The antenatal urinary tract dilation classification system accurately predicts severity of kidney and urinary tract abnormalities.

BACKGROUND: Urinary tract dilation (UTD) is a commonly diagnosed prenatal condition; however, it is currently unknown which features lead to benign and resolving or pathologic abnormalities. A consensus UTD classification system (antenatal UTD classification, UTD-A) was created by Nguyen et al. in 2014 [1], but has not yet been validated. OBJECTIVE: To evaluate the ability of the UTD-A system to identify kidney and urinary tract (KUT) abnormalities, assess whether UTD-A can predict severity of KUT conditions, and perform a cost analysis of screening ultrasound (US). METHODS: A retrospective single-center study was conducted at an academic medical center. Inclusion criteria were: neonates in the well or sick nursery who had a complete abdominal or limited renal US performed in the first 30 days of life between January 01, 2011 and December 31, 2013. Data were collected on prenatal US characteristics from which UTD-A classification was retrospectively applied, and postnatal data were collected up to 2 years following birth. RESULTS: A total of 203 patients were identified. Of the 36 abnormal postnatal KUT diagnoses, 90% were identified prenatally as UTD A1 or UTD A2-3. The remaining 10% developed postnatal KUT abnormalities due to myelomeningocele, such as VUR or UTD, which were not evident prenatally. Overall sensitivity and specificity of the UTD-A system was 0.767 (95% CI 0.577, 0.901) and 0.836 (95% CI 0.758, 0.897), respectively, when resolved UTD was counted as a normal diagnosis. Postnatal diagnoses differed by UTD-A classification as shown in the Summary fig. Of all the obstructive uropathies, 90.9% occurred in the UTD A2-3 class and none occurred in UTD-A Normal. Rate of postnatally resolved UTD was significantly higher in the UTD A1 group (78%) compared with UTD A2-3 (31%) or UTD-A Normal (12%, all P < 0.001). There was a notable trend towards more UT surgeries, UTI, and positive VUR among UTD A2-3 patients, but statistical significance was limited by a small number of patients. CONCLUSIONS: This study found that the UTD-A classification system revealed important differences in the severity of UTD abnormalities. With repeated validation in larger cohorts, the UTD-A classification may be used to offer a prognosis for parents regarding prenatally diagnosed KUT conditions. Larger prospective studies should be designed to validate whether the UTD-A system can predict postnatal events related to UTD morbidity such as need for UT-related surgery or UTI.

A Review of Pediatric Chronic Kidney Disease.

Chronic kidney disease is complex in both adults and children, but the disease is far from the same between these populations. Here we review the marked differences in etiology, comorbidities, impact of disease on growth and quality of life, issues unique to adolescents and transitions to adult care, and special considerations of congenital kidney and urinary tract anomalies for transplantation.

Isolated sarcoid granulomatous interstitial nephritis in pediatrics: a case report and review of literature.

Sarcoidosis is a multisystem disease of unknown etiology primarily affecting the lungs, skin, and lymph nodes. The disease usually manifests in young adults and is uncommon in childhood. Renal involvement, including granulomatous interstitial nephritis (GIN), is rare, and few cases of isolated sarcoid GIN have been reported in pediatrics. We report a case and review the literature.

Prevention of dialysis disequilibrium by use of CVVH.

OBJECTIVE: Dialysis disequilibrium occurs due to a rapid shift of osmols when hemodialysis is used in cases of extreme uremia. Continuous veno-venous hemofiltration (CVVH) with citrate anticoagulation may offer a safe method of urea reduction. DESIGN: Retrospective, clinical observation. SETTING: Tertiary pediatric intensive care unit and nephrology program. Patients. Two males, ages 10 and 12 years of age. INTERVENTION: CVVH with citrate anticoagulation. RESULTS: Three to four day reduction of BUN from 180 mg/dL to 22 mg/dL and from 279 mg/dL to 23 mg/dL. CONCLUSION: Slow and safe improvement of severe urea, hyperphosphatemia, hypocalcemia, and anemia without untoward side effects.

