Deepa H. Chand

Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy: The Prospective Pediatric Continuous Renal Replacement Therapy Registry

BACKGROUND Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT. STUDY DESIGN Prospective observational study. SETTING & PARTICIPANTS 297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry. PREDICTOR Fluid overload from intensive care unit (ICU) admission to CRRT initiation, defined as a percentage equal to (fluid in [L] - fluid out [L])/(ICU admit weight [kg]) x 100%. OUTCOME & MEASUREMENTS The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness. RESULTS 153 patients (51.5%) developed < 10% fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93 patients (31.3%) developed > or = 20% fluid overload. Patients who developed > or = 20% fluid overload at CRRT initiation had significantly higher mortality (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those with < 10% fluid overload (45/153; 29.4%). The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized to > or = 20% and < 20%, patients with > or = 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8-25.7). LIMITATIONS This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality. CONCLUSIONS Critically ill children who develop greater fluid overload before initiation of CRRT experience higher mortality than those with less fluid overload. Further goal-directed research is required to accurately define optimal fluid overload thresholds for initiation of CRRT.

Demographic Characteristics of Pediatric Continuous Renal Replacement Therapy: A Report of the Prospective Pediatric Continuous Renal Replacement Therapy Registry

BACKGROUND This article reports demographic characteristics and intensive care unit survival for 344 patients from the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry, a voluntary multicenter observational network. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS Ages were newborn to 25 yr, 58% were male, and weights were 1.3 to 160 kg. Patients spent a median of 2 d in the intensive care unit before CRRT (range 0 to 135). At CRRT initiation, 48% received diuretics and 66% received vasoactive drugs. Mean blood flow was 97.9 ml/min (range 10 to 350 ml/min; median 100 ml/min); mean blood flow per body weight was 5 ml/min per kg (range 0.6 to 53.6 ml/min per kg; median 4.1 ml/min per kg). Days on CRRT were <1 to 83 (mean 9.1; median 6). A total of 56% of circuits had citrate anticoagulation, 37% had heparin, and 7% had no anticoagulation. RESULTS Overall survival was 58%; survival differed across participating centers. Survival was lowest (51%) when CRRT was started for combined fluid overload and electrolyte imbalance. There was better survival in patients with principal diagnoses of drug intoxication (100%), renal disease (84%), tumor lysis syndrome (83%), and inborn errors of metabolism (73%); survival was lowest in liver disease/transplant (31%), pulmonary disease/transplant (45%), and bone marrow transplant (45%). Overall survival was better for children who weighed >10 kg (63 versus 43%; P = 0.001) and for those who were older than 1 yr (62 versus 44%; P = 0.007). CONCLUSIONS CRRT can be used successfully for a wide range of critically ill children. Survival is best for those who have acute, specific abnormalities and lack multiple organ involvement; sicker patients with selected diagnoses may have lower survival. Center differences might suggest opportunities to define best practices with future study.

The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: a report from the PPCRRT registry.

Purpose Well-functioning vascular access is essential for the provision of adequate CRRT However, few data exist to describe the effect of catheter size or location on CRRT performance in the pediatric population. Methods Data for vascular access site, size, and location, as well as type of anticoagulant used and patient demographic data were gathered from the ppCRRT registry. Kaplan-Meier curves were generated and then analyzed by log-rank test or Cox Proportional Hazards model. Results Access diameter was found to significantly affect circuit survival. None of the 5 French catheters lasted longer than 20 hours. Seven and 9 French, but not 8 French, catheters fared worse than larger diameter catheters (p=0.002). Circuits associated with internal jugular access survived longer than subclavian or femoral access associated circuits (p<0.05). Circuit survival was also found to be favorably associated with the CVVHD modality (p<0.001). Conclusions Functional CRRT circuit survival in children is favored by larger catheter diameter, internal jugular vein insertion site and CVVHD. For patients requiring catheter diameters less than 10 French, CRRT circuit survival might be optimized if internal jugular vein insertion is feasible. Conversely, when a vascular access site other than the internal jugular vein is most prudent, consideration should be given to using the largest diameter catheter appropriate for the size of the child. The CVVHD modality was associated with longer circuit survival, but the mechanism by which this occurs is unclear.

High Prevalence of the Metabolic Syndrome and Associated Left Ventricular Hypertrophy in Pediatric Renal Transplant Recipients

Wilson AC, Greenbaum LA, Barletta GM, Chand D, Lin J‐J, Patel HP, Mitsnefes M. High prevalence of the metabolic syndrome and associated left ventricular hypertrophy in pediatric renal transplant recipients.
Pediatr Transplantation 2010: 14: 52–60© 2009 John Wiley & Sons A/S.

HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68×10(-6) (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and ≤589 controls; P=1.42×10(-17)). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825×10(-5)). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS.

International Pediatric Fistula First Initiative: A Call to Action

The Centers for Medicare & Medicaid Services and the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative have emphasized the need for increased arteriovenous fistula (AVF) use and decreased central venous catheter use. A Fistula First National Vascular Access Improvement Initiative was undertaken to achieve these targets in adult patients through change concepts and process improvement. Despite increasing numbers of children receiving hemodialysis in the United States, AVF use rates decreased during the past 10 years. Studies of children dialyzed using AVFs showed superior dialysis delivery, improved access survival, and markedly lower infection rates. The purpose of this article is to alert nephrologists to consider a fistula first in long-term pediatric hemodialysis patients. In this article, we describe the status of vascular access in the United States and worldwide in children, the importance of AVF creation, and the need for surgical expertise, including microsurgery, in this population. Additionally, we introduce the International Pediatric Fistula First Initiative, a multidisciplinary team consisting of pediatric nephrologists, vascular access surgeons, and interventional radiologists aiming to increase awareness, offer educational tools, and implement the fistula first initiative in children.

