Carbonic adsorbent AST-120 retards progression of renal failure by additive effect with ACEI and protein restriction diet

Background. In order to slow the progression of chronic renal failure (CRF), a multimodal approach should be applied if the efficacy is proved. Although compelling evidence of a beneficial effect exists for the use of angiotensin-converting enzyme inhibitors (ACEIs) and low-protein diets, there is little evidence on whether carbon adsorbent has an effect on retardation of the progression of CRF.Methods. In experiment 1, we examined whether the oral carbon adsorbent, AST-120, conferred an additive effect with captopril and an 80% restriction diet on the survival rate of 3/4 nephrectomized rats (3/4 NX). The 3/4 NX rats were divided into three groups (C, control, n = 7; AD, captopril (an ACEI) +80% restriction diet (RD), n = 8; and ADK, ACEI + RD + AST-120, n = 8) and survival was observed for 72 weeks. In experiment 2, 3/4 NX rats were divided into four groups (C, control, n = 4; D, 80% restriction diet, n = 4; AD, temocapril + RD, n = 9; and ADK, temocapril + RD + AST-120, n = 9) for the examination of renal function, blood pressure, hematocrit (Ht), serum albumin, and proteinuria every month. We analyzed morphological changes in the kidney at 48 weeks.Results. In experiment 1, ADK did not improve the survival rate compared with AD, although ADK prolonged the survival significantly compared with C (C vs AD, P = 0.24; C vs ADK, P = 0.0007; AD vs ADK, P = 0.073). In experiment 2, renal function and proteinuria were significantly ameliorated in the ADK group compared with AD at 48 weeks. Concomitantly with the preservation of renal function, pathological indices, including the glomerular sclerosis index and the interstitial fibrosis index, were significantly improved in ADK compared with AD. In the ADK group, Ht and serum albumin did not change over the 48 weeks.Conclusions. Administration of AST-120 in addition to an ACEI and a restriction diet preserves renal function independently of blood pressure control, angiotensin II inhibition, and protein restriction in 3/4 NX rats at 48 weeks, but does not improve the survival significantly.     

Contribution of experimental studies on the nutritional management of children with chronic renal failure

A few of the many reports of experimental chronic renal failure have been summarized. Anorexia and food selection have been studied in experimental uremia and the findings are comparable with those observed in uraemic children. The optimal dietary protein content for growth is close to the minimal requirement for optimal growth. Protein excess leads to growth retardation and renal deterioration in uraemic rats, at least with the commonly used dry diets. The increased water requirement may be more critical for growth than the blood urea level or acidosis, although this requires further investigation. Reduction of the dietary protein by 50% and supplementation with essential amino acids (EAA) results in growth similar to that of the 100% protein diet. There is no growth improvement despite low blood urea levels, but the renal parenchymal is preserved. Supplementation with nitrogen-free analogues is more frequently associated with defective growth; the optimal mixture remains to be defined, and to date, when nutrition is identical, nitrogen-free analogues offer no benefit for renal preservation compared with EAA. Sucrose-rich diets have adverse effects on uraemia. These effects are associated with fructose intolerance and with reduced energy storage in the liver. The precise metabolic alteration remains to be defined.     

