Cyril Chantler

Long-term follow-up of childhood Henoch-Schönlein nephritis

A study of long-term outcome of 78 subjects who had had Henoch-Schonlein nephritis during childhood (at a mean of 23.4 years after onset) shows that severity of clinical presentation and initial findings on renal biopsy correlate well with outcome but have poor predictive value in individuals. 44% of patients who had nephritic, nephrotic, or nephritic/nephrotic syndromes at onset have hypertension or impaired renal function, whereas 82% of those who presented with haematuria (with or without proteinuria) are normal. 17 patients deteriorated clinically from an initial assessment in 1971; 7 of these had apparently completely recovered in 1976. 16 of 44 full-term pregnancies were complicated by proteinuria and/or hypertension, even in the absence of active renal disease. These findings indicate that childhood Henoch-Schonlein nephritis requires long-term follow-up, especially during pregnancy.

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.

Prognosis of Henoch-Schönlein nephritis in children.

All the survivors of a series of 88 patients with Henoch-Schönlein nephritis were examined after a follow-up of six and a half to 21 years (mean 9-9). Sixty-one patients had no demonstrable abnormality; six had minor urinary abnormalities; five had hypertension without urinary abnormally or renal dysfunction; four had heavy proteinuria; eight were in chronic renal failure, three of whom were on regular dialysis; and four patients had died within 25 months of onset. Neither corticosteroids nor immunosuppressive drugs alone or in combination appeared to influence the outcome. A clinical presentation with a combination of acute nephritis and a nephrotic syndrome and a high proportion of crescents in renal biopsy specimens was associated with a poor outcome. Neither the clinical presentation nor the renal morphology were, however, precise determinants of outcome. Outcome was not related to age, associated streptococcal infection, or recurrences of the rash. The clinical state two years after presentation was compared with the state six and a half years or more after presentation in 76 patients. The clinical state had changed in 32 patients, in 17 of whom it had deteriorated. It was not possible to identify with any certainty the patients who would deteriorate (or improve). Patients who have had Henoch-Schönlein nephritis should be followed up for at least five years.

Genetics of classic Alport's syndrome

41 families with classic Alports syndrome (hereditary nephritis with sensorineural deafness) were studied. All their pedigrees were compatible with X-linked inheritance. DNA probes were used to investigate genetic linkage in these families. Linkage to probe S21 (DXS17) was confirmed (LOD score = 4.72 at 0 = 0.06), localising the gene for Alports syndrome to the middle of Xq; thus the disorder is X-chromosomal in nature.

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.

The paediatric registry of the European Dialysis and Transplant Association: 20 years' experience

The first publication of the paediatric registry of the European Dialysis and Transplant Association appeared in 1971. Since then nearly 50 further articles have appeared and this paper provides a full bibliography as well as tracing the changes in the provision of care, methods and results of treatment of end-stage renal disease in childhood over the last 20 years.

Presentation, management, complications, and outcome of acute renal failure in childhood: five years' experience.

During 1971-5, 72 episodes of acute renal failure were treated in 70 children aged up to 16 years. The commonest causes were renal hypoperfusion (31 cases), haemolytic-uraemic syndrome (12), glomerulonephritis (9), septicaemia (5), and congenital abnormalities (6). Though referral from other hospitals was generally prompt, 10 out of 51 patients had been observed for up to seven days before transfer. Dailysis was used in 44 cases, the most common complications of which were peritonitis in those treated with peritoneal dialysis and acute changes in fluid balance in those treated with haemodialysis. Altogether 37 patients fully recovered, 10 were discharged with chronically impaired renal function, 17 died, and six entered the dialysis and transplantation programme. The mortality fell from 33% in 1972 to 20% in later years, which was due solely to maintenance dialysis being available. Though all patients with irrevocable kidney failure who were suitable entered the dialysis and transplantation programme, with current financial restrictions we doubt whether we shall be able to find places for all such patients in the future.

A Rat Model for the Study of Growth Failure in Uremia

Extract: The growth of children with chronic renal disease is poor and the cause of this stunting is not known. Various factors have ben implicated and it is difficult to evaluate their relative importance in clinical studies. Accordingly, there is a need for an animal model, preferably one which enables the effect on growth of a number of factors to be studied separately and over a reasonably short period of time. The growth and food intake of male and female rats rendered uremic by 5/6 nephrectomy was observed between 40 and 70 days of age for male rats and between 35 and 70 days of age for female rats. Final mean body weight for males with uremia (243 g ± 32 g) was significantly less than for control males (323 g ± 24 g); final mean body weights for female rats were also significantly different (172 g ± 17 g; 223 g ± 21 g). The differences in body weight were apparent from 50 days onwards. Final tail length was significantly less in female uremic rats compared with their control subjects (173 mm ± 8 mm; 183 mm ± 7 mm). Uremic rats matched for body weight with control rats consumed significantly fewer calories; for both groups the average difference was about 15%. Multiple regression analysis of weight gain against age and calorie intake suggests that there may be an increase in the calorie cost of growth in rats with uremia, but these findings require confirmation in paired feeding studies.Speculation: These studies suggest that this rat model can be used for the investigation of alterations in energy balance, body composition, and metabolic functions in uremia. It should be possible to study the effects of single variables in the pathogenesis of growth retardation by appropriate manipulations halfway through the growth period.

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.

Poststreptococcal glomerulonephritis in children: Clinicopathological correlations and long-term prognosis

Between 1962 and 1970, 36 children with acute biopsy-proven poststreptococcal glomerulonephritis (PSGN) entered a prospective long-term follow-up study. The initial biopsies were scored into four histological grades using criteria based on endocapillary proliferation, leucocyte infiltration, epithelial “hump” and crescent formation; 5 patients had grade-1 (least severe), 14 grade-2, 15 grade-3 and 2 grade-4 biopsies. Two children died from rapidly progressive glomerulonephritis; both had grade-4 biopsies. Early repeat biopsy in 12 patients showed improvement in all but one patient who progressed from grade 2 to type 2 mesangiocapillary glomerulonephritis (MCGN). The initial biopsy grade correlated significantly with heavy proteinuria (Ξ2 = 9.73,P<0.01) but not with hypertension, haematuria or renal functional impairment. Follow-up observations were made after mean periods of 9.5 years (range 5.4–12.4 years; 32 subjects) and 19.0 years (range 14.6–22 years; 30 subjects). None of the survivors had an abnormal plasma creatinine. Only one patient (grade-3 biopsy), a female with a subsequent history of recurrent pyelonephritis, was hypertensive. Isolated microscopic haematuria persisted in 1 grade-2 and 2 grade-3 subjects. One grade-2 subject had proteinuria secondary to MCGN and one grade-3 subject had mild proteinuria and borderline hypertension. Although 20% of subjects had urinary abnormalities, we conclude that the long-term outcome of PSGN in children is excellent.