Measurement of intercompartmental fluid shifts during haemodialysis in children.

Seven children (age range 12-19 years, post-dialysis weights 23-43 kg) were studied during 20 haemodialysis sessions. Impedance between wrist and ankle (on the non-fistula side) was recorded using the Xitron 4000B analyser. A 2 ml sample of blood was taken for total protein and haematocrit from the arterial line at the start of dialysis. At approximately 20 minute intervals during dialysis, the time and volume of ultrafiltrate removed were recorded, and a simultaneous measurement of whole body impedance made over 25 logarithmically spaced frequencies in the range 5-500 kHz. A 2 ml sample of blood was also taken, from which serum protein and haematocrit were calculated. Hypotensive episodes occurred during four haemodialysis sessions. The percentage change in extracellular fluid (ECF) volume was calculated, at each sample time for each session, using the impedance measurements and ultrafiltration measurements (denoted delta Vi and delta U respectively). Changes in the intravascular volume were estimated using measurements of haematocrit and serum protein (and denoted delta Vh and delta Vp respectively). Least-squares regression gave delta Vi = 3.77 delta Vh, 1.33 delta Vp and 0.39 delta U, and r2 = 0.72, 0.94 and 0.95 respectively (p < 0.0001 in each case) for the 16 dialysis sessions without hypotensive episodes. Similar analysis of four dialysis sessions with hypotensive episodes gave similar relationships with correlation coefficients 0.64, 0.92 and 0.94. These relationships may not be accounted for by the anthropometric terms alone in the impedance equations. Impedance measurements also detected the addition of 300 ml isotonic saline given at the onset of each of the four hypovolaemic episodes. The regression equations support the following hypothesis: during haemodialysis, ultrafiltrate is removed from the intravascular volume but is replenished by fluid from the interstitial volume. The reduction in ECF volume measured by impedance (where the ECF comprises the intravascular and interstitial volumes) delta Vi is therefore greater than delta Vh and delta Vp, which only measure intravascular volume, but less than delta U since the ECF is replenished by fluid from the interstitial space. That delta Vh is greater than delta Vp may be due to protein loss during dialysis. The results suggest that whole body impedance measurements reflect changing body water distribution during dialysis in children.

Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK.

Against the background of the increasing incidence of many immune mediated childhood conditions, this study aimed to identify recent time trends and ethnic patterns of childhood nephrotic syndrome. A population-based cohort of children (0-15 years) diagnosed according to strict criteria with nephrotic syndrome (NS) was ascertained within the northern UK region of Yorkshire between 1987 and 1998. South Asian ethnicity was assigned based on the child's full name using a dedicated computer algorithm and expert individual checks. NS was diagnosed in 194 children, 170 (88%) of whom were steroid sensitive. The incidence of steroid sensitive NS was 2.0/100,000 pyrs (95% CI 1.7-2.3), peaking in 1-4 year olds (4.1/100,000 pyrs). Over the 12-year study period incidence rates of steroid sensitive NS were fairly stable although south Asian children displayed significantly higher rates than non-south Asians (P<0.01). The size of our population-based series reflects the relative rarity of paediatric nephrotic syndrome but is nonetheless recent and includes larger numbers than previous reports. The absence of any increase in incidence over the last decade contrasts with other paediatric immune mediated conditions such as asthma and diabetes.

Plasma creatinine rises dramatically in the first 48 hours of life in preterm infants.

OBJECTIVE: Published data show that plasma creatinine falls steadily during the first 28 days of life and that creatinine levels in the neonatal period are higher in more premature infants. However, the best reference data commence on day 2 of life. The objective of this study was to document how plasma creatinine changes in the first 48 hours of life and to examine the reason for the apparently high levels of creatinine in preterm infants, compared with maternal levels. DESIGN: A prospective observational study on a regional neonatal intensive care unit. PATIENTS: A total of 42 preterm infants, mean gestational age of 29.4 weeks (range: 23-35), mean birth weight of 1.42 kg (.55-2.77), divided into 4 gestation groups: 23 to 26 weeks (n = 9), 27 to 29 weeks (n = 13), 30 to 32 weeks (n = 12), and 33 to 35 weeks (n = 8). INTERVENTIONS: Measurement of plasma creatinine and urea concentration in cord blood and in serial samples taken for routine arterial blood gas analysis. OUTCOME MEASUREMENTS: Changes in creatinine concentration with time and relationship to gestational age, birth weight, and illness severity. RESULTS: Mean creatinine at birth was 73 micromol/L (95% confidence interval [CI]: 68-79 micromol/L). Plasma creatinine rose significantly over the first 48 hours. Mean peak creatinine in the most preterm infants (23-26 weeks) was 221 micromol/L (CI: 195-247 micromol/L). Peak plasma creatinine was inversely related to gestation (Spearman's coefficient: -.73) and birth weight (Spearman's coefficient: -.76). Significant differences in creatinine concentration were seen among different gestational groups at 24 and 48 hours of life. Peak creatinine correlated with a high Clinical Risk Index for Babies score (Spearman's coefficient:. 64). The fall in creatinine began later in more premature infants. All 38 surviving infants had normal renal function; their mean plasma creatinine at discharge was 52 micromol/L (CI: 46-58 micromol/L). CONCLUSIONS: Rather than falling steadily from birth, creatinine rises dramatically in the first 48 hours of life, especially in infants of <30 weeks' gestation. Even large rises in creatinine in the first 48 hours may be expected and should not be used in isolation to diagnose renal failure.