极低蛋白饮食治疗严重慢性肾功能不全的安全性和有效性

目的观察在不补充必需氨基酸或其酮酸情况下,极低蛋白饮食对严重慢性肾功能不全患者营养状态及肾功能的影响.方法37例慢性肾功能不全患者[Scr(588.2±123.5)μmol/L,Ccr(9.77±3.48)ml@min-1@(1.73m2)-1]按实际蛋白摄入量分成两组极低蛋白饮食治疗组[VLPD,蛋白摄入量(0.33±0.04)g@kg-1@d-1],20例;低蛋白饮食治疗组[LPD,蛋白质摄人量为(0.60±0.11)g@kg-1@d-1],17例.观察患者的顺应性、营养相关生化指标及肾功能进展.结果(1)患者对极低蛋白饮食有较好的耐受性,无一例患者出现蛋白营养不良征象,观察期间患者血清白蛋白浓度稳定.和低蛋白饮食相比,极低蛋白饮食患者血清白蛋白浓度升高(P＜0.05).5例VLPD患者虽然蛋白质摄入量持续低于0.3 g@kg-1@d-1,但经过最长53个月治疗,血清白蛋白仍能维持正常范围.(2)虽然两组患者血清转铁蛋白浓度有下降趋势,但仍保持在正常范围.(3)和VLPD组比较,LPD组患者血HCO3-水平明显降低(P＜0.05),且VLPD组患者为治疗代谢性酸中毒所使用的碳酸氢盐剂量明显低于LPD组(P＜0.05).(4)两组患者血清磷浓度保持正常,LPD组增高趋势较明显,但差异无显著性意义(P＞0.05).VLPD组服用肠道磷结合剂的剂量明显小于LPD组(P＜0.05).(5)VLPD及LPD组患者肾功能不全进展速度分别为(0.125±0.072)和(0.214±0.017)ml@min-1@月-1,VLPD组显著慢于LPD组(P＜0.01),而且两组患者肾功能下降速度均明显低于文献报道(平均0.3ml@min-1@月-1).在进入透析治疗阶段,VLPD组的Ccr明显低于LPD组[(3.07±1.17)vs(8.46±2.57)ml@min-1@(1.73m2)-1].LPD组患者在(33.4±6.5)个月内进入透析治疗,而VLPD组患者从治疗开始到进入透析治疗平均(72.0±33.5)个月,比LPD组推迟4～5年.结论在未补充必需氨基酸或其酮酸的情况下,极低蛋白饮食治疗可以安全地用于透析导入前的慢性肾衰患者.其通过改善尿毒症消化道症状而维持患者营养状态,并能有效地纠正慢性肾衰伴随的代谢紊乱,减少合并症,从而推迟开始透析治疗时间.     

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

One hundred twenty-eight patients with different renal diseasesand chronic renal failure, stratified according to the underlyingdisease, were enrolled in a randomized controlled trial to investigatethe effects on the rate of decline of renal function of twodiets, a controlled protein diet (CPD) of 1 g protein/kg idealbody-weight (i.b.w.)/day, and a low-protein diet (LPD) of 0.6g protein/kg i.b.w./day, given for 27.1±21.8 months.Dietary compliance was assessed by a dietary questionnaire,dietary interviews and measurement of 24-h urinary urea excretion.At the end of 6 months, actual mean protein intake was higherthan expected (1.06±0.25 g/kg i.b.w./day) in CPD patients,and (0.80±0.21 g/kg i.b.w./day) in LPD patients: valueswere similar at 12 and 18 months after the time of enrollment.The end-point, defined as halving of creatinine clearance, wasreached in 40% of patients on CPD, and in 28.6% of those onLPD (P= 0.038 by comparative life-table analysis). Multivariateregression analysis confirmed that CPD was associated with ahigher risk of progression than LPD, and that two additionalparameters (creatinine clearance at the time of randomizationand average proteinuria during the follow-up) were significantindependent risk factors, even more important than protein intake.     

Dietary protein restriction benefits patients with chronic kidney disease

The prevalence of chronic kidney disease (CKD) is rapidly increasing so every strategy should be used to avoid the complications of CKD. Most CKD symptoms or uraemia are caused by protein intolerance; symptoms arise because the patient is unable to excrete metabolic products of dietary protein and the ions contained in protein-rich foods. Consequently, CKD patients accumulate salt, phosphates, uric acid and many nitrogen-containing metabolic products, and secondary problems of metabolic acidosis, bone disease and insulin resistance become prominent. These problems can be avoided with dietary planning. Protein-restricted diets do not produce malnutrition and with these diets even patients with advanced CKD maintain body weight, serum albumin and normal electrolyte values. Non-compliance is a problem, but this can be detected using standard techniques to provide the patient with appropriate responses. The role of dietary protein restriction in the progression of CKD has not been proven, but it can reduce albuminuria and will prevent uraemic symptoms. Until a means of preventing kidney disease or progression is found, safe methods of management such as dietary manipulation should be available for CKD patients.     

