Decreased resting energy expenditure in non-dialysed chronic kidney disease patients.

BACKGROUND: Non-dialysed chronic kidney disease (CKD) patients may have altered resting energy expenditure (REE) because of the important metabolic functions of the kidneys. The aim of the present study was to evaluate whether REE in clinically stable, non-diabetic and non-dialysed CKD patients with no clinical signs of inflammation, was different from that of gender and age pair-matched healthy controls. Subjects and methods. REE in 45 patients (20 male and 25 female; age 44.9 +/- 11.7 years; mean +/- SD) and 45 healthy individuals (20 male and 25 female; age 44.6 +/- 11.5 years) was measured by indirect calorimetry after a 12-h fast. In both groups, body composition was assessed by bioelectrical impedance. Glomerular filtration rate was assessed by creatinine clearance only in the CKD patients. RESULTS: The mean creatinine clearance and serum creatinine of the CKD patients were 29.1 +/- 14.6 ml/min/1.73 m(2) and 3.48 +/- 2.48 mg/dl, respectively. Body fat (BF) and lean body mass (LBM) were similar between the two groups (CKD patients: BF 28.6 +/- 11.3%, LBM 46.9+/-10.0 kg; and healthy individuals: BF 28.1 +/- 7.54%, LBM 49.5 +/- 10.5 kg). REE of CKD patients was significantly lower than that of healthy individuals (1325 +/- 206 vs 1448 +/- 258 kcal/day; P = 0.01, respectively) even after adjusting for LBM by multiple regression analysis. In fact, the presence of chronic renal insufficiency reduced REE by 103.2 kcal/day (P = 0.02; 95% confidence interval (-15.9; 190.5)). CONCLUSION: REE of clinically stable non-dialysed, non-diabetic patients in stages 2-5 of CKD was lower than that of age and gender pair-matched healthy individuals. Although the cause of reduced REE was unclear, it may be related to decreased food intake and to metabolic disturbances inherent with deterioration of renal function. Further studies will be necessary to clarify this issue.     

Uraemic symptoms, nutritional status and renal function in pre-dialysis end-stage renal failure patients.

BACKGROUND: Deciding on the right moment to initiate dialysis and finding the best method to establish this critical stage of chronic renal failure are both controversial issues. This study attempted to address this subject by correlating a uraemic score with the most common clinical methods for assessing renal function in pre-dialysis chronic renal failure (end-stage renal disease, ESRD) patients. METHODS: The study group consisted of 201 non-selected ESRD patients. A uraemic score, composed of the uraemic symptoms, the subjective global assessment of nutritional status, serum albumin concentration, and protein catabolic rate normalized for ideal body weight, was taken as a clinical marker of uraemic toxicity. Correlations that best fit this uraemic score with creatinine clearance (Ccr), the arithmetic mean of Ccr, urea clearance (Ccr-Cu) and Kt/V urea were then investigated. RESULTS: Thirty-six per cent of patients had malnutrition. By multiple logistic regression analysis, the presence of comorbidity, Ccr-Cu and haematocrit were the best determinants of malnutrition. The correlation that best fit Ccr or Ccr-Cu with the uraemic score was a cubic curve (r=0.38, P<0.0001, and r=0.42, P<0.0001, respectively), in which an ascending inflection was observed when Ccr and Ccr-Cu fell below 12-13 and 10 ml/min, respectively. However, the relationship between Kt/V urea and the uraemic score was less predictable, especially in male patients. CONCLUSION: Ccr or Ccr-Cu are reliable methods for establishing the degree of severity of chronic renal failure below which the development of symptoms and malnutrition are highly prevalent. In contrast, Kt/V urea may be a less sensitive and specific method for assessing the severity of uraemia in ESRD patients.     

Resting energy expenditure in morbid obesity.

