<p>Posterior urethral valves is the most common congenital cause of lower urinary tract obstruction in males, and a common cause (15–17%) for end-stage renal disease in childhood. Most commonly, posterior urethral valves is... more
<p>Posterior urethral valves is the most common congenital cause of lower urinary tract obstruction in males, and a common cause (15–17%) for end-stage renal disease in childhood. Most commonly, posterior urethral valves is suspected on basis of a screening antenatal ultrasound. Ultrasound will not detect posterior urethral valves itself, but recognizes the consequences of lower urinary tract obstruction with a dilated thick-walled bladder and dilation of the prostatic portion of the urethra. After birth, urine drainage has to be secured by placement of a bladder catheter, and imaging is needed to confirm the presence of the urethral valves and estimate the degree of damage to the kidney. Consequences of posterior urethral valves depend on the degree of renal dysplasia and bladder dysfunction. Prevention or minimization of such consequences by intrauterine urine drainage has not definitively shown a benefit of early vesico-amniotic shunting.</p>
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<p>In renal agenesis, the kidney never forms due to an absence of interaction in the developing embryo between the ureteric bud and the metanephric mesenchyme. Most cases of renal agenesis are unilateral, for which the reported... more
<p>In renal agenesis, the kidney never forms due to an absence of interaction in the developing embryo between the ureteric bud and the metanephric mesenchyme. Most cases of renal agenesis are unilateral, for which the reported incidence is around 1 in 3000. The prenatal diagnosis of unilateral renal agenesis is based on the absence of a recognizable kidney, either at the normal or an ectopic site. However, such cases of an empty renal fossa can also be explained by an involuted multicystic dysplastic kidney, or by renal aplasia. Based on the hyperfiltration hypothesis and clinical studies, glomerular hyperfiltration can be expected, resulting in hypertension, albuminuria, and renal injury, for which long-term follow-up of all patients with renal agenesis is desirable.</p>
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Renal dysplasia refers to abnormal and incomplete development of the kidney, which may be segmental, for instance, in the upper part of a duplex kidney, or affect the entire kidney. Dysplasia is by definition a histological diagnosis, but... more
Renal dysplasia refers to abnormal and incomplete development of the kidney, which may be segmental, for instance, in the upper part of a duplex kidney, or affect the entire kidney. Dysplasia is by definition a histological diagnosis, but in most patients diagnosis is made on the basis of evaluation with ultrasound and renography. This typically shows cysts and/or a small kidney with decreased corticomedullary differentiation and a reduced split renal function. The latter can also be found in other conditions, such as hypoplasia, vascular insults, renal post-infectious damage, or polycystic kidney disease, making it difficult to establish the diagnosis and thereby estimate the incidence of renal dysplasia. The clinical consequences of renal dysplasia depend upon the residual renal function and may range from hypertension to chronic kidney disease.
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In true renal hypoplasia, normal nephrons are formed but with a deficit in total numbers. As nephron number estimation is not possible in vivo, renal size is used as a marker. A widely used definition of renal hypoplasia is kidneys with a... more
In true renal hypoplasia, normal nephrons are formed but with a deficit in total numbers. As nephron number estimation is not possible in vivo, renal size is used as a marker. A widely used definition of renal hypoplasia is kidneys with a normal appearance on ultrasound but with a size less than two standard deviations below the mean for gender, age, and body size. A distinct and severe form of renal hypoplasia is called (congenital) oligomeganephronia, which is characterized by small but normal-shaped kidneys with a marked reduction in nephron numbers (to as low as 10–20% of normal), a distinct enlargement of glomeruli, and a reduced renal function. In many cases, the small kidney also shows signs of dysplasia on ultrasound, leading to the diagnosis of renal hypodysplasia. Based on the hyperfiltration hypothesis and clinical studies, glomerular hyperfiltration can be expected, resulting in hypertension, albuminuria, and renal injury, for which long-term follow-up of all patients with renal hypoplasia is desirable.
