Managing severe hypertension in children.

Severe childhood hypertension is uncommon and frequently not recognised and is best defined as a systolic blood pressure (SBP) above the stage 2 threshold of the 95th centile + 12 mmHg. If no signs of end-organ damage are present, this is urgent hypertension which can be managed by the slow introduction of oral or sublingual medication, but if signs are present, the child has emergency hypertension (or hypertensive encephalopathy if they include irritability, visual impairment, fits, coma, or facial palsy), and treatment must be started promptly to prevent progression to permanent neurological damage or death. However, detailed evidence from case series shows that the SBP must be lowered in a controlled manner over about 2 days by infusing short-acting intravenous hypotensive agents, with saline boluses ready in case of overshoot, unless the child had documented normotension within the last day. This is because sustained hypertension may increase pressure thresholds of cerebrovascular autoregulation which take time to reverse. A recent PICU study that suggested otherwise was significantly flawed. The target is to reduce the admission SBP by its excess, to just above the 95th centile, in three equal steps lasting about ≥ 6 h, 12 h, and finally ≥ 24 h, before introducing oral therapy. Few of the current clinical guidelines are comprehensive, and some advise reducing the SBP by a fixed percentage, which may be dangerous and has no evidence base. This review suggests criteria for future guidelines and argues that these should be evaluated by establishing prospective national or international databases.

The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device.

OBJECTIVES: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH). DESIGN: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence. SETTING: Clusters were six U.K. PICUs. PATIENTS: Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance. INTERVENTIONS: In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances. MEASUREMENTS AND MAIN RESULTS: At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03-0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd ) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between. CONCLUSIONS: NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.

In vitro measurements of ultrafiltration precision in hemofiltration and hemodialysis devices used in infants.

BACKGROUND: To determine in vitro whether infant hemofiltration and hemodialysis devices can reliably deliver precise ultrafiltration (UF) control. METHODS: We tested the Prismaflex, Aquarius and NIDUS devices which have different circuit types, by in vitro testing with a bag of saline set up as a dummy patient, and monitoring fluid shifts by precise weighing. We looked for differences between the UF rates set and achieved and between the UF result the device displays to the clinician and the true volumes removed, which may lead to clinical errors. We performed short studies at UF settings of zero and 40 ml/h, and with and without simulating poor withdrawal and return lines, and simulated a 4-h treatment session. RESULTS: The Prismaflex setting vs actual errors and display vs actual errors had wide variances, with SDs of 4.1 and 14.0 ml by 15 min, respectively, at both zero and 40 ml/h UF settings. The Aquarius values were wider at 17.3 and 30.3 ml, respectively. For the NIDUS, the mean UF errors were close to zero, and the variances were 0.17 ml. Stop-alarms induced by an obstructed line produced extra UF errors of up to 0.2 ml. A limitation was that we used crystalloid and not colloid for these tests. CONCLUSIONS: Hemotherapy devices with conventional circuits available in the UK do not regulate UF control sufficiently well to recommend for use in small infants, but the NIDUS volumetrically controlled circuit does. All hemotherapy devices intended for small infants should be tested for UF precision. We were unable to test the CARPEDIEM or Aquadex devices. A higher resolution version of the Graphical abstract is available as Supplementary information.

Using urine nitrite sticks to test for urinary tract infection in children aged < 2 years: a meta-analysis.

