George B. Haycock

Presymptomatic detection of familial juvenile hyperuricaemic nephropathy in children

Abstract. We studied 34 apparently healthy children and 2 propositi from kindreds with familial juvenile hyperuricaemic nephropathy (FJHN) – a disorder characterised by early onset, hyperuricaemia, gout, familial renal disease and a similarly low urate clearance relative to glomerular filtration rate (GFR) [fractional excretion of uric acid (FEur) 5.1±1.6%] in young men and women. In addition to the propositi, 17 asymptomatic children were hyperuricaemic – mean plasma urate (368±30 μmol/l), twice that of controls (154±41 μmol/l). Eight of them had a normal GFR (>80 ml/min per 1.73 m2), and 11 renal dysfunction, which was severe in 5. The FEur in the 14 hyperuricaemic children with a GFR >50 ml/min was 5.0±0.5% and in the 5 with a GFR ≤50 ml/min was still low (11.5±0.2%) compared with controls (18.4±5.1%). The 17 normouricaemic children (185±37 μmol/l) had a normal GFR (>80 ml/min) and FEur (14.0±5.3%). The results highlight the dominant inheritance, absence of the usual child/adult difference in FEur in FJHN and presence of hyperuricaemia without renal disease in 42% of affected children, but not vice versa. Since early allopurinol treatment may retard progression to end-stage renal failure, screening of all relatives in FJHN kindreds is essential.

Antidiuretic Hormone Following Surgery in Children

ABSTRACT. We studied 13 children subjected to elective tonsillectomy, 6 of whom (study patients) received supplemental intravenous isotonic saline during and after operation, and 7 of whom (controls) did not. Clinical and biochemical evidence of hypovolaemia was present in the control but not in the study patients. Plasma antidiuretic hormone (ADH) and urine osmolality were higher in controls (p<0.005 and p <0.05 respectively). Plasma sodium concentration and osmolality were similar in the two groups. We conclude that hypovolaemia is the principal stimulus to ADH release following surgery and that, in addition to replacement of observed losses of blood and other fluids by fluids of appropriate composition, hypovolaemia should be prevented by the administration of maintenance quantities of isotonic fluid, rather than exacerbated by fluid restriction, in patients in whom oral fluid intake is interrupted for more than a brief period. Hypotonic and sodium free fluids should be avoided because of the risk of hyponatraemia.

Salt and the newborn kidney

Renal function differs in term infants from that in adults, with lower glomerular filtration rate (GFR) and reduced proximal tubular reabsorption of sodium (Na) and water: nevertheless, it is adequate for their needs. This is not true of very preterm infants in whom hyponatraemia is common. Animal studies have shown that Na+, K+-ATPase and the Na+/K+ exchanger are poorly expressed at birth with rapid postnatal rises. Cell receptors for hormones that influence tubular Na transport are less numerous in the premature infant than later in life: intracellular second messenger systems may also be immature. The low GFR is due to vasoconstriction and may be necessary to prevent water and electrolyte wasting due to tubular overload. The hyponatraemia of prematurity could, in principle, be due either to Na loss or water excess and can be prevented either by giving additional Na or by restricting water intake. Na supplementation causes relative volume expansion (VE), water restriction volume contraction (VC); this is demonstrated by the effect of the two approaches on weight gain and on the levels of vasoactive hormones in the blood. We argue that moderate VE is more physiological than VC, both in attempting to simulate intrauterine conditions and in consideration of the infants nutritional needs. The much less common complication of hypernatraemia is usually due to abnormal water loss and should be prevented by increasing water intake appropriately. The above applies to well, preterm babies: sick preterm infants are much more variable in their Na and water requirements than well infants of comparable gestation and weight and each needs an individually tailored regimen based on frequent clinical assessment and laboratory measurement.

Low molecular weight protein excretion in glomerular disease: a comparative analysis.

Abstract. We studied 23 children with steroid-sensitive nephrotic syndrome (SSNS), 21 children with steroid-resistant types of nephrotic syndrome and 32 children with other types of nephritis. Our controls were 43 apparently healthy children. We measured the urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and the low molecular weight (LMW) proteins β2-microglobulin (B2M), retinol-binding protein (RBP), α1-microglobulin (A1M) and urine protein 1 (UP1). Results for B2M were considered only for a urine pH greater than 6.0. Comparisons were made with urine albumin excretion, glomerular filtration rate (GFR) and tubular abnormalities in selected renal biopsy samples. We found that abnormalities of LMW protein excretion occurred in between 50% (B2M) and 88% (UP1) of all subjects. In children with SSNS, A1M (r = 0.73), UP1 (r = 0.65) and NAG (r = 0.54) excretion were significantly correlated with albumin excretion, but not RBP or B2M excretion. Increased fractional excretion of A1M, B2M and UP1 and increased plasma A1M were demonstrated in 9 children with SSNS, suggesting competition for tubular reabsorption with albumin, most marked for UP1. In the steroid-resistant nephrotic and nephritic syndromes, correlation with albumin was found for all proteins. In these subjects, RBP (r = 0.37), B2M (r = 0.42) and A1M (r = 0.28) were inversely correlated with GFR, but not UP1, NAG or albumin. We found that RBP excretion was significantly greater in the presence of severe tubular abnormalities in 11 children with recent renal biopsies, but not A1M, UP1 or NAG. We conclude that LMW proteinuria is common in children with glomerular disease, and does not necessarily imply a poor prognosis. Factors other than histologically proven tubular abnormality may account for elevated LMW protein excretion. RBP is the LMW protein most closely associated with structural abnormality and least affected by increasing albuminuria.

