Hyperoxaluria and Genitourinary Disorders in Children Ingesting Almond Milk Products.

We describe 3 children presenting with hematuria, dysuria or kidney stones, and hyperoxaluria believed to be related to ingestion of excessive amounts of almond milk products. Our investigation of the oxalate content of several popular plant-based milk substitutes indicates that almond milk products are a particularly rich source of dietary oxalate. All genitourinary and urinary metabolic disturbances resolved after discontinuation of almond milk ingestion. Therefore, pediatricians should be aware of this potential link.

Post-transplant Burkitt lymphoma is a more aggressive and distinct form of post-transplant lymphoproliferative disorder.

BACKGROUND: Although the literature reports a low incidence of Burkitt lymphoma (BL) as a post-transplant lymphoproliferative disorder (PTLD), this entity appears to be different from other monomorphic PTLDs (M-PTLDs), both in its aggressive clinical presentation and its distinct pathologic profile. METHODS: Patients with BL, diagnosed in the post-transplant setting, (patients aged ≤ 18 years) were retrieved from the pathology archives at Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center from 1982 to 2010. Clinical outcomes were obtained along with pathologic review. RESULTS: Twelve patients with pediatric BL in the post-transplant setting (9 boys, 3 girls) were retrieved. The patients displayed a monomorphic population of small to intermediate-sized, noncleaved, lymphoid elements with a "starry-sky" pattern. The immunophenotype for patients available to the study was CD20+ (n = 9/10), CD10+ (n = 8/8), bcl-6+ (n = 11/11), with a near 100% Ki-67/MIB-1 proliferation index (n = 7/7), and negative for TdT (n = 7/7). Most pretransplant Epstein-Barr virus titers were negative (n = 8/10), with post-transplant titers positive in all tested patients (n = 11), and with positive Epstein-Barr-encoded RNA in situ hybridization in most cases (n = 9/11). The median time from transplantation to diagnosis was 52 months (range, 6-107 months). Nine patients were currently alive after immediate antineoplastic chemotherapy, with median disease-free time of 93 months from diagnosis (range, 2-199 months). CONCLUSIONS: BL-PTLD had a higher Epstein-Barr virus incidence compared with sporadic and immunodeficiency-associated BL and represented a distinct monomorphic PTLD. Although some M-PTLDs can be managed less aggressively with decreased immunosuppression alone, immediate lymphoma-specific chemotherapy was associated with a favorable outcome and was strongly recommended.

Sex differences in the development of kidney disease in individuals with type 1 diabetes mellitus: a contemporary analysis.

BACKGROUND: Kidney disease in patients with type 1 diabetes historically has been believed to be more prevalent in men. Because recent data do not reflect this pattern, we evaluated whether a sex difference persists. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We used 18-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study (n = 788; baseline mean age, 27 years; diabetes duration, 19 years). PREDICTOR OR FACTOR: Sex and diagnosis interval (1950-1964 or 1965-1980). OUTCOMES: Cumulative incidences of macroalbuminuria (albumin excretion rate >200 µg/min) and end-stage renal disease (ESRD; kidney failure, dialysis, or transplant) were evaluated at 20, 25, and 30 years of diabetes duration. To address potential survival bias, death certificate information was included in determining ESRD for those who died before baseline (n = 145). Analyses were stratified by diagnosis year (1950-1964 or 1965-1980). OTHER MEASUREMENTS: Kidney disease risk factor information was available. RESULTS: A significant interaction was noted between sex and diagnosis cohort for ESRD incidence by 25 (P = 0.002) and 30 (P < 0.001) years' duration. Thus, within the 1950-1964 cohort (210 men and 180 women), ESRD incidence was higher in men compared with women by 25 (30.6% vs 18.0%, respectively) and 30 (43.4% vs 24.6%, respectively) years' duration of type 1 diabetes. However, in the 1965-1980 cohort (260 men and 283 women), the incidence was higher in women (7.6% vs 13.8% by 25 years [P = 0.04] and 13.7% vs 21.0% by 30 years' duration [P = 0.09] in men vs women, respectively). Results were similar for macroalbuminuria. LIMITATIONS: Study participants were not followed up from the onset of diabetes; thus, risk-factor data from that period are lacking. CONCLUSIONS: Our data suggest that the male excess of type 1 diabetic kidney disease cases observed in the earlier cohort has been eliminated in the younger cohort. The reason for this dramatic change presently is unclear, but should be addressed in subsequent studies.

