G B Haycock

Idiopathic mesangiocapillary glomerulonephritis: Comparison of types I and II in children and adults and long-term prognosis

Of 104 patients with idiopathic mesangiocapillary glomerulonephritis studied for at least two years, 69 patients had type I disease and 35 had type II. Forty-five patients were children, and 59 were adults. Type II mesangiocapillary glomerulonephritis was more common in children than in adults, but no other clinical feature distinguished the two types at onset. Complement studies revealed that patients with type II had lower serum C3 concentrations and more frequently showed C3-splitting activity (C3 nephritic factor) in the serum. Children had hypertension or a lowered glomerular filtration rate less frequently at onset than did adults, but children had a higher incidence of a hematuric onset; C3 nephritic factor was also more frequent in the children. During a follow-up period of two to 21 years (mean eight years), only seven patients (five with type I and two with type II) showed clinical remission, whereas 38 percent of patients with type I and 49 percent of patients with type II died or required dialysis; a further 23 percent of patients with type I and 16 percent of patients with type II had continuing disease and reduced glomerular filtration rate. Only the presence and persistence of a nephrotic syndrome in type I predicted renal failure. In both types, the presence of sclerosis or crescents in the initial renal biopsy specimen was associated with a poorer prognosis, but no other feature was of major prognostic value.

Recurrence of focal segmental glomerulosclerosis in transplanted kidneys: Analysis of incidence and risk factors in 59 allografts

Fifty-nine allografts were placed in 43 patients with renal failure from focal segmental glomerulosclerosis (FSGS): 27 allografts were put into 16 children aged less than 15 years, and 32 allografts into 27 adolescents and adults. Recurrence of FSGS was noted histologically in 13 allografts, 10 in 8 children and 3 in adults. None of the 9 children and 24 adults who never developed an allograft nephrotic syndrome showed FSGS in their allograft biopsies. The age of onset was a strong risk factor for recurrence: recurrent FSGS developed in 8 of 16 children (50%) but only in 11% of adolescents and adults (3 of 27 patients). Although the time from apparent onset to renal replacement treatment was shorter in those with recurrence than those without in the children, there was no difference in the time spent on dialysis prior to transplantation. Mesangial prominence was observed in the original biopsy in 12 of 13 patients with recurrence, and recurrence rate was similar in living and cadaver donor allografts; class I MHC matching was similar in those with and without recurrence. Three allografts treated with cyclosporin A as well as 9 with azathioprine showed recurrence. Of 9 second or subsequent allografts placed in those with recurrence in the first allograft, only 3 showed further recurence. rence. In 3 re-grafted after 13, 11 and 5 years, normal function was seen.

Effect of salt supplementation of newborn premature infants on neurodevelopmental outcome at 10–13 years of age

Background: The nutritional requirements of prematurely born infants are different from those of babies born at term. Inadequate or inappropriate dietary intake in the neonatal period may have long term adverse consequences on neurodevelopmental function. The late effect of neonatal sodium deficiency or repletion in the premature human infant on neurological development and function has not been examined, despite evidence in animals of a serious adverse effect of salt deprivation on growth of the central nervous system. Methods: Thirty seven of 46 children who had been born prematurely (gestational age of 33 weeks or less) and allocated to diets containing 1–1.5 mmol sodium/day (unsupplemented) or 4–5 mmol sodium/day (supplemented) from the 4th to the 14th postnatal day were recalled at the age of 10–13 years. Detailed studies of neurodevelopmental performance were made, including motor function and assessment of intelligence (IQ), memory and learning, language and executive skills, and behaviour. Sixteen of the children were found to have been in the supplemented group and 21 in the unsupplemented group. Results: Children who had been in the supplemented group performed better in all modalities tested than those from the unsupplemented group. The differences were statistically significant (analysis of variance) for motor function, performance IQ, the general memory index, and behaviour as assessed by the childrens parents. The supplemented children outperformed the unsupplemented controls by 10% in all three components of the memory and learning tests (difference not significant but p < 0.1 for each) and in language function (p < 0.05 for object naming) and educational attainment (p < 0.05 for arithmetic age). Conclusions: Infants born at or before 33 weeks gestation require a higher sodium intake in the first two weeks of postnatal life than those born at or near term, and failure to provide such an intake (4–5 mmol/day) may predispose to poor neurodevelopmental outcome in the second decade of life.

The syndrome of inappropriate secretion of antidiuretic hormone.

The physiology of the release of antidiuretic hormone (ADH) from the posterior pituitary is briefly reviewed. The importance of both osmolar and non-osmolar stimuli is emphasised. Osmolar and non-osmolar factors usually reinforce each other; for example, hydropenia leads to hyperosmolality and hypovolaemia, both promoting ADH release, while hydration has the opposite effect. In disease, osmolar and non-osmolar factors may become dissociated leading to baroreceptor-mediated ADH release in the presence of hyponatraemia and hypo-osmolality. Examples include heart failure, glucocorticoid or thyroxine deficiency, hepatic cirrhosis and nephrotic syndrome with or without the superimposed effect of diuretics, i. e. conditions in which circulatory, and in particular effective arterial, volume is reduced. It is dangerous to label such conditions as ‘inappropriate’ secretion of ADH since the maintenance of circulating volume is at least as important a physiological requirement as the defence of tonicity. The syndrome of inappropriate secretion of ADH (SIADH) is uncommon in childhood and should only be diagnosed when physiological release of ADH in response to non-osmolar as well as osmolar factors has been excluded. Criteria for the correct identification of SIADH are discussed; the presence of continuing urinary sodium excretion in the presence of hyponatraemia and hypo-osmolality is essential to the diagnosis. SIADH in children is usually due to intracranial disease or injury. The mainstay of treatment is water restriction which reverses all the physiological abnormalities of the condition. Hypertonic saline is rarely indicated for the short-term control of neurological manifestations such as seizures. Drugs have little or no place in the treatment of SIADH in children. In many situations labelled as SIADH it is only the diagnosis that is inappropriate.

