Pediatric Nephrology最新文献

Knowledge of glomerular filtration rate (GFR) is essential for the treatment and monitoring of children with a malignancy. Ideally, GFR is measured using the gold standard technique of renal inulin clearance. Still, this procedure is too invasive and time-consuming for routine clinical practice. Also, the armamentarium of markers suitable for GFR measurement (mGFR) has changed in the last decades, with iohexol clearance now being used in many countries, both in Europe and the US. For daily monitoring of kidney function, cystatin C has proven to be an important adjunct to serum creatinine, the standard marker of GFR. This review gives a comprehensive update on the indications and limitations of mGFR methods as well as the estimation of GFR from serum markers (eGFR) with special emphasis on children treated for a malignancy.

Objectives: Albuminuria is an established early marker of kidney damage and a strong predictor of cardiovascular risk. This study aimed to investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and urinary albumin-to-creatinine ratio (ACR) among Korean adolescents.

Methods: In this cross-sectional analysis of the 2011-2014 Korea National Health and Nutrition Examination Survey (KNHANES), we assessed adolescents aged 10-19 years. Log-transformed urinary ACR was regressed on serum 25(OH)D using linear regression, adjusting for age, sex, BMI category, glycemic status, and blood pressure. Subgroup analyses were conducted according to vitamin D deficiency (< 20 ng/mL vs. ≥ 20 ng/mL).

Results: This analysis included 2,109 adolescents with a mean age of 14.2 ± 2.8 years. The mean serum 25(OH)D concentration was 16.5 ± 5.2 ng/mL, and the mean urinary ACR was 0.78 ± 2.29 mg/g Cr. Linear regression analysis revealed a significant inverse association between serum 25(OH)D levels and log-transformed ACR (crude regression coefficient: -0.0242; 95% CI: -0.0347 to -0.0137). This inverse association remained statistically significant after adjusting for age, sex, body mass index category, glycemic status, and blood pressure (adjusted regression coefficient: -0.0193; 95% CI: -0.0303 to -0.0083). The inverse association was stronger among participants with vitamin D deficiency (serum 25(OH)D < 20 ng/mL), with an adjusted regression coefficient of -0.0378 (95% CI: -0.0567 to -0.0189).

Conclusion: Serum vitamin D levels were inversely associated with albuminuria among Korean adolescents, independent of major confounding factors. The association was particularly pronounced among those with vitamin D deficiency, underscoring the potential role of vitamin D in early kidney health.

Background: High sodium intake is a key element in the development of hypertension, but strategies aimed at reducing its consumption have had limited impact at a population level. A potential alternative preventive and/or therapeutic opportunity may be represented by increasing kidney sodium excretion.

Methods: The Salus per Aquam Project is a multicenter, prospective, controlled, randomized study investigating whether, in healthy children, increased fluid intake for 1 year can lower blood pressure. Participants were randomized into 2 groups: one was actively encouraged to increase their water intake, especially during school days, while the other group was used as a control. At baseline and after 1 year, blood pressure was determined using multiple office blood pressure measurements. Urinary electrolytes and creatinine were measured in multiple samples at baseline, during the study period, and at the end of the study to provide details on sodium and fluid intake.

Results: One hundred and seventy-five children were enrolled (94 females, 53.7%, median age 8.6 years, IQR:8.4-8.9), but only 145 completed the study. After 12 months, children who were motivated to drink more fluids presented lower median systolic (93 vs. 95 mmHg), diastolic (63 vs. 65 mmHg), and mean (73 vs. 74 mmHg) BP, compared with controls. The median change (ΔMBP, final-baseline) differed significantly between cases and controls, with a between-group median difference of 2 mmHg (Mann-Whitney p = 0.018).

Conclusions: An increased fluid intake may prevent the age-related increase of blood pressure in healthy children. We believe this may be due to more efficient sodium excretion by the kidneys. This simple, highly acceptable, inexpensive, and harmless intervention has the potential to prevent or lessen the prevalence of hypertension and associated illnesses both in adults and children.

Background: Tacrolimus is a cornerstone of lifelong immunosuppressive therapy to prevent acute rejection post-kidney transplantation. Tacrolimus intra-patient variability (IPV) is characterized by several pharmacokinetic metrics, including the standard deviation (SD) of tacrolimus troughs, coefficient of variation (CV%), dose-normalized concentration (DNC), and time in therapeutic range (TTR). This study aimed to investigate the influence of TTR, alongside other IPV metrics, on the incidence of acute rejection in the first year after kidney transplantation.

Methods: This single-center retrospective study evaluated the relationship between IPV measures including coefficient of variation (CV%), standard deviation (SD), dose-normalized concentration (DNC), time in therapeutic range (TTR), and acute rejection during the first post-transplant year in 100 pediatric kidney recipients.

Results: Patients were stratified by TTR into two subgroups: TTR < 78% (n = 80) and TTR ≥ 78% (n = 20). The mean CV% of tacrolimus concentration was 37.1 ± 16.6%, with significantly higher variability observed in those with rejection (p = 0.031). Longitudinal analysis showed that differences in trough levels between TTR groups became evident after 3 months (p < 0.001). Multivariable modeling demonstrated that rejection risk was independently associated with higher age (p = 0.002) and post-transplant period beyond 3 months (p = 0.004), rather than TTR itself.