The association of renal dysfunction and the use of aprotinin in patients undergoing congenital cardiac surgery requiring cardiopulmonary bypass.

BACKGROUND: The use of large-dose aprotinin during cardiopulmonary bypass (CPB) in adult patients has been linked to postoperative renal dysfunction, but its effect on the pediatric population undergoing complex congenital cardiac operations is not well defined. METHODS: We used a retrospective cohort analysis to evaluate children undergoing cardiac surgery requiring CPB between July 2004 and July 2006. Demographic data and surgical risk quantified by the Aristotle surgical complexity level were analyzed as covariates. Renal dysfunction was defined according to the RIFLE criteria, an international consensus classification which defines three grades of increasing severity of acute kidney injury: risk (Class R), injury (Class I), and failure (Class F) based on serum creatinine values. A univariate and multivariate logistic regression analysis and a propensity score were used to analyze the data. The propensity score was developed using pretreatment covariates associated with the administration of aprotinin. A multivariate logistic regression was then used with the propensity score and intraoperative measures as covariates. A P value <0.05 was considered statistically significant. RESULTS: Among 395 patients who underwent cardiac surgery, 55% received aprotinin and 45% did not. Thirty-one percent of the cohort had previous cardiac surgery; 17% were neonates. According to the RIFLE criteria, 80 of the patients (20.3%) had acute kidney injury in the postoperative period; 53 (13.4%) had risk of renal dysfunction with 23 (5.8%) having injury and four patients (0.7%) having failure. Those receiving aprotinin had a higher incidence of previous cardiac surgery (54.1% vs 5%), sepsis (6.9% vs. 0.0%), heart failure (24.8% vs 12.4%), mechanical ventilation (25.2% vs 2.8%), or mechanical circulatory support (6.0% vs. 0.6%). More patients had an Aristotle level of 4 (26.6% vs 2.8%) and were treated with diuretics (63.8% vs 26.6%), angiotensin converting enzyme inhibitors (21.1% vs 7.9%), milrinone (25.7% vs 4.5%), and inotropic support (16.1% vs 2.3%). Although there was a significant difference in the unadjusted risk of renal dysfunction, adjustment with the preoperative propensity score revealed that there was no association between aprotinin and renal dysfunction (OR 1.32; 95% CI 0.55-3.19). The duration of CPB was the only independent variable associated with the development of renal dysfunction (OR 1.0; 95% CI 1.009-1.014). CONCLUSIONS: Patients who receive aprotinin are more likely to present with preoperative risk factors for the development of postoperative renal dysfunction. However, when associated risk factors are properly considered, the use of aprotinin does not seem to be associated with a higher risk of developing renal dysfunction in the immediate postoperative period in children.

The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience.

Declining incidences in Europe of overt nephropathy, proliferative retinopathy, and mortality in type 1 diabetes have recently been reported. However, comparable data for the U.S. and trend data for neuropathy and macrovascular complications are lacking. These issues are addressed using the prospective observational Pittsburgh Epidemiology of Childhood-Onset Diabetes Complications Study. Participants were stratified into five cohorts by diagnosis year: 1950-1959, 1960-1964, 1965-1969, 1970-1974, and 1975-1980. Mortality, renal failure, and coronary artery disease (CAD) status were determined on the complete cohort (n = 906) at 20, 25, and 30 years. Overt nephropathy, proliferative retinopathy, and neuropathy were assessed at 20 and 25 years on the subset of participants with a clinical examination. There was a decreasing trend by diagnosis year for mortality, renal failure, and neuropathy across all time intervals (P < 0.05), with the 1950-1959 cohort having a fivefold higher mortality at 25 years than the 1970s' cohorts. Proliferative retinopathy and overt nephropathy showed nonsignificant declines at 20 years (P < 0.16 and P < 0.13, respectively) and no change at 25 years. CAD event rates, which were lower than the other complications, also showed no trend. Although some type 1 diabetes complications (mortality, renal failure, and neuropathy) are declining, others (CAD, overt nephropathy, and proliferative retinopathy) show less favorable changes by 30 years.