Pediatric acute kidney injury: the use of the RIFLE criteria.

Outcome in pediatric acute kidney injury (AKI) is in part related to diagnosis and intervention. Standard markers of severity of illness do not identify AKI. Modified RIFLE criteria are shown to identify patients who develop AKI, potentially allowing for early intervention.

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.

Evaluation of the PRISMA M10 circuit in critically ill infants with acute kidney injury: A report from the Prospective Pediatric CRRT Registry Group.

Currently available extracorporeal circuits in the US often require blood priming to prevent hypotension/anemia in smaller pediatric patients. The PRISMA M10 circuit, available in other countries has not received extensive study and has not been cleared for use in the US. We performed an FDA mandated study of the M10 circuit in the US for use in critically ill pediatric patients with acute kidney injury <15 kg in size. FDA guidelines allowed for maximal blood pump flow of 20 ml/min. Fifteen pts (9 M, 6 F, mean size 5.8+/-2.8 kg, range 2.6-12.5 kg, age 4 d - 13 mo, mean creatinine =1.2+/-0.7 mg/dL) were studied at 4 ppCRRT centers. Sixty-one filters (range 1-4 circuits per pt) were used (mean circuit life 28.6+/-22.5 h, range 1 to 74.5 h, 55%>24 h). No blood leaks occurred. All circuits achieved Qb 20 ml/min. Forty-two out of 61 filters clotted and mean circuit life was lower for these filters than those changed for other reasons (23+/-17 vs. 41+/-28 h, <0.005). Circuits using larger access demonstrated significantly longer survival. We conclude that the M10 filter can serve well for CRRT in small pediatric patients. Further study is needed to determine in higher blood flow rates would decrease clotting rates and increase filter life span and ultrafiltration rates.

Plasma therapies in thrombotic syndromes.

BACKGROUND: Plasma therapies are being applied to thombotic syndromes, but there are limited controlled studies. OBJECTIVE: To review the evidence and the current practices for plasma therapies in thrombotic syndromes. METHODS: Expert-enhanced evidence-based analysis. Evidence obtained as of Dec 31, 2002 using PubMed electronic reference library and expert-obtained library for a total of > 3,000 references obtained using the terms plasma therapy or plasma exchange or plasmapheresis or plasmafiltration or sorbents each combined with the words thrombotic syndrome or sepsis or septic shock. The authors screened the abstracts, reviewed the agreed set of papers, and compiled the recommendations. RESULTS: Plasma therapies, which alter the plasma components in patients, have been applied in thrombotic syndromes worldwide. In these patients, there is a biologic plausibility for plasma therapies since they have molecules that are prothrombotic and/or antifibrinolytic which would put them at risk for microvascular thrombosis and end-organ damage. There are respectively one randomized controlled trial (RCT) in primary thrombotic syndrome, and secondary thrombotic syndrome, which showed an improvement in mortality in applying plasma therapies (plasma exchange by centrifugation). However, there are numerous non-randomized and case series. Plasma exchange is accepted as the standard therapy for primary thrombotic syndrome as in thrombotic thrombocytopenic purpura (TTP). However, no consensus has been reached for plasma exchange in secondary thrombotic syndromes such as in sepsis, hemolytic uremic syndrome (HUS), thrombocytopenia associated multiple organ failure, TTP/HUS, s/p bone marrow or solid organ transplant, HELLP syndrome, immunologic disorders, drug exposure, or pancreatitis. CONCLUSIONS: As we understand more about the pathophysiology of thrombotic syndromes, specific plasma therapies can be applied for the specific need of a particular patient population. There are sufficient preliminary data to recommend a definitive RCT to evaluate the efficacy of the different types of plasma therapies in secondary thrombotic syndromes.

The Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry: design, development and data assessed.

