Urinary potassium to urinary potassium plus sodium ratio can accurately identify hypovolemia in nephrotic syndrome: a provisional study.

There is evidence pointing to a decrease of the glomerular filtration rate (GFR) in a subgroup of nephrotic children, likely secondary to hypovolemia. The aim of this study is to validate the use of urinary potassium to the sum of potassium plus sodium ratio (UK/UK+UNa) as an indicator of hypovolemia in nephrotic syndrome, enabling detection of those patients who will benefit from albumin infusion. We prospectively studied 44 nephrotic children and compared different parameters to a control group (36 children). Renal perfusion and glomerular permeability were assessed by measuring clearance of para-aminohippurate and inulin. Vaso-active hormones and urinary sodium and potassium were also measured. Subjects were grouped into low, normal, and high GFR groups. In the low GFR group, significantly lower renal plasma flow (p = 0.01), filtration fraction (p = 0.01), and higher UK/UK+UNa (p = 0.03) ratio were noted. In addition, non-significant higher plasma renin activity (p = 0.11) and aldosteron (p = 0.09) were also seen in the low GFR group. CONCLUSION: A subgroup of patients in nephrotic syndrome has a decrease in glomerular filtration, apparently related to hypovolemia which likely can be detected by a urinary potassium to potassium plus sodium ratio > 0.5-0.6 suggesting benefit of albumin infusion in this subgroup. What is Known: • Volume status can be difficult to assess based on clinical parameters in nephrotic syndrome, and albumin infusion can be associated with development of pulmonary edema and fluid overload in these patients. What is New: • Urinary potassium to the sum of urinary potassium plus sodium ratio can accurately detect hypovolemia in nephrotic syndrome and thus identify those children who would probably respond to albumin infusion.

Evidence of partial anti-enuretic response related to poor pharmacodynamic effects of desmopressin nasal spray.

PURPOSE: Desmopressin is an evidence-based medicine level I, category A therapy for monosymptomatic nocturnal enuresis. However, in up to 40% of patients only partial desmopressin response is obtained. While the poor pharmacokinetic characteristics of the different available formulations may have a role in apparent therapy resistance, there are limited data available to support this theory. We sought to identify pharmacodynamic factors involved in partial desmopressin response or desmopressin resistance in children with monosymptomatic nocturnal enuresis, with special emphasis on concentrating performance, and time to reach and duration of maximal urine concentration. MATERIALS AND METHODS: We evaluated 64 children with monosymptomatic nocturnal enuresis and proved nocturnal polyuria lacking full response to desmopressin treatment. The study involved 2 separate home based test days (A and B), each consisting of 9 timed urine collections starting in the evening 1 hour before desmopressin administration and continuing for 16 hours following desmopressin administration. Test A was done during fluid restriction, and test B was done during an oral fluid load. RESULTS: Under fluid restriction 16 patients failed to achieve urine concentration greater than 850 mOsmol/l at the midnight collection following desmopressin administration. After an oral fluid load given at the start of the test the majority of patients failed to reach maximal concentration of urine as voided during hydropenia, and 45 patients failed to regain appropriate dilution of urine even when an oral water load of 15 ml/kg (urine osmolality less than 750 mOsmol/l) was given in the morning at the end of the test. This finding is suggestive of a prolonged duration of action of the drug. CONCLUSIONS: Pharmacodynamic tests reveal a suboptimal effect of desmopressin on urine concentration in a significant percentage of patients, which worsens when fluid is not restricted before desmopressin administration. Also the time to reach maximal antidiuretic effect and the duration of pharmacodynamic action show a wide range, requiring individualization of mode and time of administration. Our data demonstrate that a simple pharmacodynamic test as described may give important information on time of dosing, duration of action and influence of oral fluid intake, allowing individualization of therapy. Data also reveal that desmopressin should be administered at least 1 hour before bedtime, and that in case of therapy resistance a longer interval, up to 2 hours, might further reduce diuresis rate in the early night. Because of the documented prolonged action of desmopressin in some patients, increasing the dose without performing pharmacodynamic testing is no longer acceptable.