Renal transplantation in children managed with lymphocyte depleting agents and low-dose maintenance tacrolimus monotherapy.

OBJECTIVE: Describe the safety and efficacy of antithymocyte globulin or alemtuzumab preconditioning, steroid avoidance and reduced calcineurin inhibitor (CNI) immunosuppression in 34 children undergoing renal transplantation. METHODS: ATG (n=8) or alemtuzumab (n=26) were infused at the time of transplantation. This was followed by low-dose twice a day tacrolimus monotherapy with consolidation to once daily dosing by 6 months and once every other day dosing by 12 months. Follow-up ranged from 0.5-2.9 years (mean 1.33 years), with a minimum of 6 months. RESULTS: Both ATG and alemtuzumab were well tolerated. Lymphopenia occurred routinely and resolved after 3-6 months. Acute cellular rejection occurred in 9%; it was related to medical nonadherence in two patients and resulted in one graft loss at 1.5 years. Important adverse events included transient neutropenia in 10 children (none with serious infection), and autoimmune hemolytic anemia in two (resolved with a steroid course in both and conversion to sirolimus in one). Estimated glomerular filtration rate (e-GFR) was stable and averaged 88 mL/min/1.73 m2 at latest follow-up. Fifteen preadolescents had a greater increase in height Z-score at 1 year (1.3 vs. 0.5, P=0.001), and a higher e-GFR (94.8+/-21 vs. 76.6+/-20 ml/min/1.73 m2, P<0.05), when compared to case-matched historical controls who were weaned off steroids by 6 months after transplantation and received twice daily tacrolimus monotherapy. CONCLUSION: This simple regimen appears safe, has a low risk for acute cellular rejection or other adverse effects, and is associated with excellent growth and renal function. Such a regimen may also improve compliance and limit CNI nephrotoxicity.

Sequence of progression of albuminuria and decreased GFR in persons with type 1 diabetes: a cohort study.

BACKGROUND: The sensitivity of albuminuria in predicting loss of kidney function has been questioned. We determined the sequence of kidney disease stages (microalbuminuria, macroalbuminuria, low estimated glomerular filtration rate [eGFR], and end-stage renal disease [ESRD]) and characterized those without albuminuria before a low eGFR. STUDY DESIGN: The Pittsburgh Epidemiology of Diabetes Complications Study is a prospective cohort investigation of childhood-onset type 1 diabetes. SETTING & PARTICIPANTS: 480 study participants with eGFR greater than 60 mL/min/1.73 m(2) (mean age, 27 years; diabetes duration, 19 years at study entry) were prospectively followed up for 16 years. OUTCOMES & MEASUREMENTS: Low eGFR was defined as creatinine clearance less than 60 mL/min/1.73 m(2) from timed urine collections; microalbuminuria, as albumin excretion rate between 20 to 200 microg/min (30 to 300 mg/24 h); macroalbuminuria, as albumin excretion rate greater than 200 microg/min (>300 mg/24 h); and ESRD, as dialysis or renal transplantation. RESULTS: The 33 of 480 individuals (7%) who developed ESRD had prior albuminuria. 71 of 480 (15%) individuals developed low eGFR. 66 of 71 (93%) had prior/concurrent albuminuria, and 5 of 71 (7%) did not. Incident low eGFR values in the 5 patients were: (1) 54, (2) 58, (3) 59, (4) 59.7, and (5) 59.8 mL/min/1.73 m(2). 3 of 5 (60%; patients 1, 4, and 5) subsequently developed albuminuria. Final eGFRs in the 5 patients were: (1) 94, (2) 86, (3) 60, (4) 65, and (5) 54 mL/min/1.73 m(2), respectively. LIMITATIONS: GFR and insulin sensitivity were not measured, but estimated. Incident decreased eGFR in patients without preceding/concurrent albuminuria may be caused by misclassification or a temporary eGFR decrease. CONCLUSIONS: Moderately decreased eGFR may occur rarely in patients with type 1 diabetes without preceding albuminuria.

Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study.