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Research Interests: Medicine, Humans, Kidney, Female, Male, and 3 moreClinical Sciences, Breast feeding, and Infant Formula
Research Interests: Medicine, Humans, Kidney, Female, Male, and 15 moreFollow-up studies, Incidence, Risk factors, Diagnostic Imaging, Clinical Sciences, Spectrum, Clinical Imaging, Adult, Internal medicine Doppler ultrasonography, Risk Factors, X ray Computed Tomography, Contrast Media, Age of Onset, Severity of Illness Index, and Congenital Malformations
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Antenatal hydronephrosis is the most common abnormality detected during antenatal ultrasound screening (1 in 100–500 pregnancies). Depending on the degree of dilatation, postnatal evaluation with ultrasound and/or renography is indicated... more
Antenatal hydronephrosis is the most common abnormality detected during antenatal ultrasound screening (1 in 100–500 pregnancies). Depending on the degree of dilatation, postnatal evaluation with ultrasound and/or renography is indicated to detect urinary tract obstruction. Obstruction can be found at various levels of the urinary tract such as the pyeloureteric junction, vesicoureteric junction (resulting in a megaureter), and lower urinary tract (most commonly posterior urethral valves). The decision to surgically correct obstruction can be challenging to make, and additional markers (both radiological as urinary) are needed but are not yet available in daily practice.
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A duplex urinary tract, irrespective of the degree of duplication, is present in 0.8% at autopsy, of which about 20–35% is bilateral. The majority of duplex systems are incomplete, indicating that the ipsilateral ureters fuse before... more
A duplex urinary tract, irrespective of the degree of duplication, is present in 0.8% at autopsy, of which about 20–35% is bilateral. The majority of duplex systems are incomplete, indicating that the ipsilateral ureters fuse before entering the bladder. A complete duplex system shows anomalies of the upper moiety, with associated ureterocele or ectopic ureter, and of the lower moiety, frequently associated with vesicoureteral reflux. Renal ectopia is a rare (1/1000) congenital defect where the kidney is not located in the renal fossa, and is associated with a high rate of hydronephrosis, vesicoureteral reflux, and abnormal contralateral kidney. In a horseshoe kidney (present in 1/400 to 1/1800), fusion of the two kidneys takes place, but the two renal moieties are still located on both sides of the midline. As the lower poles are fused in the midline, a horseshoe kidney is usually located lower than normal and orientation of the renal axis is shifted, which may guide diagnosis during abdominal ultrasound.
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Kidney development includes the formation of nephrons, which ceases around the 36th week of gestation. At that time, around 900,000 nephrons are formed, but with a 10-fold variation (from 200,000 to over 2 million). Many factors have been... more
Kidney development includes the formation of nephrons, which ceases around the 36th week of gestation. At that time, around 900,000 nephrons are formed, but with a 10-fold variation (from 200,000 to over 2 million). Many factors have been described to influence the number of nephrons per individual, such as genetic variations, intrauterine growth and prematurity, maternal diseases and (nutritional) deficiencies, and drugs used during nephrogenesis. Counting nephrons is currently only possible ex vivo, even though magnetic resonance imaging techniques are getting to the stage that in vivo estimations using stereology (the gold standard methodology) can be expected to become available in the next decade. In the meantime, renal size is often used as a marker for nephron endowment.
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Two main sites of urine flow obstruction in the upper urinary tract are located at the pelviureteric and vesicoureteric junctions, both of which result in urinary tract dilatation. With current antenatal ultrasound screening, most... more
Two main sites of urine flow obstruction in the upper urinary tract are located at the pelviureteric and vesicoureteric junctions, both of which result in urinary tract dilatation. With current antenatal ultrasound screening, most patients are identified before birth, and 10–30% of infants with antenatal hydronephrosis are found to have pelviureteric junction obstruction, and 5–10% vesicoureteric junction obstruction/megaureter. In addition, a megaureter can also be based on urine reflux, even in combination with obstruction, or be a non-refluxing non-obstructed megaureter. In case of obstruction, surgery may be indicated, but identifying cases that need to be operated on is challenging and no good marker to assist in this differentiation is available yet.
