Jordan M. Symons

Nephrotic syndrome in childhood

Childhood nephrotic syndromes are most commonly caused by one of two idiopathic diseases: minimal-change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS). A third distinct type, membranous nephropathy, is rare in children. Other causes of isolated nephrotic syndrome can be subdivided into two major categories: rare genetic disorders, and secondary diseases associated with drugs, infections, or neoplasia. The cause of idiopathic nephrotic syndrome remains unknown, but evidence suggests it may be a primary T-cell disorder that leads to glomerular podocyte dysfunction. Genetic studies in children with familial nephrotic syndrome have identified mutations in genes that encode important podocyte proteins. Patients with idiopathic nephrotic syndrome are initially treated with corticosteroids. Steroid-responsiveness is of greater prognostic use than renal histology. Several second-line drugs, including alkylating agents, ciclosporin, and levamisole, may be effective for complicated and steroid-unresponsive MCNS and FSGS patients. Nephrotic syndrome is associated with several medical complications, the most severe and potentially fatal being bacterial infections and thromboembolism. Idiopathic nephrotic syndrome is a chronic relapsing disease for most steroid-responsive patients, whereas most children with refractory FSGS ultimately develop end-stage renal disease. Research is being done to further elucidate the disorders molecular pathogenesis, identify new prognostic indicators, and to develop better approaches to treatment.

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.

Effect of fluid overload and dose of replacement fluid on survival in hemofiltration

Continuous renal replacement therapy (CRRT) is used to treat renal failure in children. Despite widespread use of the technique, little research has evaluated how variations in dose of replacement fluid or degree of fluid overload at initiation relate to outcomes. We conducted a retrospective review of patients treated with convective CRRT at our institution, using a multivariable Cox regression model. Children with high fluid overload (>10%) at CRRT initiation were at 3.02 times greater risk of mortality than those with low or no fluid overload [95% confidence interval (CI) 1.50–6.10, P =0.002]. The hazard ratio for death in children treated with high-dose convective clearance was not statistically significant. Our data support previous findings that volume overload in excess of 10% is strongly correlated with poor outcome. We favor early institution of CRRT, before excessive fluid overload occurs. In contrast to findings in adults, we find no advantage to higher rates of convective clearance. Given the risks and increased complexity associated with high-volume hemofiltration, we recommend further study prior to widespread adoption of high-level convection in children treated with continuous veno-venous hemofiltration.

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.

Continuous renal replacement therapy in children up to 10 kg

BACKGROUND There is growing use of continuous renal replacement therapy (CRRT) for pediatric patients, but no large studies reporting CRRT use and outcome in young children. We describe a cohort of patients weighing 10 kg or less who underwent CRRT at five US childrens hospitals between 1993 and 2001. METHODS We reviewed records of 85 patients weighing 10 kg or less who underwent at least 24 hours of CRRT. We evaluated weight, diagnosis, pressor number, CRRT characteristics, days on CRRT, and outcome (survival to leave intensive care unit versus death). RESULTS Patients weighed 1.5 to 10 kg (mean, 5.3 +/- 2.8 kg; 16 patients < or = 3 kg). Sixty-nine percent of patients were being administered pressors at the time of CRRT initiation, 88% of patients were administered heparin, and the others were administered citrate or no anticoagulation. Mean blood flow was 48 +/- 24 mL/min (range, 15 to 106 mL/min) or 9.5 +/- 4.2 mL/min/kg. Six hundred fifty-five patient-days of therapy were studied (mean, 7.6 +/- 8.6 d/patient; range, 1 to 46 d/patient). Thirty-two patients (38%) survived; 4 of 16 patients (25%) weighing 3 kg or less survived. The smallest survivor weighed 2.3 kg. Overall, survivors and nonsurvivors showed no significant difference in weight, days on CRRT, or pressor number. However, for patients weighing more than 3 kg, 28 of 69 patients (41%) survived, and mean pressor number was lower for survivors versus nonsurvivors (0.96 +/- 1.1 versus 1.6 +/- 1.0 pressors; P < 0.03). CONCLUSION CRRT is feasible and useful in children weighing 10 kg or less. Hemodynamic instability requiring pressor support neither precludes successful CRRT nor adversely affects survival. After CRRT, the survival rate in children who weigh 3 to 10 kg is similar to that in older children and adolescents.

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.

Mycophenolate mofetil in pediatric renal transplantation

Benfield MR, Symons JM, Bynon S, Echkoff D, Herrin J, Harmon WE, Kohaut EC. Mycophenolate mofetil in pediatric transplantation. Pediatr Transplantation 1999: 3: 33–37.

