Timothy E. Bunchman

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.

Pediatric acute renal failure: outcome by modality and disease

Abstract. Two hundred and twenty-six children who underwent renal replacement therapy (RRT) from 1992 to 1998 were retrospectively reviewed. The mean age, at the onset of RRT, was 74±11.7 months and weight was 25.3±9.7 kg. RRT therapies included hemofiltration (HF; n=106 children for an average of 8.7±2.3 days), hemodialysis (HD; n=61 children for an average of 9.5±1.7 days), and peritoneal dialysis (PD; n=59 children for an average of 9.6±2.1 days). Factors influencing patient survival included: (1) low blood pressure (BP) at onset of RRT (33% survival with low BP, vs 61% with normal BP, vs 100% with high BP; P<0.05), (2) use of pressors anytime during RRT (35% survival in those on pressors vs 89% survival in those not requiring pressors; P<0.01), (3) diagnosis (primary renal failure with a high likelihood of survival vs secondary renal failure; P<0.05), (4) RRT modality (40% survival with HF, vs 49% survival with PD, vs 81% survival with HD; P<0.01 HD vs PD or HF), and (5) pressor use was significantly higher in children on HF (74%) vs HD (33%) or PD (81%; P<0.05 HD vs HF or PD). In conclusion, pressor use has the greatest prediction of survival, rather than RRT modality. Patient survival in children with the need for RRT for ARF is similar to in adults and, as in adults, is best predicted by the underlying diagnosis and hemodynamic stability.

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.

Dialysis therapy for children with acute renal failure: survey results.

Abstract We surveyed 123 pediatric nephrologists to investigate the current dialytic management of acute renal failure (ARF) in children. Data collected from 92 responding physicians revealed that hemodialysis (HD), peritoneal dialysis (PD), and continuous renal replacement therapy (CRRT) are currently used as the primary means of acute renal replacement therapy in a nearly equal percentage of centers. The preferential use of CRRT appears to be increasing, while PD usage is decreasing except for the youngest infants and those patients likely to develop end-stage renal disease (ESRD). Additional data correlating patient outcome to dialytic modality should be collected to compare the efficacy of the three techniques.

Studies of Pediatric Liver Transplantation (SPLIT) : Year 2000 outcomes

Background. Initiated in 1995, the Studies of Pediatric Liver Transplantation (SPLIT) registry database is a cooperative research network of pediatric transplantation centers in the United States and Canada. The primary objectives are to characterize and follow trends in transplant indications, transplantation techniques, and outcomes (e.g., patient/graft survival, rejection, growth parameters, and immunosuppressive therapy.) Methods. As of June 15, 2000, 29 centers registered 1144 patients, 640 of whom received their first liver-only transplant while registered in SPLIT. Patients are followed every 6 months for 2 years and yearly thereafter. Data are submitted to a central coordinating center. Results. One/two-year patient survival and graft loss estimates are 0.85/0.82 and 0.77/0.72, respectively. Risk factors for death include: in ICU at transplant (relative risk (RR)=2.63, P <0.05) and height/weight deficits of two or more standard deviations (RR=1.67, P <0.05). Risk factors for graft loss include: in ICU at transplant (RR=1.77, P <0.05) and receiving a cadaveric split organ compared with a whole organ (RR=2.3, P <0.05). The percentage of patients diagnosed with hepatic a. and portal v. thrombosis were 9.7% and 7%, respectively; 15% had biliary complications within 30 days. At least one re-operation was required in 45%. One/two-year rejection probability estimates are 0.60/0.66. Tacrolimus, as primary therapy posttransplant, reduces first rejection risk (RR=0.70, P <0.05). Eighty-nine percent of school-aged children are in school full-time, 18 months posttransplant. Conclusions. This report provides one of the first descriptions of characteristics and clinical courses of a multicenter pediatric transplant population. Observations are subject to patient selection biases but are useful for generating hypothesis for future studies.

Amino acid loss and nitrogen balance in critically ill children with acute renal failure: a prospective comparison between classic hemofiltration and hemofiltration with dialysis.

Hypothesis: Amino acid (AA) loss is not equivalent on continuous venovenous hemofiltration (CVVH) compared with continuous venovenous hemodiafiltration (CVVHD). Amino acid supplementation may be necessary to adjust for a greater clearance on CVVH to maintain nitrogen balance similar to that of CVVHD. Objective: To compare AA losses and nitrogen balance between CVVH and CVVHD in children with acute renal failure. Setting: Pediatric patients in the pediatric intensive care unit of a tertiary referral center. Design: Prospective randomized crossover study in consecutive children who required hemofiltration. Patients: A total of 12 plasma clearance studies for AA and urea, consisting of 24‐hr collections of ultrafiltrate and urine for nitrogen balance, was performed on six patients during CVVH and CVVHD. Patients received total parenteral nutrition (TPN) with caloric intake 20% to 30% above their resting energy expenditure measured by indirect calorimetry and 1.5 g/kg/day protein of TPN. Study conditions were comprised of 2 L/hr/1.73 m2 of dialysate or prefiltered replacement fluid and hemofilter flow rates of 4 mL/kg/min were maintained for all patients. Methods and Main Results: Amino acid clearances were greater on CVVH than CVVHD, except for glutamic acid, where clearance was 6.73 ± 2.31 (SEM) mL/min/1.73 m2 on CVVH and 7.59 ± 2.79 mL/min/1.73 m2 for CVVHD (NS). The clearance difference between the two modalities was 30%. Urea clearance was equivalent (30.1 ± 1.74 mL/min/1.73 m2 and 29.0 ± .97 mL/min/1.73 m2) for CVVH and CVVHD, respectively. Amino acid loss on CVVH and CVVHD was similar (12.50 ± 1.29 g/day/1.73 m2 vs. 11.61 ± 1.86 g/day/1.73 m2, respectively), representing 12% and 11%, respectively, of the daily protein intake. The catabolic state, as measured by urea nitrogen appearance, was high for all patients during the 48‐hr study period with a mean of 291 mg/kg/day during CVVH, and 245 mg/kg/day for CVVHD. Nitrogen balance varied from a negative 12.95 g/day/1.73 m2 to a positive 4.93 g/day/1.73 m2 on CVVH and a negative 7.69 g/day/1.73 m2 to a positive 5.50 g/day/1.73 m2 on CVVHD. Conclusions: Clearance of AA is greater on CVVH than on CVVHD, but no significant difference in AA loss was present between the two therapies. Nitrogen balance often is not met on either therapy when a standard 1.5 g/kg/day protein and a resting energy expenditure of 120% to 130% of calories is delivered by TPN.

