Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children

doi:10.1016/S0140-6736(96)09260-4

The Lancet

Volume 349, Issue 9059, 19 April 1997, Pages 1117-1123

https://doi.org/10.1016/S0140-6736(96)09260-4 Get rights and content

Summary

Background

Some studies have suggested that a lowprotein diet slows the deterioration of renal function in patients with chronic renal failure (CRF). The effects of a low-protein diet on renal function and growth, have not been assessed in a large, prospective randomised trial in children with CRF.

Methods

A 2-year prospective, stratified, and randomised multicentre study recruited 191 patients aged 2–18 years. After a run-in period of at least 6 months, patients were stratified into either a progressive or non-progressive category based on the change in creatinine clearance in this period. The patients were also stratified into three renal-disease categories and then randomly assigned to a control or diet group. In the diet group, the protein intake was the lowest, safe WHO recommendation-ie, 0·8–1·1 g/kg daily adjusted for age. All patients were advised to have a calorie intake of at least 70% of the WHO recommendations. Glomerular filtration rate (GFR) was measured every 2 months by creatinine clearance; dietary compliance was checked by urinary urea-nitrogen excretion and dietary diaries (weighing method). 112 patients completed an optional third year of the study.

Findings

The low-protein diet did not affect growth. However, there was no effect of diet on the mean decline in creatinine clearance over 2 years (diet vs control: progressive group −9·7 [SD 8·0] vs −10·7 [11·8] mL/min per 1·73m²; non-progressive group −2·5 [7·5] vs −4·3 [10·0] mL/min per 1·73 m²). Patients classified as having progressive disease were older and had a lower creatinine clearance and a higher blood pressure at randomisation, and had a greater decrease in creatinine clearance than non-progressive patients. On multivariate regression analysis proteinuria (partial R²=0·259) and systolic blood pressure (partial R²=0·087) were independent predictors of the change in GFR. Similar results were found after the study was extended for a third year.

Interpretation

A low-protein diet for 3 years did not affect the decrease in renal function in children with CRF. Proteinuria and blood pressure explain a large part of the variability of, and may be causally related to the decline in the GFR.

Introduction

In end-stage renal failure uraemic symptoms can be diminished and death and renal replacement therapy postponed by the restriction of dietary protein. However, whether a low-protein diet can reduce the progression of chronic renal failure (CRF) to end-stage disease is controversial. In animals, a high-protein diet accelerates kidney scarring by aggravating haemodynamic abnormalities, whereas restriction of dietary protein diminishes or prevents progressive renal damage.1, 2

For many years a low-protein diet was believed to reduce the progression of CRF in adults. However, most studies have had methodological shortcomings such as small numbers of patients, a variable duration of followup, lack of randomisation, or inadequate control-group data. In many studies, energy intake was not controlled and the results were not analysed by dietary compliance.3, 4, 5, 6, 7, 8 Primary results of a large, randomised multicentre trial on the modification of diet in renal disease in adult patients with CRF⁹ did not show a benefit from a low-protein diet but after analysis by dietary compliance, a moderately low-protein intake was beneficial in patients with advanced CRF.¹⁰

There has not been a prospective randomised trial of the effects of a low-protein diet on CRF progression in an adequate number of children-mainly because of the small number of paediatric patients available, even in specialised centres.11, 12 Paediatricians are concerned, however, that any beneficial effect on renal function may be accompanied by an adverse effect on growth.13, 14

The aims of this European multicentre randomised study were to assess the effects of a protein-restricted diet which contains adequate energy on the rate of CRF progression and growth and development in children, and to evaluate the long-term acceptance of this diet.

Section snippets

Patients

The study was approved by each local ethics committee and written informed consent was given by the parents.

Patients aged 2–18 years with creatinine clearances between 15 and 60 mL/min per 1·73 m² and well-controlled conditions on conservative treatment were eligible. The exclusion criteria were: uncontrolled arterial hypertension (higher than 2 SD above the mean for age at three consecutive outpatient visits); uraemic symptoms; systemic diseases such as systemic lupus erythematosus,

Results

284 patients from 25 European Paediatric Nephrology centres were eligible for the study. 58 patients were not stratified (figure 2). Of the 226 randomised patients, 35 later withdrew. 191 patients (97 in the diet group) completed 2 years and their clinical data are in table 1. 112 patients (53 in the diet group) completed a third year and their clinical features are in table 2.