Renal hemodynamic changes and renal functional reserve in children with type I diabetes mellitus.

Increased glomerular filtration rate (GFR) has been implicated in the development of diabetic nephropathy. Large normal interindividual variations of GFR hamper the diagnosis of renal hemodynamic alterations. We examined renal functional reserve (RFR) in children with type 1 diabetes mellitus to assess whether hyperfiltration occurs. The renal hemodynamic response following dopamine infusion was examined in 51 normoalbuminuric diabetic children (7.7 +/- 3.6 years) with a mean duration of diabetes of 6.2 years and compared them with 34 controls. Mean baseline GFR in diabetic children did not differ from the control population (130.7 +/- 22.9 vs. 124.8 +/- 25 ml/min per 1.73 m(2)), whereas renal plasma flow was significantly lower (463.7 +/- 103.9 vs. 587.2 +/- 105 ml/min per 1.73 m(2), p < 0.001), and filtration fraction was increased (29 +/- 8 vs. 21 +/- 2%, p < 0.001), compared with controls. The mean RFR was lower (p < 0.001) than in control subjects (-0.77 +/- 23 vs. 21 +/- 8 ml/min per 1.73 m(2)). This study documents an increased filtration fraction and reduced or absent RFR in children with type 1 diabetes mellitus in the stage before apparent nephropathy. GFR values were within normal range. Although the reduced RFR and increased filtration fraction indicate the presence of hemodynamic changes, their relevance to the development of hyperfiltration and subsequent diabetic nephropathy remains unknown.

Lisinopril in paediatric medicine: a retrospective chart review of long-term treatment in children.

OBJECTIVE: To investigate the antihypertensive efficacy, dosing, tolerability and effects on growth of lisinopril (off label-use) in paediatric patients during long-term treatment. DESIGN: We conducted a retrospective analysis of data from 123 patients treated with lisinopril in a paediatric nephrology clinic over a 9.3-year period. Patients were categorised by age group and predominant clinical diagnosis: hypertension (n=59), renal parenchymal disease (n=27), diabetes mellitus (n=33) and miscellaneous (n=4). RESULTS: The vast majority were Caucasian (93%) and boys (66%). Mean duration of treatment was 2.0 years. Age at start of treatment ranged from two months to 17.7 years. Mean lisinopril starting and final doses were 0.105 mg/kg/day for hypertensive patients and 0.108 mg/kg/day for patients with renal disease, respectively. The most common adverse event was hypotension (8.6% of the patients). Haematology and serum biochemistry profiles were unaffected by lisinopril. Growth was not different from data recorded by Belgian population studies. In 29 of the 47 hypertensive patients who received lisinopril monotherapy, comparing blood pressure (BP) at baseline and after six months treatment, mean reductions in systolic/diastolic BP were 19/18 mmHg. CONCLUSIONS: Lisinopril was well tolerated in paediatric patients. Doses of 0.1 mg/kg/day produced clinically significant BP reduction in hypertensive patients.

Lack of evidence of hypervolemia in children with insulin-dependent diabetes mellitus.

Hypervolemia is considered to play a major role in the pathogenesis of diabetic vasculo- and nephropathy. The aim of our study is to determine whether children and adolescents with insulin-dependent diabetes mellitus (IDDM) experience alterations in blood volume (BV) before onset of apparent nephropathy. BV (calculated as the sum of measured plasma volume (PV) and red cell volume (RCV)) was determined in 31 children (9-16 yr) with a mean duration of IDDM of 6.6 yr and without microalbuminuria. Due to dependence of these values on age, size and sex, all data were normalised for body size parameters. While no statistical difference for BV normalised for lean body mass (LBM) (86.98+/-9.5 ml/kg) was found in diabetic children compared with our control population (84.91+/-12.08 ml/kg), a difference could be shown when normalised for body surface area (BSA) (diabetic children 2.37+/-0.3 L/m(2); control population 2.15+/-0.38 L/m(2), p=0.002). Increased BV is only present when normalising for BSA and not for the theoretical superior LBM-index. Because the study population exhibited a poor glycemic control (HbA1c 10.2+/-2.4 %), an influence of glucosuria-induced polyuria on BV cannot be excluded. Taking into account these limitations our data do not confirm the presence of hypervolemia before onset of diabetic nephropathy.