BACKGROUND: This study aimed to determine whether nitrite sticks are as sensitive at detecting urinary tract infection (UTI) in children <2 years as they are in older children. METHODS: I reanalysed data on using nitrite sticks to detect UTIs for children aged either < 2 or 2-18 years. For sensitivity, evidence of a UTI was defined as level 1 when a single uropathogen grew ≥ 105 colony forming units/ml (cfu/ml) in two urine samples, level 2 when just one sample was cultured or a threshold of < 105 cfu/ml was used, and level 3 if mixed growths or Staphylococcus albus was considered to be positive. For specificity, children were defined as uninfected if they had 1 sterile urine culture. I also reanalysed our previously published data by age. RESULTS: The sensitivity was lower for children aged < 2 years (11 studies, 1321 subjects) than for older children (9 studies, 295 subjects), whether the level-1 values or all the studies were analysed (Fisher's exact test, p < 0.0001 for both). The level-1 sensitivities were 0.23 in the infants and 0.81 among older children (odds ratio = 0.07, 95% confidence interval 0.03-0.18). The specificity was very high in infants (10 studies, 1783 cases) and older children (7 studies, 5952 cases), at 0.990 and 0.996. CONCLUSIONS: Nitrite sticks only have a 23% sensitivity in children aged < 2 years, so cannot reliably rule out UTIs. A positive nitrite stick test is about 99% likely to indicate a UTI in children of any age.

Haemodialysing babies weighing <8 kg with the Newcastle infant dialysis and ultrafiltration system (Nidus): comparison with peritoneal and conventional haemodialysis.

BACKGROUND: To compare the efficacy of the Newcastle infant dialysis and ultrafiltration system (Nidus) with peritoneal dialysis (PD) and conventional haemodialysis (HD) in infants weighing <8 kg. METHODS: We compared the urea, creatinine and phosphate clearances, the ultrafiltration precision, and the safety of the Nidus machine with PD in 7 piglets weighing 1-8 kg, in a planned randomised cross-over trial in babies, and in babies for whom no other therapy existed, some of whom later graduated to conventional HD. RESULTS: Two babies entered the randomised trial; 1 recovered rapidly on PD, the other remained on the Nidus as PD failed. Additionally, 9 babies were treated on the Nidus on humanitarian grounds: 3 because of failed PD, and 3 with permanent kidney failure later converted to conventional HD. We haemodialysed 10 babies weighing between 1.8 and 5.9 kg for 2,475 h during 354 Nidus sessions without any clinically important incidents, and without detectable haemolysis. Single-lumen vascular access was used with no blood priming of circuits. The urea, creatinine and phosphate clearances using the Nidus were around 1.5 to 2.0 ml/min in piglets and babies, and were consistently higher than PD clearances, which ranged from about 0.2 to 0.8 ml/min (p ≤ 0.0002 for each chemical). Ultrafiltration was achieved to microlitre precision by the Nidus, but varied widely with PD. Fluid removal using conventional HD was imprecise and resulted in some hypovolaemic episodes requiring correction. CONCLUSION: The Nidus can provide HD in the Pediatric Intensive Care Unit (PICU) and outpatient intermittent HD without blood priming for babies weighing <8 kg, It generates higher dialysis clearances than PD, and delivers more precise ultrafiltration control than either PD or conventional HD.

Maximizing the sensitivity of the indirect radionuclide cystogram: a retrospective audit.

BACKGROUND: The indirect radionuclide cystogram (IRC) has generally been reported as being less sensitive for detecting vesico-ureteric reflux (VUR) than the micturating cystourethrogram (MCUG), so we modified it in an attempt to increase its sensitivity. METHODS: We altered our routine IRC protocol by including the data obtained during failed voids, adding extra imaging sequences at intervals during bladder filling, and by using simple mathematical criteria to determine if VUR was present when visual imaging results were equivocal. We then retrospectively compared the VUR detection rates using the standard and modified techniques. RESULTS: We assessed 707 renal units in 356 children over 3 years. We identified 91 cases of VUR using standard methodology, and 134 (47% more) with the modified technique. Of the extra 43 cases detected, 11 were noted during failed voids, ten were seen within a filling sequence, and 22 were inferred because the renal pelvic activity increased during an interval between two imaging sequences, while the bladder was filling. Mathematical evaluation was helpful in the 39 cases where the increase in activity due to VUR was ≤6 standard deviations greater than the level of background variation in activity. CONCLUSIONS: Additional imaging and mathematical assessment can significantly increase the sensitivity of the IRC for detecting VUR, possibly to equal that of the MCUG.