In the first 2 years, 12 patients in the diet group and ten patients in the control group required renal replacement

Discussion

We have found that intake of a low-protein diet for 3 years in children with chronic renal failure does not affect the rate of decline in creatinine clearance. These results are in agreement with the 3-year results of the modification diet in renal disease study in adults.⁹ Although the observation period may be too short to exclude subtle long-term effects of a low-protein diet, this study suggests that these would be small-since hypertension and proteinuria explain a large part of the

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In the adjusted model, we found differential associations between phthalates and plasticizers metabolites and renal function. We found that Mono-benzyl phthalate, Mono-(3-carboxypropyl) phthalate, and Mono-(2-ethyl-5-oxohexyl) phthalate were positively associated with lower eGFR with odds ratios (95% confidence intervals) of 1.38 (1.14, 1.67), 1.30 (1.09, 1.57), and 1.27 (1.04, 1.53). While Mono-ethyl phthalate, Mono-(2-ethyl)-hexyl phthalate, Mono-isononyl phthalate and Mono-isobutyl phthalate were negatively associated with lower eGFR with OR values of 0.79 (0.69, 0.90), 0.64 (0.52, 0.78), 0.65 (0.51, 0.82) and 0.80 (0.63, 1.00), respectively. In addition, we found that Mono(carboxyoctyl) phthalate and Mono-isobutyl phthalate were negatively associated with hypertension with ORs of 0.86 (0.78, 0.96) and 0.84 (0.72, 0.98). But phthalates and plasticizers metabolites were not associated with UACR.
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Hypertension is one of the most common causes of preventable death worldwide. The prevalence of pediatric hypertension has increased significantly in recent decades. The cause of this is likely multifactorial, related to increasing childhood obesity, high dietary sodium intake, sedentary lifestyles, perinatal factors, familial aggregation, socioeconomic factors, and ethnic blood pressure (BP) differences. Pediatric hypertension represents a major public health threat. Uncontrolled pediatric hypertension is associated with subclinical cardiovascular disease and adult-onset hypertension. In children with chronic kidney disease (CKD), hypertension is also a strong risk factor for progression to kidney failure. Despite these risks, current rates of pediatric BP screening, hypertension detection, treatment, and control remain suboptimal. Contributing to these shortcomings are the challenges of accurately measuring pediatric BP, limited access to validated pediatric equipment and hypertension specialists, complex interpretation of pediatric BP measurements, problematic normative BP data, and conflicting society guidelines for pediatric hypertension. To date, limited pediatric hypertension research has been conducted to help address these challenges. However, there are several promising signs in the field of pediatric hypertension. There is greater attention being drawn on the cardiovascular risks of pediatric hypertension, more emphasis on the need for childhood BP screening and management, new public health initiatives being implemented, and increasing research interest and funding. This article summarizes what is currently known about pediatric hypertension, the existing knowledge-practice gaps, and ongoing research aimed at improving future kidney and cardiovascular health.
Epidemiology of pediatric chronic kidney disease
2021, Nephrologie et Therapeutique
Des progrès majeurs ont été réalisés dans la prise en charge des enfants avec une maladie rénale chronique au cours des 30 dernières années. Cependant, les données épidémiologiques pédiatriques existantes proviennent essentiellement des registres de traitement de suppléance de l’insuffisance rénale terminale, et les informations disponibles aux stades plus précoces de maladie rénale chronique sont limitées. L’incidence et la prévalence de la maladie rénale chronique de stades 2 à 5 restent mal connues. De rares études en population suggèrent toutefois que la prévalence de la maladie rénale chronique tous stades confondus pourrait concerner 1 % de la population pédiatrique. Les désordres congénitaux incluant les hypodysplasies rénales et uropathies malformatives (Congenital abnormalities of the kidney and urinary tract) et les néphropahies héréditaires sont responsables de la moitié à deux tiers des cas de maladie rénale chronique de l’enfant dans les pays industrialisés, alors que les néphropathies acquises prédominent dans les pays en développement. La progression de la maladie rénale chronique est plus lente chez les enfants avec un désordre congénital que chez ceux ayant une néphropathie acquise en particulier