Extracellular fluid in individual tissues and in whole animals: the distribution of radiosulfate and radiobromide.

Radiosulfate, (35)SO(4), and radiobromide, (82)Br, were administered simultaneously to rats and dogs. In rats, the apparent volume of distribution of (82)Br averaged 30% of body weight and was constant between 0.5 and 35 hr after injection. The apparent volume of distribution of (35)SO(4), corrected for urinary loss, increased by 6% body weight/hr: the extrapolated volume at zero time was 88% of bromide space. Analysis of individual tissues and carcasses for (82)Br and inorganic (35)SO(4) showed that equilibration of both isotopes in several organs and in the whole carcass was rapidly achieved within 1 to 2 hr: no further increase in measured spaces occurred in 24 hr. The carcass inorganic sulfate space was 92%+/-2% of the bromide space in intact rats, and showed no increase with time. However, a progressively greater fraction of the injected (35)SO(4) was not recovered, owing to metabolic alteration. In eviscerated rats, the inorganic sulfate space was a smaller and much more constant fraction (79.8% +/-0.4%) of the bromide space, showing that at least 20% of body bromide (and hence chloride) is nonextracellular. The viscera chiefly responsible for the higher ratio of spaces in the intact animal were the liver, small bowel, and kidney. In the last two organs, excess inorganic (35)SO(4) (beyond the bromide space) was attributable to trapped transcellular fluid in which sulfate had been concentrated more than chloride (or bromide). Excess sulfate in liver and cartilage could not be explained in this manner: the results suggest passive binding of sulfate, but could reflect active cell uptake in these tissues. No excess sulfate was found in skin or tail. The implications of these observations with respect to the distribution of body chloride and the measurement of extracellular space are discussed. The extracellular volume of the rat is estimated to be 24% of body weight.

Familial hypoplastic glomerulocystic kidney disease: a definite entity with dominant inheritance.

Autosomal dominant (or possibly X-linked) inheritance of familial hypoplastic glomerulocystic kidneys is described in a mother and son who both had stable, chronic renal failure, cystic kidneys by ultrasound examination, glomerular cysts as demonstrated histologically, and malformed renal calyces. There was no evidence of other congenital abnormalities apart from prognathism, small stature and pyloric stenosis. Hepatic fibrosis was not evident in a liver biopsy specimen. These findings add further confirmation to the existence of the syndrome of familial hypoplastic glomerulocystic kidney disease with dominant inheritance.

An electrophysiological study on children and young adults with Alport's syndrome.

Alport's syndrome is characterised by progressive haematuric nephritis and high tone sensorineural hearing loss. Ocular signs are variable, the most consistent findings being anterior lenticonus and retinal flecks in the macula and mid peripheral areas. Previous electrophysiological studies on patients with Alport's syndrome have mostly been on adult patients undergoing haemodialysis, or after renal transplantation. A group of young patients with Alport's syndrome were studied to assess if early electrophysiological changes were detectable. A total of 20 patients (15 males and five females) between the ages of 3.5 and 22 years (mean 12.7 (years) were examined and compared with control subjects. Visual evoked potentials and electroretinograms were obtained following flash and pattern reversal stimulation. Electro-oculograms were also recorded. No significant electrophysiological changes were found in any of the 20 patients, including four who had visible fundus changes.

Tubular proteinuria in steroid sensitive multi-relapsing nephrotic syndrome.

The urinary excretion of N-acetyl-beta-D-glucosaminidase (UNAG) and retinol binding protein (URBP) was studied in 65 children with steroid sensitive multirelapsing nephrotic syndrome (MRNS): 28 on cyclosporin A (CyA) therapy, 22 on prednisolone (P), 15 off-treatment and in 32 normal children to assess renal tubular damage or dysfunction. The urinary protein excretion was expressed in relation to that of creatinine (UNAG/UC in mumol pnp/h/mmol; URBP/UC in microgram/mmol). There was a weak but significantly negative correlation between age and both, UNAG/UC (r = -0.38, p < 0.01) and URBP/UC (r = -0.50, p < 0.05) in normal children, but not in nephrotics. In normals and in patients off steroids an association between these two proteins was found (r = 0.38, p < 0.05; r = 0.56, p < 0.05 respectively). Geometric mean UNAG/UC was significantly higher in nephrotics on CyA therapy (26.5 +/- 4.0), and on P (37.0 +/- 7.9) as well as in those off-treatment (16.3 +/- 3.1) compared to normal children (9.3 +/- 3.4). There was a further increase in those with raised urinary albumin: creatinine ratio (UA/UC) (> 0.1 mg/mg). URBP/UC was not increased in any of the groups of children with MRNS. Raised NAG in urine may therefore indicate active nephrotic syndrome rather than being due to the drug therapy.