OBJECTIVE: To determine the independent risk factors for coronary artery disease (CAD) in type 1 diabetes by type of CAD at first presentation. RESEARCH DESIGN AND METHODS: This is a historical prospective cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980. The mean age and duration of diabetes at baseline were 28 (range 8-47) and 19 years (7-37), respectively, and patients were followed for 10 years. Patients with prevalent CAD were excluded from the study. Electrocardiogram (ECG) ischemia was defined by Minnesota Code (MC) 1.3, 4.1-3, 5.1-3, or 7.1; angina was determined by Pittsburgh Epidemiology of Diabetes Complications (EDC) study physician diagnosis; and hard CAD was determined by angiographic stenosis > or =50%, revascularization procedure, Q waves (MC 1.1-1.2), nonfatal myocardial infarction (MI), or CAD death. RESULTS: A total of 108 incident CAD events occurred during the 10-year follow-up: 17 cases of ECG ischemia, 49 cases of angina, and 42 cases of hard CAD (5 CAD deaths, 25 nonfatal MI or major Q waves, and 12 revascularization or > or =50% stenosis). Blood pressure, lipid levels, inflammatory markers, renal disease, and peripheral vascular disease showed a positive gradient across the groups of no CAD, angina, and hard CAD (P < 0.01, trend analysis, all variables), although estimated glucose disposal rate (eGDR) and physical activity showed inverse associations (P < 0.01, trend analysis, both variables). In addition, depressive symptomatology predicted angina (P = 0.016), whereas HbA(1) showed no association with subsequent CAD. CONCLUSIONS: These data suggest that although the standard CAD risk factors are still operative in type 1 diabetes, greater glycemia does not seem to predict future CAD events. In addition, depressive symptomatology predicts angina and insulin resistance (eGDR) predicts hard CAD end points.

Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome.

Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na(+)) and water retention; this is known as the "underfill hypothesis." Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is "primary" or "pathophysiological," Na(+) and water retention; this is known as the "overfill hypothesis." A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema.

Urinary MicroRNA Profiling Predicts the Development of Microalbuminuria in Patients with Type 1 Diabetes.

Microalbuminuria provides the earliest clinical marker of diabetic nephropathy among patients with Type 1 diabetes, yet it lacks sensitivity and specificity for early histological manifestations of disease. In recent years microRNAs have emerged as potential mediators in the pathogenesis of diabetes complications, suggesting a possible role in the diagnosis of early stage disease. We used quantiative polymerase chain reaction (qPCR) to evaluate the expression profile of 723 unique microRNAs in the normoalbuminuric urine of patients who did not develop nephropathy (n = 10) relative to patients who subsequently developed microalbuminuria (n = 17). Eighteen microRNAs were strongly associated with the subsequent development of microalbuminuria, while 15 microRNAs exhibited gender-related differences in expression. The predicted targets of these microRNAs map to biological pathways known to be involved in the pathogenesis and progression of diabetic renal disease. A microRNA signature (miR-105-3p, miR-1972, miR-28-3p, miR-30b-3p, miR-363-3p, miR-424-5p, miR-486-5p, miR-495, miR-548o-3p and for women miR-192-5p, miR-720) achieved high internal validity (cross-validated misclassification rate of 11.1%) for the future development of microalbuminuria in this dataset. Weighting microRNA measurements by their number of kidney-relevant targets improved the prognostic performance of the miRNA signature (cross-validated misclassification rate of 7.4%). Future studies are needed to corroborate these early observations in larger cohorts.

Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults.

