role of Ischemia reperfusion damage on renal transplant, what are the new treatments?

Ischemia reperfusion damage usually occurs after renal transplantation. These injuries can stimulate the innate immune system, trigger an inflammatory response and ultimately activate the adaptive immune system. These events may result in rejection, graft fibrosis and chronicallograft nephropathy. Different mechanisms contribute to innate immune system activation following ischemia reperfusion injury in renal transplants. Some of these mechanisms are known and described by investigators while the remaining are still unknown. To clarify the precise mechanisms underlying the innate immune system activation and rejection progression helps us to plan therapeutic protocols to reduce immunologic responses to ischemic events and to improve the graft function and outcome. In this review, we will discuss how innate and adaptive immune systems are activated during an ischemic insult and thereafter discuss related therapeutic interventions to block the activating pathways

Correlation between Lower Urinary Tract Scoring System, Behavior Check List, and Bladder Sonography in Children with Lower Urinary Tract Symptoms

PURPOSE: The Pediatric Lower Urinary Tract Scoring System (PLUTSS) is a standardized questionnaire used for screening and evaluation of the response of children with lower urinary tract symptoms (LUTS) to therapy. We presumed that adding the Child Behavior Check List (CBCL) and bladder volume wall index (BVWI) to the PLUTSS would increase its validity in the detection of children with LUTS. MATERIALS AND METHODS: One hundred twenty-two children aged 5 to 15 years with LUTS were enrolled in the study. Seventy-two healthy, age-matched children without urinary complaints were considered as controls. The PLUTSS and CBCL were filled out for all children. Sonography was performed to measure BVWI. Chi-square test and likelihood ratio were used to compare frequencies, receiver operating curve (ROC) analysis was used to evaluate the correlation, and Cohen's kappa was used to measure the agreement between variables. p-values 0.05). ROC analysis showed that there was no correlation between PLUTSS, CBCL, and BVWI in either the LUTS subgroup or in the controls (p>0.05). The PLUTSS had the highest sensitivity and specificity, and adding the two other tests decreased its validity for the diagnosis of children with LUTS. CONCLUSIONS: The PLUTSS by itself was the best predictor of LUTS. The CBCL and BVWI were not helpful in making a diagnosis; however, the CBCL was useful in the detection of behavior problems in children with non-monosymptomatic enuresis.

Helicobacter pylori infection in pediatric candidates for kidney transplantation

Chronic kidney failure was suggested to have a protective effect against Helicobacter pylori infection in adults. However, data about this effect in children is lacking. This study was designed to ascertain the prevalence, endoscopic findings, and histopathological features accompanying the Helicobacter pylori infection in children with end-stage renal disease. Data were collected from 117 children with end-stage renal disease aged 5 to 18 years that underwent routine upper gastrointestinal endoscopy before kidney transplantation between 1998 and 2009. The specimens that were taken from the antrum were stained with hematoxylin-eosin and Giemsa to detect Helicobacter pylori. Gastrointestinal symptoms were reported in 12% of the patients. Helicobacter pylori was detected in 24% of the children. The prevalence of Helicobacter pylori infection was high in children with abnormal endoscopic findings [P = .02]. There was no correlation between Helicobacter pylori infection and gender, dialysis status, duration of dialysis, underlying diseases, and gastrointestinal symptoms. Helicobacter pylori infection had a significant correlation with histopathological features [P = .005], age older than 10 years [P = .003], and upper gastrointestinal endoscopic findings [P = .001]. In this study, Helicobacter pylori infection had a high prevalence in children with end-stage renal disease, especially in older ones. The majority of children with Helicobacter pylori infection were asymptomatic, while they had abnormal findings on upper gastrointestinal endoscopy and chronic active gastritis features in histopathological assessment

Single dose of rasburicase for treatment of hyperuricemia in acute kidney injury: a report of 3 cases

