 5 years of diabetes revealed that a single episode of DKA was found in 63 patients and a single episode of AKI in 18 patients. Two or more episodes of DKA were found in 18 patients, and nine cases were complicated by AKI. These patients showed a significant increase in urinary albumin excretion (44.20 ± 64.21 mg/24 h), the highest values of eGFR and the worst glycaemic control. CONCLUSIONS: Diabetic children can develop AKI in the course of DKA and hyperglycaemia without ketoacidosis, which is associated with volume depletion and reflected by corrected sodium concentration. AKI in DKA seems to be complicated by stress and inflammation activation. AKI and poor glycaemic control with repeated DKA episodes can magnify the risk of progression to DKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Early kidney damage in diabetic adolescents with increased blood pressure and glomerular hyperfiltration.

BACKGROUND: The early impact of type-1 diabetes mellitus (DM1), increased blood pressure and glomerular hyperfiltration (GHF) on kidney damage in adolescents using two urinary markers of kidney injury - neutrophil gelatinase-associated lipocalin (uNGAL) and transferrin (uTransf) was assessed. METHODS: The study group consisted of 80 adolescents with DM1, of whom 42 were patients with increased blood pressure (IBP), and 38 were patients with normal blood pressure (NBP). Blood pressure was assessed by 24-hour ambulatory bloodpressure monitoring. All patients showed estimated glomerular-filtration rates (eGFRs) above 90 ml/min/1.73m2. The control group consisted of 19 healthy, age and gender-matched adolescents. RESULTS: All diabetic children showed a significant increase in uNGAL (p<0.001). This increase was not related to blood pressure. The uNGAL was elevated in all patients with normal albuminuria, normal eGFR and NBP. The concentration of uTransf was not increased in the entire studied group and was not related to blood pressure. Children with GHF had significantly higher levels of both uTransf (p=0.010) and uNGAL (p<0.001). In patients with GHF, blood pressure was normal. Patients with IBP showed a significantly higher value for triglycerides (r=0.247; p=0.032) and a longer duration of diabetes (r=0.264; p=0.019). CONCLUSIONS: Diabetes is the leading risk factor for early kidney injury. However, increased blood pressure does not lead to kidney damage, at least in the early stage of DM1. The uNGAL is the early indicator of kidney injury and increases in patients with normal albuminuria, normal glomerular filtration and normal blood pressure. Glomerular hyperfiltration seems to be a marker of diabetic-kidney involvement.

Circulating suPAR as a biomarker of disease severity in children with proteinuric glomerulonephritis.

BACKGROUND: The increase of circulating urokinase plasminogen activator receptor (suPAR) was demonstrated in various diseases showing its prognostic value as well as the link to the inflammatory reaction. In glomerular diseases, suPAR was considered a causative factor of proteinuria. In the present study we aimed to evaluate serum concentration of suPAR in children with primary and secondary glomerulonephritis (GN) and its association with disease severity. METHODS: The study involved 22 children with minimal change disease (MCD), nine with primary focal segmental glomerulosclerosis (FSGS), seven with Henoch-Schönlein nephritis, seven with lupus nephritis (LN) and 16 controls. RESULTS: Serum suPAR was significantly higher in children with FSGS and LN than controls (4.47±1.39 ng/mL vs. 3.23±0.76 ng/mL; P=0.011 and 6.17±1.12 ng/mL vs. 3.23±0.76 ng/mL, respectively; P<0.0001). Further, suPAR was increased in LN when compared to FSGS (P=0.031). In the total group suPAR showed negative correlation with eGFR, serum complement C3 and positive with left ventricular mass index. In children with MCD and FSGS the inverse association of suPAR with eGFR was also shown. CONCLUSIONS: In children with primary and secondary glomerulonephritis suPAR levels are not associated with proteinuria. In primary GN elevated suPAR levels may result from reduced eGFR reflecting renal damage. In LN circulating suPAR can be increased further indicating both multi-organ involvement and systemic inflammation reflecting disease severity.

Atypical thymic carcinoid manifesting with nephrotic-range proteinuria in a 7-year-old boy.