RENAL TRANSPLANTATION IN CHILDREN WITH SEVERE LOWER URINARY TRACT DYSFUNCTION

PURPOSE Renal transplantation in children with end stage renal disease due to congenital urological malformations has traditionally been associated with a poor outcome compared to transplantation in those with a normal urinary tract. In addition, the optimal urological treatment for such children remains unclear. To address these issues, we retrospectively reviewed our experience with renal transplantation in this population. MATERIALS AND METHODS Between 1986 and 1998, 12 boys and 6 girls a mean age of 8.4 years with a severe dysfunctional lower urinary tract underwent a total of 15 living related and 6 cadaveric renal transplantations. Urological anomalies included posterior urethral valves in 8 cases, urogenital sinus anomalies in 4, the prune-belly syndrome in 2, and complete bladder duplication, ureterocele, lipomeningocele and the VATER syndrome in 1 each. In 11 children (61%) bladder augmentation or continent urinary diversion was performed, 2 (11%) have an intestinal conduit and 5 (28%) have a transplant into the native bladder. RESULTS In this group patient and overall allograft survival was 100 and 81%, respectively. These values were the same in all children who underwent renal transplantation at our center during this era. In the 17 children with a functioning transplant mean serum creatinine was 1.4 mg./dl. Technical complications occurred in 4 patients (22%), including transplant ureteral obstruction in 2 as well as intestinal conduit stomal stenosis and Mitrofanoff stomal incontinence. CONCLUSIONS Renal transplantation may be successfully performed in children with end stage renal disease due to severe lower urinary tract dysfunction. Bladder reconstruction, which may be required in the majority of these cases, appears to be safe when performed before or after the transplant. A multidisciplinary team approach to surgery is advantageous.

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.

Invited Review Recognition and management of angiotensin converting enzyme inhibitor fetopathy

Angiotensin converting enzyme (ACE) inhibitors are extensively used for the treatment of hypertension, to decrease proteinuria, and to mitigate hyperfiltration. These drugs now have been shown to be fetotoxic causing profound fetal hypotension, renal tubular dysplasia, anuria-oligohydramnios, growth restriction, hypocalvaria, and death when used in the second and third trimesters of pregnancy. We recommend that ACE inhibitors not be used in pregnancy. However, if a child is born with ACE inhibitor fetopathy, aggressive therapy with dialysis to remove the inhibitor may mitigate the profound hypotensive effects. Therapy will depend on the specific ACE inhibitor, and care recommendations cannot be generalized for the entire class of drugs as their protein binding and volume of distribution differ substantially.

Treatment of Henoch-Schönlein Purpura Glomerulonephritis in Children with High-Dose Corticosteroids plus Oral Cyclophosphamide

Background: Henoch-Schönlein Purpura (HSP) is a common childhood vasculitis with manifestations in numerous organ systems, including glomerulonephritis. Patients with more severe HSP-associated glomerulonephritis may develop chronic renal failure. Currently, no widely accepted treatment protocols exist for patients with significant renal involvement. Methods: We retrospectively reviewed the clinical courses of 12 children (mean age 9 years) with HSP glomerulonephritis treated with high-dose corticosteroids plus oral cyclophosphamide. All patients had nephrotic-range proteinuria, and all had significant histopathologic changes on biopsy, including crescentic nephritis in 10 patients. Treatment consisted of either intravenous pulse methylprednisolone or oral prednisone followed by oral cyclophosphamide (2 mg/kg/day) for 12 weeks, along with either daily or alternate-day oral prednisone. Prednisone was tapered following completion of cyclophsophamide. Results: Serum albumin rose significantly after treatment from 2.8 ± (SD) 0.5 to 3.7 ± 0.4 g/dl (p < 0.001), and there was a concurrent reduction in proteinuria, as reflected by decreasing serial protein-to-creatinine ratios: from 6.3 ± 4.4 to 0.8 ± 0.8 (p = 0.002). Renal function remained normal in all patients. Hypertension developed during treatment in 10 patients, all but 1 of whom were normotensive at last follow-up, 35 ± 17 months following biopsy. Conclusions: We conclude that treatment of children with HSP nephritis with high-dose corticosteroids plus oral cyclophosphamide is safe and, as in nephrotic syndrome, appears to significantly reduce proteinuria which is a known risk factor for the development of renal insufficiency in HSP. Further studies with larger numbers of patients should be conducted to confirm this finding.