Posterior urethral valves (PUV) associated with renal dysplasia are one of the most common causes of end stage kidney disease (ESKD) in childhood. In order to identify risk factors for the ...progression of this condition to early renal failure, we have retrospectively analyzed the clinical course, renal function, and first postnatal renal ultrasound in a sample of 42 young male patients with PUV, who were followed at a single center. Twelve (28.6%) were diagnosed with ESKD at a median age of 11.3 years. Our comparison of PUV patients without decreased estimated glomerular filtration rate (eGFR) (group A; K/DOQI CKD stage 0–1) with PUV patients showing a decreased eGFR (group B; K/DOQI CKD stage 2–5) revealed the following significant risk factors for loss of eGFR: renal volume <3rd percentile (
P
< 0.001), elevated echogenicity (
P
= 0.001), pathologic corticomedullary differentiation (
P
< 0.001), >3 febrile urinary tract infections (
P
= 0.012), and decreased eGFR at 1 year of age (
P
< 0.001). Receiver operating characteristic curve analysis in the cohort confirms that patients showing a renal volume >88.2 ml/m
2
body surface area (BSA) are not at risk to develop K/DOQI CKD stage 5 (sensitivity 75%, specificity 77.3%, positive/negative predictive value 37.5/94.4%). Ultrasound promises to be a valuable tool for identifying endangered patients.
Background. Long-term corticosteroid treatment impairs growth and increases cardiovascular risk factors. Hence, steroid withdrawal constitutes a major topic in paediatric renal transplantation and ...maintenance immunosuppression. Methods. The lack of data from randomised controlled trials caused us to conduct the first prospective, randomised, multicentre study on late steroid withdrawal among paediatric kidney allograft recipients treated with standard-dose cyclosporine microemulsion (CsA) and mycophenolate mofetil (MMF) for 2 years. Forty-two low- or regular-immunologic risk patients were randomly assigned, ≥1 year post-transplant, to continue taking or to withdraw steroids over 3 months. Results. Two years after steroid withdrawal, they showed a longitudinal growth superior to controls mean height standard deviation score (SDS) gain, 0.6 ± 0.1 SDS versus −0.2 ± 0.1 SDS (P < 0.001). The prevalence of the metabolic syndrome declined significantly (P < 0.05), 2 years after steroid withdrawal, from 39% (9/23) to 6% (1/16). Steroid-free patients had less frequent arterial hypertension (50% versus 93% (P < 0.05)) and required fewer antihypertensive drugs 0.6 ± 0.2 versus 1.5 ± 0.3 (P < 0.05 versus control). Additionally, they had a significantly improved carbohydrate and lipid metabolism with fewer hypercholesterolaemia and hypertriglyceridaemia (P < 0.05 versus control). Patient and graft survival amounted to 100%. Allograft function remained stable 2 years after steroid withdrawal. The incidence of acute rejections was similar in the steroid-withdrawal group (1/23, 4%) and controls (2/19, 11%). Conclusion. Late steroid withdrawal in selected CsA- and MMF-treated paediatric kidney transplant recipients improves growth, mitigates cardiovascular risk factors and reduces the prevalence of the metabolic syndrome, at no increased risk of acute rejection or unstable graft function.
Thrombotic microangiopathies (TMA) represent a spectrum of related disorders associated with newly formed thrombi that block perfusion and thus affect the function of either renal or neurological ...organs and tissue. Recent years have seen a dramatic development in the field of TMA and for the two major forms hemolytic uremic syndrome (HUS) and thrombocytopenic purpura (TTP), new genetic causes and also autoimmune forms have been identified. This development indicates a similar pathophysiology and suggests that the two acute disorders are based on common principles. HUS is primarily a kidney disease and TTP also develops in the kidney and at neurological sites. In HUS thrombi formation is likely due to a deregulated complement activation and inappropriate platelet activity. In TTP thrombi formation occurs because of inappropriate processing of released multimers of von Willebrand Factor (vWF). Defining both the similarities and the unique features of each disorder will open up new ways and concepts that are relevant for diagnosis, for therapy, and for the prognostic outcome of kidney transplantations. Here we summarize the most relevant topics and timely issues that were presented and discussed at the 4th International Workshop on Thrombotic Microangiopathies held in Weimar in October 2009 (
https://doi.org/www.hus-ttp.de
).
