Can the new CKD-EPI BTP-B2M formula be applied in children?

Although measuring creatinine to determine kidney function is currently the clinical standard, new markers such as beta-trace protein (BTP) and beta-2-microglobulin (B2M) are being investigated in an effort to measure glomerular filtration rate more accurately. In their recent publication, Inker et al. (Am J Kidney Dis 2015; 67:40-48) explored the use of these two relatively new markers in combination with some commonly available clinical characteristics in a large cohort of adults with chronic kidney disease. Their research led them to develop three formulae using BTP, B2M, and a combination of the two. The combined formula is particularly attractive as it removes all gender bias, which applies to both serum creatinine and cystatin C. Using data from a cohort of 127 pediatric patients from our center, we sought to determine whether these formulae would be equally as effective in children as in adults. Unfortunately, we found that the formulae cannot be applied to the pediatric population.

Renin Angiotensin System Blocker Fetopathy: A Midwest Pediatric Nephrology Consortium Report.

OBJECTIVES: Fetuses continue to be exposed to renin angiotensin system (RAS) blockers despite their known teratogenicity and a black box warning. We hypothesized that fetopathy from in utero exposure to RAS blockers has a broader spectrum of clinical manifestations than described previously and that there are a variety of clinical scenarios leading to such exposures. STUDY DESIGN: This was a retrospective study performed through the Midwest Pediatric Nephrology Consortium. Cases of RAS blocker fetopathy were identified, with determination of renal and extrarenal manifestations, timing of exposure, and the explanation for the fetal exposure. RESULTS: Twenty-four cases were identified. RAS blocker exposure after the first trimester was associated with more severe renal manifestations. Chronic dialysis or kidney transplantation was required in 8 of 17 (47%) patients with RAS blocker exposure after the first trimester and 0 of 7 patients with exposure restricted to the first trimester (P = .05). Extrarenal manifestations, some not previously noted in the literature, included central nervous system anomalies (cystic encephalomalacia, cortical blindness, sensorineural hearing loss, arachnoid cysts) and pulmonary complications (pneumothorax, pneumomediastinum). RAS blocker exposure usually was secondary to absent or poor prenatal care or undiagnosed pregnancy. CONCLUSION: RAS blocker fetopathy continues to be a cause of considerable morbidity, with more severe renal manifestations associated with exposure after the first trimester. A variety of significant extrarenal manifestations occur in these patients. Clinicians should emphasize the risk of fetopathy when prescribing RAS blockers to women of childbearing age.

Patient-Reported Outcome Instruments for Physical Symptoms Among Patients Receiving Maintenance Dialysis: A Systematic Review.

BACKGROUND: Patients with end-stage renal disease (ESRD) receiving dialysis have poor health-related quality of life. Physical symptoms are highly prevalent among dialysis-dependent patients and play important roles in health-related quality of life. A range of symptom assessment tools have been used in dialysis-dependent patients, but there has been no previous systematic assessment of the existing symptom measures' content, validity, and reliability. STUDY DESIGN: Systematic review of the literature. SETTINGS & POPULATION: Patients with ESRD on maintenance dialysis therapy. SELECTION CRITERIA FOR STUDIES: Instruments with 3 or more physical symptoms previously used in dialysis-dependent patients and evidence of validity or reliability testing. INTERVENTION: Patient-reported physical symptom assessment instrument. OUTCOMES: Instrument symptom-related content, validity, and reliability. RESULTS: From 3,148 screened abstracts, 89 full-text articles were eligible for review. After article exclusion and further article identification by reference reviews, 58 articles on 23 symptom assessment instruments with documented reliability or validity testing were identified. Of the assessment instruments, 43.5% were generic and 56.5% were ESRD specific. Symptoms most frequently assessed were fatigue, shortness of breath, insomnia, nausea and vomiting, and appetite. Instruments varied widely in respondent time burden, recall period, and symptom attributes. Few instruments considered recall periods less than 2 weeks and few assessed a range of symptom attributes. Psychometric testing was completed for congruent validity (70%), known-group validity (25%), responsiveness (30%), internal consistency (78%), and test-retest reliability (65%). Content validity was assessed in dialysis populations in 57% of the 23 instruments. LIMITATIONS: Consideration of physical symptoms only and exclusion of single symptom-focused instruments. CONCLUSIONS: The number of available instruments focused exclusively on physical symptoms in dialysis patients is limited. Few symptom-containing instruments have short recall periods, assess diverse symptom attributes, and have undergone comprehensive psychometric testing. Improved symptom-focused assessment tools are needed to improve symptom evaluation and symptom responsiveness to intervention among dialysis-dependent patients.

TNXB mutations can cause vesicoureteral reflux.

