Apolipoprotein E in childhood idiopathic nephrotic syndrome

Idiopathic nephrotic syndrome [INS] is one of the common renal disorders in childhood. Dyslipidemia is not only an important manifestation of INS, but is also involved in cardiovascular diseases and in progressive glomerular damage leading to renal failure. Apolipoprotein E [apo E] has been identified as an important candidate gene for lipid metabolism abnormalities. In the kidney, apo E gene mutation may play a role in aggravating the glomerular basement membrane lesion and promoting proteinuria. Our objective is to investigate the association of apo E serum level and genetic polymorphism [E[2], E[3], and E[4]] with responsiveness to steroid treatment as well as renal pathology in children with INS. Design: Case-control study. One study center at Center of Pediatric Nephrology and Transplantation [CPNT], Cairo University Children's Hospital. Forty seven pediatric patients with INS and 11 age and sex-matched controls were enrolled in the study, Twenty two of the patients had steroid-sensitive nephrotic syndrome [SSNS] and 25 had steroid-resistant nephrotic syndrome [SRNS]. Genomic DNA was extracted from children with INS and controls, and ape E genotype was determined by Real time-PCR analysis. The serum ape E, total cholesterol [TC], albumin, creatinine, and urine protein to creatinine ratio [UP/UCr] were also measured in both groups. Serum ape E was significantly higher in SRNS than SSNS [p=0.01] and controls [p=0.03]. Serum total cholesterol [TC] was significantly higher in SRNS than controls [p=0.028]. Significant positive correlation was found between serum apo E and UP/UCr [r=0.327, p=0.03]. Apo E[4] allele was only found in NS [8.5%] and absent in the control group. Apo E genotype E4E4 was found in one patient only in SRNS group with pathology of Focal segmental glomeruloscierosis [FSGS] while it was absent in SSNS and control groups, but this was not statistically significant. Heterozygous E[3]E[4] was only present in MS groups and not in control group [12% In SRNS and 13.64% in SSNS]. E[2]E[2] genotype was also found only in SRNS [4%] with the pathology of FSGS, which was not significant but the allelic frequency of E[2] was significantly higher in SRNS than SSNS [P=0.036]. E[3]E[3] was the most common genotype in the 3 groups and the allelic E[3] presentation was statistically higher in SSNS than in SRNS [P=0.04] The high frequency of E[4] only in nephrotic children and not in controls suggests that E[4] may share, as a genetic marker, in predisposition to childhood INS. The higher frequency of the E[2] allele in SRNS patients suggests that the E[2] allele gives a possible genetic predilection to steroid resistance in our population while the significantly higher E[3] in SSNS group may convey a readiness to steroid responsiveness related to E3, but further studies are needed to clarify this subject

Relation between maternal plasma concentration of serum endoglin in patients with IUGR and preeclampsia: correlation with doppler study

The aim of the study was to compare between the rise in serum endoglin [sEng] in pregnant women with normotensive IUGR and preeclamptic pregnant women with and without IUGR and to compare between serum placental growth factor [PIGF] and endoglin levels in serum of pregnant patients with IUGR. Prospective analytic comparative study. The study includes group [1] 17 cases with manifest preeclampsia without IUGR, group [2] 11 cases with preeclampsia and IUGR, group [3] 12 normotensive pregnancies with IUGR and 15 gestational age matched control. sEng and PIGF were determined by ELISA, Doppler examination of the umbilitcal vessels in the form of PI and S/D ratio were done. The three groups show significantly higher sEng concentration compared to the control group [32.2 +/- 6.0 ng/ml, 42.3 +/- 10.5 ng/ml, 24.5 +/- 7.1 ng/ml and 12.2 +/- 3.6 ng/ml in the 4 groups respectively, p<0.001]. The three groups showed significantly lower level of PIGF [45.4 +/- 20.4 pg/ml, 23.3 +/- 12.1 pg/ml, 73.1 +/- 54.7 pg/ml and 111.1 +/- 58.4 pg/ml in the 4 groups respectively. P<0.003]. There was no significant difference between sEng in the three groups. Significant difference was found for serum levels of PIGF between normotensive IUGR and the other 2 groups. There was a significant positive correlation between sEng levels and S/D ratio [r= .939 p< 0.001] and PI [r=.695 p<0.001] of the umbilical vessels in group of preeclampsia without IUGR and insignificant correlation between serum levels of PIGF and Doppler study of the umbilical vessels in the same group. sEng increased in all cases with placental pathology even in normotensive IUGR, while PIGF has the reverse relationship, it decreased in placental pathology with negative relationship with severity. The correlation between maternal serum levels of sEng and PIGF and Doppler ultrasound indices of umbilical arteries in pre-eclampsia and IUGR reflect the severity of the disorders