Dietary protein and growth in infants with chronic renal insufficiency: a report from the Southwest Pediatric Nephrology Study Group and the University of California,San Francisco

This report describes growth and nutrition data from the feasibility phase of a clinical trial that was designed to evaluate the effect of diet protein modification in infants with chronic renal insufficiency (CRI). The purpose of the proposed trial was to compare the safety (effect on growth in length) and efficacy [effect on glomerular filtration rate (GFR)] of a diet with a low protein:energy (PE) ratio versus a control diet in such patients. Twenty-four infants with GFRs less than 55 ml/min per 1.73 m² were randomly assigned at 8 months of age to receive either a low-protein (PE ratio 5.6%) or control protein (PE ratio 10.4%) formula, which resulted in average protein intakes of 1.4 and 2.4 g/kg per day in the low and control groups, respectively. Overall energy intakes over a 10-month period of study averaged 92%±12% recommended dietary allowance (RDA) for length in the low-protein group and 92±15% RDA in the control group. Weight for age standard deviation scores (SDS) were comparably low in both groups at the time of randomization (low-protein —2.0±1.3, control –1.9±1.1) and at the end of the study (low –1.9±1.2, control –1.7±0.9). Length for age SDS at entry tended to be lower in the low-protein group but were not significantly different in the two groups (low –2.2±1.4 vs. control –1.7±1.4). However, at 18 months the low-protein group had a significantly lower SDS for length (–2.6±1.2 vs. –1.7±1.4). The length velocity SDS from 12 to 18 months were also different, with the low-protein group remaining strongly negative (–1.0±0.9) while the control group improved (–0.1±1.1). We conclude from this feasibility study that there is a need for caution in advising the use of low-protein intake in infants with CRI. However, our findings should be regarded as preliminary because of the small number of patients and the observation that the weight gains were the same in the two groups.Southwest Pediatric Nephrology Study Group centers/participantsBaylor College of Medicine, Houston, Tex.Phillip L. Berry, M. D., Andrea Forbes, R. N.Baylor University Medical Center, Dallas, Tex.Ronald J. Hogg, M. D., Tracy Shuck, R. N., Kaye GreenTulane University Medical Center, New Orleans, La.Frank Boineau, M. D., Karen Welling, R. N.University of Arkansas, Little Rock, Ark.Watson C. Arnold, M. D., Donna Floyd-Gimon, R.N.University of Colorado, Denver, Colo.Gary M. Lum, M.D., Leff Paulsen, R. N., Gail D'Amico, R. N.University of Tennessee, Memphis, Tenn.F. Bruder Stapleton, M. D., Patti Lawson, R. N., Judy Vinson, R. N.University of Texas Medical Branch, Galveston, Tex.Ben H. Brouhard, M. D., Lisa Hollander, R. N., Susan Gemma, R. D.University of Texas Medical School, Houston, Tex.Susan B. Conley, M. D., Ann InceUniversity of Texas Southwestern Medical Center, Dallas, Tex.Ricardo Uauy, M. D., Ph. D., Joan Reisch, Ph. D., Steven Alexander,M. D., Nancy Simonds, R. N., Cynthia Cunningham, R. D.University of Utah, Salt Lake City, UtahEileen Brewer, M. D., Miriam Turner, M. D., Jean Tealey, R. N.,Greg Done, R. N., Patricia Reading, R. D., Cynthia Terrill, R. D.University of California at San Francisco participants:Malcolm Holliday, M. D., Jon Block, Ph. D., Martin Glasser, M. D.,Jane Turner, Suzanne Young, R. N., Julie DuBois, R. N., Jon Hidayat, Jean Harrah(Note that the location of the individual investigators reflects their institution during the time period of this study)     

Growth in young children with chronic renal failure

Statural growth and its relation to growth potential, renal function, blood urea nitrogen (BUN), mineral metabolism hormones and dietary intake were studied in 17 prepubertal children (aged 1.6–9.3 years) on conservative treatment for chronic renal failure due to tubulo-interstitial nephropathy. Statural growth (height SDS) was related to the degree of renal failure, was more retarded than ossification, and was independent of the chronological age of the patients. We observed that the lower the glomerular filtration rate (GRF), the lower was the growth potential (increased bone age/statural age ratio). Growth velocity may be normal regardless of statural and bone maturation delay and the degree of renal insufficiency. Impaired growth rate correlated with parathyroid hormone levels, caloric intake and increased blood urea nitrogen during the year of observation. These data show that comprehensive monitoring and suitable treatment must be performed in order to prevent growth retardation at any GFR level.     