Performing renal biopsies in children under general anaesthesia in the lateral position.

BACKGROUND: Renal biopsies are usually performed in the prone position, often under general anaesthesia. Because it is theoretically and pragmatically safer to anaesthetise children in the lateral rather than the prone position, we compared the efficacy and safety of ultrasound-guided renal biopsy in these two positions. CASE-DIAGNOSIS/TREATMENT: In our department, physician preference dictates positioning during renal biopsy. We retrospectively audited the case notes and biopsy quality of 50 consecutive biopsies performed in each position, reviewing a total of 44 lateral and 47 prone position biopsies. Patient characteristics were similar for age and sex. Endotracheal intubation was carried out in all patients in the prone position and 18 % of patients in the lateral position. All patients were successfully biopsied, and the diagnostic yield and complications were similar in both groups. CONCLUSIONS: Renal biopsy under general anaesthesia is as successful in the lateral position as when it is performed prone. Therefore, the lateral position should be considered as an alternative because it reduces the anaesthetic risk.

Can prompt treatment of childhood UTI prevent kidney scarring?

The aim of the study reported here was to determine whether kidney scarring after urinary tract infections (UTI) in children can be prevented and to identify the risk factors for developing scars. We identified children in the Northern health region of the UK who had been seen to develop scars, identified as new defects on dimercapto-succinic acid (DMSA) scanning. Risk factors were sought by reviewing case-notes and interviews with parents. Twenty girls were identified whose new scarring was strongly associated with having both vesicoureteric reflux (VUR) and a UTI (p = 0.0001); 19/23 (83%) of kidneys exposed to both of these factors developed scars. Children were much more likely to be febrile (94 vs. 30%, p < 0.0001) or unwell (82 vs. 10%, p < 0.0001) during their earlier UTIs when they were of median age 2.8 years (range 0.3-5.0 years) and did not scar, compared to their later UTIs at age 7.3 years (1.2-12.5 years), when they did scar. However, most patients were treated within 1 day of their symptoms for their early UTIs, compared to a wait >or=7 days for later UTIs (p = 0.001). Being febrile or unwell during a UTI does not predict the development of scars, but prompt treatment appears to prevent scarring in children with VUR.

Follow-up of early unilateral nephrectomy for hypertension.

Early unilateral nephrectomy was carried out in four young children with unilateral renovascular disease, a poorly functioning kidney and hypertension. At follow-up 5-16 years later all showed normal growth, blood pressure and renal function, and only one child had low-grade albuminuria. Unilateral nephrectomy seems to be a safe and effective alternative to long-term hypotensive treatment.

Renovascular hypertension commencing during fetal life.

We report three infants with severe, early hypertension due to unilateral renovascular disease, whose cardiovascular changes, or polycythaemia, or both, indicated they had been affected as fetuses. All underwent unilateral nephrectomy, and had a similar histology, with patchy areas having relatively normal glomeruli but immature proximal tubules. This pattern may be a marker for renovascular disease in fetal life.

Acute hydrothorax complicating peritoneal dialysis.

AIM: To determine whether gradually increasing the peritoneal dialysate fill volume from 10 to 40 mL/kg over 6 days, rather than commencing at 40 mL/kg, prevents hydrothorax in children and reverses it if present. METHODS: A review of children peritoneally dialyzed in a single center. RESULTS: During the 20 years beginning June 1985, 416 children were peritoneally dialyzed, of which 327 (79%) had acute and 89 had end-stage renal failure. Among 253 children who had gradually increasing fill volumes, none developed acute hydrothoraces, but 13/163 (8%) who began with 40 mL/kg cycles did (p < 0.000, Fisher's exact test). These were diagnosed after a median (range) of 48 (6-72) hours and were predominantly right sided. Initially, we readily abandoned peritoneal dialysis; 2 were changed to hemodialysis. Subsequently, we found that peritoneal dialysis could be continued by using small volumes with the patients sitting up; cycle volumes were then gradually increased again. One pre-term baby died soon after developing an acute hydrothorax. One patient on chronic peritoneal dialysis developed an acute hydrothorax after forceful vomiting, but recovered after being dialyzed sitting up with low fills. CONCLUSION: Acute hydrothorax can be prevented and treated using graduated cycle volumes, and is not a contraindication for peritoneal dialysis.