A review of acute renal failure in children: incidence, etiology and outcome.

We reviewed our experience of children with acute renal failure. St James's University Hospital, Leeds, UK is a tertiary referral center that serves a relatively stable regional population (former Yorkshire region). It is a mixed rural and urban population providing a unique profile of the nature of the cases and workload experienced. The data is expressed as a function of age and compared against a previous era of paediatric nephrology and current adult incidence data. Over an 8-year period (1984-1991) 227 children were referred for dialysis management of acute renal failure. The yearly incidence was 0.8 per 100,000 total population. Acute renal failure in the child population was almost a fifth of the adult incidence. Age-related incidence however shows the highest incidence in the neonate/infant population and is comparable to adult data. The intensive care unit was needed for nearly half the children. For all ages hemolytic uremic syndrome was the commonest cause (45%). Surgery for congenital heart disease was predominant (63%) in the neonate group. The overall mortality was 25%. Primary renal disease accounts for only 7% of the etiologies and was the source for the majority that went on to require chronic renal replacement therapy. Acute renal failure is nearly always a secondary event in the face of other organ failure and the majority of the mortality arises from surgery for congenital heart disease. If the underlying condition is treatable, the prognosis for recovery from acute renal failure with appropriate supportive care is excellent.

Total body water measurement in renal insufficiency.

Total body water was measured in 15 children with renal insufficiency (glomerular filtration rate < 25 ml/min per 1.73 m2) using deuterium oxide dilution. Total body water was also measured using bioelectrical impedance and skinfold anthropometry in the same 15 children. There was a linear correlation (r = 0.98, P < 0.01) between total body water measured by deuterium and height2/impedance. The 95% confidence limits for estimates of total body water were -1.5 to 0.9 for impedance and 0.65-3.16 l for skinfold anthropometry when compared with deuterium dilution. Bioelectrical impedance estimation of total body water is better than the current existing non-invasive method of skinfold anthropometry.

Acute renal failure due to xanthine stones.

A 9-month-old child with the skeletal abnormalities of Fuhrmann's syndrome presented with acute renal failure secondary to bilateral renal calculi. Hereditary xanthinuria was shown to be the underlying metabolic defect. Treatment with allopurinol was unsuccessful at reducing the xanthine excretion.

Assessment of the sensitivity of bioimpedance to volume changes in body water.

The sensitivity of whole-body electrical impedance measurements to changes in the volume of total body water in 12 children undergoing haemodialysis has been assessed. The impedance (I) of each child was measured at 20-min intervals during dialysis using the standard four-electrode technique to apply a constant current (800 microA, 50 kHz) between the wrist and ankle on the non-fistula side of the patient. The ultrafiltration volume (U) was also recorded. A simple electrical model suggests that U = aHt2 ((1/I0)-(1/I)), where I0 is the whole body impedance at the start of dialysis, a is a constant and Ht is patient height. No significant changes in I were measured on 4 patients undergoing dialysis without ultrafiltration, whereas in 8 patients undergoing ultrafiltration and dialysis I increased. Linear regression analysis and the above equation gave a mean value for a = 0.566 1 Ohm/cm2 (coefficient of variation = 3%), (mean r = 0.97), values comparable to those values obtained from isotope dilution studies. Predicted fluid loss in 8 patients following a single dialysis session gave a mean overestimate of 4.3% (limits of agreement 27.3% and -19.7%), although in 6 of the patients agreement was to within 6%. Changes in impedance reflect changes in total body water in children undergoing haemodialysis and are relatively insensitive to factors such as the possible differences in electrolyte levels between these patients.

