Racial and Ethnic Disparities in Acute Care Utilization Among Patients With Glomerular Disease.

RATIONALE & OBJECTIVE: The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort. EXPOSURE: Race and ethnicity as a participant-reported social factor. OUTCOME: Acute care utilization defined as hospitalizations or emergency department visits. ANALYTICAL APPROACH: Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization. RESULTS: Black or Hispanic participants had lower SES and more severe glomerular disease than White or Asian participants. Acute care utilization rates were 45.6, 29.5, 25.8, and 19.2 per 100 person-years in Black, Hispanic, White, and Asian adults, respectively, and 55.8, 42.5, 40.8, and 13.0, respectively, for children. Compared with the White race (reference group), Black race was significantly associated with acute care utilization in adults (rate ratio [RR], 1.76 [95% CI, 1.37-2.27]), although this finding was attenuated after multivariable adjustment (RR, 1.31 [95% CI, 1.03-1.68]). Black race was not significantly associated with acute care utilization in children; Asian race was significantly associated with lower acute care utilization in children (RR, 0.32 [95% CI 0.14-0.70]); no significant associations between Hispanic ethnicity and acute care utilization were identified. LIMITATIONS: We used proxies for SES and lacked direct information on income, household unemployment, or disability. CONCLUSIONS: Significant differences in acute care utilization rates were observed across racial and ethnic groups in persons with prevalent glomerular disease, although many of these difference were explained by differences in SES and disease severity. Measures to combat socioeconomic disadvantage in Black patients and to more effectively prevent and treat glomerular disease are needed to reduce disparities in acute care utilization, improve patient wellbeing, and reduce health care costs.

Practice patterns and approach to kidney biopsy in lupus: a collaboration of the Midwest Pediatric Nephrology Consortium and the Childhood Arthritis and Rheumatology Research Alliance.

BACKGROUND: There is no clear consensus regarding optimal indications or timing of initial or repeat kidney biopsy in the management of pediatric systemic lupus erythematosus (pSLE). METHODS: A web-based survey was designed to assess current practice patterns among pediatric nephrologists and pediatric rheumatologists and distributed to members of Midwest Pediatric Nephrology Consortium (MWPNC) and Childhood Arthritis and Rheumatology Research Alliance (CARRA). RESULTS: Respondents included 111 rheumatologists and 71 nephrologists from 65 and 34 centers, respectively. Numbers of years in sub-specialty practice were comparable. Rheumatologists and nephrologists frequently collaborate in the care of children with lupus nephritis (LN). More than 90% of respondents refer patients to each either other after diagnosing LN. Over 60% describe shared decision making regarding when to perform kidney biopsy and how to interpret biopsy findings. Many pediatric nephrologists consider biopsy to be of higher risk for complication in pSLE and alter their standard pre-or post-biopsy management. CONCLUSIONS: It is uncommon for pediatric nephrologists to manage LN without input from pediatric rheumatologists and vice versa. Consensus exists between specialties in general, and practice differences that exist occur between individual physicians rather than between specialties. A systematic approach to biopsy may result in improved health related outcomes in pSLE.

Recognition of elevated blood pressure in an outpatient pediatric tertiary care setting.

OBJECTIVE: To assess the prevalence of elevated blood pressure (BP) and its identification among outpatients at a pediatric tertiary care hospital and to assess clinician attitudes towards BP management. STUDY DESIGN: A retrospective review was undertaken of electronic medical record data of visits over the course of 1 year to 10 subspecialty divisions and 3 primary care services at an urban tertiary care hospital. Interviews of division/service representatives and a clinician survey on perceived role on BP care, practices, and protocols related to BP management were conducted. Elevated BP was defined as ≥90th percentile (using US references); identification of elevated BP was defined as the presence of appropriate codes in the problem list or visit diagnoses. RESULTS: Among 29,000 patients (ages 2-17 years), 70% (those with ≥1 BP measurement) were analyzed. Patients were as follows: 50% male; 42% white, 31% Hispanic, 16% black, 5% Asian, and 5% other/missing; 52% had Medicaid insurance. A total of 64% had normal BPs, 33% had 1-2 elevated BP measurements, and 3% had ≥3 elevated BP measurements. Among those with ≥3 elevated BP measurements, the median frequency of identification by division/service was 17%; the greatest identification was for Kidney Diseases (67%), Wellness & Weight Management (60%), and Cardiology (33%). Among patients with ≥3 elevated BP measurements, 21% were identified vs 7% identified among those with 1-2 increased measurements (P<.001). All clinician survey respondents perceived self-responsibility for identification of elevated BP, but opinions varied for their role in the management of elevated BP. CONCLUSIONS: The identification of patients with elevated BP measurements was low. Strategies to increase the identification of elevated BPs in outpatient tertiary care settings are needed.

