Pediatric Nephrology最新文献

The conventional methods for assessing kidney function, such as glomerular filtration rate and microalbuminuria, provide only partial insight into kidney function. Multi-parametric and multi-nuclear functional resonance magnetic imaging (MRI) techniques are innovative approaches to unraveling kidney physiology. Multi-parametric MRI includes various sequences to evaluate kidney perfusion, tissue oxygenation, and microstructure characterization, including fibrosis-a key pathological event in acute and chronic kidney disease and in transplant patients-without the need for invasive kidney biopsy. Multi-nuclear MRI detects nuclei other than protons. ²³Na MRI enables visualization of the corticomedullary gradient and assessment of tissue sodium storage, which can be particularly relevant for personalized medicine in salt-wasting tubular disorders. Meanwhile, ³¹P-MRS measures intracellular phosphate and ATP variations, providing insights into oxidative metabolism in the muscle during exercise and recovery. This technique can be useful for detecting subclinical ischemia in chronic kidney disease and in tubulopathies with kidney phosphate wasting. These techniques are non-invasive and do not involve radiation exposure, making them especially suitable for longitudinal and serial assessments. They enable in vivo evaluation of kidney function on a whole-organ basis within a short acquisition time and with the ability to distinguish between medullary and cortical compartments. Therefore, they offer considerable potential for pediatric patients. In this review, we provide a brief overview of the main imaging techniques, summarize available literature data on both adult and pediatric populations, and examine the perspectives and challenges associated with multi-parametric and multi-nuclear MRI.

Background: Shear wave elastography (SWE) is proven for liver fibrosis. However, there are challenges in assessing the kidney owing to its surrounding structures, retroperitoneal location, and visceral fat. Kidney biopsy is the gold standard for estimating fibrosis, but is associated with inherent risks of bleeding and sedation. This study explores SWE's potential in assessing kidney fibrosis in CKD.

Methods: A total of 160 children < 18 years old with CKD or those undergoing kidney biopsy were enrolled from June 2022 to June 2024 in a cross-sectional study. SWE on a Philips Epic Elite system provided Young's modulus (YM) values. We analysed SWE with estimated glomerular filtration rate (eGFR, (CKD stages)) and urine protein creatinine ratio, in patients with CKD. Forty-one patients who underwent kidney biopsy were assessed for interstitial fibrosis and tubular atrophy (IFTA) and SWE.

Results: There was no relation between CKD stages, GFR, or proteinuria with YM/SWE. YM/SWE poorly predicted CKD with eGFR < 60 ml/min/1.73 m² (left kidney, 8 kPa (sensitivity 53.57%, specificity 65.62%, AUC 0.5), and right kidney, 9 kPa (sensitivity 57.14%, specificity 50%, AUC 0.39)). YM had fair diagnostic utility (AUC = 0.7) in detecting > 50% fibrosis in right kidney (11 kPa) and left kidney (6 kPa) (right side 75% sensitivity, 80% specificity, left side 100% sensitivity, and 31.43% specificity). Significant differences were noted in YM between right and left side (p = 0.013).

Conclusions: SWE was limited in differentiating CKD stages but could predict fibrosis over 50%. SWE might be helpful in identifying increasing fibrosis, but it is not useful in detecting early fibrosis or chronicity.

Background: We evaluate the association of early postoperative urinary c-c motif chemokine ligand 14 (CCL14) and persistent severe acute kidney injury (AKI) in pediatric post-cardiac surgery patients.

Methods: This is a retrospective single-center cohort study of patients < 18 years of age undergoing cardiac surgery who provided a biorepository urine sample within the first 24 postoperative hours. Persistent severe AKI was defined as any AKI stage lasting for ≥ 72 h with at least one time point of AKI stage 2 or 3 during that time frame. Patients with persistent severe AKI were matched 2:1 with non-AKI patients on age and sex. Urine samples were measured for CCL14 concentration. Logistic regression was used to evaluate associations between CCL14 and persistent severe AKI.

