Effect of body size and malnutrition on renal size in childhood

SUMMARY: Malnutrition is associated with multi-organ manifestations including urinary concentrating defects. the purpose of our study was to prospectively determine the effect of body size and malnutrition on kidney size in children. the length and width of both kidneys were assessed in 525 children with no renal disease (289 male: 236 female; age: newborn–12 years) by real time ultrasonography. the nutritional status was assessed using the Indian Academy of Pediatrics classification, where the expected weight (EW) for age is the 50th percentile for Harvard statistics. Thus, Grade 0: 80–100% of EW; Grade I: 70–80% of EW; Grade II: 60–70% of EW; Grade III: 50–60% of EW; Grade IV: <50% of EW. There was no difference in renal size between males and females, or between right and left kidneys. the relationship between kidney area and age and grade of malnutrition was as follows: kidney area (mm²) = 13.74 age (months)—110.9 grade + 1265 ( P < 0.001). the partial r for grade and age were—0.318 ( P < 0.001) and 0.849 ( P < 0.001), respectively. Normal Indian children (Grade 0) had smaller kidneys than those obtained in age matched children in the Western world. We conclude that severe malnutrition (Grade IV) reduces kidney size independent of age. Furthermore, we attribute the smaller kidney size in normal (grade 0) children, to the smaller body habitus of Indian children. Age based data alone, which are widely used currently to determine if kidney size is appropriate, may not be sufficient in geographic regions where malnutrition is prevalent and/or the growth curves of the population vary from Western derived standards.     

Reversal of experimental myoglobinuric acute renal failure in rats by quercetin, a bioflavonoid

The occurrence of acute renal failure (ARF) following rhabdomyolysis has been put at between 10 and 40% of cases, and accounts for between 3 and 15% of all cases of ARF. Reactive oxygen intermediates have been demonstrated to play an etiological role in myoglobinuric renal failure. This study was performed to explore the protective effect of quercetin, a bioflavonoid, in an experimental model of myoglobinuric ARF in rats. Four groups of rats were employed in this study: group 1 served as control, group 2 was given 50% glycerol (8 ml/kg, i.m.), group 3 was given glycerol + quercetin (2 mg/kg, i.p.), and group 4 was given glycerol + DMSO (the solvent for quercetin, 5 ml/kg, i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of catalase, glutathione reductase, and superoxide dismutase. Glycerol administration resulted in a marked renal oxidative stress, significantly deranged the renal functions as well as renal cytoarchitecture. All these factors were significantly improved by quercetin treatment. Because of its radical-scavenging and iron-chelating properties, quercetin protected the kidney against the glycerol-induced oxidative stress and resultant renal dysfunction. Based on these results, this study confirms the role of oxidative stress and demonstrates the renoprotective potential of quercetin in this rhabdomyolysis-mimicking model.     

Preeclampsia: a renal perspective

Preeclampsia is a syndrome that affects 5% of all pregnancies, producing substantial maternal and perinatal morbidity and mortality. The aim of this review is to summarize our current understanding of the pathogenesis of preeclampsia with special emphasis on the recent discovery that circulating anti-angiogenic proteins of placental origin may play an important role in the pathogenesis of proteinuria and hypertension of preeclampsia.     

Obesity-related Differential Gene Expression in the Visceral Adipose Tissue

Background:This study investigates the expression patterns in human adipose tissue, and identifies genes that may be involved in the abnormal energy homeostasis. Methods: Subjects were prospectively recruited from morbidly obese patients undergoing bariatric surgery and from non-obese organ donors. Extensive clinical data and visceral fat specimens were obtained from each subject at the time of surgery. A group of 50 obese patients and 9 non-obese controls were selected for further study. Two custom two-color cDNA microarrays were produced with 40,173 human individual cDNA clones. Microarray experiments were performed for each sample, and a selected group of gene expression values were confirmed with real-time RT-PCR. Results: A comparison of gene expression profiles from obese and non-obese patients identified 1,208 genes with statistically significant differential expression between the 2 groups. Most prominent among these genes are multiple glycolysis enzyme encoding genes; others are involved in oxysterol biosynthesis and signaling, or are ATP-binding transporters and solute carriers. Conclusion: Differential gene expression in the adipose tissue of morbidly obese patients includes genes related to lipid and glucose metabolism, membrane transport, and genes promoting the cell cycle. These findings are a first step toward clarifying the molecular pathogenesis of obesity and identifying potential targets for therapeutic intervention.     