Volumetric control of continuous haemodialysis in multiple organ failure.

A system for precise volumetric control of continuous haemodialysis and its use in providing renal replacement treatment in the intensive care unit to 10 children with multiple organ failure are described. The system, termed slow efficient dialysis, provided effective clearance of urea, creatinine, potassium, and phosphate. It provided precise control of the volume of ultrafiltrate removed in a prospective manner ('dial up' fluid balance) to reduce haemodynamic instability and fluid management problems. The ease of use of this system for intensive care nurses meant that the system ran without the assistance of a second intensive care or renal nurse.

Reliability of haemodialysis urea kinetic modelling in children.

The reliability of urea kinetic modelling (UKM) in paediatric haemodialysis was tested by comparing results of the classic variable volume model (UKM3), a recently introduced two-sample modification of this (UKM2) and direct quantification by a partial dialysate collection method (PDC). Urea generation rate (G) was also found from a 1-week collection of dialysate and urine (OWC). Nine children aged 2-18 years and weighing 10.6-39.9 kg were examined over 1 week (25 treatments). UKM3 and UKM2 gave almost identical results, but deviated from PDC and OWC. The two indirect methods overestimated G by 24% and 18%. However, the correlations between the results were very high for all variables and all methods (r > or = 0.96). Repeating UKM3 and UKM2 mid-week for 5 consecutive weeks, the following coefficients of variation were found: for the normalised whole body urea clearance (Kt/V) 10% and 11%, respectively; for normalised protein catabolic rate 17% and 14%. It is concluded that all tested methods can be used, but each method requires its own reference interval. Results of UKM seem to vary somewhat more than in adults. This should be considered when assessing children by such methods.

Comparison of extra-cellular fluid volume measurement in children by 99Tcm-DPTA clearance and multi-frequency impedance techniques.

Comparisons of extra-cellular fluid (ECF) volume estimates made by isotope dilution and electrical impedance techniques have been made in a group of 16 children. For each patient an estimate of ECF volume (Vt) was obtained from measurements of the blood clearance of 99Tcm-diethylene triamine penta-acetate (DPTA) which was compared with two estimates (Vi1 and Vi2) of ECF volume obtained from measurements of the whole-body electrical impedance at 50 frequencies in the range 1 kHz to 1.348 MHz and a third estimate Vh based on patient height, L, alone. The observed frequency response of the impedance measurements was fitted to a three-element equivalent-circuit model of whole-body impedance and gave a value of the ECF resistance R. Vi1 was obtained from Vi1 = a (L2/R) + b. Vi2 was given by c(W1/2L2/R)2/3 where W is the patient weight, and Vh was given by dL2 + e. The constants a, b, c, d, e were determined by comparison with Vt and were equal to 0.335 l omega m-2 (standard error = 0.01 1 omega m-2), 0.42 l (0.25 l), 0.33 l (omega 2kg-1m-4)1/2 0.007 l (omega 2kg-1m-4)1/3, 4.92 l m-2 (2.8 x 10(-5) lm-2), 0.13 l (0.41 l), respectively. Vi1, Vi2, Vh were linearly correlated with Vt (r2 = 0.98, 0.99, 0.95, respectively, p < 0.001), and upper and lower levels of agreement were given by +/- 0.95 l (Vt and Vi1), 1.44 l and -1.12 l (Vt and Vi2), +/- 1.5 l (Vt and Vh), respectively. Thus inclusion of the impedance data accounted for greater volume variation, but differences between the techniques were not significant (paired t-test and Mann-Whitney analysis) suggesting that more accurate and detailed measurements are required.

Treatment of hyperkalaemia using intravenous and nebulised salbutamol.

In 11 children (aged 5-18 years) with end stage chronic renal failure, the effect on plasma potassium of two doses of salbutamol (separated by two hours) given intravenously (4 micrograms/kg) and on a separate date, of salbutamol administered by nebuliser (2.5 mg if the child weighed below 25 kg, 5 mg if above) was observed. Within 30 minutes of the first dose, the mean plasma potassium concentration fell significantly by 0.87 and 0.61 mmol/l after intravenous and nebulised administration respectively. Sixty minutes after the second dose the plasma potassium was significantly reduced by a further 0.28 and 0.53 mmol/l respectively. There was a significant difference between the two methods of administration at 300 minutes after the first dose favouring nebulisation. No major side effects were observed. Nebulised salbutamol should be the first choice emergency treatment of hyperkalaemia.