Renal function following cardiopulmonary bypass surgery in children: a randomized comparison of the effects of gentamicin and cloxacillin with cephalothin.

Renal function was studied in 36 children who were randomly allocated to receive either gentamicin and cloxacillin or cephalothin as prophylactic antibiotic cover for complex cardiopulmonary bypass surgery. Both groups of children developed a similar degree of impairment of glomerular function with significant elevations in plasma creatinine concentrations and urine albumin excretion compared to preoperative levels which tended to resolve by the 5th postoperative day. The urine excretion of N-acetyl-glucosaminidase increased in both groups postoperatively but remained significantly elevated only in those children who had received gentamicin. These findings suggest that whilst gentamicin exerts a demonstrable nephrotoxic effect on the proximal renal tubules it does not contribute significantly to either the incidence or severity of postoperative renal glomerular impairment.

The beneficial effect of mannitol on postoperative renal function in children undergoing cardiopulmonary bypass surgery.

A randomized prospective controlled study of prophylactic administration of mannitol 0.5 g/kg body weight in 40 children undergoing cardiopulmonary bypass surgery showed significant lower plasma creatinine concentrations and urinary albumin excretion rates in the treated compared to the control group.

Duplex Doppler ultrasound in the investigation of occult nephropathy following haemolytic uraemic syndrome.

Duplex doppler ultrasound has been reported to be of value in the detection of raised vascular resistance, particularly in the renal tract. A prospective single blind study investigating the use of duplex Doppler ultrasound to measure resistive index (RI) in patients with impaired renal function and a history of diarrhoea-associated haemolytic uraemic syndrome (D+ HUS) was performed. There was considerable overlap in the range of RIs, with RIs greater than 70% in children with normal renal function and in those with renal impairment following D+ HUS. There was no significant difference in the mean RI between the groups studied. We feel that the RI is not of value in predicting the presence of occult nephropathy following haemolytic uraemic syndrome.

Renal parenchymal determination and analysis during dynamic 99Tcm-DTPA scans in children.

Twenty-six children underwent a total of 75 99TCm-DTPA scans. Two experienced operators, using different techniques were able to identify parenchyme in 77 of 111 kidneys. Parenchymal regions of interest were drawn by an entirely operator dependent and a relatively operator-independent technique. Transit time analysis, using a matrix algorithm, through the parenchyme of both normal and abnormal kidneys showed a high degree of correlation (tau = 0.595, P less than 0.001). The technique concurred in the studies for which the analysis could not be applied, generally due to poor technical factors or gross hydronephrosis with insufficient parenchyme to generate a time activity curve. Either technique may be used in clinical practice to identify renal parenchyme for further analysis.

Spectrum of 2,8-dihydroxyadenine urolithiasis in complete APRT deficiency.

APRT deficiency may be totally benign or life threatening. The importance of early recognition/diagnosis is thus stressed. Urolithiasis (2,8-DHA stones: the precipitating factor in all cases) is treatable. With early recognition and treatment allopurinol without alkali and a diet low in purine homozygotes have remained clinically and biochemically normal to date. 'Uric acid' stones in children must always be suspect and subjected to sophisticated analysis. Diagnosis from red cell APRT activity may also have its pitfalls.

Long term renal outcome of childhood haemolytic uraemic syndrome.