Reflux nephropathy in kidney transplants, demonstrated by dimercaptosuccinic acid scanning.

BACKGROUND: This study determines why kidney transplants develop new focal defects. METHODS: Thirty children at a U.K. pediatric nephrology department receiving kidney transplants had early and late dimercaptosuccinic acid (DMSA) scans to detect acquired focal defects, and their presence correlated with possible risk factors. Associations between clinical events and focal DMSA lesions appearing in grafts were measured. RESULTS: Of the 30 early DMSA scans (within 2 weeks of function), one child with a thrombosed polar artery had a focal defect. On rescanning later, 11 (37%) had acquired segmental defects; five were multiple, and their glomerular filtration rates were 20 ml/min/1.73 m lower (95% CI 7-34). Histology in one case showed pyelonephritic scarring. Reflux into the transplant ureter occurred in 19/27 (70%) of children tested (by radiological or indirect radionuclide cystography). Nine of 13 children (69%) who had a combination of reflux and a urine infection had acquired scars, whereas only 1/14 (7%) did without this combination (P = 0.001). Scarring was not associated with the age or sex of the donor or recipient, rejection episodes, renal biopsy, or drug-induced nephrotoxicity. CONCLUSION: Kidney transplants are at high risk of developing segmental pyelonephritic scars if infected urine refluxes into the graft, either early through a transanastomotic stent or later from vesicoureteric reflux. These scars may reduce the renal function and are readily seen on DMSA, but not ultrasound scans. Consideration should be given to more effective antireflux surgery for transplants, with subsequent testing for reflux, urinary antibiotic prophylaxis, and prompt treatment of urine infections.

The management of neonatal acute and chronic renal failure: A review.

Most babies with chronic renal failure are identified antenatally, and over half that are treated with peritoneal dialysis receive kidney transplants before school age. Most infants that develop acute renal failure have hypotension following cardiac surgery, or multiple organ failure. Sometimes the falls in glomerular filtration and urine output are physiological and reversible, and sometimes due to kidney injury, but (illogically) it is now common to define them all as having 'acute kidney injury'. Contrary to widespread opinion, careful interpretation of the plasma creatinine concentrations can provide sensitive evidence of early acute renal failure. Conservative management frequently leads to under-nutrition or fluid overload. Acute peritoneal dialysis is often technically fraught in very small patients, and haemotherapies have been limited by vascular access and anticoagulation requirements, the need to blood-prime circuits, and serious limitations in regulating fluid removal. Newer devices, including the Nidus, have been specifically designed to reduce these difficulties.

Oedema in kwashiorkor is caused by hypoalbuminaemia.

It has been argued that the oedema of kwashiorkor is not caused by hypoalbuminaemia because the oedema disappears with dietary treatment before the plasma albumin concentration rises. Reanalysis of this evidence and a review of the literature demonstrates that this was a mistaken conclusion and that the oedema is linked to hypoalbuminaemia. This misconception has influenced the recommendations for treating children with severe acute malnutrition. There are close pathophysiological parallels between kwashiorkor and Finnish congenital nephrotic syndrome (CNS) pre-nephrectomy; both develop protein-energy malnutrition and hypoalbuminaemia, which predisposes them to intravascular hypovolaemia with consequent sodium and water retention, and makes them highly vulnerable to develop hypovolaemic shock with diarrhoea. In CNS this is successfully treated with intravenous albumin boluses. By contrast, the WHO advise the cautious administration of hypotonic intravenous fluids in kwashiorkor with shock, which has about a 50% mortality. It is time to trial intravenous bolus albumin for the treatment of children with kwashiorkor and shock.