Milena Brugnara

Therapy for Children with Henoch-Schonlein Purpura Nephritis: A Systematic Review

Although severe kidney involvement in children with Henoch-Shonlein purpura (HSP) is rarer than that in adults, morbidity should not be underevaluated and follow-up is mandatory. Some drugs are introduced as well-defined treatment options, others can be promising therapeutic alternatives. Therapy of HSP nephritis in children can range from simply steroids to combined immunosuppressant treatments. The prophylactic treatment for renal complication of patients with HSP has been sometimes suggested, but with conflicting results and ultimately not clearly proven. The treatment of overt HSP nephritis includes steroids and other immunosuppressant drugs. Methylprednisolone pulse therapy and prednisone per os are tested drugs. These steroids could be used in combination with other immunosuppressant drugs, such as cyclosporin A and cyclophosphamide. Unfortunately, of these two drugs, only cyclophosphamide is demonstrated as effective in a recent randomized controlled trial. However, since there are insufficient data and unstructured study designs, ACE-I, azathioprine, mycophenolate mofetil, and urokinase need to be more tested in childhood HSP nephritis. In addition to drugs, other techniques are used to treat the severe form of nephritis. Of these, in a multicenter study, plasmapheresis demonstrated efficacy in delaying the progression of kidney disease. However, no convincing studies have been made to date concerning either intravenous immunoglobulin, factor XIII administration, antioxidant vitamin E, and fish oil to treat HSP nephritis.

Renal function and volume of infants born with a very low birth‐weight: a preliminary cross‐sectional study

Aim:  The aim of our study was to compare the function and volumes of kidneys of very low birth‐weight (VLBW) and of extremely low birth‐weight (ELBW) infants at pre‐school ages.

Hidden high-grade vesicoureteral reflux is the main risk factor for chronic renal damage in children under the age of two years with first urinary tract infection.

Abstract Objective. The aim of the present prospective trial was to investigate, in a cohort of young children with first urinary tract infection (UTI) and negative prenatal history, the role of imaging in screening babies at risk of renal deterioration. Material and methods. Children who had experienced the first febrile UTI at or under the age of 2 years were enrolled. They had had normal foetal routine ultrasound. All the children underwent renal ultrasound after admission; those with sonographic signs of obstruction were excluded. Voiding cystoureterogram (VCUG) and 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy were performed approximately 1 month and 6 months after the UTI, respectively. Finally, 65 babies (47.7% males, 38.6 ± 1.3 weeks of gestational age) were prospectively followed up. Results. In 15.4% and 29.2% of cases, the renal pelvis was ≤7 and >7 mm in diameter, respectively. Vesicoureteral reflux (VUR) was detected in 55.4% of the children and renal scarring in 18.5%. Stepwise binary logistic regression analysis showed that the severity of VUR correlated significantly with renal scarring, excluding all the other variables from the model. In this cohort of babies, the severity of VUR seriously enhanced the risk of renal damage (odds ratio = 6.658, p = 0.004). Conclusion. Follow-up renal scintigraphy 6 months after a UTI can predict severe VUR in very young children showing renal scarring, detecting only those who are at risk of loss of kidney function and who would require further assessment. After the first episode of UTI, the practice of performing VCUG in babies with normal DMSA scintigraphy is of doubtful value.

Is serum procalcitonin able to predict long-term kidney morbidity from urinary tract infections in children?

Abstract A new diagnostic strategy for children with febrile urinary tract infections could be the routine use of procalcitonin assessment to identify children requiring closer follow-up since being at risk for kidney damage. A total of 11 studies were published between 1998 and 2007. Children with very high procalcitonin levels during urinary tract infections are likely to be at risk of renal damage and vesico-ureteral reflux. Therefore, the prediction of long-term renal damage showed contradictory results. However, high procalcitonin values at diagnosis and positive scintigraphic scans may suggest the need to investigate for vesico-ureteral reflux. Consequently, procalcitonin levels should be included in follow-up protocols for urinary tract infections to aid in decision making concerning scintigraphic scans and voiding cystourethrograms. Clin Chem Lab Med 2008;46:1358–63.

Are children with congenital solitary kidney at risk for lifelong complications? A lack of prediction demands caution

Congenital solitary functioning kidney (CSFK), which develops during embryo or fetal life, means having either one anatomical/functional kidney or two kidneys, one of which does not function. Similar anomalies have been seen in every other organ system and involve a large percentage of newborns. Still, prediction of long-term renal morbidity in congenital functioning solitary kidney is complicated by the great variability of renal and extrarenal phenotypes. Classification of different solitary renal types, whether or not a syndrome, may help to predict the possible evolution of complications; this may be hindered, however, by the gene-environment role during kidney development. Since the risk of renal failure in children with CSFK depends on several variables, it is always advisable to have a precise clinical description at diagnosis. This condition often requires long-term follow-up into adulthood.

Acute non-oliguric kidney failure and cholestatic hepatitis induced by ibuprofen and acetaminophen: a case report

The combined use of acetaminophen with ibuprofen has long been in clinical use because the target of action of each drug is different and they do not interfere with each other. Appropriate dosing and managing of these drugs do not likely lead to organ toxicity. However, both acetaminophen and ibuprofen can induce liver problems and acute kidney failure, respectively, if administered at high doses. We report the case of a female child, in treatment with both acetaminophen and ibuprofen, administered at therapeutic antipyretic doses in condition of volume depletion, who suffered acute kidney and liver failure.