glomérulaire, résultant en une plus faible proportion de Congenital abnormalities of the kidney and urinary tract comme cause d’insuffisance rénale terminale par rapport aux stades moins avancés de maladie rénale chronique. L’incidence du traitement de suppléance rénale dans la population pédiatrique variait selon les pays de 1 à 14 par million d’enfants du même âge en 2018 (environ 8 par million d’enfants en France) chez les patients de moins de 20 ans. La prévalence du traitement de suppléance rénale chez les moins de 20 ans en 2018 variait de 15 à 30 par million d’enfants dans certains pays d’Europe de l’Est et d’Amérique latine à 100 par million d’enfants en Finlande et aux États-Unis (56 par million d’enfants en France). La plupart des enfants atteints d’insuffisance rénale terminale démarrent un traitement de suppléance par dialyse (plus fréquemment hémodialyse que dialyse péritonéale). Dans environ 20 % des cas, le traitement initial est une greffe rénale préemptive. Dans les pays industrialisés, 60 à 80 % des patients prévalents vivent avec un greffon fonctionnel (75 % en France). Alors que la survie des enfants atteints de maladie rénale chronique s’est continuellement améliorée au cours du temps, la mortalité reste de l’ordre de 30 fois supérieure à celle de la population générale pédiatrique.
Major advances have been made in the management of children with chronic kidney disease over the past 30 years. However, existing epidemiology data are primarily from kidney replacement therapy registries, and information available at earlier stages of chronic kidney disease is limited. The incidence and prevalence of chronic kidney disease stages 2 to 5 remain poorly understood. However, rare population-based studies suggest that the prevalence of all-stage chronic kidney disease may be as high as 1% of the pediatric population. Congenital disorders including congenital abnormalities of the kidney and urinary tract and hereditary nephropathies account for one-half to two-thirds of pediatric chronic kidney disease cases in middle and high-income countries, whereas acquired nephropathies seem to predominate in low-income countries. The progression of chronic kidney disease is slower in children with congenital disorders than in those with acquired nephropathy, particularly glomerular disease, resulting in a lower proportion of congenital abnormalities of the kidney and urinary tract as a cause of end-stage kidney disease compared to less advanced stages of chronic kidney disease. The incidence of kidney replacement therapy in the pediatric population ranged by country from 1 to 14 per million children of the same age in 2018 (approximately 8 per million children in France) in patients younger than 20 years. The prevalence of kidney replacement therapy in children under 20 years of age in 2018 ranged from 15-30 per million children in some Eastern European and Latin American countries to 100 per million children in Finland and the United States (56 per million children in France). Most children with end-stage kidney disease initiate kidney replacement therapy with dialysis (more frequently hemodialysis than peritoneal dialysis). In about 20% of cases, the initial kidney replacement therapy modality is a pre-emptive kidney transplantation. In high-income countries, 60-80% of prevalent children with end-stage kidney disease live with a functioning transplant (75% in France). While the survival of children with chronic kidney disease has continuously improved over time, mortality remains about 30 times higher than in the general pediatric population.

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ArticlesRandomised multicentre study of a low-protein diet on the progression of chronic renal failure in children

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Patients

Results

Discussion

Lancet

Lancet

Am J Kidney Dis

Pediatr Clin North Am

Am J Kidney Dis

Kidney Int

Kidney Int

Importance of early initiation of dietary protein restriction for the prevention of experimental progressive renal disease

Nephron

Effects of age at the time of unilateral nephrectomy and dietary protein on long-term renal function in rats

Pediatr Nephrol

The effect of protein restriction on the progression of renal insufficiency

N Engl J Med

Protein-restricted diets in chronic renal failure: a four year follow-up shows limited indications

Kidney Int

Controlled low protein diets in chronic renal insufficiency: metaanalysis

BMJ

Effect of dietary protein restriction on the progression of renal failure: a prospective randomized study

Nephrol Dial Transplant

Effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease

N Engl J Med

Articles
Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children