Free radicals in exhaled breath condensate in cystic fibrosis and healthy subjects.

Many markers of airway inflammation and oxidative stress can be measured non-invasively in exhaled breath condensate (EBC). However, no attempt has been made to directly detect free radicals using electron paramagnetic resonance (EPR) spectroscopy. Condensate was collected in 14 children with cystic fibrosis (CF) and seven healthy subjects. Free radicals were trapped by 5,5-dimethyl-1-pyrroline-N-oxide. EPR spectra were recorded using a Bruker EMX spectrometer. Secondly, to study the source of oxygen centered radical formation, catalase or hydrogen peroxide was added to the condensate. Radicals were detected in 18 out of 21 condensate samples. Analysis of spectra indicated that both oxygen and carbon centered radicals were trapped. Within-subject reproducibility was good in all but one subject. Quantitatively, there was a trend towards higher maximal peak heights of both oxygen and carbon centered radicals in the children with CF. Catalase completely suppressed the signals in condensate. Addition of hydrogen peroxide resulted in increased radical signal intensity. Detection of free radicals in EBC of children with CF and healthy subjects is feasible using EPR spectroscopy.

A reference frame for blood volume in children and adolescents.

BACKGROUND: Our primary purpose was to determine the normal range and variability of blood volume (BV) in healthy children, in order to provide reference values during childhood and adolescence. Our secondary aim was to correlate these vascular volumes to body size parameters and pubertal stages, in order to determine the best normalisation parameter. METHODS: Plasma volume (PV) and red cell volume (RCV) were measured and F-cell ratio was calculated in 77 children with idiopathic nephrotic syndrome in drug-free remission (mean age, 9.8 +/- 4.6 y). BV was calculated as the sum of PV and RCV. Due to the dependence of these values on age, size and sex, all data were normalised for body size parameters. RESULTS: BV normalised for lean body mass (LBM) did not differ significantly by sex (p < 0.376) or pubertal stage (p < 0.180), in contrast to normalisation for the other anthropometric parameters. There was no significant difference between reference values for children and adults. CONCLUSION: LBM was the anthropometric index most closely correlated to vascular fluid volumes, independent of age, gender and pubertal stage.

Exhaled breath condensate in children: pearls and pitfalls.

Exhaled breath condensate (EBC) is a rapidly growing field of research in respiratory medicine. Airway inflammation is a central feature of chronic lung diseases, like asthma, cystic fibrosis, bronchopulmonary dysplasia and primary ciliary dyskinesia. EBC may be a useful technique for non-invasive assessment of markers of airway inflammation. The non-invasive character of EBC "inflammometry" and the general lack of appropriate techniques makes it particularly interesting for paediatrics. We provide a detailed update on the methods currently used for EBC collection and measurement of mediators. We emphasize on paediatric data. The apparent simplicity of the EBC method must not be overstated, as numerous methodological pitfalls have yet to overcome. Comparison and interpretation of data on this rapidly growing field of research is mainly hampered by the lack of standardization and the lack of specific high-sensitivity immunochemical or colorimetric assays. The initiative of the European Respiratory Society to institute a task force on this topic is a first step towards a uniform technique of EBC. Meanwhile, when using this technique or when interpreting research data, one should be fully aware of the possible methodological pitfalls.

ARF in children with minimal change nephrotic syndrome may be related to functional changes of the glomerular basal membrane.