BACKGROUND: BK virus (BKV)-associated nephropathy (BKVAN) has been increasingly recognized as an important cause of renal transplant dysfunction. We report the role of quantitative viral load monitoring in the management of BKVAN. METHODS: We developed a real-time quantitative polymerase chain reaction (PCR) assay for BKV detection in urine and plasma. Four renal allograft recipients, including two children, with BKVAN were treated with low-dose cidofovir and followed prospectively. RESULTS: The PCR assay showed a detection limit of 10 viral copies with an intra-assay coefficient of variation of 19%. All four patients with BKVAN demonstrated intranuclear inclusions on allograft biopsy and a progressive rise in serum creatinine; three patients underwent multiple biopsies before the diagnosis of BKVAN was made. Three of the patients experienced a "viral syndrome" before the onset of renal dysfunction. One child also demonstrated an echogenic renal mass. All of the patients demonstrated strongly positive urinary PCR values (>100,000 copies/microL). BKV DNA was also detected in the plasma of three patients. All the patients were treated with intravenous low-dose cidofovir (0.25-1 mg/kg per dose, every 2-3 weeks, without probenecid). BK viruria resolved within 4 to 12 weeks (after 1-4 doses) of the cidofovir therapy, and all patients remain with stable renal function 6 to 26 months posttherapy. CONCLUSIONS: Quantitative PCR for BKV is a sensitive and reliable method for following the course of the infection in renal transplant patients. In addition, cidofovir therapy may be useful in the treatment of some of these patients, and its role needs to be investigated further.

Antihypertensive and renoprotective efficacy and safety of losartan. A long-term study in children with renal disorders.

BACKGROUND: Hypertension is a major risk factor for progressive renal failure. We assessed the long term efficacy and safety of losartan in lowering blood pressure (BP) and in preserving renal function in hypertensive children with chronic renal disorders. METHODS: Losartan was used in 45 consecutive hypertensive children with chronic renal parenchymal disorders and mean glomerular filtration rate (GFR) 99.4 mL/min/1.73 m(2). Of the children, 21 had hypertension alone (H) and 24 had both hypertension and proteinuria (H+P). Assessment was done at baseline and at preselected time points: visit I, <0.25 years; visit II, >/=0.25 and <0.5 year;visit III, 0.5 to 1.0 year; and visit IV >1 year. Both BP control and GFR were the principal outcome measures, and proteinuria was a secondary outcome measure. RESULTS: The mean age was 12.85 years and follow-up was 2.42 years (visit IV). Compared with baseline the systolic, diastolic, and mean arterial BP (MABP) fell by 9 to 12 mm Hg (all P < .01) in visit I. Diastolic BP and MABP remained significantly lower in all visits (P < .05 to .001), whereas systolic BP was not statistically lower in visit II. In visit IV the proportion of normotensive children increased significantly compared with baseline (P < .03 for systolic BP, P < .0004 for diastolic BP). In the H+P subgroup, optimal reduction in proteinuria ranging from 66% to 71% occurred in visits II to IV (all P < .01). Mean GFR declined at a rate of 9.3 mL/min/1.73 m(2) /year before starting losartan, and 1.4 mL/min/1.73 m(2) /year subsequently (P = NS). On long term follow-up, GFR fell by 15.9 mL/min/1.73 m(2) in the H subgroup and by 5.5 mL/min/1.73 m(2) in the H+P subgroup (P = NS). There was no correlation between BP measures and GFR or between the magnitude of BP lowering and proteinuria. Adverse effects (one serious) led to discontinuation of losartan in five children (11%). CONCLUSIONS: Losartan therapy was associated with prolonged and sustained antihypertensive and renoprotective benefits in children with a variety of chronic renal parenchymal disorders. Such benefit may be more pronounced in children with combined hypertension and proteinuria. The agent was well tolerated in the majority of the children.

Changing impact of modifiable risk factors on the incidence of major outcomes of type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications Study.

OBJECTIVE: The incidence of type 1 diabetes complications appears to be decreasing, but relative contributions of risk factors are unclear. We thus estimated the effect of modifiable risk factors on the incidence of a composite end point, major outcomes of diabetes (MOD). RESEARCH DESIGN AND METHODS: The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study was used to derive two cohorts based on diabetes diagnosis year (1960-1969 and 1970-1980). Baseline exam data in the current analysis for the 1960s group were collected in 1986-1988 and for the 1970s in 1996-1998. Each group was followed for 8 years for MOD incidence (diabetes-related death, myocardial infarction, revascularization procedure/blockage ≥50%, stroke, end-stage renal disease, blindness, and amputation). Assessed risk factors include the following: HbA1c, hypertension, microalbuminuria, BMI, hypercholesterolemia, and smoking. Accelerated failure time models were used to estimate the acceleration factor. RESULTS: MOD incidence decreased in the 1970s cohort (15.8% [95% CI 11.6-21.4]) compared with the 1960s (22.6% [17.0-29.1]) over the 8-year follow-up (P = 0.06). Hypertension and microalbuminuria were associated with significantly accelerated MOD incidence in both cohorts (P < 0.01 for both). High HbA1c (P = 0.0005), hypercholesterolemia (P = 0.01), and current smoking (P = 0.003) significantly accelerated the incidence of MOD in the 1960s but not 1970s cohort. BMI was not associated with MOD in either cohort. CONCLUSIONS: These results suggest that hypertension and microalbuminuria remain important predictors of complications that are not being adequately addressed.

