Structural Inequities and Barriers to Accessing Kidney Healthcare Services in the United States: A Focus on Uninsured and Undocumented Children and Young Adults.

The population of children living in poverty and lacking healthcare insurance has increased in the United States of America in the last decade. Several factors have been responsible for this trend including illegal immigration, socioeconomic deprivation, young age, racial segregation, environmental degradation, and discriminatory housing policies. These systemic barriers have contributed to the exclusion of families from essential healthcare services. They are also contributory to the development of chronic illnesses (such as dialysis-dependent kidney disease) that are debilitating and frequently require considerable therapeutic resources. This unfortunate scenario creates a never-ending vicious cycle of poverty and diseases in a segment of society. For pediatric nephrologists, the challenges of caring for uninsured children with chronic kidney disease are all too familiar. Federally funded healthcare programs do not cover this patient population, leaving them the option of seeking care in emergency healthcare settings. Presentation with a critical illness often necessitates urgent placement of vascular catheters and the choice of acute hemodialysis. Adverse social environment influences the need for protracted chronic hemodialysis and a delay in kidney transplantation. Consequently, there is greater comorbidity, recurrent hospitalization, and a higher mortality rate. New policies should address the deficit in health insurance coverage while promoting social programs that will remove structural barriers to health care resources for undocumented children and young adults.

Malnutrition in Chronic Kidney Disease.

Patients with chronic kidney disease are at substantial risk for malnutrition, characterized by protein energy wasting and micronutrient deficiency. Studies show a high prevalence rate of malnutrition in both children and adults with chronic kidney disease. Apart from abnormalities in growth hormone-insulin like growth factor axis, malnutrition also plays a role in the development of stunted growth, commonly observed in children with chronic kidney disease. The pathogenic mechanisms of malnutrition in chronic kidney disease are complex and involve an interplay of multiple pathophysiologic alterations including decreased appetite and nutrient intake, hormonal derangements, metabolic imbalances, inflammation, increased catabolism, and dialysis related abnormalities. Malnutrition increases the risk of morbidity, mortality and overall disease burden in these patients. The simple provision of adequate calorie and protein intake does not effectively treat malnutrition in patients with chronic kidney disease owing to the intricate and multifaceted derangements affecting nutritional status in these patients. A clear understanding of the pathophysiologic mechanisms involved in the development of malnutrition in chronic kidney disease is necessary for developing strategies and interventions that are effective, and capable of restoring normal development and mitigating negative clinical outcomes. In this article, a review of the pathophysiologic mechanisms of malnutrition in chronic kidney disease is presented.

Immunogenicity of Augmented Compared With Standard Dose Hepatitis B Vaccine in Pediatric Patients on Dialysis: a Midwest Pediatric Nephrology Consortium Study.

BACKGROUND AND OBJECTIVES: Patients on maintenance dialysis have a higher risk of unresponsiveness to hepatitis B vaccination and loss of hepatitis B immunity. Adult guidelines recommend augmented dosing (40 mcg/dose), resulting in improved response in adults. We sought to determine whether children on dialysis mount a similar antibody response when given standard or augmented dosing of hepatitis B vaccine. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective review of patients on dialysis aged <19 years from May 1, 2008 to May 1, 2013 at 12 pediatric dialysis units. Hepatitis B surface antibody (HBsAb) titers ≥10 mIU/ml were defined as protective. RESULTS: A total of 187 out of 417 patients received one or more hepatitis B vaccine boosters. The median age was 13 years; the cohort was 57% boys and 59% white. Booster dose or HBsAb titers were missing in 17 patients. Conversion to protective HBsAb titers was achieved in 135 out of 170 patients (79%) after their first single-dose booster or multidose booster series. In patients receiving a single-dose booster, the response rate was 53% (nine out of 17) after a 10 mcg dose, 86% (65 out of 76) after a 20 mcg dose, and 65% (17 out of 26) after a 40 mcg hepatitis B vaccine dose. In patients receiving a multidose booster series, the response rate was 95% (19 out of 20) after a 10 mcg/dose series, 83% (20 out of 24) after a 20 mcg/dose series, and 71% (five out of seven) after a 40 mcg/dose series. Patients receiving a multidose booster series had a response rate of 86% (44 out of 51), compared with 76% (91 out of 119) in patients receiving a single-dose booster (P=0.21). Twenty-seven patients received more than one single-dose booster or multidose series, and 26 out of 27 (96%) eventually gained immunity after receiving one to three additional single-dose boosters or multidose booster series. CONCLUSIONS: There was no clear gradient of increasing seroconversion rate with increasing vaccine dose in this cohort of pediatric patients on dialysis.