BACKGROUND: Acute renal failure (ARF) is a rare complication in children with minimal change nephrotic syndrome (MCNS). Several etiologic factors (renal vein thrombosis, side effect of such drugs as nonsteroidal anti-inflammatory drugs, and infections) have been described, but often such conditions are lacking, and hemodynamic derangements or changes in glomerular permeability are suspected. METHODS: We assessed the role of alterations in renal perfusion and glomerular permeability by measuring clearances of inulin and para-aminohippurate before and during intravenous administration of a 20% albumin solution in patients with MCNS and oliguric ARF (serum creatinine > 1 mg/dL [88 micromol/L], urine output < 0.5 mL/kg body weight/h). RESULTS: Eleven patients aged 2.5 to 15 years with biopsy-proven MCNS were studied. Before albumin administration, all patients had a significantly decreased glomerular filtration rate (GFR), whereas most renal plasma flow (RPF) values were within the normal range. This resulted in a significantly decreased filtration fraction (FF; GFR/RPF x 100), which was extremely low (<7%) in 4 patients. There was a heterogeneous response to albumin administration. Albumin infusion tended to increase RPF, but changes did not reach statistical significance. Some patients showed an increase in glomerular filtration, whereas in others, it decreased. In 7 patients, FF remained unchanged or decreased even further. CONCLUSION: Our data suggest that, although in some patients decreased intravascular volume may contribute to reduced renal function, changes in glomerular permeability may have a major role in ARF occurring in uncomplicated MCNS.

Re-establishment of the ERA-EDTA Registry.

The European Dialysis and Transplant Association (EDTA) Registry was established in the mid 1960s and its annual reports for many years provided important information on the treatment of children in Europe with renal diseases. The last report of the former European Renal Association (ERA)-EDTA Registry, based in London, was in 1996. Unfortunately, shortly thereafter, for a number of reasons the Registry collapsed. However, in June 2000 the ERA-EDTA Registry was re-established in Amsterdam, The Netherlands, and the first report of this new European Registry on renal replacement therapy is now published. Effective collaboration of single national registries with the new ERA Registry is important for the future development of new successful treatment strategies in pediatric renal medicine.

Comparison of interhospital pediatric intensive care transport accompanied by a referring specialist or a specialist retrieval team.

OBJECTIVE: Interhospital transfers of critically ill pediatric patients in The Netherlands are accompanied by referring specialists or by specialist retrieval teams. We compared the interventions before and directly after transports and the complications and the equipment available during transports in the two groups. DESIGN AND SETTING: Prospective observational clinical study in pediatric intensive care units of Dutch university hospitals. PATIENTS: 249 pediatric patients requiring interhospital intensive care transport. METHODS: Data were collected on interhospital pediatric intensive care transports. We compared patient characteristics, interventions before and directly after transport, complications and equipment available during transport (137 accompanied by referring specialists, 112 by specialist retrieval teams). RESULTS: Interhospital transports accompanied by referring specialists had a longer average transport time (74.6 vs. 60.2 min), higher incidence of respiratory insufficiency (56.9% vs. 41.1%), and lower incidence of circulatory insufficiency (27.0% vs. 41.1%) than primary admission diagnoses. These transports had a lower percentage of ventilatory support (47.4% vs. 72.3%), higher need for acute interventions directly upon arrival on the pediatric ICU, and higher incidence of critical and serious complications. In 75% of the transfers accompanied by retrieval teams interventions before the transport were deemed to be necessary. During the transports accompanied by referring specialists the equipment and materials available proved rather limited. CONCLUSIONS: During pediatric intensive care transports accompanied by nontrained referring specialists there appears to be a higher incidence of complications, specialized equipment is more often not available, and more acute interventions are required upon arrival in the pediatric ICU.

Interhospital paediatric intensive care transport: a novel transport unit based on a standard ambulance trolley.

A recent development in providing intensive care for children is that it is more and more centralized in tertiary centres. The centralization of intensive care facilities for children in tertiary centres demands a safe and well-organized transport system. The transfer of critically ill children from a referring general hospital to a tertiary paediatric intensive care centre should be performed by a specially trained and fully equipped transport team. During the transfer of these children continuous intensive care facilities should be provided. The minimal requirements of equipment and materials for transport that allow such care have been determined. The equipment consists of a monitor allowing continuous measurement of vital signs, a defibrillator, tools for airway and ventilatory management, an oxygen source, suction unit, fluid and electrolyte management, medication, resuscitation chart and a communication system. A mobile paediatric intensive care unit was constructed in order to store this equipment, including easily accessible ventilator and materials optimized for close patient observation and ventilator control.