Many issues plague the pediatric ARF outcome literature, which include data only from single center sources, a relative lack of prospective study, mixture within studies of renal replacement therapy modality without stratification and inconsistent use of methods to control for patient illness severity in outcome analysis. Since January 2001, the Prospective Pediatric CRRT (ppCRRT) Registry Group has been collecting data from multiple United States pediatric centers to obtain demographic data regarding pediatric patients who receive CRRT, assess the effect of different CRRT prescriptions on circuit function and evaluate the impact of clinical variables on patient outcome. The aim of the current paper is to describe the ppCRRT Registry design, review the decision process and rationale for the options chosen for the ppCRRT format and discuss the analysis plan and future projects envisioned for the ppCRRT Registry.

Indications, results, and complications of tacrolimus conversion in pediatric renal transplantation.

It is the practice of many pediatric renal transplant programs to 'convert' children taking cyclosporin A (CsA) to tacrolimus, although the indications for, outcome, and complications of this practice remain obscure. To better understand these aspects of tacrolimus 'conversion', a fax survey was sent to 119 North American pediatric renal transplant centers. Analyzable responses were received from 52 centers (44%), and included data from approximately 1,815 pediatric renal transplants performed between 1991 and 98. Strong indications for tacrolimus conversion were: antibody-resistant rejection, CsA-resistant rejection, and CsA intolerance (strong indication in 72%, 65%, and 52% of centers, respectively). Steroid-resistant rejection and cosmetic side-effects were considered strong indications less often. Initial anti-rejection therapy was usually increased corticosteroid dose (47/52 centers). Antibody therapy was most commonly used for steroid-resistant rejection (44 centers). For steroid- and antibody-resistant rejection, tacrolimus conversion was most common (33 centers). Tacrolimus conversion for antibody-resistant rejection led to improvement of serum creatinine (SCr) in 27% of patients, stabilization of SCr in 46%, worsening of SCr in 11%, and graft loss in 16%. Reported complications after tacrolimus conversion included hyperglycemia, hyperkalemia, lymphoproliferative disorder, infection, and neurologic problems. We conclude that the major indication for tacrolimus conversion in pediatric transplant programs appears to be rejection. Outcome after tacrolimus conversion appears good, with the majority of patients experiencing stable or improved allograft function. These data provide direction for further study, including timing of tacrolimus conversion and interaction with other therapies.

Peritoneal dialysis for management of pediatric acute renal failure.

BACKGROUND: While the use of continuous renal replacement therapies in the management of children with acute renal failure (ARF) has increased, the role of peritoneal dialysis (PD) in the treatment of pediatric ARF has received less attention. DESIGN: Retrospective database review of children requiring PD for ARF over a 10-year period. SETTING: Pediatric intensive care unit at a tertiary-care referral center. PATIENTS: Sixty-three children without previously known underlying renal disease who required PD for treatment of ARF. RESULTS: Causes of ARF were congestive heart failure (27), hemolytic-uremic syndrome (13), sepsis (10), nonrenal organ transplant (7), malignancy (3), and other (3). Mean duration of PD was 11 +/- 13 days. Children with ARF were younger (30 +/- 48 months vs 88 +/- 68 months old, p < 0.0001) and smaller (11.9 +/- 15.9 kg vs 28 +/- 22 kg, p < 0.0001) than children with known underlying renal disease who began PD during the same time period. Percutaneously placed PD catheters were used in 62% of children with ARF, compared to 4% of children with known renal disease (p < 0.0001). Hypotension was common in patients with ARF (46%), which correlated with a high frequency of vasopressor use (78%) at the time of initiation of PD. Complications of PD occurred in 25% of patients, the most common being catheter malfunction. Recovery of renal function occurred in 38% of patients; patient survival was 51%. CONCLUSIONS: Peritoneal dialysis remains an appropriate therapy for pediatric ARF from many causes, even in severely ill children requiring vasopressor support. Such children can be cared for without the use of more expensive and technology-dependent forms of renal replacement therapies.

Intravenous nicardipine for treatment of severe hypertension in children.