BACKGROUND: Nephrotic-range proteinuria as a paraneoplastic syndrome (PNS) is an exceptional presentation, especially in children. It is usually associated with hematologic malignancies. Solid tumors are very rare causes of proteinuria. CASE-DIAGNOSIS/TREATMENT: We present the case of a 7-year-old boy with an extremely rare atypical thymic carcinoid accompanied by nephrotic-range proteinuria as PNS. The kidney biopsy was consistent with minimal change disease (MCD). Tests for a neuroendocrine tumor were performed due to symptoms of hypercortisolemia and an elevated concentration of chromogranin A in the serum. The chest computed tomography revealed a tumor in the anterior mediastinum, which was diagnosed as an atypical thymic carcinoid. A complete resolution of the nephrotic-range proteinuria was observed within 1 week after the first thoracoscopic surgery, with almost complete reduction of the tumor mass. CONCLUSIONS: This extremely rare case shows that MCD can occur as a PNS even in children. Nephrotic-range proteinuria can be a symptom of malignant solid tumor. This case highlights the possibility of secondary causes of MCD in children.

Citrate anticoagulation for continuous renal replacement therapy in small children.

BACKGROUND: Regional citrate anticoagulation (RCA) is one of the methods used to prevent clotting in continuous renal replacement therapy (CRRT). The aim of this study was to describe the outcomes and complications of RCA-CRRT in comparison to heparin anticoagulation (HA)-CRRT in critically ill children. METHODS: This study was a retrospective review of 30 critically ill children (16 on RCA- and 14 on HA-CRRT) who underwent at least 24 h of CRRT. The mean body weight of the children was 8.69 ± 5.63 kg. RCA-CRRT was performed with a commercially available pre-dilution citrate solution (Prismocitrate 18/0). RESULTS: The mean time on RCA-CRRT and HA-CRRT was 148.73 ± 131.58 and 110.24 ± 105.38 h, respectively. Circuit lifetime was significantly higher in RCA-CRRT than in HA-CRRT (58.04 ± 51.18 h vs. 37.64 ± 32.51 h, respectively; p = 0.030). Circuit clotting was observed in 11.63 % of children receiving RCA-CRRT and 34.15 % of those receiving HA-CRRT. Episodic electrolyte and metabolic disturbances were more common in children receiving RCA-CRRT. The survival at discharge from the hospital was 37.5 and 14.3 % among children receiving RCA-CRRT and HA-CRRT, respectively. CONCLUSIONS: In critically ill children with a low body weight, RCA appeared to be safe and easy to used. Among our patient cohort, RCA was more effective in preventing circuit clotting and provided a better circuit lifetime than HA.

Urinary angiotensinogen and urinary sodium are associated with blood pressure in normoalbuminuric children with diabetes.

BACKGROUND: The aim of this study was to evaluate the association between blood pressure (BP) and urinary angiotensinogen excretion (uAGT) and renal sodium excretion (uNa) in children with type 1 diabetes mellitus (DM1). METHODS: The study group consisted of 52 children with DM1 (28 males and 24 females) with albumin/creatinine ratio (ACR) below 30 mg/g and glomerular filtration rate (eGFR) above 90 ml/min/1.73 m(2). BP was assessed by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: The patients showed significantly increased uAGT values with respect to controls (median 0.00 and range 1.76 vs. 0.00 and 0.00 ng/mg, respectively). The significant increase of uAGT was observed even in prehypertensive patients. uAGT concentrations showed positive correlation with systolic and diastolic 24-h BP and with mean arterial pressure (MAP) (r = 0.594). uNa values were negatively correlated with BP parameters, uAGT, ACR and eGFR. CONCLUSIONS: An increase in uAGT precedes hypertension (HTN) in normoalbuminuric children with DM1 and may be considered as a new marker of HTN. Decreased sodium excretion seems to be involved in the development of HTN and early renal injury. Both uAGT and uNa are associated with BP in normoalbuminuric diabetic children.

Hypertensive nephropathy in children - do we diagnose early enough?

