The effect of a low protein diet with amino acid/keto acid supplements on glucose metabolism in children with uremia.

Six children with chronic renal failure were treated with dietary protein restriction and essential amino acid and keto acid supplements for 6 months. Dietary protein and phosphate intake decreased, dietary calcium increased, and dietary carbohydrate and energy did not change. Plasma urea and urea to creatinine ratio decreased significantly during treatment. Glucose metabolism was studied before and after 6 months of treatment using the hyperglycemic clamp technique. Fasting hyperglycemia, glucose intolerance, and insulin resistance improved during treatment, while fasting insulin and insulin levels during hyperglycemia did not change. These metabolic changes were not related to hyperparathyroidism and were probably due to reduction in nitrogen toxicity.

The influence of hyperparathyroidism on glucose metabolism in uremia.

We studied glucose metabolism in a group of adolescents and young adults with uremia using the hyperglycemic clamp technique. In eight adolescent patients, the glucose metabolic rate correlated negatively with PTH levels and positively with the glomerular filtration rate. Six patients, one adolescent and five adults on regular hemodialysis with severe hyperparathyroidism, had low glucose metabolic rates and reduced insulin sensitivity compared to normal subjects. After parathyroidectomy, the glucose metabolic rate improved by 47%; plasma insulin concentrations during hyperglycemia increased by 37%, and insulin sensitivity did not change significantly. Thus, correction of hyperparathyroidism was associated with normalization of glucose metabolic rates and increased insulin secretion, but insulin resistance did not change.

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.

The management of renal transplant artery stenosis in children by percutaneous transluminal angioplasty.

Between 1967 and 1989 in this unit 262 children (age at transplantation 9 months to 17 years, mean 9.6 years) had 345 renal transplants performed. Transplant artery stenosis (TAS) was found in 30 (8.7%) as demonstrated by arteriography, performed only when there was unexplained deterioration in transplant function, hypertension that was difficult to control, or in the presence of a vascular bruit. All patients with TAS except one had received a cadaveric allograft. From 1980 onward, percutaneous transluminal angioplasty (PTA) has been available for TAS, and this was attempted on 21 occasions in 16 patients. Nine patients demonstrated angiographic improvement following the procedure, and 7 showed immediate clinical improvement. On one occasion angioplasty precipitated graft loss. Five patients underwent planned corrective surgery, 4 after unsuccessful angioplasties. Our experience suggests that PTA should be the first method of intervention for TAS. Moderate success, both in angiographic and clinical terms, can be achieved, negating the need for surgery, while failure of PTA does not preclude surgical attempts at correction.

A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine.

Based on statistical analysis of data in 186 children, a formula was derived which allows accurate estimation of glomerular filtration rate (GFR) from plasma creatinine and body lenght (GFR(ml/min/1.73 sq m) = 0.55 length (cm)/Per (mg/dl). Its application to clearance data in a separate group of 223 children reveals excellent agreement with GFR estimated by the Ccr (r = .935) or Cin (r = .905). This formula should be useful for adjusting dosages of drugs excreted by the kidney and detecting significant changes in renal function.

von Willebrand factor-cleaving protease in childhood diarrhoea-associated haemolytic uraemic syndrome.

A deficiency of von Willebrand factor (vWF)-cleaving protease, either due to a congenital deficiency or to the presence of a protease inhibitor of vWF-cleaving protease has been associated with thrombotic thrombocytopenic purpura (TTP). We have studied vWF-cleaving protease in diarrhoea-associated haemolytic uraemic syndrome (D+ HUS), which shares clinical features with TTP. 29 children with acute D+ HUS and 13 control children were studied. vWF-cleaving protease activity was normal (range 50-150%) in 39 of 42 plasma samples. Levels of protease activity between 25 and 50% were noted in plasma from two D+ HUS patients. One D+HUS patient, who had clinical features of TTP, had a vWF-cleaving protease inhibitor producing a severe deficiency of vWF-cleaving protease. Thus a deficiency of vWF-cleaving protease appears to be atypical in D+HUS. The detection of a vWF-cleaving protease inhibitor in one patient suggests it may be associated with infection such as E. coli O157.

Activation of coagulation and fibrinolysis in childhood diarrhoea-associated haemolytic uraemic syndrome.

Diarrhoea-associated haemolytic uraemic syndrome (D+ HUS) is usually caused by verotoxin producing Eschericia coli. We hypothesized that verotoxin binding to glomerular endothelial cells causes localised endothelial cell activation and thus activation of coagulation and reduction of fibrinolytic potential. We also proposed that treatment with fresh frozen plasma or dialysis would not affect these changes. Markers of activation of coagulation and fibrinolysis were measured in 30 children with acute D+ HUS serially, in healthy children and in children on dialysis. In acute D+ HUS, levels of thrombin-antithrombin III complex and prothrombin fragment 1+2 were significantly increased (p <0.001). The source of thrombin generation was unclear. Factor XIIa levels were increased in patients and controls with renal failure. Factor VIIa levels were not significantly raised in children with acute D+ HUS. D-dimers were increased, but fibrinolytic potential as measured by fibrin plate was reduced. Levels of plasminogen activator inhibitor antigen and activity and tissue plasminogen activator antigen were increased. Neither peritoneal dialysis nor administration of blood products, the most common treatments, altered parameters of coagulation or fibrinolysis.

Glucose intolerance in children with chronic renal failure.