Clinical and radiographic delineation of odontochondrodysplasia

The association of dentinogenesis imperfecta (DI) with a distinct form of chondrodysplasia in a boy was reported by Goldblatt et al. [1991; Am J Med Genet 39:170–172] and has been given the name of Goldblatt syndrome or odontochondrodysplasia (ODCD; OMIM#184260). Since the original description, only four further individuals have been reported (one sib pair and two unrelated cases). We report on an additional six individuals, including a second sib pair (brother and sister), with clinical and radiographic features that cluster and thus confirm the nosologic status of this entity. The main radiographic features are congenital platyspondyly with coronal clefts, severe metaphyseal changes particularly of the hands, wrists, and knees, mesomelic limb shortening, and coxa valga. The main physical signs are short stature, joint laxity, narrow chest, scoliosis, and DI. This combination of clinical and radiographic findings allows clear recognition of this syndrome in early childhood. Of note, the signs that are present in the newborn period are not entirely specific and the differential diagnosis includes spondylometaphyseal dysplasia (SMD) Sedaghatian type or platyspondylic lethal dysplasia (PSLD) Torrance type. The occurrence of two sib pairs in a group of only 11 patients suggests an autosomal recessive inheritance pattern. Overmodification of cartilage‐extracted collagen 2 has been reported in two sibs, but mutation analysis of COL2A1 as well as of COMP, FGFR3, RMRP, and SBDS in one or more patients have given negative results, and the molecular etiology is as yet unknown.

Renal Elasticity Quantification by Acoustic Radiation Force Impulse Applied to the Evaluation of Kidney Diseases: A Review

For centuries, clinicians have used palpation to evaluate abdominal organs. After exploring almost all the different methods of interaction between x-rays, ultrasound, and magnetic fields on tissues, recent interest has focused on the evaluation of their mechanical properties. Acoustic radiation force impulse (ARFI) is a recent, established ultrasound-based diagnostic technique that allows physicians to obtain a measure of the elastic properties of an organ. Shear wave velocity, obtained by the ARFI technique, depends on the elasticity of tissues. To date, there are studies on the ARFI technique applied to normal kidneys, chronic kidney diseases, and kidney transplants. Mechanical properties of the kidney, such as stiffness and deformity, depend on various conditions that alter its histology, in particular the amount of fibrosis in the renal parenchyma; urinary pressure and renal blood perfusion may be other important contributing factors. Unfortunately, the ARFI technique applied to native renal pathologies is still limited, and not all studies are comparable because they used different methods. Therefore, the results reported in recent literature encourage further improvement of this method and the drawing up of standardized guidelines of investigation.

Renal involvement in children with vesicoureteral reflux: Are prenatal detection and surgical approaches preventive?

Objective. Surgical correction of vesicoureteral reflux (VUR) and prolonged administration of antibiotics seem to lead to similar renal outcomes. However, it is not known whether prenatal recognition and the position of VUR modify the outcome in different ways. The purpose of this study was to investigate the effects of prenatal detection and different treatment methods on the outcome of unilateral refluxing renal units. Patients and methods. This retrospective study enrolled 119 children (mean age 2.8±3.5 years) with primary VUR. Kidney growth and renal function were measured with ultrasound and scintigraphy, respectively. To compare the ultrasound readings among patients of different ages the comparative-length index or index was calculated, as a percentage of the ratio of unilateral and the sum of bilateral renal length. Results. In unilateral refluxing renal units there was a reduction in both index and function, whereas not-refluxing was increased. In the follow-up, unilateral refluxing renal units had a worse index, whereas not-refluxing was better. Unexpectedly, surgical therapy of the left-refluxing renal unit led to a reduction in the index, whereas its function always stayed low in diagnosis but stable. The outcome of severely refluxing renal units was similar after both interventions. Prenatal and postnatal diagnosis did not seem to modify the renal result. Conclusions. Surgery showed similar renal outcomes to medical treatment. A kidney growth defect from high-grade VUR was detected in the diagnosis. Therefore, a congenitally damaged kidney does not ameliorate after each treatment. Finally, prenatal detection of VUR does not seem to modify the outcome of the kidney significantly.

Lack of IL7Rα expression in T cells is a hallmark of T-cell immunodeficiency in Schimke immuno-osseous dysplasia (SIOD)

Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive, fatal childhood disorder associated with skeletal dysplasia, renal dysfunction, and T-cell immunodeficiency. This disease is linked to biallelic loss-of-function mutations of the SMARCAL1 gene. Although recurrent infection, due to T-cell deficiency, is a leading cause of morbidity and mortality, the etiology of the T-cell immunodeficiency is unclear. Here, we demonstrate that the T cells of SIOD patients have undetectable levels of protein and mRNA for the IL-7 receptor alpha chain (IL7Rα) and are unresponsive to stimulation with IL-7, indicating a loss of functional receptor. No pathogenic mutations were detected in the exons of IL7R in these patients; however, CpG sites in the IL7R promoter were hypermethylated in SIOD T cells. We propose therefore that the lack of IL7Rα expression, associated with hypermethylation of the IL7R promoter, in T cells and possibly their earlier progenitors, restricts T-cell development in SIOD patients.