Levels of cystatin C in low- and high-flux hemodialysis in children with end-stage renal disease.

BACKGROUND: Cystatin-C (CyC) is a middle molecule that is freely filtered at the glomerulus and almost completely reabsorbed by the proximal tubules. The aim of this study was to evaluate serum CyC and its reduction ratio as a biomarker for assessing the adequacy of the hemodialysis (HD) sessions in children with end-stage renal disease on maintenance HD. We also compared levels of CyC in patients on low-flux HD (LFH) and high-flux HD (HFH). METHODS: Forty patients were included in the study and divided into two groups, with one group (16 patients) receiving HFH and the other group receiving LFH (24 patients) (high-flux and low-flux polysulfone filters, respectively). Before and after each dialysis session serum CyC and beta-2-microglobulin (B2M) levels were measured using an ELISA technique, and routine laboratory tests were performed for each patient. RESULTS: Pre-dialytic levels of CyC were significantly lower in the patients receiving HFH than in those receiving LFH (7.33 ± 1.35 vs. 9.73 ± 0.93, respectively; p < 0.0001). In the HFH group, post-dialytic levels of serum CyC were significantly lower than pre-dialytic levels (4.49 ± 0.71 vs. 7.33 ± 1.35, respectively; p < 0.0001). The reduction ratio (RR) of CyC was significantly higher in the HFH group than in the LFH group (38.2 ± 3.91 vs. -6.49 ± 5.05, respectively; p < 0.0001). Serum CyC level significantly correlated with B2M, urea and creatinine levels in both the LFH and HFH groups, whereas its RR significantly correlated with the RRs of urea, creatinine, and B2M in the HFH group. CONCLUSION: The results of our study emphasize the role of CyC as a good marker for assessing the adequacy of HD sessions in children on HFH and show that the CyC RR may be used as an index of middle-molecule toxin clearance following HFH sessions.

Novel adipokines vaspin and irisin as risk biomarkers for cardiovascular diseases in type 2 diabetes mellitus.

AIMS: Vaspin and irisin are novel cytokines proposed as potential new biomarkers of insulin resistance and endothelial dysfunction. This work is to investigate circulating levels of vaspin and irisin in patients with type 2 diabetes mellitus (T2DM) with and without cardiovascular disease (CVD) to study potential association with disease risk. MATERIALS AND METHODS: Circulating levels of vaspin and irisin were assayed in serum from 135 T2DM patients (with and without CVD) and 70 control subjects by ELISA. RESULTS: Vaspin levels were significantly higher in T2DM patients than in control subjects (6798 ±â€¯3540 pg/ml vs. 3215 ±â€¯3209 pg/ml, p = 0.001) and in CVD patients than in non-CVD patients (7417.3 ±â€¯3507.6 pg/ml vs. 6017.3 ±â€¯3606.4 pg/ml, p = 0.001), with significant positive correlations with BMI, FPG, serum insulin and HOMA-IR. Irisin levels were significantly lower in T2DM patients than in controls (71.15 ±â€¯67.57 ng/ml vs.127 ±â€¯71.57 ng/ml, p = 0.004), and in CVD patients than in non-CVD patients (55.77 ±â€¯54.82 ng/ml vs. 115.5 ±â€¯67 ng/ml, p = 0.003), with significant correlations with HbA1c, HOMA-IR and BMI in diabetic patients, and with HbA1c and TG in CVD patients. Elevated levels of vaspin was associated with 1.7 times increased CVD risk (p = 0.001, OR = 1.7, 95%CI = 1.21-2.39), while lower levels of irisin associated with 1.6 times increased CVD risk (p = 0.007, OR = 1.6, 95%CI = 1.45-2.28). ROC analysis indicated serum vaspin and irisin as independent CVD risk biomarkers with sensitivity, 94% and 73.7%, and specificity, 74% and 74.1%; respectively. CONCLUSION: Our results indicate that circulating vaspin and irisin are potential new independent CVD risk biomarkers in T2DM.

Utilizing the KCNJ11 Gene Mutations in Spotting Egyptian Patients With Permanent Neonatal Diabetes Who Can Benefit From Treatment Shift.

BACKGROUND: Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes mellitus. Until now, patients in developing countries who had this condition had been misdiagnosed as having type 1 diabetes mellitus and accordingly directed to erroneous, ineffective, and costly therapeutic regimens. OBJECTIVE: To detect Egyptian patients who harbor pathological variant in the KCNJ11 gene, so that their treatment regimen can be modified as needed to increase its effectiveness. METHODS: We sequenced KCNJ11 in 17 ethnic Egyptian probands diagnosed with diabetes mellitus before age 2 years. RESULTS: A preliminary case individual harboring a KCNJ11 pathological variant (p.R201H) was identified. The patient was successfully shifted from insulin therapy to sulfonylurea. Four previously identified benign variants, namely, E23K, I337V, L270V, and A190A, were detected in this patient. CONCLUSION: Implementing the findings of this molecular analysis could have a major clinical and nationwide economic impact on world health, especially in developing countries.

Relationship between Biochemical Bone Markers and Bone Mineral Density in Patients with Phenylketonuria under Restricted Diet.

OBJECTIVE: Most of phenylketonuria (PKU) develops bone turnover impairment and low bone mineral density (BMD). Measurements of BMD reflect only bone mineral status but not the dynamics of bone turnover. Bone markers are a noninvasive tool useful for the assessment of bone formation and bone resorption processes. Our study was to assess the levels of bone markers in PKU in order to select a screen marker and detect the most specific marker which can be combined with BMD for appropriate follow up. METHODS: Thirty three classic PKU patients were studied. BMD and bone mineral content (BMC) were measured. Total alkaline phosphatase (ALP), osteocalcin (OC) and carboxy-terminal propeptide of type I collagen (CICP), osteoprotegerin (OPG), receptor activator of nuclear factor κß ligand (RANKL) and Deoxypyridinoline (DPD) were measured. Findings : Nineteen (57.6%) male and fourteen (42.4 %) female PKU patients were involved in the current study. Their mean age was 8.4±4.6 yrs and the age range 3-19 yrs. The control group consisted of twenty two (52.4%) males and twenty (47.6%) females. Their mean age was 8.5±3.3 yrs and th age range 2-17 yrs. Using the Z score values, there was a significant decrease of total BMC (TBMC-Z), BMD of the femoral neck BMD-FN-Z, BMD of lumbar vertebrae (BMD-L-Z), BMD-FN and DPD while RANKL increased. There was a negative correlation between CICP and TBMC and between CICP and BMD-L in these patients. Also, a negative correlation between ALP and TBMC and between ALP and BMD-L was observed. It was concluded that the ALP provides a good impression of the new bone formation in the PKU patients and it has a highly significant negative correlation with the many parameters of the bone mineral status beside the wide availability of inexpensive and simple methods. So a screening test and/or follow up for the PKU patients using ALP would be available. Once the level of ALP decrease is detected, one can combine it with BMD to explore the bone mineral status and with specific bone markers (OC, RANKL and DBD), to verify the dynamics of bone turnover. CONCLUSION: This schedule will reduce the risk of exposure of these patients to the risk hazards of DXA and limit its use only to a limited number of the highly suspected cases.