OBJECTIVE: To examine the effect of intravenous nicardipine in the treatment of children with severe hypertension. METHODS: The medical records of 29 children (mean age 94 months) treated with intravenous nicardipine were retrospectively reviewed. The mean duration of severe hypertension before nicardipine use was 12.5 hours. Most (74%) patients were receiving other antihypertensive agents before nicardipine. RESULTS: The initial nicardipine dose was 0.8 +/- 0.3 microg/kg/min (mean +/- SD). The mean effective dose was 1.8 +/- 1.0 microg/kg/min (range, 0.3 to 4.0). Blood pressure control was achieved within 2.7 +/- 2.1 hours after nicardipine was started. Nicardipine treatment produced a 16% reduction in systolic blood pressure, a 23% reduction in diastolic blood pressure, and a 7% increase in heart rate. Nicardipine was effective as a single agent on 26 (84%) of 31 occasions. Adverse effects included tachycardia, flushing, palpitations, and hypotension. CONCLUSIONS: When administered in the intensive care unit setting with close patient monitoring, intravenous nicardipine effectively lowered blood pressure in children with severe hypertension. Larger prospective studies should be conducted to confirm these findings.

AN-69 membrane reactions are pH-dependent and preventable.

We report two pediatric patients who required blood priming for continuous venovenous hemodiafiltration. Both of these patients developed a significant hypotensive episode with initiation of continuous venovenous hemodiafiltration with immediate resolution on discontinuation. The most notable common characteristics of these patients were the use of the Multi-flo 60 (AN-69) dialyzer membrane and blood priming. No similar episodes were encountered when patients were primed with saline or albumin. The AN-69 membrane is exquisitely pH sensitive. The lower the pH concentration of the blood passing by the membrane, the greater the activation of bradykinin, a known hypotensive-inducing agent, by the dialyzer. On review of blood available from our blood bank, the following parameters became apparent. The pH of standard blood available from our blood bank ranged from 6.1 to 6.4. The blood obtained from our blood bank had significant hyperkalemia, hyponatremia, and hypocalcemia. No reactions were noted when patients were primed with normal saline, which has a pH of around 5.9. We speculate that the presence of endogenous blood substances, such as bradykinin, may have induced the hypotensive episodes. We describe two techniques we developed that should allow for the increased safe and effective use of the AN-69 membranes in continuous venovenous hemodiafiltration circuits. These observations indicate the requirement for careful and close attention to detail when delivering renal replacement therapy to anyone, but especially patients weighing less than 10 kg.

Comparison of polyclonal induction agents in pediatric renal transplantation.

Collective pediatric data suggest that anti-T-cell induction therapy with polyclonal antibodies improves the outcome of both short- and long-term renal allograft survival. Polyclonal agents, including thymoglobulin (Thy), a rabbit anti-thymocyte globulin; Minnesota (horse) anti-lymphoblast globulin (ALG); and ATGAM, a horse anti-thymocyte globulin (ATG), all suppress B and T cells. While no specific T-cell subset marker exists to measure the adequacy of immunosuppression with polyclonal induction, flow cytometric analysis has been used to evaluate the suppression of CD3, CD4, and CD8 cells. Thy is currently undergoing pediatric trials at our center, and we have utilized ATG and ALG in previous pediatric induction protocols. ALG (20 mg/kg/day) and ATG (15 mg/kg/day) were administered over 10 days, whereas Thy (2 mg/kg/day) was given over 5 days. All inductions were accompanied by preoperative intravenous solumedrol (10 mg/kg) followed by oral prednisone (2 mg/kg/day) with taper. Preoperative (1.5 mg/kg/day) and post-operative (2 mg/kg/day) azathioprine was administered to patients receiving ALG or ATG. Mycophenolate mofetil (MMF) (1200 mg/m2/day) was given to the patients receiving Thy. Post-operative cyclosporin A (CsA) (14 mg/kg/day) was started (for all groups) once renal function permitted (creatinine < 50% of baseline with brisk urine output) (trough goal 150-250 ng/mL via HPLC). Values for CD3, CD4, and CD8 T cells were determined by flow cytometry in 2-18-yr-old renal transplant recipients, comparing the polyclonal induction agent utilized [Thy (n = 8), mean age 9.7 +/- 2.3 yr; ATG (n = 13), mean age 10.1 +/- 4.1 yr; and ALG (n = 9), mean age 9.3 +/- 3.7 yr] over days 2-10 post-induction. Data were expressed as the average percentage of cells remaining relative to the baseline T-cell subsets (day 1 = 100%), because of the large age variation present in basal T-cell subset values. The flow cytometric data suggest that 5 days of Thy appears to give an equal or greater peripheral blood T-cell suppression by day 10 than a 10-day course of either ATG or ALG.