Effects of parathyroid hormone-related peptide receptor in tibial growth plate on tibial extension in chronic renal insufficiency rats

Objective To observe the expression of parathyroid hormone-related peptide (PTHrp) receptor in tibial growth plate and its effects on tibial extension in chronic renal insufficiency rats. Methods Two-week-old male Sprague-Dawley rats were randomly divided into sham group, model group and enalapril group, each with 20 rats. In model group and enalapril group rats had chronic renal insufficiency induced by left ureteral obstruction, and rats were respectively given saline and enalapril by gavage after the operation. In sham group, left ureter was only exposed without ligation, and rats were given saline. The urine was collected 4 weeks after the operation and the total protein content was measured. Then all rats were killed. The concentrations of PTHrp, creatinine and urea nitrogen in intracardiac blood were detected. HE staining and Masson staining were performed on the left kidney to observe pathological changes of glomeruli and renal tubules. The total length of bilateral tibia was measured. The number of columnar cells in the growth plate proliferative zone was measured by safranin O staining and the expression of PTHrp receptor in the growth plate was detected by immunohistochemistry. Results The 24 h urine total protein, creatinine and urea nitrogen in model group were higher than those in sham group (all P＜0.05), while these 3 renal functional parameters in enalapril group were lower than those in model group (all P＜0.05). In model group and enalapril group rats had higher blood concentrations of PTHrp than that in sham group (all P＜0.05), but blood PTHrp in enalapril group was lower than that in model group (P＜0.05). HE staining and Masson staining showed that in the model group rats had severe tubular dilation, inflammatory cell infiltration and the tissue fibrosis, while in enalapril group renal tubules slightly dilated and had a few inflammatory cell infiltration and tissue fibrosis. Compared with those in the sham group, in model group the tibia length, the chondrocyte number of column structure in the growth plate proliferative zone and the PTHrp receptor decreased (all P＜0.05). But in enalapril group those indexes increased than model group (all P＜0.05). Conclusions Chronic renal insufficiency rats had increased PTHrp concentration in the blood but decreased PTHrp receptors expression in tibial growth plate, which lead to their limited tibial extension.     

Growth hormone binding protein and free growth hormone in chronic renal failure

Chronic renal failure in children is associated with growth failure. While the pathogenesis of uremic growth failure is multifactorial, an abnormal growth hormone/insulin-like growth factor (GH-IGF) axis is an important contributory element. Patients with uremia exhibit insensivivity to the action of GH, as exemplified by high plasma GH levels, low IGF-I activity, and poor somatic growth. This insensitivity can be overcome by supraphysiological doses of exogenous GH. Plasma GH binding protein (GHBP, the circulating ectodomain of the GH receptor) levels are decreased in patients with renal failure, as are hepatic GH receptor levels in animal models. Since GHBP levels are thought to reflect GH receptor levels in tissues, it is likely that the uremic GH insensitivity in humans is mediated by a decreased number of GH receptors. Another implication of the low plasma GHBP is a disproportionate elevation of free plasma GH (the biologically active moiety) relative to total GH, lending additional support to the concept of GH insensitivity in uremia. GH kinetics are altered in renal failure because of: (1) inability to excrete GH and (2) changes in the bound fraction of GH in the circulation.     

Growth in children with chronic renal failure and after renal transplantation

Growth retardation is a major problem for many children with chronic renal failure (CRF) and transplantation. The aim of this study is to assess the relation between height, glomerular filtration rate (GFR), hormonal alterations in children with CRF on regular haemodialysis (HD), and the impact of functioning graft after kidney transplantation. Thirty-six hemodialysed children were included in the study beside 32 pediatric transplants. Mean duration on HD was 14.72 ± 7.73 months for the CRF group, while the mean interval after transplantation was 1.97 ± 0.9 years for the second group. Moreover, twenty healthy children of matched age and sex served as controls. Assessment of growth parameters included height, expressed as standard deviation scores (Ht SDS) for chronological age, serum levels of growth hormone (hGH), and parathormone (PTH). Growth performance was evaluated twice: at the start of the study and one year later. Children with CRF and transplantation had significantly higher levels of both serum hGH and PTH compared to their controls, while CRF children experienced significantly higher serum levels of both hGH and PTH compared to those with functioning graft. Furthermore, analysis of our results by non-parametric Kendall’s correlation at the start and one year later revealed negative correlation concerning dialysis duration, serum creatinine, and PTH. On the other hand, positive correlation was achieved for serum calcium and GFR.     