Urinary microRNA profiling in the nephropathy of type 1 diabetes.

BACKGROUND: Patients with Type 1 Diabetes (T1D) are particularly vulnerable to development of Diabetic nephropathy (DN) leading to End Stage Renal Disease. Hence a better understanding of the factors affecting kidney disease progression in T1D is urgently needed. In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression in many different health conditions. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease. METHODS AND FINDINGS: We studied urine microRNA profiles with qPCR in 40 T1D with >20 year follow up 10 who never developed renal disease (N) matched against 10 patients who went on to develop overt nephropathy (DN), 10 patients with intermittent microalbuminuria (IMA) matched against 10 patients with persistent (PMA) microalbuminuria. A Bayesian procedure was used to normalize and convert raw signals to expression ratios. We applied formal statistical techniques to translate fold changes to profiles of microRNA targets which were then used to make inferences about biological pathways in the Gene Ontology and REACTOME structured vocabularies. A total of 27 microRNAs were found to be present at significantly different levels in different stages of untreated nephropathy. These microRNAs mapped to overlapping pathways pertaining to growth factor signaling and renal fibrosis known to be targeted in diabetic kidney disease. CONCLUSIONS: Urinary microRNA profiles differ across the different stages of diabetic nephropathy. Previous work using experimental, clinical chemistry or biopsy samples has demonstrated differential expression of many of these microRNAs in a variety of chronic renal conditions and diabetes. Combining expression ratios of microRNAs with formal inferences about their predicted mRNA targets and associated biological pathways may yield useful markers for early diagnosis and risk stratification of DN in T1D by inferring the alteration of renal molecular processes.

Primary hypertension and special aspects of hypertension in older children and adolescents.

The prevalence of hypertension has increased at an accelerated rate in older children and adolescents. This has raised great concern about premature development of cardiovascular disease, which has major long-term health and financial implications. While obesity and sedentary habits largely explain this phenomenon, there are other social and cultural influences that may unmask genetic susceptibility to hypertension in the pediatric population. While it is essential to exclude numerous causes of secondary hypertension in every child, these disorders are not discussed in this review. Rather, the aim of this review is to familiarize pediatricians with casual and ambulatory blood pressure measurement, epidemiology, pathophysiology, and management of several common conditions that play a role in the development of hypertension in children and adolescents. Besides primary hypertension and obesity-related hypertension, emphasis is given to epidemiology, measurement of blood pressure, including ambulatory blood pressure monitoring, hypertension associated with drug use, teenage pregnancy, and video and computer games. Lastly, because pediatricians are increasingly confronted with special issues concerning the management of the hypertensive athlete, this topic is also addressed.

Haptoglobin genotype and renal function decline in type 1 diabetes.