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.

Hemodialysis followed by continuous hemofiltration for treatment of lithium intoxication in children.

Hemodialysis is the usual recommended treatment for severe lithium intoxication; however, rebound of lithium levels may require repeated hemodialysis treatments. We proposed that the addition of continuous hemofiltration after hemodialysis would prevent rebound by providing ongoing clearance of lithium. We report two pediatric patients with lithium intoxication treated by hemodialysis followed by continuous venovenous hemofiltration with dialysis (CVVHD). Both patients were symptomatic at presentation and had initial lithium levels more than three times the usual therapeutic range. Hemodialysis followed by CVVHD resulted in rapid resolution of symptoms, followed by continuous clearance of lithium without requiring repeated hemodialysis sessions. Both patients had return of normal mental status during CVVHD treatment, and neither patient experienced complications of hemodialysis or CVVHD. Total duration of treatment with hemodialysis followed by CVVHD was 34.5 hours for the first patient and 26 hours for the second patient. We conclude that hemodialysis followed by CVVHD is a safe and effective approach to the management of lithium intoxication in children.

Pediatric acute renal failure: outcome by modality and disease.

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.

Treatment of hypertensive children with amlodipine.

Amlodipine, a long-acting dihydropyridine calcium channel blocking agent, was administered to 55 children (age: 11.5 +/- 5.4 years) with hypertension, 49 of whom (89%) had secondary hypertension. Efficacy was assessed by comparing pretreatment blood pressure (BP) to follow-up BP obtained in our outpatient Pediatric Nephrology clinic. Thirty-two (58%) patients achieved BP control with amlodipine alone, and 31 (55%) patients received amlodipine twice daily. Eleven patients received amlodipine as a suspension. Mean amlodipine dose was 0.16 +/- 0.12 mg/kg/day; there was an inverse relationship between patient age and amlodipine dose. Follow-up BP were significantly lower than pretreatment BP: systolic BP fell from 129 +/- 12 to 122 +/- 12 mm Hg (P = .004), and diastolic BP fell from 78 +/- 13 to 70 +/- 19 mm Hg (P = .003). A small, clinically insignificant increase in heart rate (from 91 +/- 19 beats/min to 99 +/- 26 beats/min; P = .02) occurred during amlodipine treatment. Adverse effects reported included dizziness (three patients), fatigue (two patients), flushing (two patients), and leg edema (one patient). All improved with dose reduction. We conclude that amlodipine provides effective BP control without significant adverse effects in children with hypertension, and can be used as monotherapy in most children. Young children appear to require significantly higher doses per kilogram of body weight than older children. Twice-daily dosing may be required in many children to achieve BP control. Detailed pharmacokinetic studies are needed to confirm these observations.

High-efficiency dialysis for carbamazepine overdose.

BACKGROUND: Carbamazepine intoxication is associated with seizures, coma, arrhythmias, and death. In acute intoxications, charcoal hemoperfusion enhances removal of the drug but is associated with thrombocytopenia, coagulopathy, hypothermia, and hypocalcemia. Alternatively, high-efficiency hemodialysis can be used without the side effects of charcoal hemoperfusion. CASE REPORT: We report an 18-month-old comatose, convulsing child with plasma carbamazepine 27 microg/mL treated with high efficiency hemodialysis. Therapeutic carbamazepine levels were obtained after 4.5 hours of high-efficiency hemodialysis. The patient developed no untoward side effects, improved clinically, and was subsequently discharged home without sequelae. We conclude that high-efficiency hemodialysis is a safe, effective alternative to charcoal hemoperfusion in the pediatric population.