Balloon dilatation of pulmonary valve in Tetralogy of Fallot's

In some children of Tetralogy of Fallot's (TOF) presenting with progressive cyanosis, are palliative Blalock-Taussing (BT) shunt may be required. There are no reports of this modality of management in India, though this has been practiced in the other countries. The author reports an infant with Tetralogy of Fallot's who successfully underwent ballon dilatation of the pulmonary valve. Review of literature shows 332 patients with TOF undergoing pulmonary valve balloon dilatation as an alternative to BT shunt in 12 studies with significant increase in pulmonary artery 'Z' score and low incidence of conversion to shunt. This modality of management should be considered in selected patients to change a palliative surgery to an intervention.     

The juxtamembrane wedge negatively regulates CD45 function in B cells

CD45 is a receptor-like protein tyrosine phosphatase highly expressed on all nucleated hematopoietic cells. We previously generated mice containing a point mutation in the juxtamembrane wedge of CD45. Demonstrating the critical negative regulatory function of the wedge, the CD45 E613R mutation led to a lymphoproliferative disorder (LPD) and a lupus-like autoimmune syndrome. Here we show the central role of B cells in this phenotype. Genetic elimination of B cells, but not T cells, ablates the LPD. In contrast to CD45-deficient B cells, the E613R mutation generates hyperresponsive B cells. Comparison of CD45-deficient and CD45 E613R mice reveals dichotomous effects of these mutations on B cell development. Together, the results support a role for CD45 as a rheostat, with both positive and negative regulatory functions, that fine-tunes the signal transduction threshold at multiple checkpoints in B cell development.     

Risk for post-transplant lymphoproliferative disorder after polyclonal antibody induction in kidney transplantation

The adjusted relative risk (aRR) for development of post-transplant lymphoproliferative disorder (PTLD) is higher in kidney transplant recipients receiving monoclonal antibody induction therapy, but the aRR between the different available polyclonal agents has not been investigated in detail. We analyzed data from the United Network of Organ Sharing registry on all kidney transplants performed between 1987 and 2003. The aRR for PTLD development was calculated using SAS 9.0 statistical software and Cox proportional hazards modeling, adjusting for multiple covariates. There were 539 cases of PTLD among 84 907 kidney transplant recipients, who received either polyclonal antibody induction or no induction therapy. In adjusted analysis, the aRR for PTLD development (vs. no induction) was significantly higher with use of equine anti-thymocytic globulin (E-ATG; aRR = 1.61, p = 0.0003) or anti-lymphocytic globulin (ALG; aRR = 1.35, p = 0.0055) but not with rabbit anti-thymocytic globulin (R-ATG; aRR = 1.17, p = 0.29, NS). Median follow up times were significantly shorter in the R-ATG cohort than the ALG or E-ATG cohort (median 368 vs. 1433 and 2055 day). However, in an analysis restricted to pediatric recipients, where median times to PTLD are less than 200 days, only E-ATG was associated with a higher aRR for PTLD (aRR = 2.16, p = 0.0078), while R-ATG and ALG were not. There is a higher aRR for PTLD after kidney transplantation with E-ATG, but not R-ATG. This may only partially be explained by shorter follow up time and may represent differential hazard for PTLD among the agents.     

Isolated idiopathic hypomagnesemia presenting as aphasia and seizures

Isolated hypomagnesemia of the idiopathic form is a rare condition that is known to present as generalized motor seizures in children. This report describes a 4-year-old African-American male who presented with a predominant symptom of sudden onset aphasia and no clear initial motor seizure activity. An evaluation revealed an isolated and severe hypomagnesemia (initial serum magnesium levels <1.0 mg/dL) and inappropriate renal handling of magnesium (fractional excretion of magnesium >40% under conditions of hypomagnesemia). The child had subsequent generalized tonic-clonic seizures that were brought under control with valproic acid therapy and magnesium supplementation. Six months after the diagnosis, he had regained 50-60% of his speech and had no further staring spells or motor seizure activity after the initial episode. Isolated and idiopathic hypomagnesemia caused by defective renal reabsorption of magnesium is a rare familial condition with variable inheritance. Aphasia as the solitary presenting symptom has not been described before. The exact pathophysiology of hypomagnesemic aphasia and seizures is not known but may relate to disinhibition of specific types of glutamate receptors. In the present case, neuronal depolarization may have been localized to language areas in the temporal lobes.