Gaining the Patient Reported Outcomes Measurement Information System (PROMIS) perspective in chronic kidney disease: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND AND OBJECTIVES: Chronic kidney disease is a persistent chronic health condition commonly seen in pediatric nephrology programs. Our study aims to evaluate the sensitivity of the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric instrument to indicators of disease severity and activity in pediatric chronic kidney disease. METHODS: This cross sectional study included 233 children 8-17 years old, with chronic kidney disease from 16 participating institutions in North America. Disease activity indicators, including hospitalization in the previous 6 months, edema, and number of medications consumed daily, as well as disease severity indicators of kidney function and coexisting medical conditions were captured. PROMIS domains, including depression, anxiety, social-peer relationships, pain interference, fatigue, mobility, and upper extremity function, were administered via web-based questionnaires. Absolute effect sizes (AES) were generated to demonstrate the impact of disease on domain scores. Four children were excluded because of missing glomerular filtration rate (GFR) estimations. RESULTS: Of the 229 children included in the final analysis, 221 completed the entire PROMIS questionnaire. Unadjusted PROMIS domains were responsive to chronic kidney disease activity indicators and number of coexisting conditions. PROMIS domain scores were worse in the presence of recent hospitalizations (depression AES 0.33, anxiety AES 0.42, pain interference AES 0.46, fatigue AES 0.50, mobility AES 0.49), edema (depression AES 0.50, anxiety AES 0.60, pain interference AES 0.77, mobility AES 0.54) and coexisting medical conditions (social peer-relationships AES 0.66, fatigue AES 0.83, mobility AES 0.60, upper extremity function AES 0.48). CONCLUSIONS: The PROMIS pediatric domains of depression, anxiety, social-peer relationships, pain interference, and mobility were sensitive to the clinical status of children with chronic kidney disease in this multi-center cross sectional study. We demonstrated that a number of important clinical characteristics including recent history of hospitalization and edema, affected patient perceptions of depression, anxiety, pain interference, fatigue and mobility. The PROMIS instruments provide a potentially valuable tool to study the impact of chronic kidney disease. Additional studies will be required to assess responsiveness in PROMIS score with changes in disease status over time.

Gaining the PROMIS perspective from children with nephrotic syndrome: a Midwest pediatric nephrology consortium study.

BACKGROUND AND OBJECTIVES: Nephrotic syndrome (NS) represents a common disease in pediatric nephrology typified by a relapsing and remitting course and characterized by the presence of edema that can significantly affect the health-related quality of life in children and adolescents. The PROMIS pediatric measures were constructed to be publically available, efficient, precise, and valid across a variety of diseases to assess patient reports of symptoms and quality of life. This study was designed to evaluate the ability of children and adolescents with NS to complete the PROMIS assessment via computer and to initiate validity assessments of the short forms and full item banks in pediatric NS. Successful measurement of patient reported outcomes will contribute to our understanding of the impact of NS on children and adolescents. DESIGN: This cross-sectional study included 151 children and adolescents 8-17 years old with NS from 16 participating institutions in North America. The children completed the PROMIS pediatric depression, anxiety, social-peer relationships, pain interference, fatigue, mobility and upper extremity functioning measures using a web-based interface. Responses were compared between patients experiencing active NS (n = 53) defined by the presence of edema and patients with inactive NS (n = 96) defined by the absence of edema. RESULTS: All 151 children and adolescents were successfully able to complete the PROMIS assessment via computer. As hypothesized, the children and adolescents with active NS were significantly different on 4 self-reported measures (anxiety, pain interference, fatigue, and mobility). Depression, peer relationships, and upper extremity functioning were not different between children with active vs. inactive NS. Multivariate analysis showed that the PROMIS instruments remained sensitive to NS disease activity after adjusting for demographic characteristics. CONCLUSIONS: Children and adolescents with NS were able to successfully complete the PROMIS instrument using a web-based interface. The computer based pediatric PROMIS measurement effectively discriminated between children and adolescents with active and inactive NS. The domain scores found in this study are consistent with previous reports investigating the health-related quality of life in children and adolescents with NS. This study establishes known-group validity and feasibility for PROMIS pediatric measures in children and adolescents with NS.

Elevated preoperative serum asymmetrical dimethylarginine (ADMA) is associated with poor outcomes after pediatric cardiac surgery.