Resting energy expenditure (REE) was measured in 112 morbidly obese adults prior to elective gastric bypass surgery. The patients studied ranged from 157 to 327% of ideal body weight. Standard nutritional assessment indices (serum total protein, albumin, total iron binding capacity, hematocrit, and white blood cell count) were within normal limits. REE was estimated by the Harris-Benedict formula using both current weight and ideal weight. Measured REE was significantly less than expected (p less than 0.01) using current weight and significantly greater than expected (p less than 0.01) when ideal weight was used as the standard. Linear regression analysis between standard indices that reflect resting metabolic rate in normal adults and measured REE in study patients did not demonstrate sufficient correlation to be clinically useful in this patient population. Standard surgical therapy may result in highly variable weight loss in this population if the wide range of resting energy expenditure and the consequential variability in individual caloric deficits is not considered. Standard predictors do not identify those patients likely to be unsuccessful with a given weight loss regimen.     

Urinary prostaglandins (PGE2 and PGI2) in hyporeninaemic hypoaldosteronism in diabetic patients with chronic renal failure

The present work studies the urinary excretion of PGE₂ and PGI₂(6-keto PGF 1) in 11 insulin-dependent diabetic patients withchronic renal failure with a glomerular filtration rate of 33.9±9.03 ml/min who had hyporeninaemic hypoaldosteronismto evaluate the influence of these prostaglandins on the appearanceof this latter process. The results obtained in this group ofpatients were compared with those of a control group of healthyindividuals, another group of nine non-diabetic patients withCRF, and a last group of eight insulin-dependent diabetic patientswith normal renal functión to evaluate to what extentthe possible variations in prostaglandin excretion could berelated to the diabetes, CRF, or a conjunction of both processes. The results of the groups of diabetic patients with CRF wereC_cr 33.9 ±9.03 ml/min, decreased (P< 0.0001) withrespect to the control group and with no difference with theCRF group without diabetes; plasma potassium (4.7 ±0.4mEq/l), increased P<0.005) with respect to the values foundin the control group; plasma bicarbonate (17.8 ± 1.8mEq/l), decreased (P< 0.005) with respect to the controlgroup and also, though not significantly, with respect to thegroup of non-diabetic patients with CRF. Plasma aldosterone(pg/ml): resting 44.3±14.9; standing 65.7 ±63.5and post-frusemide 65.5 ±58.6, decreased (P<0.01)with respect to the other three groups. Plasma renin activity(PRA) (ng/ml/h): resting 0.34±0.3; standing 0.6 ±0.4, post-fmsemide 0.9 ±0.5, decreased significantlywith respect to the other three groups. PGE₂ (pg/mg Cr): basal1720±397; post-frusemide 2636±462, increased (P<0.05)with respect to the control group and that of the diabetic patientswithout CRF, but with no differences compared with the non-diabeticpatients with CRF. PGI₂ (pg/mg cr): basal 369 ±45 andpost-frusemide 699 ± 103, increased (P<0.01) withrespect to the controls and diabetic patients with normal renalfunction and with no differences compared with the non-diabeticpatients with CRF. Our findings indicate that patients with diabetes mellitus andCRF showing hyporeninaemic hypoaldosteronism have high urinaryexcretion of PGE₂ and PGI₂. The increase in the urinary prostaglandinsis related to CRF. The data rule out the hypothesis that thehyporeninaemic hypoaldosteronism of these patients is due toa deficit of prostaglandins.     

A dramatic reduction of normalized protein catabolic rate occurs late in the course of progressive renal insufficiency.