BACKGROUND/AIMS: The aim was to evaluate the level of neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18) and retinol binding protein (RBP) in children with primary hypertension and no features of hypertensive nephropathy. METHODS: The study group consisted of 19 children (15 males) aged 14.8 ± 2.18 years with primary hypertension. Estimated glomerular filtration rate (eGFR) and albumin/creatinine ratio (ACR) were within the normal range. Mean blood pressure (BP) was 141/79 mmHg (mean systolic BP percentile was 98, mean diastolic BP percentile was 80). Ambulatory BP measurement (ABPM), blood and urine biochemical measurements and features of end organ damage were assessed. The control group consisted of 20 healthy children. RESULTS: Hypertensive children showed significantly increased serum and urine NGAL concentration vs controls. Urine RBP was significantly higher in the study group vs controls. A positive correlation was found between urine NGAL and the index of mean systolic BP measured in ABPM, between urine IL-18 and the index of office diastolic BP, between serum NGAL and ACR, and between urine NGAL concentration and serum HDL. CONCLUSION: In children with primary hypertension, increased serum and urine NGAL may reflect kidney injury earlier than typical markers of hypertensive nephropathy.

Normal-range albuminuria does not exclude nephropathy in diabetic children.

Clinically detectable diabetic nephropathy (DN) begins with the development of microalbuminuria (MA). However, early renal dysfunction may be overlooked despite using that method. On the other hand, the gold standard in DN detection-that is, renal biopsy-is highly invasive. The aim of this study was to evaluate the level of neutrophil-gelatinase-associated lipocalin (NGAL) and interleukin (IL)-18 and their relations to albumin excretion rate (AER) in children with normal-range albuminuria, e.g. in those considered as not presenting diabetic nephropathy. The study group consisted of 22 children (age 12.7 +/- 3.5 years) with type 1 diabetes mellitus (T1DM). Long-term glycemic control was assessed on hemoglobin A1c (HbA1c) levels (8.52 +/- 1.78%). All patients presented normal estimated glomerular filtration rate (eGFR) (141 +/- 23 ml/min/1.73 m(2)) and normal urinary albumin excretion (13.09 +/- 7.63 mg/24 h). Fourteen healthy children served as a control group. Children with T1DM showed increased NGAL values with respect to controls-interestingly, both in serum (sNGAL) (867.43 +/- 341.98 vs. 655.29 +/- 196.17 ng/ml; p = 0.04) and in urine (uNGAL) (420.04 +/- 374.16 vs. 156.53 +/- 185.18 ng/ml, p = 0.04). IL-18 levels were not different in both groups both in serum (58.52 +/- 20.11 vs. 69.79 +/- 58.76 ng/ml; NS) and in urine (14.53 +/- 12.74 vs. 14.60 +/- 10.92 ng/ml; NS). Despite the relatively small study group, the positive correlation between sNGAL and AER was found [AER (mg/24 h) = 3.1893 + 0.01141 x sNGAL (ng/ml); r = 0.51; p = 0.014] as well as between uNGAL and AER [AER (mg/24 h) = 8.7538 + 0.01032 x uNGAL (ng/ml); r = 0.51; p = 0.016]. No relationship between sNGAL and uNGAL, and GFR and HbA1c were found. Normal-range albuminuria does not exclude diabetic nephropathy defined as increased sNGAL and uNGAL concentration. NGAL measurement can be more sensitive than MA and may become a useful tool for evaluating renal involvement in diabetic children.

Interest of URS-L in the Treatment of Ureterolithiasis in Preschool Children.

Urolithiasis can affect all children even preschool ones. Diagnostic difficulties in the youngest children are due to the problems in locating pain and determining its character and severity. In keeping with the ALARA (As Low As Reasonably Achievable) protocol, the number of imaging tests possible to perform is very limited. Ultrasound is the first line exam of choice. After diagnosis of the presence of a stone, ESWL (Extracorporeal Shock Wave Lithotrypsy) should always be considered and offered to parents due to its high effectiveness and minimal invasiveness. If ESWL is contraindicated or not well-accepted by parents, authors suggest another minimal invasive approach: URS-L (Uretherorenoscopy-Lithotrypsy). Our study clinically analyzes 87 children, which were treated between 2009 and 2017 using the URS-L procedure. URS-L treatments were performed using Lithoclast until 2009, and after that time, using the holmium laser Ho:YAG. The overall effectiveness of treatments was 93.3%. There was no failure in the access to the stones. A macroscopic hematuria (Clavien-Dindo I grade) was observed through the second post-operative day in 9.2% of treated patients. No urosepsis was observed. Full metabolic evaluation was performed on all patients. Children remained under constant urological and nephrological observation. A recurrence of urolithiasis was observed in 35.6% of the cases. Treating ureteral lithiasis in young infants remains a big challenge. Our series shows that modern minimal invasive techniques used by very experienced pediatric urologists in high volume centers gives excellent results. In most cases, surgery should no longer need to be an option.