OBJECTIVE: Haptoglobin (Hp) binds free Hb, inhibiting Hb-induced oxidative damage. As oxidative stress has been associated with microvascular complications, we evaluated the relationship between Hp genotype and microalbuminuria, macroalbuminuria, end-stage renal disease (ESRD), and early renal function decline in type 1 diabetes. RESEARCH DESIGN AND METHODS: Participants from the Epidemiology of Diabetes Complications Study with DNA available were studied for the incidence of microalbuminuria (albumin excretion rate [AER] 20-200 microg/min), macroalbuminuria (AER >200 microg/min), ESRD (renal dialysis or transplantation), and renal function decline (a decline > or =30 ml/min per 1.73 m(2) from baseline estimated [by the Cockcroft-Gault equation] glomerular filtration rate [eGFR] in those with baseline eGFR >60 ml/min per 1.73 m(2)). RESULTS: The proportions with the Hp 2/2, 2/1, and 1/1 genotype were 43.4, 44.4, and 12.1%, respectively. During 18 years of follow-up, the incidence of eGFR decline, microalbuminuria, macroalbuminuria, and ESRD was 42.0, 40.5, 16.7, and 12.2%, respectively. No significant univariate differences were observed by Hp genotype. However, in multivariable Cox models, an approximately twofold increased risk was observed for the Hp 2/2 compared with the Hp 1/1 genotype for eGFR decline (hazard ratio 1.79 [95% CI 1.06-3.00]) and ESRD (2.74 [1.17-6.45]); no significant associations were observed for microalbuminuria or macroalbuminuria. CONCLUSIONS: These data suggest that although Hp genotype is not associated with albuminuria per se, it may be an independent determinant of early renal function decline and progression to ESRD. Understanding these apparent contradictory findings may provide further insight into the pathogenesis of renal disease in type 1 diabetes.

Kidney after nonrenal transplantation-the impact of alemtuzumab induction.

BACKGROUND: Calcineurin inhibitor nephrotoxicity in nonrenal allograft recipients can lead to end-stage renal disease and the need for kidney transplantation. We sought to evaluate the role of alemtuzumab induction in this population. PATIENTS AND METHODS: We evaluated 144 patients undergoing kidney transplantation after nonrenal transplantation between May 18, 1998, and October 8, 2007. Seventy-two patients transplanted between January 15, 2003, and October 8, 2007, received alemtuzumab induction and continued their pretransplant immunosuppression. Seventy-two patients transplanted between May 18, 1998, and July 21, 2007, did not receive alemtuzumab induction, but received additional steroids and maintenance immunosuppression. Donor and recipient demographics were comparable. RESULTS: Overall, 1- and 3-year patient survival and renal function were comparable between the two groups. One- and 3-year graft survival was 93.0% and 75.3% in the alemtuzumab group and 83.3% and 68.7% in the no alemtuzumab group, respectively (P=0.051). The incidence of acute rejection was lower in the alemtuzumab group, 15.3%, than in the no alemtuzumab group, 41.7% (P=0.0001). The incidence of delayed graft function was lower in the alemtuzumab group, 9.7%, than in the no alemtuzumab group, 25.0% (P=0.003). The incidence of viral complications was comparable. CONCLUSION: Alemtuzumab induction with simple resumption of baseline immunosuppression in patients undergoing kidney transplantation after nonrenal transplantation represents a reasonable immunosuppressive strategy.

Pediatric living donor kidney transplantation under alemtuzumab pretreatment and tacrolimus monotherapy: 4-year experience.

BACKGROUND: Alemtuzumab has been used in off-label studies of solid organ transplantation. METHODS: We analyzed the first 42 pediatric consecutive living donor kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning. We focused especially on the causes of recipient death and graft loss and the characteristics of rejection. RESULTS: Laparoscopic live-donor nephrectomy was associated with no mortality and no delayed graft function. The actuarial 1, 2, 3, and 4 years patient and graft survivals were 97.6% and 97.6%, 93.5% and 85.4%, 93.5% and 85.4%, and 93.5% and 85.4%, respectively. The incidence of cumulative acute cellular rejection (ACR) at 1, 2, 3, and 4 years was 0%, 2.4%, 4.8%, and 4.8%, respectively. The mean serum creatinine (mg/dL) and glomerular filtration rate (mL/min/1.73 m) at 1, 2, and 3 years were 0.8+/-0.4 and 94.0+/-36.8, 0.9+/-0.4 and 79.6+/-31.9, and 0.9+/-0.4 and 95.0+/-21.7, respectively. Two (4.7%) recipients had ACR, and both Banff 1a ACRs were steroid sensitive. No patients had antibody-mediated rejection. Weaning to spaced dose (qod or less) tacrolimus monotherapy was attempted in 16 (38%) and was successful in 12 (26%) patients. All patients are currently steroid free. There was no tissue invasive cytomegalovirus disease or infection, no BK/polyoma viral nephropathy, and no posttransplant proliferative disease. CONCLUSION: This experience confirms the 4-year safety and efficacy of this approach in pediatric recipients.