BACKGROUND: Spontaneous reduction in dietary protein intake is a recognized feature of severe renal failure, and previous studies have suggested that this may occur at an early stage of renal functional decline. METHODS: We examined the effects of progressive renal insufficiency on the normalized protein catabolic rate (nPCR) in 1282 patients (mean age 55.8+/-15.5 years; 60.4% male) over a 7 year period. All values of nPCR (n = 5082) obtained before commencement of dialysis were included. A total of 361 (28.2%) patients later developed end-stage renal failure and were started on dialysis. RESULTS: Cross-sectional analysis showed nPCR being significantly less at lower creatinine clearance. Mean nPCR was 1.17+/-0.31 at a clearance >50, 1.04+/-0.27 at 25-50, 0.93+/-0.21 at 10-25 and 0.74+/-0.18 at <10 ml/min. Mean nPCR in each clearance group was different from that in all other groups (P<0.001 in all cases). When nPCR was studied longitudinally in relation to time of initiation of dialysis, the fall in nPCR only became significant in the 3 months preceding initiation. Curve fitting suggested a two-phase exponential association between nPCR and renal function, a gentle decline of nPCR in mild and moderate renal failure culminating in a dramatic decline when CrCl reached 15 ml/min and weekly Kt/V(urea) 2.5. nPCR at dialysis initiation predicted survival on dialysis even when corrected for age, diabetes and non-renal co-morbid load. However, it was no longer significant when residual renal function was included in the model. The group initiating dialysis with a normal nPCR maintained this throughout the first 3 years on dialysis whilst the group initiating with a low nPCR, though improving initially, continued to have significantly lower nPCR levels throughout follow-up than their normal nPCR counterparts. CONCLUSION: A significant reduction of nPCR occurs late in progressive renal insufficiency and may predict the need for dialysis initiation. nPCR levels <0.8 at initiation predict future low nPCR levels and mortality on dialysis. The correlation between nPCR and CrCl in early renal insufficiency may be partly artefactual.     

Predictors of hospitalization and death among pre-dialysis patients: a retrospective cohort study.

BACKGROUND: Although there is abundant research describing predictors of patient morbidity and mortality among dialysis patients, predictors of adverse clinical outcomes among pre-dialysis patients are less well defined. The purpose of this study was to identify baseline predictors of first non-elective hospitalization among a retrospective cohort of 362 pre-dialysis patients. METHODS: Univariate and multivariate Cox proportional hazard models were used to identify predictors of hospitalization prior to dialysis initiation, adjusted for baseline creatinine level. Dialysis initiation, loss to follow-up, and study conclusion were censored events. Secondary outcomes included cause-specific hospitalization and death. RESULTS: Univariate analysis indicated that advanced age (RR 1.026, CI 1.016-1.037), number of prescribed anti-hypertensive medications (RR 1.149, CI 1.019-1.296), history of myocardial infarction (RR 1.979, CI 1.339-2.926), congestive heart failure (RR 2.299, CI 1.616-3.270), angina (RR 2.289, CI 1.695-3.091), peripheral vascular disease (RR 1.841, CI 1.282-2.644), renal failure secondary to nephrosclerosis (RR 1.413, CI 1.033-1.933) or renal artery stenosis (RR 1.587, CI 1.036-2.430), lower baseline haemoglobin level (RR 0.986, CI 0.979-0.992), and baseline creatinine greater than 300 micromol/l (RR 1.636, CI 1.233-2.171) were predictors of hospitalization. Gender, diabetes, diastolic blood pressure, mean arterial pressure, history of stroke, and hypoalbuminaemia did not predict outcome. Multivariate analysis, adjusted for baseline creatinine level, selected advanced age (RR 1. 017, CI 1.006-1.027), angina (RR 1.893, CI 1.371-2.613), peripheral vascular disease (RR 1.545, CI 1.054-2.266), and haemoglobin level (RR 0.987, CI 0.944-0.979) as independent predictors of hospitalization. CONCLUSION: Advanced age, co-morbid cardiovascular illness and anaemia are independent predictors of non-elective hospitalization prior to dialysis initiation. Further study is needed to determine the extent to which aggressive pre-dialysis management of anaemia and cardiovascular disease can improve patient outcomes.     

Incidence of anaemia, and use of epoetin therapy in pre-dialysis patients: a prospective study in 403 patients.