Uromodulin: old friend with new roles in health and disease.

The most abundant urinary protein, Tamm-Horsfall protein, later renamed uromodulin, is expressed exclusively by the thick ascending limb cells of the kidney and released into urine from the apical cell membrane. Uromodulin is believed to protect against urinary tract infections and stones, but its other physiologic functions have remained obscure until recently. Renewed interest in uromodulin has been brought about by the identification of uromodulin mutations as causes of a discrete group of diseases that are distinct from nephronophthisis. The three overlapping clinical uromodulin-associated kidney diseases (UAKD) are medullary cystic disease type 2, familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Previously thought of as "adult diseases", it is now recognized that they may also present in childhood and even in infancy. Common characteristics of all three diseases are autosomal dominant inheritance, unremarkable urine sediment and slow progression to end-stage renal disease (ESRD). They are frequently associated with hyperuricemia and gout. These diseases appear to result from failure of the mutant uromodulin to be incorporated into the apical cilium, thereby placing UAKD in the category of "ciliopathies". In addition to causing specific UAKD, certain uromodulin gene polymorphisms have been linked to ESRD in general, suggesting that uromodulin plays a modulatory role in kidney disease progression.

Pilot validation of objective malnutrition-inflammation scores in pediatric and adolescent cohort on chronic maintenance dialysis.

BACKGROUND: In recognition of the challenges inherent with the use of single-item indices for the diagnosis of malnutrition-inflammation morbidity in pediatric dialysis patients, to enhance accuracy, we validated a composite scoring system in a pilot study. The objective malnutrition-inflammation score seeks to validate the use of a composite scoring system as a tool for assessing malnutrition-inflammation burden in a pediatric dialysis population. METHODS: We enrolled 20 patients on hemodialysis (n = 14) and peritoneal dialysis (n = 6) over a period of 12 months. We derived composite scores from selected indices of renal pathology, nutrition, dialysis adequacy, protein catabolism, and dialysis modality. We assessed reliability by a test-retest method and measured validity by defining the relationship of the indices with serum C-reactive protein in a multiple regression analysis. We calculated sensitivity, specificity, accuracy, and precision for the malnutrition-inflammation score. RESULTS: The mean age was 12.8 years (standard deviation = 6.1), and male-female ratio was 12:8. Patients (n = 8) with elevated serum C-reactive protein (>0.3 mg/dL) had higher composite score for malnutrition-inflammation morbidity. Similarly, the pediatric cohort on hemodialysis had higher score than those on peritoneal dialysis. Upon reliability testing, a low value of typical error (0.07) and high correlation coefficient (r = 0.95) supported validity of the instrument. Moreover, multiple regression analysis showed a strong predictive relationship (R(2) = 0.9, p = 0.03) between the indices and serum C-reactive protein. Sensitivity of malnutrition-inflammation score was 62.5%, specificity was 83%, accuracy was 75%, and precision was 71%. CONCLUSION: Using criterion-validation method, we established the potential use of multi-diagnostic approach to quantify malnutrition-inflammation morbidity in a pediatric dialysis cohort. Given the small sample size, large-scale population-specific studies are needed to ratify these findings and to demonstrate its clinical effectiveness.

Steroid avoidance using sirolimus and cyclosporine in pediatric renal transplantation: one year analysis.

Steroids are commonly used in pediatric renal transplantation, but have numerous adverse effects. This retrospective study compares one-yr outcomes in 22 pediatric renal transplant recipients receiving SRL and CSA as primary immunosuppression (steroid-avoidance group) to age- and gender-matched historical controls receiving CSA, MMF, and prednisone (steroid group). At one yr, both groups had similar graft survival, acute rejection, and estimated GFR. Subjects in the steroid-avoidance group had better linear growth, less excessive weight gain and were less likely to have an increase in antihypertensive medication use. Subjects in the steroid-avoidance group were more likely to be started on lipid lowering medications and erythropoiesis stimulating agents. Despite having a greater proportion of living donors, the steroid-avoidance group had a similar GFR compared to the steroid group at one month. The steroid-avoidance group was also more likely to have a biopsy for elevated Cr that was not because of rejection and had more interstitial fibrosis noted. We conclude that using a steroid-avoidance immunosuppression regimen of SRL and CSA results in comparable rejection rates and short-term graft function with less steroid-associated morbidity. However, early findings also suggest possible potentiation of CSA nephrotoxicity by SRL in some children.