Blood pressure control in pediatric hemodialysis: the Midwest Pediatric Nephrology Consortium Study

Hypertension is frequent in pediatric patients receiving dialysis, with an especially high rate reported in children on hemodialysis (HD). We performed the present study to assess blood pressure (BP) status and identify risk factors for poor BP control in children on maintenance HD. One month’s dialysis records were collected from 71 subjects receiving HD in ten dialysis units participating in the Midwest Pediatric Nephrology Consortium (MWPNC). For each HD session, data on pre- and posttreatment weights and BPs were recorded. Hypertension, defined as mean BP ≥ 95th percentile, was found in 42 (59%) subjects. Eleven subjects (15.5%) had prehypertension, defined as mean BP between the 90th and 95th percentiles, while 18 subjects (25.3%) had normal BP (<90th percentile). BP significantly decreased at the end of a dialysis session; however, only 15 of 42 hypertensive subjects (35%) normalized their BP. Hypertensive subjects were younger (p = 0.03), had higher serum phosphorus (p = 0.01), and had more elevated posttreatment weight above estimated dry weight (p = 0.02). Logistic regression showed that younger age (p = 0.02) and higher serum phosphorus (p = 0.02) independently predicted hypertensive status. In conclusion, this study emphasizes the difficulty of BP control in pediatric HD patients. Especially poor BP control was found in younger children; those patients who do not reach their posttreatment weight goals, perhaps reflecting their hypervolemic state; and those who have higher serum phosphorus levels.

A Vascular Access Team Can Increase AV Fistula Creation in Pediatric ESRD Patients: A Single Center Experience

The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF‐DOQI) recommends the use of a permanent vascular access for pediatric hemodialysis (HD) patients; however, central venous catheters are the most common vascular access used among children. In children receiving HD, central venous catheters, while suboptimal, are the most common vascular access used. As such, it is imperative that pediatric HD providers optimize vascular access techniques. We report outcomes of arteriovenous fistula (AVF) creation by a single surgeon in pediatric HD patients dialyzed at a single center. We further describe our experience and outcomes with the use of the operating microscope in the United States in children receiving HD under 15 kg in weight and as young as 4 years of age. AVF usage rates as well as short‐ and long‐term patency rates can be quite high with proper management. We further illustrate that the Fistula First principles can be applied to the pediatric population in the setting of a single surgeon with single center experience. As such, we have surpassed the current NKF‐DOQI recommendation of 50% fistula use in prevalent HD patients.

Obstacles to the prescribing of growth hormone in children with chronic kidney disease

Despite its effectiveness, recombinant human growth hormone (rhGH) is under-utilized in short children with chronic kidney disease (CKD). We conducted a multicenter study to explore the obstacles preventing children with CKD from receiving rhGH. We investigated the use of rhGH in 307 children with CKD from seven pediatric nephrology centers. Among the 110 patients who fell below the 5th percentile, 56 (51%) had not received rhGH. The most common reasons given for these children not receiving rhGH were family refusal, secondary hyperparathyroidism, and non-compliance. However, no explanation was apparent for 25% of the short children with CKD. Boys were more likely than girls to receive rhGH (65% vs 31%; P = 0.002). Use of rhGH was similar in African Americans and non-Hispanic Whites. Children who had received rhGH achieved a 0.5 increase in height z-score in the first year after the initiation of rhGH therapy. Children who had not received rhGH achieved a 0.03 increase in height z-score during the first year after falling below the 5th percentile (P = 0.005 vs the children who had received rhGH). Waiting for insurance company approval led to a significant delay in the initiation of rhGH treatment in 18% of patients. The fact that more than 50% of short children with CKD did not receive rhGH is secondary to multiple factors, many of which may be amenable to intervention efforts.

Trial of metronidazole vs. azithromycin for treatment of cyclosporine‐induced gingival overgrowth

Abstract:  Gingival overgrowth usually characterized by increased cellular growth of gingival fibroblasts appears to be multifactorial. In patients receiving CyA for more than 3 months, the incidence can approach 70% and can be attributed to pharmaceutical immunosuppression. Case reports have reported regression of overgrowth with both metronidazole and azithromycin. The goal of this study was to determine the efficacy of metronidazole and azithromycin in reducing CyA‐induced gingival overgrowth. Twenty‐five patients were included in this double‐blinded randomized study. All patients were receiving CyA as medically indicated and diagnosed with gingival overgrowth by a dentist. Patients were randomized to receive either 5‐days of azithromycin or 7‐days of metronidazole given at baseline only. The extent of gingival overgrowth was measured at 0, 2, 4, 6, 12, and 24 wk. Fourteen patients at CCF and 11 patients at CCHMC were studied. Repeated measures anova was performed to assess differences within and between groups. Gingival overgrowth at baseline was not statistically different between groups. The mean degree of gingival overgrowth after treatment was different across all time intervals (p = 0.0049) showing azithromycin to be more effective than metronidazole. Therapy with azithromycin offers an effective alternative to the management of CyA‐induced gingival overgrowth.