Growth after renal transplants.

The growth of every child with a bone age less than 15 years who received a first renal transplant between 1975 and 1980 was analysed to determine the growth expectation of children with renal transplants substantially maintained on alternate-day prednisolone. Growth was expressed as a standard deviation score defined as the difference between the standard deviation for height at the time of the transplant and at the end of 1981. Average growth achieved by the 46 children. 41 with functioning transplants, was normal with a mean standard deviation score of +0.7 +/- 0.3 (SEM) for boys and -0.3 +/- 0.3 (SEM) for girls; 25 of the children had accelerated growth. Mean standard deviation scores per year of advance of bone age in 29 children was +0.003, which suggested no overall loss of growth potential. No difference in growth per year of advance in bone age was detected in children with a bone age less than 12 years at transplant compared with more mature children, but boys with a bone age less than 12 years grew better per year of advance in chronological age; this appeared to be related at least in part to their greater growth deficit at transplant. Glomerular filtration rate, alternate-day prednisolone dose, and level of plasma phosphate did not appear to affect growth in the 11 prepubertal children with functioning first grafts.

Comparison of high-dose intravenous methylprednisolone with low-dose oral prednisolone in acute renal allograft rejection in children.

Two corticosteroid regimens were compared in a randomised, prospective study of 48 consecutive acute rejection episodes occurring at least one month after transplantation in 22 children who had received renal allografts. The higher dose schedule (intravenous methylprednisolone 600 mg/m2 daily for three days) was no more effective than the lower (oral prednisolone 3 mg/kg daily for three days) in reversing rejection, being successful in 70% as opposed to 72% of episodes. Few major side effects were seen with either treatment, but unpleasant sensations were reported much more frequently in the group given intravenous methylprednisolone; this regimen was much more disruptive of the patients life. Oral prednisolone in the dosage described is as effective as about 10 times that dose of intravenous methylprednisolone; it is much cheaper and is viewed as less unpleasant by patients.

Distinguishing between salt poisoning and hypernatraemic dehydration in children

Hypernatraemia caused by salt poisoning or dehydration must be distinguished correctly, as the two situations need different legal and medical approaches. Two nephrologists discuss the physiology of hypernatraemia and explain how to differentiate between cases caused by salt poisoning and dehydration

Management of acute and chronic renal failure in the newborn

Acute renal failure may be caused by a failure of renal perfusion (pre-renal failure), damage to the renal parenchyma (intrinsic renal failure) or obstruction of the urinary tract (post-renal failure). Most cases of intrinsic renal failure in the newborn are due to asphyxia, often in combination with sepsis and nephrotoxic drugs. Persistent elevation of the plasma creatinine concentration above 132.5 micromol/l (1.5mg/dl) is widely accepted as a diagnostic criterion. Oliguria or anuria may occur but is not always present. Post-renal failure is diagnosed by renal ultrasonography and is treated by relief of the obstruction. Pre-renal and post-renal failure can be distinguished by an analysis of urinary indices, especially the fractional sodium excretion, and by the response to fluid replacement. The conservative management of intrinsic renal failure includes careful attention to fluid balance, maintenance of adequate nutrition and prevention or correction of hyperkalemia, acidosis and hyperphosphatemia. Severe cases may require dialysis: peritoneal dialysis is used in most cases, but extracorporeal methods, including intermittent hemodialysis, hemofiltration and hemodiafiltration, are possible. Congenital chronic renal failure, usually caused by renal dysplasia with or without obstruction, presents in a manner similar to that of acute renal failure, with a progressive deterioration of plasma biochemical values. Dialysis is rarely necessary in the newborn period. The conservative management of chronic renal failure is similar to that of acute renal failure, with particular emphasis on nutrition, control of acidosis and the prevention of renal osteodystrophy by the use of dietary phosphate binders and vitamin D analogs.

Sodium homeostasis in term and preterm neonates. II. Gastrointestinal aspects.

Eighty five 24 hour balance studies were performed on 70 healthy newborn infants of gestational age 27-40 weeks; dietary intake and stool losses of sodium were measured. There was a relation between gastrointestinal sodium absorption and conceptional age (the sum of gestational and postnatal age), whether expressed as absolute stool sodium losses or as the ratio of stool sodium to dietary sodium intake. The stool K:Na ratio rose appreciably with maturation, although stool content of potassium was not greatly increased. These findings suggest that intestinal sodium absorption is inefficient in immature babies and that the degree of malabsorption is inversely related to conceptional age.

Effect of indomethacin on clinical progress and renal function in cystinosis.

Three children with nephropathic cystinosis were treated with indomethacin 3 mg/kg a day for periods ranging from 9 to 18 months. The drug produced worthwhile clinical improvement in all, with marked beneficial effects on polyuria, polydipsia, and general wellbeing. Clearance studies performed under conditions of maximal water diuresis showed that proximal tubular sodium reabsorption was increased in all children, with consequent reduction in sodium delivery to the distal nephron leading to reduced free water clearance and distal tubular cation exchange. Plasma sodium and potassium concentrations became normal in all patients, with improvement in phosphate and bicarbonate concentrations in one. Renal function continued to deteriorate, but without obvious acceleration of the process by the drug. We were unable to demonstrate a beneficial effect on growth; nevertheless, indomethacin is a useful adjunct to the symptomatic treatment of children with severe nephropathic cystinosis.