: Arterial hypertension is a common complication in patients with autosomal recessive polycystic kidney disease (ARPKD), occurring in 33-75% of children when measured by office blood pressure (OBP). ...Ambulatory blood pressure monitoring (ABPM) is a superior tool for investigating blood pressure relative to OBP. The aim of our study was to investigate the prevalence and control of hypertension in children with ARPKD based on ABPM.
This retrospective study evaluated 36 children with ARPKD and at least one ABPM performed in two our tertiary paediatric nephrology centres and 29 children with at least two ABPM. Ambulatory hypertension was defined as mean daytime or night-time BP at least 95th percentile or use of antihypertensives and controlled hypertension as normal ambulatory BP in children on antihypertensive drugs.
The first ABPM study revealed ambulatory hypertension in 94% of children. Untreated or uncontrolled ambulatory hypertension was diagnosed in 67% and controlled hypertension in only 28%. Masked hypertension was found in 5.5% and white-coat hypertension in 14%. The last ABPM study revealed ambulatory hypertension in 86% (all 86% hypertensive children on drugs, i.e. no untreated hypertension), the prevalence of controlled hypertension increased to 59%. Masked hypertension was detected in 8.3% and white-coat hypertension in 10%. Ambulatory blood pressure correlated neither with kidney length nor with glomerular filtration rate. Echocardiography demonstrated left ventricular hypertrophy (LVH) in 27% of children at the time of their first ABPM.
The prevalence of ambulatory hypertension is very high in children with ARPKD, while the control of hypertension improves over time.
Background
Renal oligohydramnios (ROH) describes an abnormally low volume of amniotic fluid (AF) during pregnancy. ROH is mostly caused by congenital fetal kidney anomalies. The ROH diagnosis ...frequently implies an increased risk of peri- and postnatal fetal mortality and morbidity. The present study aimed to evaluate the impact of ROH on pre-and postnatal development in children with congenital kidney anomalies.
Methods
This retrospective study included 168 fetuses with anomalies in the kidney and urinary tract. Based on the amount of AF measured by ultrasound, patients were divided into three groups: normal amniotic fluid (NAF), amniotic fluid in the lower normal range (LAF), and ROH. These groups were compared with respect to prenatal sonographic parameters, perinatal outcomes, and postnatal outcomes.
Results
Among the 168 patients with congenital kidney anomalies, 26 (15%) had ROH, 132 (79%) had NAF, and 10 (6%) had LAF. Of the 26 families affected by ROH, 14 (54%) decided to terminate pregnancy. Of 10 live-born children in the ROH group, 6 (60%) survived the observation time; of these, 5/6 presented with chronic kidney disease, stages I–III, at their last examination. The main differences in postnatal development between the ROH group and the NAF and LAF groups were: restricted height and weight gain, respiratory issues, complicated feeding, and the presence of extrarenal malformations.
Conclusions
ROH is not a mandatory indicator of severe postnatal kidney function impairment. However, children with ROH have complicated peri-and postnatal periods, due to the presence of concomitant malformations, which must be considered in prenatal care.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Background
The hereditary kidney disease Alport syndrome (AS) has become a treatable disease: intervention with angiotensin-converting enzyme (ACE)-inhibitors delays end stage renal failure by years. ...The efficiency of ACE inhibition depends on the onset of therapy—the earlier the better. Therefore, early diagnosis has become increasingly important. To date, robust diagnosis requires renal biopsy and/or expensive genetic analysis, which is mostly performed late after onset of the profound clinical symptoms of this progressive renal disease. Thus, disease biomarkers enabling low-invasive screening are urgently required.
Methods
Fourteen potential proteomic candidate markers (proteins) identified in a previous study in sera from patients exhibiting manifest AS were evaluated in the plasma, serum, and urine collected from a cohort of 132 subjects, including patients with AS and other nephropathies and healthy controls. Quantitation was performed by immunoassays.