Results: Persistent severe AKI occurred in 14 (5.4%) patients and was more common in patients with higher surgical complexity and longer cardiopulmonary bypass and cross-clamp duration. Patients with persistent severe AKI had longer median cardiac intensive care unit (CICU) (5 [3, 10] vs. 2 [1.5, 5.5], p-value = 0.039) and hospital length of stays (13.5 [7.8, 16.8] vs. 6 [4,8], p-value = 0.009). There was no difference in CCL14 levels between patients with and without persistent severe AKI (46.7 pg/ml [31.0, 82.9] vs. 44.2 pg/ml [25.1, 74.9], p-value = 0.49) in univariable and logistic regression.

Conclusions: In this heterogenous cohort of children undergoing cardiac surgery, CCL14 was not associated with persistent severe AKI. Future studies are needed to evaluate the use of CCL14 for predicting persistent severe AKI in children.

Background: Haemolytic uremic syndrome (HUS) is a life-threatening disease with a historically poor prognosis in children receiving maintenance kidney replacement therapy (KRT). This study aimed to analyse the incidence and outcome of chronic kidney disease stage 5 (CKD5) due to Escherichia coli-HUS (STEC-HUS) and complement-mediated HUS (CM-HUS) in children, compared with controls with non-HUS CKD5 over the last 24 years.

Methods: The study included 1488 children undergoing KRT in Poland between 2000 and 2023. Thirty-nine patients with CM-HUS and 18 with STEC-HUS were identified and analysed for incidence, KRT modality and survival.

Results: The incidence rate of CKD5 was 0.09 cases/million age-related population (marp) for STEC-HUS and 0.23/marp for CM-HUS, while no new cases have been observed in recent years. CKD5 due to CM-HUS developed significantly earlier from initial HUS manifestation than in STEC-HUS (median 0.2 vs. 9.8 years). CM-HUS was associated with younger age at initiation of KRT compared to STEC-HUS and non-HUS controls (median 6.0 years vs. 10.9 and 10.9 years), with higher risk of death (Hazard Ratio 1.92, 95% confidence interval 0.9-4.13) and worse 5-year kidney graft survival at 77%, 93% and 90%, respectively (p < 0.001).

Conclusions: In recent years, both CM-HUS and STEC-HUS have become increasingly rare causes of CKD5 in children. CKD5 due to CM-HUS in the eculizumab era and due to STEC-HUS after improving supportive treatment is exceptional. Children on KRT due to STEC-HUS had a significantly better survival, shorter waiting time for kidney transplantation and better kidney graft survival compared to the CM-HUS group.

Background: Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a severe condition mainly affecting children. It is one of the leading causes of acute kidney injury in the pediatric population. There is no established therapy for this disease. INM004 is an anti-Shiga toxin composed of equine polyclonal antibodies. This study is aimed at assessing the safety, pharmacokinetics, and efficacy of INM004 in pediatric patients with STEC-HUS.

Methods: Phase 2, open-label clinical trial with an historical control arm. Patients in the treatment arm received two doses of INM004. The primary endpoints were the safety profile, pharmacokinetics, and efficacy (dialysis days) of INM004. Secondary endpoints included other kidney and extrarenal outcomes. Propensity score matching was used for efficacy comparisons between arms.

Results: Fifty-seven and 125 patients were enrolled in the treatment and control arm, respectively. After propensity score matching, 52 patients remained in each arm. INM004 was well-tolerated. Eight adverse events were considered possibly related, none of which were serious or severe. In the primary efficacy endpoint, patients of the treatment arm presented a non-statistically significant difference of two dialysis days. On secondary endpoints, non-statistically significant trends toward fewer patients needing dialysis and dialysis for more than 10 days, and shorter time to glomerular filtration rate normalization, were observed favoring the treatment arm.