Effects of low protein diet supplemented with ketoacids on local renin - angiotensin system enzyme activities and podocytes loss in patients with diabetic nephropathy

Objective To explore the effects of low-protein diet supplemented with ketoacids on podocytes as well as local RAS in the kidney of patients with diabetic nephropathy. Methods A tal of 61 patients with T2DN and CKD stages 3-4 were included. All the patients were randomly divided into two groups: low protein group (0.6 g•kg BW-1•d-1 and 30 kcal•kg BW-1•d-1, LPD) and LPD +Ketoacids (KA) group (0.6 g•kg BW-1•d-1, 30 kcal kg BW-1•d-1, and Ketoacids 100 mg•kg BW-1• d-1). Blood and 24 h urine samples were collected at baseline and every 3 months for routine examination to evaluate the efficacy of LPD + KA diet. Podocytes loss was evaluated by mRNA expression of nephrin, podocin, and synaptopodin in urine at baseline and every 3 months. Urinary angiotensinogen was detected by ELISA at baseline and every 3 months. Results After 12 months of follow-up, there were no significant difference statistically in declines of GFR between LPD and LPD+ KA group (P＞0.05). Compared with LPD group, proteinuria in LPD+KA group was decreased [(0.43± 0.35) vs (0.15±0.36) g/24 h, P＜0.01]. Patients in two groups were both in good nutritional condition, and KA independently increased the levels of serum albumin and prealbumin (all P＜0.05). The urinary angiotensinogen/creatinine ratio was correlated with GFR (r＝-0.437, P＝0.001), serum creatinine (r＝-0.733, P＝0.000) and proteinuria (r＝-0.851, P＝0.000); while urinary mRNA expression of podocyte markers (podocin and synaptopodin were correlated with proteinuria (r＝0.340, P＝0.012; r＝0.333, P＝0.014; respectively), but had no correlation with GFR and serum creatinine. After 12 months of follow-up, the urinary angiotensinogen/creatinine ratio in LPD+KA group was lower than in LPD group (P＜0.05). The mRNA expression of podocin and synaptopodin were lower in LPD+ KA group compared with LPD group in urinary sediment (P＜0.05). Further correlation analysis suggested that the change of urinary expression of podocin and synaptopodin had a modest but significant correlation with the change urinary angiotensinogen creatinine ratio change (r＝0.305, P＝ 0.026; r＝0.281, P＝0.04, respectively) after treatment for one year. Conclusions Low protein diet supplemented with Ketoacids (LPD + KA) is associated with amelioration of proteinuria, meanwhile nutrition status remains well. The mechanism of these effects may be explained by the role of LPD+KA diet in reducing urine podocyte loss and lowering the angiotensinogen level in the urine.     

Left ventricular geometry in children with mild to moderate chronic renal insufficiency

Left ventricular hypertrophy (LVH) is the most important independent marker of cardiovascular risk in adults with chronic kidney disease. Cardiovascular morbidity seems increased even in children with chronic renal insufficiency (CRI), but the age and stage of CRI when cardiac alterations become manifest are unknown. For assessing the prevalence and factors associated with abnormal LV geometry in children with CRI, echocardiograms, ambulatory BP monitoring, and biochemical profiles were obtained in 156 children aged 3 to 18 yr with stages 2 through 4 chronic kidney disease (GFR 49 +/- 19 ml/min per 1.73 m2) and compared with echocardiograms obtained in 133 healthy children of comparable age and gender. LV mass was indexed to height2.7. Concentric LV remodeling was observed in 10.2%, concentric LVH in 12.1%, and eccentric LVH in 21% of patients. LVH was more common in boys (43.3 versus 19.4%; P < 0.005). Probability of LVH independently increased with male gender (odds ratio [OR] 2.62; P < 0.05) and standardized body mass index (OR 1.56; P = 0.01). Low hemoglobin, low GFR, young age, and high body mass index were independent correlates of LV mass index (0.005 < P < 0.05). LV concentricity (relative wall thickness) was positively associated with serum albumin (P < 0.05). Probability of abnormal LV geometry increased with C-reactive protein >10 mg/dl (OR 26; P < 0.001). In conclusion, substantial cardiac remodeling of both concentric and eccentric type is present at young age and early stages of CRI in children. Prevalence of LVH is related to male gender, anemia, and ponderosity but not to BP. Additional effects of volume status and inflammation on cardiac geometry are also evident.     

Measurement of growth in children with renal insufficiency.

