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Bone impairment appears to be a novel complication of nephropathic cystinosis despite cysteamine therapy. Its exact underlying pathophysiology is nevertheless unclear. The objective of this study was to evaluate bone status among patients included in the French Crystobs study. In addition to clinical data, bone status was evaluated using biomarkers (ALP, PTH, 25-D, 1-25D, FGF23), DXA (spine and total body), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and radius. Results were compared to age- and gender-matched healthy controls (1:2 basis) from the local reference cohorts. At a median age of 22.5 (10.2–34.6) years, 10 patients with nephropathic cystinosis were included (2 receiving conservative therapies, 2 undergoing hemodialysis, 6 with a past of renal transplantation); 7 out of 10 patients complained of a bone symptom (past of fracture, bone deformations, and/or bone pain). Biochemicals and spine DXA did not show any significant abnormalities. Using HR-pQCT, significant decreases in cortical parameters (e.g., cortical thickness 850 (520–1100) versus 1225 (480–1680) μm; p < 0.05) and total volumetric bone mineral density (290 (233–360) versus 323 (232–406) mg/cm3; p < 0.05) were observed in cystinotic patients in comparison to controls at the tibia. There were no differences for trabecular parameters. Similar results were observed at the radius. In this pilot study, bone impairment (rather cortical than trabecular) is a significant clinical problem in nephropathic cystinosis; 70% of patients displayed significant bone symptoms, during teenage or young adulthood. This new complication should be known by physicians because of its potential dramatic impact on quality of life.

Focal and segmental glomerulosclerosis (FSGS) is an important cause of steroid-resistant nephrotic syndrome in adults and children. It is responsible for 5–20% of all cases of end-stage kidney disease (ESKD) in the United States. The pathogenesis of FSGS has not been fully elucidated; however, data from molecular studies of familial cases in the last two decades suggest that FSGS is a defect of the podocyte. The therapeutic agents available for treatment of FSGS are not very effective and only a small percentage of affected individuals will achieve complete remission. Recent data from molecular biology and molecular genetics has provided insight into the mechanisms of action of old agents and also identification of other novel therapeutic targets. This review focuses on recent advances in the molecular pathogenesis of FSGS and currently available therapeutic agents as well as potential novel therapies.

The prognostic significance of distal renal tubular acidosis (DRTA) in the development of overt nephropathy (ON) in children with posterior urethral valves (PUV) is not clear. This condition was studied prospectively in 22 children with posterior urethral valve (PUV), with normal renal function. Prior to surgery, the children with ON had a higher incidence of bilateral reflux (P=0.006), but the difference was not significant for age at surgery (P=0.31), duration of voiding symptoms prior to surgery (P=0.30), presence of DRTA (P=0.35) and bladder abnormalities (P=0.27), with none of these factors being significant on logistic regression analysis. At the end of the follow-up, after surgery, age at surgery (P≤0.0001), duration of voiding symptoms prior to surgery (P≤0.0003), persistent DRTA (P=0.0001) and persistent bladder dysfunction (P=0.02) after surgery were significantly higher in children with ON. On univariate logistic regression analysis, age at surgery (P=0.009), duration of voiding symptoms prior to surgery (P=0.01), persistent DRTA (P=0.002) and persistent bladder abnormalities (P=0.03) after surgery were significant for ON after surgery, but on stepwise multivariate logistic regression analysis only persistent DRTA (P=0.002) turned out to be significant. We conclude that persistent DRTA after surgery can predict overt nephropathy in children with PUV after surgery.

The average worldwide prevalence of neural tube defects (NTDs) is 1.0 per 1000 births. Its development is multifactorial due to genetic and non-genetic factors. Spina bifida (SB) is one of main representatives of NTD. The spinal cord lesion level is the main determinant of the level of paralysis, numbness, and difficulties with bladder/bowel functions. Myelomeningocele prenatal repair reduces hydrocephalus and hindbrain herniation and improves motor function. The severity of hydrocephalus is associated with poorer neurodevelopmental outcomes whether operated on prenatally or after birth. People with SB tend to have a lower IQ and cognitive difficulties. Early diagnosis, proactivity, and lifelong multidisciplinary follow-up are key protective issues. Invasive urological interventions should be considered in selected patients after failure of conservative treatment. Transition to adult care should be well planned as it is challenging. Health literacy is directly associated with success at transition. Sexuality and fertility should be addressed before/during puberty. Overall, the rates of fecal and urinary continence and skin breakdown increase with age, whereas the ability to ambulate declines with age. Bowel and urinary incontinence are independent predictors of lower health-related quality of life (HRQoL) in adults with SB. Bowel incontinence has negative impact on HRQoL regardless of frequency or amount. Long-term caregiver support should be offered at diagnosis. Survival at a mean of 50 years is poor, at 32%, due to central nervous system deaths, cancer, urological disease, and sepsis. Challenges to implementation of recommended practices exist, especially in low and middle-income countries.

A boy developed recurrent steroid-responsive nephrotic syndrome following renal transplantation for congenital nephrotic syndrome. The first episode was associated with mild tubulointerstitial rejection on kidney biopsy. Subsequent episodes showed normal histology by light microscopy and epithelial foot process fusion on electron microscopy, consistent with minimal change nephrotic syndrome. Serum analysis for soluble immune response suppressor was negative pre-nephrectomy, positive during each bout of nephrotic syndrome, and negative during each remission. This case represent de novo occurrence of steroid-sensitive minimal change nephrotic syndrome following renal transplantation for congenital nephrotic syndrome. We stress the need for histological examination of the renal allograft to diagnose rejection, recurrent disease, or de novo disease.

