Higher urine heat shock protein 70/creatinine ratio in type 1 diabetes mellitus.

Insidious progressive renal damage caused by type 1 diabetes mellitus (T1DM) begins in childhood before it becomes manifest in adult ages. Heat shock proteins (HSPs) regulate the cell response to any hazardous factors to prevent cell structure. The aim of the study is to determine whether urine levels of HSPs increase in diabetic children with time and indicate a progressive renal injury in T1DM. Thirty-three patients with T1DM and 24 healthy children were enrolled in the study. Renal function was normal in all patients. Urine levels of HSP27, HSP40, HSP60, HSP70, and HSP90 were measured by enzyme-linked immunosorbent assay at two consecutive years (2012 and 2013). The results were evaluated as urine HSP/creatinine ratios (uHSP/Cr). Mean urine HSP27/Cr, HSP40/Cr, HSP60/Cr, HSP70/Cr, HSP90/Cr in patient group were significantly higher than in controls in 2012 (uHSP27/Cr 460.12 ± 217.64 versus 270.02 ± 136.83 pg/mgCr; uHSP40/Cr 180.89 ± 118.59 versus 99.44 ± 62.49 pg/mgCr; uHSP60/Cr 114.40 ± 64.91 versus 70.50 ± 43.70 pg/mgCr; uHSP70/Cr 41.17 ± 28.42 versus 16.47 ± 7.32 pg/mgCr; uHSP90/Cr 175.64 ± 102.22 versus 107.61 ± 75.85 pg/mgCr) (p < 0.05). In 2013, uHSP70/Cr level increased significantly (51.08 ± 27.72 pg/mgCr; p = 0.001), whereas uHSP60/Cr level decreased and uHSP27/Cr, uHSP40/Cr, uHSP90/Cr levels remained stable (p > 0.05). Area under the curve (AUC) for uHSP70/Cr (0.957) was significantly higher than the others. Using a cutoff 22.59 pg/mgCr for uHSP70/Cr to predict of diabetic damage, sensitivity and specificity were 85% and 96%, respectively. Our results suggest that uHSP70/Cr increases over time and may indicate early phases of progressive kidney damage in diabetic children.

Clinical importance of renal calyceal microlithiasis in children.

BACKGROUND: Renal calyceal microlithiasis refers to a hyperechogenic spot in renal calyces <3 mm in diameter detected on renal sonography. These spots possibly represent the first step in calculus formation. The aim of this study was to analyze the clinical presentation, predisposing factors, prognosis and clinical importance of these hyperechogenic spots in renal calyces, renal calyceal microlithiasis, during childhood. METHODS: The data of 292 children (135 girls, 157 boys) with microlithiasis diagnosed between January 1998 and December 2010 were evaluated retrospectively. Demographic data, serum biochemistry, urinary metabolic factors, and renal sonography results were obtained from patient files. A total of 228 patients were re-evaluated at least 6 months after the first observation of renal calyceal microlithiasis and at 6-12 month intervals thereafter. RESULTS: Mean age was 16.8 ± 14.9 months, and mean follow-up duration was 14.6 ± 5.9 months. Presenting symptoms were abdominal or flank pain (41.1%), hematuria (35.6%), dysuria (24.7%) and urinary tract infection (34.6%). Previous ultrasounds were normal in 35% of the children. Metabolic and anatomic abnormalities were found in 55.5% and 17.8%, respectively. Hypercalciuria was the most common metabolic abnormality (88.9%). Among 228 patients who had been re-evaluated, microlithiasis disappeared in 37.7%; decreased in number or size in 23.7%; progressed to renal stone formation in 10.6%; increased in number of microlithiasis in 19.0%; and remained unchanged on radiology in 9.0%. CONCLUSION: Renal calyceal microlithiasis represents a spectrum of clinical situations and underlying metabolic abnormalities that need further investigation in children.

Matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in vesicoureteral reflux.