The serial measurement of stature, weight, skin-fold thickness, mean arm circumference, skeletal maturity, and where appropriate, stage of sexual development are recommended as suitable indices for assessing growth in children with kidney disease. Methods of expressing the data for evaluating the individual child are generally used methods. Emphasis is given to relating stature to bone age in evaluating growth potential. Methods for comparing growth rates in groups of children are less well-developed. Using standard deviation scores is recommended for comparing stature in two groups of children or in the same child observed at the end of two different regimens. Weight using ideal weight-for-height as reference from a group of children can be treated statistically. Data of skinfold thickness and arm circumference from two groups can be handled statistically only when the groups are comparable in age and sex.     

Dietary protein restriction in chronic renal failure: nutritional efficacy, compliance, and progression of renal insufficiency.

Two findings prompted investigators to examine the effects of dietary manipulation on progression of chronic renal failure: dietary protein restriction is an effective method of ameliorating uremic symptoms and the course of renal insufficiency in an individual patient is predictable. Results from studies of patients and animals with chronic renal failure suggested that a low-protein, phosphorus-restricted diet could slow the rate of loss of renal function. In evaluating these studies, three questions should be considered. First, is the diet nutritionally adequate? Second, has dietary compliance been monitored and achieved? Third, is there evidence that restricting the diet will change the rate of loss of renal function? The scientific basis for each of these questions is addressed in this review.     

Low protein diets delay end-stage renal disease in non-diabetic adults with chronic renal failure.

BACKGROUND: The objective of this study was to determine the efficacy of low protein diets in delaying the need to start maintenance dialysis based on an analysis of published literature. METHODS: The search strategy involved a Medline and Embase search from January 1966 through to June 1999, congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, International Society of Nephrology since 1987) and direct contacts with investigators. The selection criteria included randomized trials comparing two different levels of protein intake in adult patients suffering from moderate to severe renal failure, followed for at least 1 year. Patients with diabetic nephropathy were excluded. Seven trials were selected from 40 studies since 1975. A total of 1494 patients were analysed: 753 had received reduced protein intake and 741 a higher protein intake. The numbers of 'renal deaths' (defined as the need for starting dialysis, the death of a patient or kidney transplant during the trial) were collected. RESULTS: 242 renal deaths were recorded, 101 in the low protein diet and 141 in the higher protein diet group, giving an odds ratio of 0.61 with a 95% confidence interval of 0.46 to 0.83 (P=0.006). CONCLUSION: Reducing protein intake in patients with chronic renal failure reduces the occurrence of renal death by about 40% as compared with larger or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.     

Intracellular amino acid concentrations in children with chronic renal insufficiency

We studied amino acid concentrations in granulocytes and plasma of 24 children with chronic renal failure and 15 healthy children. Granulocytes were isolated from 10 ml of blood using a dextran-Ficoll-Hypaque procedure. Intracellular levels of leucine, isoleucine, methionine, phenylalanine, lysine, histidine, tyrosine, and arginine were significantly lower in children with chronic renal failure than healthy children. There were no significant differences in intracellular and plasma amino acid concentrations between children with chronic renal failure on a well-balanced protein-restricted diet and children with chronic renal failure with a normal protein intake.     

Reduced systolic myocardial function in children with chronic renal insufficiency

Increased left ventricular (LV) mass in children with chronic renal insufficiency (CRI) might be adaptive to sustain myocardial performance in the presence of increased loading conditions. It was hypothesized that in children with CRI, LV systolic function is impaired despite increased LV mass (LVM). Standard echocardiograms were obtained in 130 predialysis children who were aged 3 to 18 yr (59% boys) and had stages II through IV chronic kidney disease and in 130 healthy children of similar age, gender distribution, and body build. Systolic function was assessed by measurement of fractional shortening at the endocardial (eS) and midwall (mS) levels and computation of end-systolic stress (myocardial afterload). The patients with CRI exhibited a 6% lower eS (33.1 +/- 5.5 versus 35.3 +/- 6.1%; P < 0.05) and 10% lower mS (17.8 +/- 3.1 versus 19.7 +/- 2.7%; P < 0.001) than control subjects in the presence of significantly elevated BP, increased LVM, and more concentric LV geometry. Whereas the decreased eS was explained entirely by augmented end-systolic stress, mS remained reduced after correction for myocardial afterload. The prevalence of subclinical systolic dysfunction as defined by impaired mS was more than five-fold higher in patients with CRI compared with control subjects (24.6 versus 4.5%; P < 0.001). Systolic dysfunction was most common (48%) in patients with concentric hypertrophy and associated with lower hemoglobin levels. CRI in children is associated with impaired intrinsic LV contractility, which parallels increased LVM.