Semaphorin3a (sema3a), a member of class 3 semaphorins, is a guidance protein that regulates angiogenesis, branching morphogenesis, axon growth, and cell migration, and has pleiotropic roles on organogenesis, immune response, and cancer. Sema3a is secreted by podocytes and is required for normal kidney patterning and glomerular filtration barrier development. We recently discovered that after completion of kidney development, Sema3a gain-of-function in podocytes leads to proteinuric glomerular disease in mice. Excess sema3a causes foot process effacement, glomerular basement lamination, and endothelial damage in vivo, and disrupts cell autonomously podocyte shape by down-regulating nephrin and inhibiting αvβ3 integrin. We identified a novel direct interaction between nephrin and plexinA1, the sema3a signaling receptor. Nephrin–plexinA1 interaction links the slit-diaphragm signaling complex to extracellular sema3a signals. Hence, sema3a functions as an extracellular negative regulator of the structure and function of the glomerular filtration barrier.

Dilatation of the urinary tract does not necessarily imply obstruction, and other factors may be operative: maldevelopment, infection, reflux, and polyuria. Obstruction of the urinary tract in intra-uterine life is associated with renal dysplasia: the original obstructive lesion may be transient but the consequent dysplasia and dilatation may be permanent. Routine antenatal ultrasound identifies a new population of infants with urinary tract dilatation, many of whom remain asymptomatic and would not otherwise have come to medical attention: the natural history and appropriate schedules of investigation and management of this group are still being evaluated. Anatomical imaging by ultrasound establishes the presence and extent of dilatation. Micturating cystourethrography, intravenous urography and antegrade pyelography establish the site but not the functional significance of an obstructive lesion. Isotope renal scaning with99mTc-DTPA may identify an acutely obstructed kidney with a decreased renal uptake, prolonged parenchymal transit time, and delayed clearance of the isotope from the renal pelvis after furosemide. However, such analyses often give equivocal results in infants with poor renal function and markedly dilated urinary tracts. Obstructive uropathy should be seen as a disturbance of the normal pressure-flow relationships in the urinary tract, and be defined and investigated as such. Antegrade perfusion with renal pelvic pressure measurements has technical pitfalls, but is the definitive method of establishing upper tract obstruction. Videocystourethrography is the established method of investigating the lower urinary tract in older children but needs further development to be applicable to infants.

Patients with nephrotic syndrome (NS) are at increased risk for infection. Peritonitis is difficult to diagnose in the absence of peritoneal fluid analysis and empiric therapy carries significant risks. We identified factors present at initial presentation that are associated with an increased risk for the later development of spontaneous bacterial peritonitis in children with NS. A case-control study of patients admitted to Children's Hospital and Regional Medical Center, Seattle from 1989 to 1999 with a diagnosis of NS was conducted; 8 cases of NS and peritonitis (aged 20–113 months) and 24 controls with NS alone (aged 10–193 months) were identified and matched on year of diagnosis of NS. Medical charts were reviewed and laboratory values at the time of initial presentation of NS were recorded. Odds ratios (OR) were estimated, Fischer's exact test was used to obtain P values, and 95% exact confidence intervals (CI) were also calculated. Cases tended to be younger than controls (mean age 50.5 months vs. 65.3 months), and were more likely to be white and male. There was a suggestion of an association between serum albumin level at presentation and the risk of subsequent peritonitis. Those patients with a serum albumin level less than or equal to 1.5 g/dl at initial presentation were estimated to have a 9.8-fold (95% CI 0.93, 472; P=0.06) increase in the odds of developing peritonitis than those with an initial albumin greater than 1.5 g/dl. A platelet count greater than 500 cells/mm3 tended toward a reduced risk (OR=0.12, 95% CI 0.002,1.29; P=0.10) for subsequent peritonitis when compared with patients with a platelet count less than 500 cells/mm3, but was not statistically significant. Hypertension, hematuria, or normal serum complement levels (C3, C4) at the time of initial diagnosis were not associated with an increased risk of subsequent peritonitis. Low serum albumin (≤ 1.5 g/dl) at presentation was associated with an increased risk of peritonitis among children with NS at our institution.

Quantitative histomorphometric assessment of bone biopsies represents a powerful and informative method for the study of metabolic bone diseases. It is the gold standard against which the noninvasive ”diagnostic” markers of bone metabolism as well as newly available therapeutic modalities are tested. With the rapid progress in technology of molecular biology, identification of systemic and local biomolecules known to regulate bone metabolism can now be achieved. The study of localization, levels of expression, and synthesis of these factors in bone and its microenvironment is possible through applications of in situ hybridization histochemistry (ISHH) and immunohistochemistry (IHC). Application of ISHH allows study of specific mRNA expression. IHC determines the presence and distribution of target protein in cells. These two methodologies provide the link between the cellular processes of mRNA transcription and translation to the working protein. Combining the established bone histomorphometric techniques with ISHH and IHC elevates the study of bone to new heights, i.e., cellular and molecular mechanistic issues can now be studied.