Serum osteocalcin and urinary deoxypyridinoline: response prediction in children on recombinant human growth hormone replacement therapy

In children and adolescents, markers of bone and collagen metabolism reflect the dynamics of skeletal growth and development. Treatment with recombinant human growth hormone [rhGH] has a marked effect on bone formation and resorption. This bone remodeling is well reflected on specific markers that can be measured in blood and urine. The aim of this study was to assess the potential role of bone remodeling markers in the assessment of the response to rhGH in GHD children. The study included 35 children and adolescents, 20 of which had GHD [14 boys and 6 girls], with a mean age of 14.46 +/- 2.47 years and 15 controls [8 boys and 7 girls], 11.3 +/- 2.01 years old, Anthropometric measurements were performed, and blood and morning urine samples were collected for estimation of total serum calcium, inorganic phosphorus, total ALP, OC and urinary DPD. DPD values were corrected to urinary creatinine concentrations and expressed as deoxypyridinoline/creatinine [DPD/cr] ratio. Patients started rhGH therapy, laboratory assays were repeated after 3 months, and anthropometric measurements were repeated at 3-monthly intervals for one full year. Bone turnover markers [calcium, phosphate, ALP, OC, and urinary DPD] were measured before and after 3 months of onset of rhGH. The results showed that in all patients, rhGH evoked continuous improvements in height standard deviation scores [SDS], with no significant effect on weight SDS. Height velocity SDS [HVSDS] was high during the first 3 months of rhGH, decreased thereafter, supporting the waning of rhGH, Pre-treatment Level of the ALP and OC were lower in patients than controls. Differences in serum OC levels between patients and controls were high enough to discriminate between the two groups [p<0.0001]. Both increased substantially after rhGH, Basal and after 3 months value of ALP, OC and DPDlcr ratio was 106.95 +/- 32.76 and 144.75 +/- 38.20 IUIL; 6.80 +/- /- 3.74 and 31.78 +/- 26.12 nglml; 23.69 +/- 22.49 and 37.75 +/- 29.28; with p=0.008, p=0.0001 and p>0.05, respectively. There was a significant positive correlation between the both serum ALP basal and after 3 months and overall 1st year HVSDS [r=0.69, p=0.019, p=0.86, p=0.001, respectively]. There was a significant positive correlation between serum levels of OC and urinary DPDlcr ratio in both, patients before rhGH [r=0.538, p=0.014] and controls [r=0.654, p=0.008]. Basal values of DPD/cr were positively correlated with HVSDS after 3 months [r=0.48, p0.034] and after 3 months of rhGH DPD/cr were positively correlated with height SDS [r=0.46, p=0.04]

Conclusion: bone formation markers, namely ALP and OC and bone resorption markers, namely DPD increase during growth hormone [GH] therapy. At least, one full year of observation is mandatory to detect the impact of rhGH on height measurements, while bone-remodeling markers may be used as early predictors of the long-term response to the expensive rhGH in a child with GHD. OC measurement may be used as an adjuvant assay, together with height measurements and GH stimulation tests, in the initial diagnosis of GHD as it could differentiate between patients and controls