Carbohydrate metabolism was studied by the hyperglycemic clamp technique in 14 children with moderate to severe chronic renal failure (CRF) (8 pubertal and 6 prepubertal) and was compared with 5 healthy prepubertal children and 7 healthy young adults. Constant hyperglycemia was maintained for 120 min. Under these conditions, the average glucose infusion rate (M) is an index of glucose metabolic rate, the average insulin response (I) is an index of beta cell responsiveness to hyperglycemia, and the M/I ratio is an index of insulin sensitivity. Children with CRF were glucose intolerant (lower M), hyperinsulinemic (higher I), and insulin resistant (lower M/I) compared with the control children. An age-related difference in glucose tolerance and insulin sensitivity was noted. Pubertal children with CRF had lower M and lower M/I compared with prepubertal children with CRF. The 7 adult controls also had lower M and lower M/I compared with the 5 children controls. M and M/I correlated with glomerular filtration rate (GFR) in the 8 pubertal children, while M/I also correlated with GFR in the 6 prepubertal children with CRF. The hyperglycemic clamp provides a useful tool in studying the pathogenesis of carbohydrate disturbances in children with CRF.

Secondary hyperparathyroidism and glucose intolerance in children with uremia.

Glucose metabolism was studied using the glucose clamp technique in 8 children with CRF (4 pubertal and 4 prepubertal) before and after correction of secondary hyperparathyroidism (HPD) by a regime of phosphate binders and dietary phosphate restriction. Glucose metabolic rate (M) increased by 34%, insulin response (I) increased by 32%, and insulin sensitivity (M/I) did not change. Compared to corresponding normal values, these patients were glucose-intolerant (low M) before treatment and became glucose-tolerant after treatment (normal M). They were insulin-resistant (low M/I) before treatment and remained so after treatment. The 5 uremic children without secondary HPD were treated with the same regime to prevent the secondary HPD. Their M, I, and M/I did not change after treatment. The change in I correlated closely with the change in M in all 13 patients. One pubertal patient with uremia was studied on three occasions. Initially, without secondary HPD, he had a normal M and a low M/I. When he developed secondary HPD, M decreased by 39%, I decreased by 37%, and M/I did not change. Treatment of his secondary HPD restored M and I values back to initial levels, and M/I again did not change. Treatment of secondary HPD by correction of phosphate retention led to an improvement of glucose intolerance with an increase in insulin secretion.

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 children's 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). CONCLUSION: 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.

Hyperlipidemia after renal transplantation in children on alternate day corticosteroid therapy.

We studied the serum lipid profiles of 29 children, 3.9-17.9 years of age who were 0.6-7.6 years after renal transplantation (Tx). Twenty normoglycemic and non-proteinuric children had a well functioning allograft and 5 children had reduced renal function. Both groups were at least 7 months on alternate day corticosteroid (ADCS) therapy. Four additional patients had good renal function but were only 2.3 +/- 0.5 months on an ADCS regimen. Fifteen normal children served as controls. The levels of serum triglycerides (STG) and total cholesterol (CHOL) were elevated and high-density lipoprotein CHOL (HDL-CHOL) were low in all patients compared to control subjects (p less than 0.01). Their cardiovascular risk factor (CHOL/HDL-CHOL) was increased. The lipid abnormalities were most prominent in Tx patients with reduced graft function. These data show that treatment with ADCS does not prevent post-Tx hyperlipidemia. More insight is needed into the mechanisms responsible for the hyperlipidemia after Tx in order to reduce possible future morbidity (and mortality) from premature cardiovascular disease in this group of young, high-risk patients.

Diagnostic puncture in renal cystic dysplasia (multicystic kidney). Evidence on the aetiology of the cysts.

Five cases of cystic dysplastic (multicystic) kidney occurring in infancy are described, in whom diagnostic puncture was used to confirm the suspected diagnosis. The characteristic finding on contrast injection was that the cystic spaces communicated via tubular structures, presumably nephronic, so ruling out the possibility of hydronephrosis. This finding also supports the view that cysts in multicystic kidney derive from nephrons and are not due to dilated calices. Although urography and ultrasonography both give appearances highly suggestive of multicystic kidney, the appearances on renal puncture are pathognomonic. When such appearances are demonstrated there is no urgent need for operative removal, except when necessitated by the size of the mass.

Quantitative microfocal radiography of children with renal osteodystrophy; comparison with laboratory and histological findings.

High definition microfocal radiography permitted the quantitative assessment of the radiographic features of renal osteodystrophy in the phalanges of 11 children in stable chronic renal failure, treated with phosphate binders for 1 year. The most consistent feature was subperiosteal cortical resorption, expressed as a ratio total length of resorbed subperiosteal bone/total length subperiosteal bone x 100. It was found that the extent of resorbed bone was significantly greater in the middle phalanx and on the ulnar surface of the phalanges. The radiological findings over the duration of the disease were compared with laboratory assessments and bone histomorphometry. The extent of the percentage of subperiosteal resorption at base line and its change during the study period correlated significantly with the level of serum parathyroid hormone levels and its change over the same period. No other significant correlations were found between radiographic features and laboratory assessments or with bone histomorphometry.

The negative influence of delayed renal allograft function on longer-term graft survival in a pediatric population.

The influence of delayed graft function on renal allograft survival has been studied in a review of 322 renal transplants performed at one pediatric institution. The appearance of the first radionuclide renal scan was used to indicate early function in patients receiving their first cadaveric allograft. Patients whose first radionuclide renal scan showed both good renal perfusion and good function (n = 52) were compared with those whose scans demonstrated good perfusion but no function (n = 32). the actuarial graft survival of those with no function was significantly worse (P < .05). The difference in graft survival was not solely due to grafts lost in the early posttransplant period. Analysis of serial serum creatinine estimations suggests a process of continued inexorable nephron loss in some patients whose grafts showed a delay in achieving function.