The aim of this study was to investigate whether urine levels of matrix metalloproteinase 9 (uMMP9) and tissue inhibitor of metalloproteinase 1 (uTIMP1) are novel biomarkers of vesicoureteral reflux (VUR) and to determine the optimal cut-off levels of these enzymes to predict VUR in children. The study group consisted of 67 children with VUR and 20 healthy children. Urine MMP9 and TIMP1 levels were measured by an enzyme-linked immunosorbent assay. Children with VUR had significantly higher uMMP9 (1,539.8 vs. 256.4 pg/mL; p = 0.0001) and uTIMP1 (182 vs. 32.6 pg/mL; p = 0.0001) levels than healthy children. For the prediction of VUR, the sensitivity of uMMP9 was 67%, with a specificity of 85% [cut-off value 1,054 pg/mL; area under the curve (AUC) 0.77], and the sensitivity of uTIMP1 was 74%, with a specificity of 65% (cut-off value 18.7 pg/mL; AUC 0.73). Both uMMP9 and uTIMP1 levels were significantly higher in patients with renal scar (uMMP9: 3,117.3 vs. 1,234.15 pg/mL; p = 0.0001; uTIMP1: 551.05 vs. 128.64 pg/mL; p = 0.0001). Urine MMP9 levels had a sensitivity of 81.2%, with a specificity of 85% to predict renal scar in the VUR group (cut-off 1,054 pg/mL; AUC 0.88). The sensitivity of uTIMP1 was 75%, with a specificity of 90% to predict renal scar (cut-off 243.7 pg/mL; AUC 0.82). Based on these results, we suggest that uTIMP1 may be a useful marker to predict renal scarring with a different cut-off value from VUR and a high specificity at this cut-off point. Although uMMP9 seemingly cannot distinguish renal scar from VUR, the simultaneous increase in the level of both markers may indicate ongoing renal injury due to VUR.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with Henoch-Schönlein purpura.

AIM: Associations between several vascular diseases such as Kawasaki disease, venous and arterial thromboembolism, cardiovascular disease, diabetic nephropathy, focal segmental glomerulosclerosis and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have been reported. This is a clinical study designed to investigate the possible effects of MTHFR C677T polymorphism on the development of Henoch-Schönlein purpura (HSP). METHODS: Forty-one patients with HSP (25 male/16 female) with a mean age of 7.8 ± 2.9 years were included in the study. The control group consisted of 50 healthy children. MTHFR genotypes were determined by polymerase chain reaction and by Hindf I restriction enzyme analysis and subsequent 3% agarose gel electrophoresis techniques. RESULTS: No significant differences were observed in the distribution of MTHFR genotypes or allele frequencies in the HSP cases versus controls. Plasma homocysteine levels and vitamin B(12) levels were almost comparable in the HSP patients and control group without a significant difference. Folic acid levels were within normal limits in the HSP cases and the control group, HSP patients' levels being significantly higher than the control group. No significant relationship was present with the MTHFR genotype and plasma homocysteine, vitamin B(12) and folic acid levels in HSP patients. CONCLUSION: No association with MTHFR gene polymorphism and homocysteine plasma levels could be found in patients with HSP. The results of this study indicate that other mechanisms should be operative in the development of HSP.

Is paraoxonase 192 gene polymorphism a risk factor for membranoproliferative glomerulonephritis in children?

We investigated the effects of paraoxonase (PON1) 192 polymorphism on serum PON1 activity and the impact of phenotypic expression on the risk and prognosis of Turkish children with membranoproliferative glomerulonephritis (MPGN). Eighteen children with biopsy-proven Type I MPGN (10 boys, 8 girls) and age-matched 53 healthy controls were included in the study. PCR (polymerase chain reaction), RFLP (restriction fragment length polymorphism) and agarose gel electrophoresis techniques were used to determine the PON1 192 genotype. PON1 activity was measured by spectrophotometric assay of p-nitrophenol production following addition of paraoxon. We found that PON1 192 genotype distribution (AA, AB, BB) in MPGN patients were 61.1%, 22.3%, 16.6% and 15.1%, 35.8%, 49.1% in controls, respectively. The frequency of AA genotypes was significantly higher in the MPGN group (0.611) compared with the healthy controls (0.151) (p < 0.001). Although the serum PON1 activity was lower in MPGN patients (103.3 +/- 55.2 U/l) than the healthy controls (130.9 +/- 71.2 U/mol), the difference was not statistically significant (p = 0.0563). In the genotypes of patients and controls classified according to PON1 A/B polymorphism; serum PON1 activities were significantly increased (p < 0.001, ANOVA) in the order of PON1 AA, AB and BB in both MPGN patients (82.4, 91.7 and 173.6 U/l) and healthy controls (85.9, 119.9 and 193.1 U/l), respectively. There was a significant relationship between the poor prognosis and having AA genotype and low PON1 activity. Of the 8 patients with poor prognosis, 7 had genotype AA and the remaining one was AB heterozygote. Our results suggest that homozygosity for the A allele might have an important role on the risk for developing MPGN and may also be associated with the poor prognosis of disease. In conclusion, we suggest that the PON1 activities are affected by PON1 genetic variability in Turkish patients with MPGN.