Efficacy of plasma exchange in septic shock: a case report.

The mortality rate for severe sepsis and septic shock remains high. Additionally, this life-threatening state poses serious difficulties for the treatment of patients. Unfortunately, the mechanism of sepsis is complex and not well understood. In this paper, we present the case of a 2.5-year-old female with septic shock treated with plasma exchange (PE) as a nonstandard therapy. We analysed the medical history of disease, including patient data, physical examination, laboratory tests and treatment. Unexpectedly, we achieved clinical improvement after the first PE. During PE, the dose of catecholamine was reduced. In addition, the level of C-reactive protein seemed to be a better predictor of the efficacy of PE in septic shock compared to procalcitonin. We conclude that PE may improve the survival rate for patients with septic shock. These data could be useful in the search and introduction of new or alternative methods of treatment for critically ill children.

Neutrophil gelatinase-associated lipocalin and Cathepsin L as early predictors of kidney dysfunction in children with type 1 diabetes.

INTRODUCTION: The aim of this study was to evaluate serum levels and urinary excretion of neutrophil-gelatinase associated lipocalin (respectively sNGAL and uNGAL) and urinary excretion of Cathepsin L (uCathL) in children with type 1 diabetes mellitus (DM1) who presented normoalbuminuria and the estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73 m2. MATERIAL AND METHODS: The study group consisted of 63 children with a diabetes duration of 5.16 ± 3.39 years. The degree of albuminuria was based on urine albumin-to-creatinine ratio (ACR), while eGFR was based on serum cystatin C. Glomerular hyperfiltration (GH) was defined as an eGFR value above 135 mL/min/1.73 m2. RESULTS: Children with DM1 showed significantly higher concentrations of uNGAL, and lower sNGAL and uCathL. Significant changes of uNGAL and uCathL levels were even found in children without GH and with optimal glycaemic control (HbA1c < 7.5%). Positive correlations between uNGAL, ACR and eGFR were shown, as well as between uCathL and eGFR. CONCLUSIONS: Significant changes in the concentration of markers of early kidney injury: sNGAL, uNGAL, and uCathL, can occur in children with DM1 and normoalbuminuria. The changes of uNGAL and uCathL can be even found in children without GH and with optimal glycaemic control. The earliest signs of diabetic kidney dysfunction seem to result from tubular damage.

Efficacy and safety of rituximab treatment in children with primary glomerulonephritis.

BACKGROUND: The aim of our study was to analyze the efficacy and safety of rituximab, a chimeric monoclonal antibody against CD20 lymphocytes, as a nonstandard immunosuppressive therapy in children with different types of primary glomerulonephritis who were not eligible for routine treatment. METHODS: The study group was composed of 16 children with proteinuric glomerulopathies, not responding to standard immunosuppressive therapy. The indications included steroid-resistant nephrotic syndrome (n=14) and steroid-dependent nephrotic syndrome (n=2). The dose of rituximab was established as 375 mg/m2 of body surface area, administered by intravenous infusion once weekly for 1 to 4 weeks, depending on the CD19 lymphocyte count. We evaluated proteinuria and plasma concentration of CD19 lymphocytes at intervals of 1, 3 and 6 months, after which patients received a single repeat dose. RESULTS: Remission, defined as proteinuria less than 150 mg per 24 hours, was observed in 7 of the 16 children. There were no statistically significant differences in leukocyte counts between single and multiple rituximab doses. We also did not observe any clinical or biochemical side effects. CONCLUSIONS: In conclusion, we postulate that alternative rituximab therapy should be taken into consideration in nephrotic patients not responding to standard therapy.