OBJECTIVE: To evaluate the long term outcome of renal function in infants and children after diarrhoea associated haemolytic uraemic syndrome. SETTING: The Hospital for Sick Children, Great Ormond Street, and the Royal Free Hospital, London. SUBJECTS: 103 children with the syndrome who presented between 1966 and 1985; 88 attended for follow up investigations (40 male, 48 female) with a mean age 11.6 (range 5.2-22.6) years and a mean duration of follow up of 8.5 (range 5.1-21.3) years. MAIN OUTCOME MEASURES: Blood pressure, ratio of early morning urine albumin to creatinine concentration, glomerular filtration rate, and plasma renin activity. RESULTS: The mean (SD) systolic blood pressure standard deviation score was 0.38 (0.67) and diastolic blood pressure SD score was 0.10 (0.76). The geometric mean ratio of overnight urine albumin to creatinine concentration was 1.27 (range 0.03-48.2), significantly higher than the value observed in 77 normal children (0.32 (0.05-1.95), p less than 0.0001). Glomerular filtration rate estimated from the plasma clearance of chromium-51 EDTA was 95.1 (22.7) ml/min/1.73 m2 surface area, and 16 children had a rate of less than or equal to 80 ml/min/1.73 m2. Significant negative correlations were found between glomerular filtration rate and urinary albumin to creatinine ratio (r = -0.41, p less than 0.0001) and glomerular filtration rate and systolic blood pressure SD score (r = -0.48, p less than 0.0001). A significant positive correlation was found between urinary albumin to creatinine ratio and systolic blood pressure SD score (r = 0.25, p = 0.02). CONCLUSIONS: After an acute episode of diarrhoea associated haemolytic uraemic syndrome 31% (27/88) of children had an increased albumin excretion, 18% (16/88) had a reduced glomerular filtration rate and 10% (9/88) had both, in association with a higher systolic blood pressure, indicating considerable residual nephropathy in this group.

Investigation of the dilated urinary tract.

Dilatation of the urinary tract does not necessarily imply obstruction, and other factors may be operative: maldevelopment, infection, reflux, and polyuria. Obstruction of the urinary tract in intra-uterine life is associated with renal dysplasia: the original obstructive lesion may be transient but the consequent dysplasia and dilatation may be permanent. Routine antenatal ultrasound identifies a new population of infants with urinary tract dilatation, many of whom remain asymptomatic and would not otherwise have come to medical attention: the natural history and appropriate schedules of investigation and management of this group are still being evaluated. Anatomical imaging by ultrasound establishes the presence and extent of dilatation. Micturating cystourethrography, intravenous urography and antegrade pyelography establish the site but not the functional significance of an obstructive lesion. Isotope renal scanning with 99mTc-DTPA may identify an acutely obstructed kidney with a decrease renal uptake, prolonged parenchymal transit time, and delayed clearance of the isotope from the renal pelvis after furosemide. However, such analyses often give equivocal results in infants with poor renal function and markedly dilated urinary tracts. Obstructive uropathy should be seen as a disturbance of the normal pressure-flow relationships in the urinary tract, and be defined and investigated as such. Antegrade perfusion with renal pelvic pressure measurements has technical pitfalls, but is the definitive method of establishing upper tract obstruction. Videocystourethrography is the established method of investigating the lower urinary tract in older children but needs further development to be applicable to infants.

Imaging the kidneys and urinary tract in the neonate with acute renal failure.

Transitional nephrology seriously affects the manner in which radiological investigations and other forms of imaging are undertaken in the neonate. When this is complicated by acute renal failure then caution must be exerted in taking care of the neonate. The use of ultrasound and micturating cystourethrography are well described and form the baseline for all imaging of the renal tract. The physiological handling of TC99m DTPA and the contrasts used for IVU are described as well as the normal appearances of these techniques in the neonate. TC99m DMSA is also included, as are other modalities of imaging.

IgA immune complexes in Henoch-Schönlein purpura.

Raised levels of IgA immune complexes were found in 13 of 18 children with Henoch-Schönlein purpura irrespective of whether they developed nephritis or not. In contrast, only those children who developed nephritis had raised levels of IgG immune complexes as well. In 2 children with nephritis, two discrete peaks of IgA complexes were found, corresponding to 4 x 10(5) to 8 x 10(5) and 2.5 x 10(6) to 4 x 10(6) daltons. IgG complexes were found only in the larger-molecular-weight peak. Such differences in immune complexes may underlie the different manifestations of this disease.