CXCR3 renal expression in glomerulonephritis in children: is there a connection with the course of the disease?

Glomerulonephritis [GN] is a common childhood disease that may represent a significant cause of chronic kidney disease at one point of its course. The role of chemokines in glomerulonephritis, has been long anticipated and studied and the possible link between certain chemokines and different renal pathologies, if proved, can pave the road for future use of such markers for early prognosis and possible therapies for this common disease. Objective: in this study, we aimed at detecting CXCR3 in the renal biopsies done for children with glomerulonephritis and to correlate it to the nature of renal pathology and response to therapy. Methods: The glomerular and interstitial expression of CXCR3 in renal biopsies done for 22 patients with glomerulonephritis was studied using immunohistochemical staining. Pathologies already diagnosed in these biopsies were proliferative GN [mesangioproliferative GN, diffuse proliferative GN, focal proliferative GN, IgA nephropathy and crescentic GN] as well as non-proliferative GN [Minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diffuse mesangial sclerosis and advanced hypertensive nephrosclerosis]. History, clinical findings and laboratory investigations in the initial presentation and at the time of the study were obtained. Results: The degree of glomerular and interstitial CXCR3 expression did not vary with gender, age of presentation, response to steroids, or cumulative doses of steroids. Percentage of strong glomerular CXCR3 expression was much higher in proliferative GN compared to non-proliferative GN although the difference was not statistically significant, percentage of renal dysfunction was more among strong glomerular and mild/moderate interstitial CXCR3 expression with no statistically significant difference from the counterparts. Conclusion: Our study revealed that enhanced CXCR3 renal expression on glomerular and interstitial levels did not affect the response to steroids along the course of the disease and so can probably act as a therapeutic target rather than a prognostic marker

Renal expression of vascular endothelial growth factor in lupus nephritis the pediatric age groupin

Vascular endothelial growth factor [VEGF] plays a crucial role in preservation of renal functions and may also serve as a useful biomarker in monitoring the progression of lupus nephritis [LN]]. We thought to correlate VEGF expression in the kidney with renal histopathology in lupus nephritis to unveil its possible relation to disease activity and severity. We consecutively enrolled 15 patients with lupus nephritis and ten renal biopsy specimens from patients with cystic renal diseases as controls. The study measurements included SLEDAI, SLICC/ ACR damage index and BILAG renal score. Paraffin sections from renal biopsies were subjected to routine haematoxylin and eosin staining and Immunohistochemical staining for VEGF. Results: Among SLE patients, 7 [46.7%] showed mild expression of VEGF, 5 [33.3%] showed moderate while 3 [20%] had strong expression of the marker. On the contrary, the control samples [100%] revealed strong marker expression. All subjects with class IV and V lupus nephritis had mild renal expression of VEGF. Renal expression of VEGF had a significant positive correlation with serum creatinine and complement C3 levels. The 24 hours' excretion of urinary proteins had a significant negative correlation with the renal expression of the marker. On the other hand, the activity indices and therapeutic modalities did not correlate with VEGF expression. Conclusion: This pilot study among pediatric cases of SLE revealed mild to moderate VEGF expression in most cases of proliferative LN. Further longitudinal studies are needed to investigate the consequences of this finding on the prognosis of the disease

Neonatal screening for absolute lymphopenia

Background: Blood counts with manual differentials could diagnose nearly all cases of severe combined immune deficiency [SCID] at birth

Objective: The aim of this study was to outline the prevalence of neonatal lymphopenia among newborns of Obstetrics and Gynecology Hospital, Ain Shams University as an entry to neonatal screening for SCID

Methods: Complete blood counting [CBC] with manual differential was performed in the cord blood of 500 newborns. Absolute lymphopenia was considered if the count was less than 2500 lymphocytes/mm3. Parents of lymphopenic infants were advised not to give them any live attenuated vaccines before doing further investigations. The lymphopenic infants were followed up by another CBC after one month

Results: In the present study, absolute lymphopenia was found in 8 [1.6%] neonates at delivery. Among our series 44.4% were primigravida and 55.6% were multigravida. Also, 84 [16.8%] experienced pre-mature rupture of membrane, 89 [17.8%] reported maternal diseases and maternal drug intake was reported in 73 [14.6%]. Three neonates had congenital anomalies, one only experienced dysmorphic features and 8 [1.6%] had family history of unexplained death but these data could not be linked to the presence of lymphopenia in the studied sample. APGAR scores at 1 and 5 minutes were significantly lower in neonates with lymphopenia [p = 0.001]. A significant positive correlation was elicited between the absolute lymphocyte count [ALC] and maternal age, total leukocyte count, and HCT [p = 0.003, 0.001 and 0.031 respectively]. Also a significant negative correlation was found between ALC and gestational age, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration [p = 0.013, 0.003 and < 0.001 respectively]

Conclusion: Lymphopenia is not an uncommon finding among neonates at screening and is noted to be associated with a lower Apgar score. Serial counting and follow up is needed before considering the diagnosis of SCID

C-Reactive protein as a marker of cardiac abnormalities in children on regular hemodialysis

End stage renal disease [ESRD] is a situation with a cardiovascular risk profile of unique severity; this study was designed to detect the cardiac abnormalities among children with ESRD and to evaluate the relation between inflammation as detected by CRP and these disorders. The present study was carried out on 60 children with ESRD on regular hemodialysis. [30 hypertensive, and 30 normo-tensive] and 30 apparently healthy age and sex matched children studied as a control group. All studied children were subjected to full history taking, thorough clinical examination and anthropometric measurements. Echocardiography, ECG and chest X-ray were also performed. Laboratory investigations included: Hb, S.alb, S.Ca, S.P, alkaline phophatase, lipid profile, kidney functions as well as CRP both by latex agglutination and ELISA for high sensitive detection. The results of the present study demonstrated echocardiographic changes in patients with end stage renal disease in the form of significant increase in inter-ventricular septal diameter [IVSD], posterior wall thickness [PWT], left ventricular mass index [LVMI], velocity of circumferential fiber shortening [vCFS], and isovolumetric relaxation time [IVRT], [P<0.001, P<0.001, P<0.01 and P<0.001 resespectively] as well as significant decrease of e/a ratio [P<0.001] as compared to the controls. Furthermore, there was significant increase of LVMI in hypertensives as compared to normotensives [P<0.001]. CRP measured by latex agglutination was significantly increased in patients as compared to controls [+ve in 17 patients, 13 were hypertensive and 4 were normotensive], it was correlated inversely with body mass index [P<0.05] and directly with LVMI [P<0.05]. The highly sensitive [hs] CRP was also significantly elevated in patients than controls [+ve in 21 patients, 12 were hypertensive and 9 were normotensive, with median of 31.35 micro g/ml and IQR of 33.028] [P<0.001], it was significantly higher in patients with cardiovascular events [P<0.001] and those with lowered e/a ratio[P<0.05] and the level was affected by S. Ca, S.p and CaXP products[P<0.01]. The only mortality during this study demonstrated high levels of conventional and [hs] CRP. LV hypertrophy and diastolic dysfunction are the main CV changes in children with ESRD. There is high prevalence of inflammation related mainly to the BMI and CaXp products but not to the usual lipid risk factors. This inflammation [as detected by conventional and [hs] CRP] can help in prediction of LV structural and functional abnormalities