Results
The serum and plasma levels of none of the 14 proteins evaluated were significantly different among the three groups and therefore could not be used to discriminate between the groups. In contrast, the levels of various biomarker combinations in the urine were significantly different between AS patients and healthy controls. Importantly, some combinations had the potential to discriminate between AS and other nephropathies.
Conclusions
These findings open a window of opportunity for the sensitive and specific early diagnosis of AS. Our results increase the potential for larger scale evaluation of an increased number of patients.
We report a male newborn presenting with sonographically normal kidneys, oligohydramnios during late pregnancy, and persisting anuric renal failure. Despite intensive treatment, the patient suffered ...from severe hypotension and died at the age of 4 weeks. At autopsy, kidneys were found to be normal; on histology, deranged renal structures, in particular proximal tubuli and vessels, were noted, leading to the diagnosis of renal tubular dysgenesis (RTD). The diagnosis was confirmed by 2 heterozygous nonsense mutations of the ACE gene. Because the recurrence rate of RTD is 25% for the autosomal recessive trait, knowledge and genetic diagnosis of the disease is important for the parents.
Abstract
Context
Burosumab has been approved for the treatment of children and adults with X-linked hypophosphatemia (XLH). Real-world data and evidence for its efficacy in adolescents are lacking.
...Objective
To assess the effects of 12 months of burosumab treatment on mineral metabolism in children (aged <12 years) and adolescents (aged 12-18 years) with XLH.
Design
Prospective national registry.
Setting
Hospital clinics.
Patients
A total of 93 patients with XLH (65 children, 28 adolescents).
Main Outcome Measures
Z scores for serum phosphate, alkaline phosphatase (ALP), and renal tubular reabsorption of phosphate per glomerular filtration rate (TmP/GFR) at 12 months.
Results
At baseline, patients showed hypophosphatemia (−4.4 SD), reduced TmP/GFR (−6.5 SD), and elevated ALP (2.7 SD, each P < .001 vs healthy children) irrespective of age, suggesting active rickets despite prior therapy with oral phosphate and active vitamin D in 88% of patients. Burosumab treatment resulted in comparable increases in serum phosphate and TmP/GFR in children and adolescents with XLH and a steady decline in serum ALP (each P < .001 vs baseline). At 12 months, serum phosphate, TmP/GFR, and ALP levels were within the age-related normal range in approximately 42%, 27%, and 80% of patients in both groups, respectively, with a lower, weight-based final burosumab dose in adolescents compared with children (0.72 vs 1.06 mg/kg, P < .01).
Conclusions
In this real-world setting, 12 months of burosumab treatment was equally effective in normalizing serum ALP in adolescents and children, despite persistent mild hypophosphatemia in one-half of patients, suggesting that complete normalization of serum phosphate is not mandatory for substantial improvement of rickets in these patients. Adolescents appear to require lower weight-based burosumab dosage than children.
ObjectivesIt is known that transition, as a shift of care, marks a vulnerable phase in the adolescents’ lives with an increased risk for non-adherence and allograft failure. Still, the transition ...process of adolescents and young adults living with a kidney transplant in Germany is not well defined. The present research aims to assess transition-relevant structures for this group of young people. Special attention is paid to the timing of the process.SettingIn an observational study, we visited 21 departments of paediatric nephrology in Germany. Participants were doctors (n=19), nurses (n=14) and psychosocial staff (n=16) who were responsible for transition in the relevant centres. Structural elements were surveyed using a short questionnaire. The experiential viewpoint was collected by interviews which were transcribedverbatim before thematic analysis was performed.ResultsThis study highlights that professionals working within paediatric nephrology in Germany are well aware of the importance of successful transition. Key elements of transitional care are well understood and mutually agreed on. Nonetheless, implementation within daily routine seems challenging, and the absence of written, structured procedures may hamper successful transition.ConclusionsWhile professionals aim for an individual timing of transfer based on medical, social, emotional and structural aspects, rigid regulations on transfer age as given by the relevant health authorities add on to the challenge.Trial registration numberISRCTN Registry no 22988897; results (phase I) and pre-results (phase II).
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