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.

Analysis of proteinuria using a commercial system for automated electrophoresis and isoelectric focusing.

We describe an investigation of proteinuria using Pharmacia PhastSystemTM electrophoresis apparatus. The analysis of urinary proteins by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of unconcentrated urine followed by silver staining took about 2 h and could clearly demonstrate tubular dysfunction or glomerular damage in urines with a negative or only trace-positive dip-stick test for protein. In addition, we show the identification of urinary proteins by immunoblotting from SDS-PAGE gels and the characterisation of Bence-Jones proteins by isoelectric focusing (IEF) and immunoblotting.

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.

The separation of unbound prednisolone in plasma by centrifugal ultrafiltration.

To study variable plasma protein binding of prednisolone in children with nephrotic syndrome we have devised a simple rapid method for measuring unbound prednisolone. The plasma was initially ultrafiltered at 37 degrees C fixed angle head at 1500 g for 30 min then the filtrate was analysed by high pressure liquid chromatography. The effects of variable ultrafiltration conditions were studied. The method was used to compare the AUC unbound prednisolone in a nephrotic child (plasma albumin concentration 18 g L-1) with a control (plasma albumin concentration 43 g L-1); their respective AUC unbound prednisolone values were 4.02 mg h L-1 and 1.07 mg h L-1.

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.

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.

Cure og giggle micturition..

Two boys, aged 11 and 13, had involuntary, unstoppable, and complete emptying of the bladder on laughter. In one the wetting occurred only when standing and in company, but in the other occurred regardless of posture or company. One boy had a strong family history of wetting including a grandmother who had giggle micturition as a teenager. The symptoms had been present for between 1 and 2 years. However, unlike cases previously reported, each boy was cured--one within 6 weeks and the other within 6 months. It is not clear how much of the success was due to the general sympathetic and confidence-building measures used, advice about posture, or to the drug propantheline.

Height attainment in children with steroid-responsive nephrotic syndrome.

The heights of 80 patients with steroid-responsive nephrotic syndrome (SRNS) were measured 5-24 years after diagnosis. During childhood most patients had received repeated courses of high-dose corticosteroids and prolonged maintenance therapy. Although at the time of taking corticosteroids growth was suppressed, those who had completed growth had a mean height standard deviation score (SDS) of -0.22, equivalent to a height on the 40th centile. Total corticosteroid dose prescribed was correlated only weakly with height SDS; there was no correlation between total dose and height when the post-pubertal patients were studied separately, indicating that their ultimate height attainment was not affected significantly.

Sublingual nifedipine in acute severe hypertension.

Sublingual nifedipine was used for the treatment of acute severe hypertension in 12 children with renal disease. An average dose of 0.24 mg/kg was safe and proved effective on most occasions within 30 minutes with a median duration of action of three hours. There were no major adverse effects.

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.

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.

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.

Indices of intact serum parathyroid hormone and renal excretion of calcium, phosphate, and magnesium.

Up to date reference ranges were established for fasting renal excretion of calcium, phosphorus, and magnesium on 101 healthy children aged 2-15 years. A normal range for intact parathyroid hormone was also measured. The indices of calcium and magnesium excretion showed no correlation with age or sex so that a common range for all children could be established. The 97th centile values for urinary calcium:creatinine and magnesium:creatinine ratios were 0.69 mmol:mmol and 1.05 mmol:mmol respectively. The calculated tubular maximum for phosphate/litre of glomerular filtrate (TmPO4/GFR) showed no correlation with age with a geometric mean value of 1.67 mmol/l. The normal range for intact serum parathyroid hormone for the age group was 11-35 ng/l, which is lower than the adult normal range using the same assay. There was an inverse correlation between TmPO4/GFR and intact parathyroid hormone in this group of normal children.

Which bone age in chronic renal insufficiency and end-stage renal disease?

One hundred radiographs of the left hand and wrist from 40 children with chronic renal insufficiency or end-stage renal disease were examined to determine which method of bone age estimation provided the most useful information in these children. The Tanner and Whitehouse method showed better repeatability than the Greulich and Pyle atlas or the Buckler handbook when a sample of the radiographs were assessed twice by the same observer. The Tanner and Whitehouse 20 (TW20) bone age showed less inter-observer bias than the radius, ulna and short bone age or the carpal bone age when three observers independently assessed the same sample of radiographs. TW20 was the most useful method of bone age assessment in this study of British children. An unexpected finding was that the carpal bones were significantly more retarded than the radius, ulna and short bones. Separate assessment of the carpal bone age may provide extra information of clinical relevance.

Which routine test for kidney function?

Eighty measurements of plasma creatinine concentration, height:creatinine ratio, and plasma beta 2 microglobulin concentration were made on 72 children (age 4 months-18.5 years) with known renal disease. Results were compared with simultaneous measurements of glomerular filtration rate using plasma clearance of 51Cr edetic acid to assess the performance of each test as an initial screening procedure of renal insufficiency. Height:creatinine index less than 2.1 was found to have a higher sensitivity and predictive value of a normal result than the other tests and is therefore the preferred test for a screening procedure.

Continuous arteriovenous haemofiltration in the newlyborn with acute renal failure and congenital heart disease.

Newlyborn infants with congenital heart disease who develop acute renal failure are particularly difficult to treat. There are often complex associated medical problems and the mortality is high. Continuous arteriovenous haemofiltration (CAVH) provides a slow and gentle removal of fluid, together with the possibility of correcting metabolic abnormalities. We used CAVH in six newlyborn infants all with severe congenital heart disease, who developed acute renal failure early in life. In four patients it was necessary to insert a blood pump into the circuit to maintain adequate blood flow. CAVH alone, with or without a blood pump, was unable to reduce the plasma urea and creatinine, and in three of the infants, dialysis across the filter was required. CAVH was effective in controlling fluid balance. Although mortality remains high we feel CAVH has an important role in selected patients.

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.

Acute renal failure and hypoglycaemia due to sulphadiazine poisoning.

A 3-year-old girl is described who became oliguric and hypoglycaemic whilst receiving an excessive dose of sulphadiazine. The mechanism of the hypoglycaemia is discussed.

Corticosteroid-induced cataracts in idiopathic nephrotic syndrome.

Th incidence and severity of posterior subcapsular cataracts were studied in 58 children with steroid-sensitive nephrotic syndrome. Eight (14%) children had cataracts. Visual acuity was normal in all but one child. There was no relationship between total dose or mean daily dose of prednisolone (corrected for body surface area) and cataract formation. Alternate-day treatment with prednisolone for an average of half the total treatment time did not prevent cataracts. These studies show there is little risk of causing permanent visual handicap in children with steroid sensitive nephrotic syndrome, provided prednisolone treatment is carefully controlled.