Hyponatraemia in Premature Babies and Following Surgery in Older Children

ABSTRACT. Hyponatraemia implies water retention in excess of sodium with or without increased loss of sodium from the body; extracellular fluid volume may be increased, normal or reduced. It has many causes which are briefly reviewed. Among these is the rare syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is suggested that SIADH is often diagnosed incorrectly because the raised ADH levels are appropriate for the volume status of the child. Precision in the diagnosis is important because whilst water restriction is necessary for the treatment of SIADH, other measures including the administration of extra fluid are often required if the raised ADH is appropriate. Hyponatraemia in the newborn may be caused by prerenal failure, renal failure or renal sodium wasting which is common in premature infants. Careful control of sodium intake as well as water intake is vital in this age group. Surgery is associated with water retention, but recent studies suggest that ADH levels are raised post‐operatively because of volume depletion and that present recommendations for fluid therapy during and following surgery are inadequate. The use of electrolyte‐free dextrose solutions should be abandoned and more liberal use of physiological saline or colloid is recommended.

Creatinine, body size and renal function

The paper by Brion et al. in this issue of Pediatric Nephrology [1] is the latest in a series of attempts to estimate glomerular filtration rate (GFR) from the plasma creatinine concentration (Pot) and body size. Creatinine clearance (Ce3 is an approximate measure of GFR, less accurate than the clearance of substances such as inulin, EDTA and sodium iothalamate but easier to perform because infusion of an exogenous marker is not necessary. Its major disadvantage, as with all standard clearance techniques, is the need for an accurate, timed urine collection. The renal clearance of any substance is calculated by dividing its excretion rate by its plasma concentration. Thus:

A practical approach to evaluating urinary tract infection in children

All children with urinary tract infections should be investigated byeither excretory urographyor abdominal X-ray, ultrasonography and technetium 99 m—dimercaptosuccinic acid scintigraphy. Patients in the following categories should also have micturating (voiding) cystourethrography to diagnose or exclude vesico-ureteral reflux: infants aged less than 1 year, children with recurrent (second or subsequent) infections, children with clinically diagnosed acute pyelonephritis and those with a family history of reflux or chronic pyelonephritis. Cystography can safely be omitted in children over 1 year of age with unscarred kidneys and none of the additional risk factors listed. They should be followed for 1–2 years following the first infection for evidence of recurrence.

The treatment of glomerulonephritis in children.

The results of treatment of glomerulonephritis (GN) in childhood with oral corticosteroids, immunosuppressive drugs, anticoagulants and the newer regimens of pulsed, high-dose intravenous methylprednisolone and plasma exchange are reviewed and compared with the natural history of the untreated condition. Poststreptococcal GN and the nephritis of Schönlein-Henoch purpura need no specific treatment unless extensive glomerular crescents are present. The progression of mesangiocapillary GN can probably be slowed or even reversed with long-term, alternate-day steroid therapy. As in adults, recovery of renal function in GN due to antibody to glomerular basement membrane can be achieved in some patients using plasma exchange, but only those in whom some renal function is still present when treatment is started. In rapidly progressive (extracapillary) GN with crescents, “traditional” therapy with oral steroids, immunosuppressive drugs and anticoagulants reduces renal mortality from 85%–90% to about 50%, while pulsed methylprednisolone and plasma exchange improve the outcome further, mortality falling to about 25%. It is recommended that children with crescentic GN and deteriorating function be treated initially with pulsed methylprednisolone, followed by plasma exchange in those who fail to respond or who deteriorate following temporary response to pulse therapy. Treatment must be given early in the course of the illness if good results are to be obtained.

Long-term suppression of hyperparathyroidism by phosphate binders in uremic children.

Forty-five children with stable chronic renal failure, not on dialysis, were treated conservatively with a regimen of mild dietary phosphate restriction and high-dose phosphate binders for up to 5 years. Both aluminum hydroxide and calcium carbonate were used initially, but almost all patients were taking calcium carbonate towards the end of the period. Serum immunoreactive parathyroid hormone concentrations were significantly decreased and were within the normal range after 1 year and remained normal during treatment. There was no significant change in renal function over the same treatment period. We conclude that calcium carbonate should be used as the phosphate binder of choice in the long-term suppression of hyperphosphatemia and hyperparathyroidism in uremic children.

Acute renal failure complicating diabetic ketoacidosis.

Two previously healthy children, aged 13 and 14 years, respectively, presented with diabetic ketoacidosis. Both children developed acute renal failure, a rare complication of diabetic ketoacidosis and required dialysis.