BACKGROUND: Recent American and European guidelines recommend that epoetin therapy should be considered whenever the blood haemoglobin (Hb) level is <10-11 g/dl in dialysis patients and in pre-dialysis patients. Thus, data on the current prevalence of anaemia with respect to the degree of chronic renal insufficiency are needed in order to determine the potential indications of epoetin therapy in the pre-dialysis period. METHODS: We prospectively studied 403 consecutive ambulatory pre-dialysis patients whose serum creatinine (Scr) was 200 micro mol/l or more at their first passage at our out-patient clinic between January 1 and June 30, 1999. Hb and Scr values were determined at each visit until June 30, 2000, or until the start of maintenance dialysis. Patients had a clinical and laboratory evaluation every 2-3 months, and monthly when treated with epoetin. RESULTS: The mean (+/-SD) age of patients was 60.9+/-17.2 years at presentation. The Hb level was <11 g/dl in 62% of patients with Scr > or =400 micro mol/l, and in 58% of patients with an estimated creatinine clearance (Ccr) <20 ml/min/1.73 m(2). The proportion of anaemic patients was higher for any given Ccr value in females than in males. A total of 136 patients were treated with epoetin during the observation period. At the start of epoetin, their mean Hb value was 9.5+/-0.6 g/dl and Ccr level 13.9+/-4.9 ml/min/1.73 m(2). Among the 123 patients who began maintenance dialysis therapy during the observation period, 85 (or 69%) received epoetin therapy before the start of dialysis. Their mean Hb value at the start of dialysis was 10.8+/-1 g/dl compared with 10.5+/-1.1 g/dl in the 41 dialysed patients who did not require epoetin therapy during the pre-dialysis period. CONCLUSIONS: Based on the data gained in a large cohort of patients receiving regular pre-dialysis nephrological care, the proportion of subjects with a Hb level <11 g/dl may be estimated at approximately 60% when the Ccr is <20 ml/min/1.73 m(2). If the Hb level is to be maintained at no less than 11 g/dl, at least two-thirds of patients at this advanced stage of chronic renal failure should require pre-dialysis epoetin therapy.     

Resting energy expenditure and subsequent mortality risk in peritoneal dialysis patients

Cardiovascular disease is the leading cause of death in ESRD patients and is strongly associated with malnutrition. The mechanism of malnutrition is not clear, but hypermetabolism is suggested to contribute to cardiac cachexia. This study examined resting energy expenditure (REE) in relation to the clinical outcomes of ESRD patients who receive continuous ambulatory peritoneal dialysis (CAPD) treatment. A prospective observational cohort study was performed in 251 CAPD patients. REE was measured at study baseline using indirect calorimetry together with other clinical, nutritional, and dialysis parameters. Patients were followed up for a mean +/- SD duration of 28.7 +/- 14.3 mo. REE was 39.1 +/- 9.6 and 40.1 +/- 9.0 kcal/kg fat-free edema-free body mass per day for men and women, respectively (P = 0.391). Using multiple regression analysis, fat-free edema-free body mass-adjusted REE was negatively associated with residual GFR (P < 0.001) and serum albumin (P = 0.046) and positively associated with diabetes (P = 0.002), cardiovascular disease (P = 0.009), and C-reactive protein (P = 0.009). At 2 yr, the overall survival was 63.3, 73.6, and 95.9% (P < 0.0001), and cardiovascular event-free survival was 72.3, 84.6, and 97.2% (P = 0.0003), respectively, for patients in the upper, middle, and lower tertiles of REE. Adjusting for age, gender, diabetes, and cardiovascular disease, patients in the upper and middle tertiles showed a 4.19-fold (95% confidence interval, 2.15 to 8.16; P < 0.001) and a 2.90-fold (95% confidence interval, 1.49, 5.63; P = 0.002) respective increase in the risk of all-cause mortality compared with those in the lower tertile. However, the significance of REE in predicting mortality was gradually reduced when additional adjustment was made for C-reactive protein, serum albumin, and residual GFR in a stepwise manner. In conclusion, a higher REE is associated with increased mortality and cardiovascular death in CAPD patients and is partly related to its close correlations with residual kidney function, cardiovascular disease, inflammation, and malnutrition in these patients.     