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<b><i>Background:</i></b> Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation... more
<b><i>Background:</i></b> Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. <b><i>Methods:</i></b> Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. <b><i>Results:</i></b> Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p &lt; 0.001, -10% at necropsy; p &lt; 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. <b><i>Conclusion:</i></b> Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings.
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Nephrotic syndrome (NS) is characterized by massive proteinuria; podocyte loss or altered function is a central event in its pathophysiology. Treatment with glucocorticoids is the mainstay of therapy, however, many patients experience one... more
Nephrotic syndrome (NS) is characterized by massive proteinuria; podocyte loss or altered function is a central event in its pathophysiology. Treatment with glucocorticoids is the mainstay of therapy, however, many patients experience one or multiple relapses and prolonged use may be associated with severe adverse effects. Recently the beneficial effects of glucocorticoids have been attributed to a direct effect on podocytes in addition to the well-known immunosuppressive effects. The molecular effects of glucocorticoid action have been studied using animal and cell models of NS. This review provides a comprehensive overview of different molecular mediators regulated by glucocorticoids, including an overview of the model systems that were used to study them. Glucocorticoids are described to stimulate podocyte recovery by restoring pro-survival signalling of slit diaphragm–related proteins and limiting inflammatory responses. Of special interest is the effect of glucocorticoids on stabilizing the cytoskeleton of podocytes, since these effects are also described for other therapeutic agents used in NS, such as cyclosporin. Current models provide much insight but do not fully recapitulate the human condition since the pathophysiology underlying NS is poorly understood. New and promising models include the glomerulus-on-a-chip and kidney organoids, which have the potential to be further developed into functional NS models in the future.
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Dear Editor, In their recent communication, Marzuillo and Polito state that congenital solitary kidney in childhood is not so bad [1]. They base this statement on a recently published analysis of a cohort of 306 children with a congenital... more
Dear Editor, In their recent communication, Marzuillo and Polito state that congenital solitary kidney in childhood is not so bad [1]. They base this statement on a recently published analysis of a cohort of 306 children with a congenital solitary functioning kidney (SFK) [2]. Marzuillo and colleagues are to be applauded for their systematic follow-up of this large cohort of children. I completely agree with the need for such follow-up, for which I suggested a standard scheme in my recent educational review on SFK [3]. The follow-up in the cohort from Marzuillo et al. showed signs of renal injury in up to 4.1% of subjects with an SFK without additional congenital anomalies of the kidney or urinary tract (CAKUT) and up to 18.7% in individuals with an SFK and CAKUT. This is considerably lower than the 60% of 15-year-old children with an SFK that showed signs of renal injury in our KIMONO cohort [4]. One of the explanations that Marzuillo and Polito provide is the difference in cohorts. Whereas all children in their cohort were diagnosed antenatally or shortly after birth, the congenital SFK was diagnosed later in life in a considerable proportion of the KIMONO cohort. This indeed allows for selection bias, as only cases with clinical problems may have presented to the pediatrician, thereby selecting themore severe cases. However, we did address this issue in our original publication [4], and did not find a difference in renal injury in individuals that were diagnosed antenatally. This group consisted of 127 children with a mean age of 5.2 (SD 4.1) years at the latest follow-up. At that time, a high blood pressure was found in 18.1%, proteinuria in 4.7%, a low glomerular filtration rate in 1.6%, and 10.2% used renoprotective medications. Overall, 22.0% of this group showed at least 1 sign of renal injury. These numbers are still considerably higher than the numbers presented byMarzuillo et al. [2]. Additional CAKUT has been shown to be a risk factor for renal injury in both cohorts. CAKUT was found only slightly more in our group (19.7%) as compared with the cohort of Marzuillo et al. (14.6%). This may play a role in the difference, but is therefore unlikely to explain the majority of the difference