Conclusions: INM004 showed an adequate safety profile. Efficacy non-statistically significant trends suggesting a beneficial effect in the amelioration of kidney injury were observed. These results encourage the conduction of a phase 3 study of INM004 in pediatric patients with STEC-HUS.

Background: Enuresis has a complex pathophysiology involving nocturnal polyuria, reduced bladder capacity at nighttime, and impaired arousability. Desmopressin has long been used as a treatment. However, approximately 30% of children do not fully respond to it, suggesting the involvement of other factors. Solute handling and osmotic excretion have been studied in refractory patients. Nevertheless, data on the effect of desmopressin on these factors are sparse.

Methods: We conducted a post hoc analysis of the SLEEP study. We analyzed the circadian rhythm of solute and water excretion before and after desmopressin in 30 children with monosymptomatic enuresis and nocturnal diuresis > 100% of expected bladder capacity by means of a 24-h urine concentration profile (four daytime and four nighttime urine portions at equivalent time intervals).

Results: Under desmopressin, nocturnal diuresis (rate) and Na/creatinine ratio were significantly lower compared to day values (p = 0.009, p = 0.021, respectively). Osmolality, Na/creatinine, and osmotic excretion showed a significant day vs. night variance only after desmopressin. Nighttime osmotic and sodium excretion were significantly lower (p = 0.004, p = 0.019, respectively) under treatment, indicating the impact of desmopressin on kidney sodium handling. During desmopressin treatment, nocturnal diuresis (rate) showed strong positive correlation with nighttime Na/creatinine (r = 0.436, p < 0.05) and very strongly with nighttime osmotic excretion (r = 0.875, p < 0.0001). However, no correlation was observed with osmolality under desmopressin treatment.

Conclusions: The anti-enuretic and antidiuretic effects of desmopressin therapy are not only related to urinary concentration and nocturnal diuresis but also to the amelioration of circadian rhythms of sodium and solute handling.

Pseudohypoaldosteronism type 2 (PHA2) is a rare inherited condition of altered tubular salt handling. It is characterized by the specific constellation of hyperkalaemic hyporeninemic hypertension, hyperchloremic metabolic acidosis and hypercalciuria. Molecular genetic testing confirms the diagnosis in the majority of cases. Thiazides constitute effective treatment. Due to its rarity, the diagnosis is often delayed. We here present two children with PHA2, who were initially treated with fludrocortisone and bicarbonate complicated mainly by exacerbation of their hypertension. Discontinuation of their previous therapy and commencement of thiazide diuretics led to normalisation of their blood pressure and electrolyte and acid-base status.

Background: TikTok, a popular social media platform, is increasingly used for health information dissemination; however, the accuracy and quality of medical content remain uncertain, including in the context of nephrotic syndrome (NS). This study aims to identify prominent patient and caregiver experiences with NS on TikTok and demonstrate how they may vary.

Methods: A convenience sample of TikTok videos containing the hashtag "nephrotic syndrome" posted between July 1, 2020, and February 29, 2024, was analyzed. Videos underwent cyclical and inductive coding, followed by content and discourse analysis to identify common themes and narratives.

Results: One hundred twenty-three videos were included in the analysis. 62.6% of videos (N = 77) consisted of caregivers sharing their experiences of their child's disease. Three prominent topics included: (1) navigating healthcare and managing illness, where users shared their disease journeys; (2) emotional and physical wellbeing, where caregivers focused on physical disease signs while patients highlighted the mental health toll of the illness; and (3) education, awareness, and support systems, where users shared feelings of social isolation post-diagnosis. The discourse analysis revealed language portraying patients as "warriors," reflecting the resiliency promoted by TikTok support systems.

Conclusions: We uncovered a hidden disease burden associated with NS that affects everyday life, reinforcing the importance of the journey and stress patients and caregivers experience outside of the clinician's office. Our findings also highlight that patient priorities may differ from those reported by caregivers, particularly in pediatrics. TikTok may also be an outlet for feelings of isolation and community-building within NS.