Protein and calorie prescription for children and young adults receiving continuous renal replacement therapy : A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group

Objective:Few published reports describe nutrition provision for critically ill children and young adults with acute kidney injury receiving continuous renal replacement therapy. The goals of this study were to describe feeding practices in pediatric continuous renal replacement therapy and to evaluate factors associated with over- and under-prescription of protein and calories. Design:Retrospective database study. Setting:Multicenter study in pediatric critical care units. Patients:Patients with acute kidney injury (estimated glomerular filtration rate <75 mL/min/1.73 m2 at continuous renal replacement therapy initiation) enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Interventions:None. Measurements:Nutrition variables: initial and maximal protein (g/kg/day) and caloric (kcal/kg/day) prescription and predicted resting energy expenditure (kcal/kg/day). We determined factors predicting initial and maximal protein and caloric prescription by multivariate analysis. Results:One hundred ninety-five patients (median [interquartile range] age = 8.1 [12.8] yrs, 56.9% men) were studied. Mean protein and caloric prescriptions at continuous renal replacement therapy initiation were 1.3 ± 1.5 g/kg/day (median, 1.0; range, 0–10) and 37 ± 27 kcal/kg/day (median, 32; range, 0–107). Mean maximal protein and caloric prescriptions during continuous renal replacement therapy were 2.0 ± 1.5 g/kg/day (median, 1.7; range, 0–12) and 48 ± 32 kcal/kg/day (median, 43; range, 0–117). Thirty-four percent of patients were initially prescribed <1 g/kg/day protein; 23% never attained >1 g/kg/day protein prescription. By continuous renal replacement therapy day 5, median protein prescribed was >2 g/kg/day. Protein prescription practices differed substantially between medical centers with 5 of 10 centers achieving maximal protein prescription of >2 g/kg/day in ≥40% of patients. Caloric prescription exceeded predicted resting energy expenditure by 30%–100%. Factors independently associated with maximal protein and caloric prescription while on continuous renal replacement therapy were younger age, initial protein and caloric prescription and number of continuous renal replacement therapy treatment days (p < 0.05). Conclusions:Protein prescription in pediatric continuous renal replacement therapy may be inadequate. Inter-center variation exists with respect to nutrition prescription. Feeding practice standardization and research in pediatric acute kidney injury nutrition are essential to begin providing evidence-based feeding recommendations.

Acute kidney injury: can we improve prognosis?

The incidence of pediatric acute kidney injury (AKI) is increasing. AKI has been found to be independently associated with increased mortality, and current management options are limited in that they are mainly supportive. The use of various definitions of AKI can still be found in the literature, making it difficult to discern the epidemiology behind pediatric AKI. The use of a more uniform definition is a necessary first step to clarify AKI epidemiology and direct our research efforts, and it will ultimately improve prognosis. There is evidence that neonates and infants may be at higher risk for AKI than adults. However, the least amount of research is found for this youngest age group, and more focused efforts on this population are necessary. This paper reviews existing data on and definitions for pediatric AKI, general preventive and treatment strategies, as well as ongoing research efforts on AKI. We are hopeful that the prognosis of AKI will improve with collaboration on a multicenter, multinational scale in the form of prospective, long-term studies on pediatric AKI.

Nonrenal indications for continuous renal replacement therapy: A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

Objective: Continuous renal replacement therapy is the most often implemented dialysis modality in the pediatric intensive care unit setting for patients with acute kidney injury. However, it also has a role in the management of patients with nonrenal indications such as clearance of drugs and intermediates of disordered cellular metabolism. Measurements and Methods: Using data from the multicenter Prospective Pediatric Continuous Renal Replacement Therapy Registry, we report a cohort of pediatric patients receiving continuous renal replacement therapy for nonrenal indications. Nonrenal indications were obtained from the combination of “other” category for continuous renal replacement therapy initiation and patient diagnosis (both primary and secondary). This cohort was further divided into three subgroups: inborn errors of metabolism, drug toxicity, and tumor lysis syndrome. Results: From 2000 to 2005, a total of 50 continuous renal replacement therapy events with nonrenal indications for therapy were included in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Indication-specific survival of the subgroups was 62% (inborn errors of metabolism), 82% (tumor lysis syndrome), and 95% (drug toxicity). The median small solute dose delivered among the subgroups ranged from 2125 to 8213 mL/1.73 m2/hr, with 54%–59% receiving solely diffusion-based clearance as continuous venovenous hemodialysis. No association was established between survival and dose delivered, modality of continuous renal replacement therapy, or use of intermittent hemodialysis prior to continuous renal replacement therapy. Conclusions: Pediatric patients requiring continuous renal replacement therapy for nonrenal indications are a distinct cohort within the population receiving renal replacement therapy with little published experience of outcomes for this group. Survival within this cohort varies by indication for continuous renal replacement therapy and is not associated with continuous renal replacement therapy modality. Additionally, survival is not associated with small solute doses delivered within a cohort receiving >2000 mL/1.73 m2/hr. Our data suggest metabolic control is established rapidly in pediatric patients and that acute detoxification may be provided with continuous renal replacement therapy for both the initial and maintenance phases of treatment using either convection or diffusion at appropriate doses.