PURPOSE: Asymmetrical dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, is elevated in vascular pathologies such as hypertension and chronic kidney disease. Children undergoing cardiac surgery are at high risk of poor hemodynamic and renal outcomes secondary to cardiopulmonary bypass (CPB). This study tested the hypothesis that elevated preoperative ADMA levels are associated with overall worse clinical outcomes after pediatric CPB. METHODS: This was a prospective, observational study of 100 patients aged from 2 weeks to 18 years who underwent cardiac surgery involving CPB. Serum ADMA levels were obtained preoperatively and on postoperative days zero through four. Clinical outcomes measured included acute kidney injury (AKI) by pRIFLE criteria, low cardiac output syndrome (LCOS), length of mechanical ventilation, hospital and ICU length of stay, unplanned reoperation, and mortality. RESULTS: The 29 patients with an elevated preoperative ADMA were more likely to have prolonged mechanical ventilation, increased ICU and hospital length of stay, unplanned reoperation, and LCOS than those with a normal preoperative level. ADMA levels inversely correlated with estimated glomerular filtration rate (eGFR), but did not differ between patients with and without AKI after CPB. Preoperative ADMA levels correlated with hospital length of stay (r(s) = 0.289), ICU length of stay (r(s) = 0.308), and length of mechanical ventilation (r(s) = 0.402); [all p < 0.05]. ADMA levels before surgery had good predictive power for prolonged mechanical ventilation (AUC-ROC 0.809; 95 % CI 0.704, 0.914; p < 0.001). CONCLUSIONS: Patients with elevated ADMA before surgery were more likely to have prolonged mechanical ventilation, develop LCOS, require an extended length of stay, and require reoperation. ADMA levels inversely correlated with eGFR, but did not predict AKI. Preoperative serum ADMA appears to identify pediatric cardiac surgery patients at risk of poor postoperative outcomes following CPB.

Predictive power of serum cystatin C to detect acute kidney injury and pediatric-modified RIFLE class in children undergoing cardiac surgery.

OBJECTIVE: Acute kidney injury is a frequent and serious complication of cardiopulmonary bypass. In current clinical practice, serum creatinine is used to detect acute kidney injury. Cystatin C is a novel biomarker for kidney function that has been shown to be superior to serum creatinine in predicting acute kidney injury in adults after cardiopulmonary bypass. The aim of this study was to determine whether early cystatin C levels predict acute kidney injury associated with cardiopulmonary bypass in pediatric patients undergoing cardiac surgery and if cystatin C could predict pediatric-modified RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) class and renal injury as determined by estimated glomerular filtration rate. We also investigated whether ultrafiltration during cardiopulmonary bypass affects cystatin C levels. DESIGN: Prospective, observational cohort study. SETTING: Cardiac intensive care unit in a tertiary, academic pediatric hospital. PATIENTS: One hundred pediatric patients who underwent cardiac surgery involving cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute kidney injury was defined as a 50% increase in serum creatinine from a preoperative baseline anytime through postoperative day 4. Severity of acute kidney injury was determined by pediatric RIFLE class using estimated glomerular filtration rate criteria only. Renal injury was also determined by an absolute estimated glomerular filtration rate <80 mL/min/1.73 m. Cystatin C levels were measured before and after ultrafiltration. Twenty-eight patients (28%) developed acute kidney injury. Cystatin C predicted acute kidney injury as early as 8 hrs after surgery. When applying pediatric RIFLE criteria to the entire study, 30 patients reached "risk" and five developed "injury." Cystatin C was a good predictor of the development of "injury" (under the receiver operating characteristic curve, 0.834-0.875) and of renal injury by estimated glomerular filtration rate (under the receiver operating characteristic curve, 0.717-0.835) (all p < .05). Cystatin C levels decreased perioperatively and correlated with volume of fluid removed by ultrafiltration. CONCLUSIONS: Cystatin C is an early predictor of acute kidney injury in children after cardiopulmonary bypass. Cystatin C is a good predictor of pediatric RIFLE classification and of decreased estimated glomerular filtration rate after cardiopulmonary bypass. Serum cystatin C may be cleared by ultrafiltration.

Clinical grand rounds: atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening, chronic, genetic disease of uncontrolled alternative pathway complement activation. The understanding of the pathophysiology and genetics of this disease has expanded over recent decades and promising new developments in the management of aHUS have emerged. Regardless of the cause of aHUS, with or without a demonstrated mutation or autoantibody, blockade of terminal complement activation through C5 is of high interest as a mechanism to ameliorate the disease. Eculizumab, an existing monoclonal antibody directed against C5 with high affinity, prevents the perpetuation of the downstream activation of the complement cascade and the damage caused by generation of the anaphylotoxin C5a and the membrane attack complex C5b-9, by blocking C5 cleavage. We report the successful use of eculizumab in a patient after kidney transplantation and discuss the disease aHUS.

Hemofiltration circuit use beyond 72 hours in pediatric continuous renal replacement therapy.