Primary vesicoureteral reflux (VUR) is the most common congenital anomaly of the kidney and the urinary tract, and it is a major risk factor for pyelonephritic scarring and CKD in children. Although twin studies support the heritability of VUR, specific genetic causes remain elusive. We performed a sequential genome-wide linkage study and whole-exome sequencing in a family with hereditary VUR. We obtained a significant multipoint parametric logarithm of odds score of 3.3 on chromosome 6p, and whole-exome sequencing identified a deleterious heterozygous mutation (T3257I) in the gene encoding tenascin XB (TNXB in 6p21.3). This mutation segregated with disease in the affected family as well as with a pathogenic G1331R change in another family. Fibroblast cell lines carrying the T3257I mutation exhibited a reduction in both cell motility and phosphorylated focal adhesion kinase expression, suggesting a defect in the focal adhesions that link the cell cytoplasm to the extracellular matrix. Immunohistochemical studies revealed that the human uroepithelial lining of the ureterovesical junction expresses TNXB, suggesting that TNXB may be important for generating tensile forces that close the ureterovesical junction during voiding. Taken together, these results suggest that mutations in TNXB can cause hereditary VUR.

Early Use of Tacrolimus Extended-Release in a Pediatric Kidney Transplant Recipient.

Tacrolimus extended-release pharmacokinetics and its once-daily formulation provide beneficial properties, and its use has been evaluated in the adult kidney transplant population. Here, we report a case of successful conversion from tacrolimus immediate-release capsules to tacrolimus extended-release tablets in a pediatric kidney transplant recipient.

Trajectories in estimated glomerular filtration rate in youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study.

AIMS: We sought to characterize the direction and associated factors of eGFR change following diagnosis of youth-onset type 1 and type 2 diabetes. METHODS: We assessed the direction of eGFR change at two visits (mean 6.6 years apart) in SEARCH, a longitudinal cohort study of youth-onset type 1 and type 2 diabetes. We used the CKiDCr-CysC equation to estimate GFR and categorized 'rising' and 'declining' eGFR as an annual change of ≥3 ml/min/1.73 m2 in either direction. Multivariable logistic regression evaluated factors associated with directional change in eGFR. RESULTS: Estimated GFR declined in 23.8% and rose in 2.8% of participants with type 1 diabetes (N = 1225; baseline age 11.4 years), and declined in 18.1% and rose in 15.6% of participants with type 2 diabetes (N = 160; baseline age 15.0 years). Factors associated with rising and declining eGFR (versus stable) in both type 1 and type 2 diabetes included sex, age at diagnosis, baseline eGFR and difference in fasting glucose between study visits. Additional factors in type 1 diabetes included time from baseline visit, HbA1c and body mass index. CONCLUSIONS: Over the first decade of diabetes, eGFR decline is more common in type 1 diabetes whereas eGFR rise is more common in type 2 diabetes.

Orthotopic Heart Transplantation in a Patient With Gitelman Syndrome and Dilated Cardiomyopathy.

Gitelman syndrome (GS) is a rare hereditary tubulopathy affecting the distal tubule leading to significant electrolyte disturbances.1 Although generally a benign condition, rare associations with arrhythmias and sudden cardiac death have been reported.1 A paucity of literature exists associating GS with cardiomyopathy. We present a child with dilated cardiomyopathy and GS who was successfully treated with orthotopic heart transplantation.

Hemodialysis outcomes in a global sample of children and young adult hemodialysis patients: the PICCOLO MONDO cohort.

BACKGROUND: The aim of this study was to describe the experience of pediatric and young adult hemodialysis (HD) patients from a global cohort. METHODS: The Pediatric Investigation and Close Collaborative Consortium for Ongoing Life Outcomes for MONitoring Dialysis Outcomes (PICCOLO MONDO) study provided de-identified electronic information of 3244 patients, ages 0-30 years from 2000 to 2012 in four regions: Asia, Europe, North America and South America. The study sample was categorized into pediatric (≤18 years old) and young adult (19-30 years old) groups based on the age at dialysis initiation. RESULTS: For those with known end-stage renal disease etiology, glomerular disease was the most common diagnosis in children and young adults. Using Europe as a reference group, North America [odds ratio (OR) 2.69; CI 1.29, 5.63] and South America (OR 4.21; CI 2.32, 7.63) had the greatest mortality among young adults. North America also had higher rates of overweight, obesity, hypertension, cardiovascular disease, hospitalizations and secondary diabetes compared with all other regions. Initial catheter use was greater for North American (86.4% in pediatric patients and 75.2% in young adults) and South America (80.6% in pediatric patients and 75.9% in young adults). Catheter use at 1-year follow-up was most common in North American children (77.3%) and young adults (62.9%). Asia had the lowest rate of catheter use. For both age groups, dialysis adequacy (equilibrated Kt/V) ranged between 1.4 and 1.5. In Asia, patients in both age groups had significantly longer treatment times than in any other region. CONCLUSIONS: The PICCOLO MONDO study has provided unique baseline and 1-year follow-up information on children and young adults receiving HD around the globe. This cohort has brought to light aspects of care in these age groups that warrant further investigation.