Conclusions: In pediatric kidney transplant patients, the rejection risk was significantly associated with the magnitude of CV% rather than TTR. Special attention is warranted for therapeutic drug monitoring, especially beyond 3 months post-transplant, due to the increased risk of rejection compared to earlier stages post-transplantation.

Background: Neonatal acute kidney injury (AKI) is common in infants born extremely preterm (EPT, < 28 weeks' gestation). Neonatal AKI is independently associated with increased mortality and is likely to be associated with kidney dysfunction later in life. This study aimed to describe the epidemiology of AKI in EPT infants in a single tertiary neonatal centre.

Methods: Retrospective study of EPT infants admitted to a tertiary neonatal centre in Australia between August 2020 and December 2022. AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) definition (including creatinine and oliguria criteria). Comparisons between AKI and non-AKI cohorts used linear, logistic, or quantile regression.

Results: Of 204 infants admitted during the study period, 193 were included in the study (11 excluded due to death or medical transfer within 48 h after birth). Sixty infants (31%) had an episode of AKI during their inpatient admission: 31 (51.7%) had AKI stage 1, 11 (18.3%) had stage 2, and 18 (30%) had stage 3. Among these, 27 (45%) were recognised by the treating team, 18 (30%) had the diagnosis documented on their discharge summary, and three (5%) were referred for nephrology follow-up. Compared with the non-AKI cohort, infants with AKI were of lower gestational age and lower birth weight and had greater exposure to nephrotoxic medication. Infants with AKI had more episodes of sepsis, more days on respiratory support, and more days admitted to a tertiary centre than those without AKI.

Conclusions: AKI in EPT infants is common and associates with multiple comorbidities and treatments in the NICU. These data highlight risk factors on which AKI screening and stewardship programmes can be focused.

Blood pressure is the product of a complex interplay between the pumping action of the heart and the resistance capacity of both large and small arteries. These are modulated by several physiological processes, including the autonomic nervous system, renin angiotensin aldosterone system, neurohormonal influences and fluid balance. Dysregulation of one or more of these can lead to hypertension. Consideration of the key concepts underlying the generation and regulation of blood pressure is important to consider when selecting an appropriate antihypertensive agent. This review will outline the main physiological processes contributing to blood pressure and discuss their relevance to the pathophysiology and treatment of primary hypertension in children and young people.

Background: Adolescent primary hypertension is associated with decreased neurocognitive performance, a finding suggestive of early target organ damage to the brain. We aimed to determine if adolescent hypertension is associated with altered brain magnetic resonance imaging metrics when compared to normotensive controls.

Methods: Fifty-four newly diagnosed hypertensive subjects and 54 matched controls (age 13-18 years) were studied. All participants had neurocognitive testing and brain MRI to measure cortical thickness and gray matter volume, as well as diffusion metrics to determine white matter microstructural integrity.

Results: The hypertension and control groups showed no significant differences with respect to age, sex, maternal education, income, race, ethnicity, obesity, or laboratory evaluation. While both groups experienced high neighborhood disadvantage, control subjects had higher disadvantage scores (p = 0.03). Adjusted analyses revealed that subjects with hypertension performed similarly to controls on direct neurocognitive testing but received worse parent ratings of executive function. Multivariate analyses found no association between hypertension and brain MRI metrics. However, high neighborhood disadvantage correlated with significantly reduced gray matter volume, and increased BMI z-scores were linked to changes in white matter diffusion metrics but not cortical thickness or gray matter volume.

Conclusions: Adolescent hypertension itself was not directly linked to changes in brain MRI metrics. High neighborhood disadvantage and obesity, both common in adolescents with primary hypertension, were independently associated with altered gray matter volume and white matter microstructure, respectively.

Background: Although use of inhibitors of the renin-angiotensin-aldosterone system (RAAS-I) is contraindicated in the second and third trimesters of pregnancy, a relevant number of pregnancies is still exposed. Fetopathy in children exposed after gestational week (GW) 20 is well described, but data on long-term outcomes are scarce. Our study aims to describe postnatal and long-term outcomes after fetal exposure to RAAS-I.

Methods: We included all pregnancies in the German Pharmacoepidemiological Research Database GePaRD (claims data; 20% of the total German population) with exposure to RAAS-I or the antihypertensives recommended during pregnancy, i.e., metoprolol or methyldopa (HYP) after GW 20. We assessed diagnoses characteristic of RAAS-I-related fetopathy in the first 180 days after birth and examined long-term outcomes of children with and without neonatal fetopathy, especially hypertension and kidney disease.

Results: Overall, we identified 203 live born children exposed to RAAS-I, of whom 61 were exposed to angiotensin II receptor blockers (ARBs), and 29,674 live born children exposed to HYP. Diagnoses consistent with RAAS-I-related fetopathy were seen in eight of the RAAS-I exposed newborns (3.9%) and in seven of the 61 ARB-exposed newborns (11.5%). Median follow-up in children without fetopathy was 4.0 years in both exposure groups. Among non-fetopathy children exposed to RAAS-I, three (1.5%) were diagnosed with hypertension or received antihypertensive prescriptions, compared to 176 children (0.6%) exposed to HYP.

Conclusions: Risk of fetopathy is higher after fetal exposure to ARBs than to angiotensin-converting enzyme inhibitors. In a small proportion of children, sequelae of fetal RAAS-I exposure might only manifest in the years following birth.