Mathematical modelling of haemodialysis in children.

The single-pool urea kinetic model (UKM), utilising "Kt/V" (the normalised whole body urea clearance), is widely used to help assess the adequacy of haemodialysis in adults. In the presence of an adequate dietary protein intake, a value of unity is acceptable for thrice weekly dialysis. Children could benefit from this approach but, with their relatively higher protein intakes and dialysis needs, this model may not be applicable. Urea kinetics, studies in six children with chronic renal failure by serial timed blood urea measurements during and after haemodialysis, were compared with the kinetics of a one-pool and a two-pool UKM. The two-pool UKM with intra- and extracellular pools best fitted the observed data, re-equilibration between pools accounting for the marked rebound increase in blood urea seen in the 1st h after dialysis (mu 17%, SD 5). Kt/V calculated using the end-dialysis blood urea was higher (mu 21%, SD 5) than when the more correct equilibrated value was used. The post-dialysis rebound indicates significant disequilibrium between the two pools at the end of dialysis. Dialysis efficiency may be substantially overestimated unless this is allowed for by using the rebounded post-dialysis blood urea when calculating Kt/V.

Paediatric haemodialysis: estimation of treatment efficiency in the presence of urea rebound.

The 2-pool urea kinetic model has been developed analytically and applied to the description of the observed increase in blood levels of urea following dialysis (urea rebound), assuming that the dialyser urea clearance K less than 0.4X where X is the urea mass transfer coefficient between the intracellular and extracellular pools (volumes V1, V2 respectively). Urea generation was also neglected. Measurements were made in a group of six children suffering from chronic renal failure. From the model X, the efficiency of dialysis, and the equilibrium urea concentration C infinity were estimated in the presence of urea rebound using a blood urea measurement taken 90 min following start of dialysis, in addition to the conventional samples taken immediately pre- and post-dialysis. In three of the patients agreement between the experimental value of X derived from a multi-blood-sample technique post-dialysis, and the model value, was within 10%, for the range V1 = 0.4 W - 0.38 W, V2 = 0.2 W - 0.238 W, (W = patient's weight). Experimental values of X were in the range 93 - 300 ml min-1. Model estimates of C infinity were accurate to within 10%. An approximate technique was also developed which permitted an estimate of C infinity which was independent of V1, V2, K. The results indicated that C infinity was estimated to within 10% of the true equilibrium urea concentration. The error in the estimate of dialysis efficiency based on a single pool model was reduced by at least 50% using the model. The model may be applied clinically to the estimation of dialysis efficiency in the presence of significant urea rebound.

The tubular maximum for calcium reabsorption: a normal range in children.

OBJECTIVE: We aimed to establish a normal range for the tubular maximum rate of reabsorption of calcium corrected for glomerular filtration rate. DESIGN: A prospective survey was used. PATIENTS: One hundred and ten normal children aged 2-14 years were studied. MEASUREMENTS: Total plasma calcium, ultrafiltrable calcium and parathyroid hormone. Urinary calcium, sodium and creatinine excretion. RESULTS: The normal range was found to be 1.87-3.39 mmol/l of glomerular filtrate with a geometric mean value of 2.40 mmol/l. There was a significant inverse relationship between the tubular maximum for calcium and the urinary sodium excretion. No significant relationship was found between the tubular maximum for calcium and the level of parathyroid hormone in this group of normal children. CONCLUSIONS: The normal range seen in children is higher than that seen in adults with a higher mean value. This normal range should be useful in the assessment of renal calcium handling in children with disorders of calcium homeostasis.

Autosomal recessive hypoparathyroidism with renal insufficiency and developmental delay.

Four children (two boys and two girls) with hypoparathyroidism, renal insufficiency, and developmental delay are described. They were the products of consanguineous marriages in three related Asian families presenting over a six year period. All the children died within the first 15 months of life despite treatment. Postmortem examination on one child showed absent parathyroid glands. We believe these children represent a previously undescribed syndrome that appears to be inherited in an autosomal recessive manner.

Long-term outcome for children with acute renal failure following cardiac surgery.

Acute renal failure requiring dialysis occurred in 34 children (2.9%) following cardiac surgery over a five year period. 17 children (50%) recovered renal function with 11 (32%) long-term survivors. The long-term outcome for the survivors, in terms of renal function, was studied from 1 to 5 years after their episodes of acute renal failure. Three children had significant abnormalities of renal function despite normal urinalysis. Detailed assessment of renal function is advocated for children who survive acute renal failure following cardiac surgery.