Severe hyperuricemia accompanied by the other comorbidities such as anuria, fluid overload, calcium-phosphate imbalance, and/or tumor lysis syndrome is one of the indications for dialysis in the setting of acute kidney injury. Rasburicase is used in different clinical conditions such as tumor lysis syndrome and uric acid nephropathy. Among referred patients to our center from 2008 to 2010, there were 3 patients who had an indication for dialysis because of hyperuricemia. Contributing factors to the acute kidney injury were multi-organ dysfunction, rapidly progressive glomerulonephritis, and spontaneous tumor lysis syndrome. None of the patients showed any response to treatment with bicarbonate and hydration. After rasburicase administration, serum uric acid level declined, and urine output increased. Treatment with a single low dose of rasburicase would be effective to decrease the serum uric acid level and reverse kidney injury secondary to uric acid nephropathy

value of serum uric acid as a mortality prediction in critically ill children

The role of initial serum uric acid on admission in critically ill patients is controversial; we presumed that uric acid level can predict the mortality of the admitted patients to intensive care unit as a simple test. Totally 220 consecutively admitted children [96 girls, 124 boys] with mean age 3.5 years, who were at least 24 hours in pediatric intensive care unit [PICU], were enrolled in a prospective cohort study during January 2006 to December 2007. The subsequent PICU admission in the same hospitalization, those who were discharged from the hospital and then re-admitted to the PICU during the observation period, and the patients with chronic renal failure were excluded. Serum uric acid level was measured during the first day of PICU admission. Death or transfer from PICU was considered as final outcome. The statistical analysis was done by suing linear regression analysis, ROC curve, student t-test, and Chi-square. P value less than 0.05 was considered significant. From 44 patients who had serum uric acid level more than 8 mg/dl, 17 cases died showing with a higher relative risk of 1.88, higher mortality [P<0.05]. The relative risk of death in patients who had serum uric acid > 8mg/dl and needed vasopressor was 1.04, and in those under mechanical ventilation 1.33. In patients who scored pediatric risk of mortality of > 38 it was 1.4, and in septic cases 4 [P<0.05]. Stepwise linear regression analysis showed that mainly the need for mechanical ventilation [P=0.001] and vasopressor had statistically significant correlation with the poor outcome [P=0.001]. Uric acid level during the first day of intensive critical care admission is not an independent risk of mortality in PICU. Need for mechanical ventilation or inotropic agents was associated with poor outcome and only higher uric acid level in sepsis played an additive risk factor role

NPHS2 mutations in children with steroid-resistant nephrotic syndrome

Congenital nephrotic syndrome may be caused by mutations in NPHS1 and NPHS2, which encode nephrin and podocin, respectively. Since the identification of the NPHS2 gene, various investigators have demonstrated that its mutation is an important cause of steroid-resistant nephrotic syndrome. We aimed to evaluate frequency and spectrum of podocin mutations in the Iranian children with steroid-resistant nephritic syndrome. We examined 20 children with steroid-resistant nephritic syndrome referred to Ali Asghar Children's Hospital, in Tehran, Iran. Mutations in the 5th and 7th exons of NPHS2 were assessed. The mutational analysis of NPHS2 was performed by DNA sequencing. The mean age at the onset of proteinuria was 6.4 +/- 3.6 years. None of the children had mutations in the exons 5 or 7. Our study suggests that NPHS2 mutations in exons 5 and 7 are not seen in our children. Therefore, we cannot recommend NPHS2 [exons 5 and 7] mutation for screening in Iranian children with steroid-resistant nephritic syndrome. Other exons of podocin or other podocyte proteins in Iranian children may play a role in pathogenesis of steroid-resistant nephritic syndrome

Management and outcome of steroid-resistant nephrotic syndrome in children

Steroid-resistant nephrotic syndrome [SRNS] is uncommon in children, but often leads to ESRD. We report our experience with SRNS and its treatments and outcomes. We assessed 73 children with SRNS admitted to Ali Asghar Children Hospital in Tehran, Iran. Their clinical presentations, treatment, and disease courses were reviewed. The mean follow-up duration was 6.0 +/- 4.2 years. Moreover, survival times were calculated and the Cox regression method was used to determine variables able to predict survival of the kidneys. Age at the onset of the disease, sex, and hematuria were not predictive of the response to treatment with immunosuppressive drugs in the children with SRNS. The type of resistance [early or late] was associated with the responsiveness to immunosuppressives. Response to any of the immunosuppressive drugs determined the responsiveness to other immunosuppressive drugs. Cyclosporine was more effective than cyclophosphamide as initial therapy. The mean kidney survival time was 11.62 years. Kidney survival rates were 94.6%, 70.0%, 56.0%, and 34.0% at 1, 5, 10, and 15 years, respectively, in patients with initial resistance to steroid, while these were 100%, 100%, 83.0%, and 83.0% in those with late resistance, respectively [P = .03]. We showed that patients with late steroid resistance had better response to immunosuprressive drugs than patients with early resistance. We also showed that resistance to immunosuppressive therapies increased the risk of resistance to other immunosuppressive drugs. Achievement of complete or partial remission with any therapy reduced the risk of ESRD