INTRODUCTION: During continuous renal replacement therapy (CRRT), hemofiltration circuits ideally are changed after 72 h since tubing integrity and flow rates are not guaranteed after this time interval. This potential risk must be weighed against the risk of hypotension during elective circuit changes in the unstable patient. The aim of this study was to examine the safety of circuits used beyond 72 h in pediatric CRRT. METHODS: A retrospective chart review of all patients who underwent CRRT at our institution from January 2003 to October 2005 was performed. Procedures were divided into standard (≤72 h) and extended (>72 h) circuit duration groups. Patients who had more than one CRRT procedure (n=13) were excluded from study. RESULTS: 71 CRRT procedures were performed for 71 patients. A total of 254 circuits were used, of which 64 (25%) were used for >72 h. For circuits >72 h, the mean duration of use was 5.5 days ± 1.8 (range 4-11). There were no differences between the groups in age (p=0.12), weight (p=0.48), diagnosis (p=0.21), CRRT indication (p=0.07), CRRT mode (p=0.37), anticoagulation (p=0.53), blood flow rate (p=0.06), replacement rate (p=0.50) or dialysate rate (p=0.89). There were no incidents of membrane or tubing rupture in either group. CONCLUSIONS: Use of hemofiltration circuits beyond 72 h may be safe in pediatric patients undergoing CRRT without increased risk of tubing rupture. Our data suggest a need to redefine the limits of prolonged circuit use in pediatric CRRT.

Prevalence of sleep disturbances in children and adolescents with chronic kidney disease.

Although sleep disorders are common in adults with chronic kidney disease, little is known about the prevalence of sleep problems in children and adolescents with chronic kidney disease and their relationship to health-related quality of life measurements. We performed a clinic-based survey of sleep habits and common symptoms of sleep disturbances in 159 school-aged patients with chronic kidney disease. Three patient groups of chronic kidney disease were assessed: group 1, those not on dialysis and not transplanted; group 2, those on dialysis; and group 3, those with a functioning renal allograft. Four symptom domains for sleep disorders were assessed: excessive daytime sleepiness; sleep disordered breathing; restless legs syndrome symptoms; and insufficient sleep. Patients and the parent-proxy also completed the Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales questionnaire. Ninety-three (93) patients (58.5%) had symptoms of a sleep disturbance. The presence of a sleep disturbance correlated with a decrease in health-related quality of life scores that was independent of the chronic kidney disease study group or estimated glomerular filtration rate. We conclude that sleep disturbances are common throughout the spectrum of chronic kidney disease in children and adolescents and are associated with diminished health-related quality of life scores.

Relapsing peritonitis in children who undergo chronic peritoneal dialysis: a prospective study of the international pediatric peritonitis registry.

BACKGROUND AND OBJECTIVES: The International Pediatric Peritonitis Registry (IPPR) was established to collect prospective data regarding peritoneal dialysis (PD)-associated peritonitis in children. In this report, we present the IPPR results that pertain to relapsing peritonitis (RP). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was an online, prospective entry into the IPPR of data that pertain to peritonitis cases by participating centers. RESULTS: Of 490 episodes of nonfungal peritonitis, 52 (11%) were followed by a relapse. There was no significant difference between RP and non-RP in distribution of causative organisms and antibiotic sensitivities. Initial empiric therapy-ceftazidime with either first-generation cephalosporin or glycopeptide (vancomycin or teicoplanin)-was not associated with relapse. Switching to monotherapy with a first-generation cephalosporin on the basis of culture results was associated with higher relapse rate (23%) than other final antibiotic therapies (0 to 9%). Culture-negative RP was less likely to have a satisfactory early treatment response than non-RP (82 versus 98%). Young age, single-cuff catheter, downward-pointing exit site, and chronic systemic antibiotic prophylaxis were additional independent risk factors for RP in the multivariate analysis. Compared with non-RP, RP was associated with a lower rate of full functional recovery (73 versus 91%), higher ultrafiltration problems (14 versus 2%), and higher rate of permanent PD discontinuation (17 versus 7%). CONCLUSIONS: This is the largest multicenter, prospective study to date to examine RP in children. In addition, this is the first report in the literature to examine specifically the relationship of postempiric antibiotic treatment regimens to the subsequent risk for relapse.

Pediatric nephrotic syndrome: from the simple to the complex.

Remarkable advances have been made in the past decade in understanding the pathophysiology of idiopathic nephrotic syndrome. Although the initiating events leading to the onset of proteinuria still are not well defined, it has become increasingly clear that many glomerular diseases can be classified as podocytopathies, with injury to the podocyte playing a major role in the development and progression of disease. A complex interaction of immune system mediators, slit diaphragm signal transduction, podocyte injury and conformational change, and mediators of apoptosis and fibrosis determine the extent and nature of proteinuria and progression of glomerulosclerosis. New insights into the pathogenesis of idiopathic nephrotic syndrome likely will lead to innovative therapies and new approaches to management and prevention.

Pasteurella aerogenes hamster bite peritonitis.

Pasteurella multocida has been reported to cause peritoneal dialysis-associated peritonitis after a cat bite or scratch to the catheter. We report a teenager with hamster bite peritonitis caused by P. aerogenes, an organism predominantly isolated from swine.