in renal injury. A remarkable difference is that in high blood pressure, which was present in 0.6% of the cohort from Marzuillo et al. [2] and 18.1% in the KIMONO cohort [4], to which (at least some of) the patients on antihypertensives (10.2%) should be added. Marzuillo et al. appear to have based this solely on office blood pressure measurements, whereas we have previously shown that a large proportion of SFK individuals can be diagnosed with masked hypertension [5]. It would be of interest to study ambulatory blood pressure measurements in the cohort of Marzuillo et al. [2]. The combination of these 2 cohorts illustrates that we need more clearly defined and unbiased cohorts of individuals with a congenital SFK. Such cohorts may allow for a better evaluation of the risk of renal injury in the group as a whole. More importantly, it may allow us to identify additional risk factors that may be used in clinics to construct a personalized risk assessment. Finally, it may assist to elucidate the reasons and pathways that result in the renal injury in an SFK. Irrespective of the Btrue^ incidence of renal injury in individuals with a congenital SFK, being 4% or 60% in adolescence, these risks are still much too high to consider an SFK to be Bnot so bad^. Therefore, all these patients deserve a systematic follow-up [3], as was done excellently by Marzuillo et al. [2]. * Michiel F. Schreuder michiel.schreuder@radboudumc.nl
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Research Interests: Obesity, Clinical Trial, Folic acid, Medicine, Pregnancy, and 15 moreHumans, Multivitamins, Kidney, Female, Assisted Reproduction, Journal Article, Alcohol Drinking, Male, Birth Defects, Adult, Odds ratio, Cakut, Congenital abnormalities, Congenital Malformations, and Paediatrics and reproductive medicine
Research Interests: Endocrinology, Physiology, Biology, Medicine, Birth Weight, and 15 morePregnancy, Internal Medicine, Kidney, Female, Animals, American, Kidney development, Medical Physiology, Eating, Caloric Restriction, Animal Diseases, Intrauterine Growth Restriction, Litter Size, Food Restriction, and Kidney glomerulus
Research Interests: Pediatrics, Chronic illness, Medicine, Birth Weight, Children, and 15 moreHumans, Child, Low Birth Weight, Female, Male, Meta Analysis, Clinical Sciences, Newborn Infant, Odds ratio, Intrauterine Growth Restriction, Confidence Interval, Cohort Studies, Adverse effect, Fetal Growth Retardation, and normal birth weight
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EnglishDrs. Hotta and Ota1 reported the case of a boy with nephrotic syndrome who presented with alopecia attributable to tinea capitis, for which he was treated with oral itraconazole during 8 weeks. However, the patient also received... more
EnglishDrs. Hotta and Ota1 reported the case of a boy with nephrotic syndrome who presented with alopecia attributable to tinea capitis, for which he was treated with oral itraconazole during 8 weeks. However, the patient also received cyclosporine for his nephrotic syndrome. The article did not comment on an important drug interaction. For both drugs, the cytochrome P450 3A4 (CYP3A4) enzyme is important, as itraconazole is a well-known inhibitor of CYP3A4 and cyclosporine is a substrate.2 Taking both drugs together may result in higher, possibly even (nephro)toxic, concentrations of cyclosporine, with an estimated increase of the area under the concentration-time curve of cyclosporine of about 3- to 4-fold.3 It is essential to perform therapeutic drug monitoring of cyclosporine in a patient who is started on a CYP3A4 inhibitor such as itraconazole. In clinical practice, we lower the dosage of cyclosporine preemptively by 33% before therapeutic drug monitoring is performed in patients who are started on azole antifungals. Once the itraconazole is stopped, an increase in cyclosporine dosage is needed, preferably guided by therapeutic drug monitoring. The clinical awareness of such drug-drug interactions is vital to balance underdosing (with the risk of a relapse of nephrotic syndrome for the patient described) and toxicity. EnglishWe agree with Dr Schreuder and colleagues about the importance of the drug interaction between cyclosporine and itraconazole and the necessity of strict therapeutic drug monitoring of cyclosporine. It is well known that periodic therapeutic drug monitoring is necessary when cyclosporine is administered. The therapeutically effective blood concentration of cyclosporine is narrow, and there are many foods and medicines that influence cyclosporine metabolism, including grapefruit and other citrus fruits, cola beverages, St John’s wort, calcium antagonists, macrolide antibiotics, human immunodeficiency virus protease inhibitors, estrogen and progestogen hormone preparations, and azole antifungals.