Urinary sulfate excretion and risk of late graft failure in renal transplant recipients – a prospective cohort study

Hydrogen sulfide (H₂S), produced from metabolism of dietary sulfur-containing amino acids, is allegedly a renoprotective compound. Twenty-four-hour urinary sulfate excretion (USE) may reflect H₂S bioavailability. We aimed to investigate the association of USE with graft failure in a large prospective cohort of renal transplant recipients (RTR). We included 704 stable RTR, recruited at least 1 year after transplantation. We applied log-rank testing and Cox regression analyses to study association of USE, measured from baseline 24 h urine samples, with graft failure. Median age was 55 [45–63] years (57% male, eGFR was 45 ± 19 ml/min/1.73 m²). Median USE was 17.1 [13.1–21.1] mmol/24 h. Over median follow-up of 5.3 [4.5–6.0] years, 84 RTR experienced graft failure. RTR in the lowest sex-specific tertile of USE experienced a higher rate of graft failure during follow-up than RTR in the middle and highest sex-specific tertiles (18%, 13%, and 5%, respectively, log-rank P < 0.001). In Cox regression analyses, USE was inversely associated with graft failure [HR per 10 mmol/24 h: 0.37 (0.24–0.55), P < 0.001]. The association remained independent of adjustment for potential confounders, including age, sex, eGFR, proteinuria, time between transplantation and baseline, BMI, smoking, and high sensitivity C-reactive protein [HR per 10 mmol/24 h: 0.51 (0.31–0.82), P = 0.01]. In conclusion, this study demonstrates a significant inverse association of USE with graft failure in RTR, suggesting high H₂S bioavailability as a novel, potentially modifiable factor for prevention of graft failure in RTR.     

Resting energy expenditure and lung disease in cystic fibrosis.

Optimal nutritional support is considered to be an integral part in the management of cystic fibrosis (CF). Several factors contribute to increased resting energy expenditure (REE), which itself can lead to energy imbalance and thus contribute to deterioration of the nutritional status. We aimed to assess the impact of lung parenchyma damage on REE and correlated these findings with forced expiratory volume in 1 s (FEV(1)). Twenty patients performed respiratory function testing (FEV(1)), pulmonary high-resolution computed tomography (HRCT) and assessment of REE with open circuit indirect calorimetry. HRCT was scored by using a modified Bhalla method. Mean HRCT score was 8.4 and mean REE value was 108.4% predicted vs. 96.5% predicted of 16 healthy subjects (P<0.01). There was a significant correlation between HRCT score and REE (P<0.01), HRCT score and FEV(1) (P<0.001) and REE and FEV(1) (P<0.05). The correlations demonstrate a close correlation between lung damage and elevated REE in people with CF. Prevention of negative energy balance is an important part in follow-up of patients with CF. Any increase in REE should raise suspicion of progress in lung impairment.     

Resting energy expenditure and oxygen cost of breathing in patients with cystic fibrosis.

BACKGROUND: Resting energy expenditure (REE) is often increased and may contribute towards energy imbalance in patients with cystic fibrosis. Several mechanisms may lead to increased REE including the gene defect, the effect of chronic infection, and abnormal pulmonary mechanics. Increased oxygen cost of breathing (OCB) has been demonstrated in patients with chronic obstructive pulmonary disease (COPD), but has not been the subject of extensive study in cystic fibrosis. METHODS: Ten clinically stable patients with cystic fibrosis and 10 healthy control subjects were studied. OCB was estimated using the dead space hyperventilation method. Mixed expired gas fractions were measured by online gas analysers and ventilation by a pneumotachograph. After measurement of resting ventilation and gas exchange, minute ventilation (VE) was stimulated by 6-10 1/min by the addition of a dead space and OCB calculated from the slope of the differences in oxygen uptake (VO2) and VE. REE and the non-respiratory component of REE were calculated from gas exchange data. To assess the repeatability of OCB all subjects had a further study performed one week later. RESULTS: The patients had lower weight, fat free mass (FFM), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and transfer factor for carbon monoxide (TLCO) than controls. Resting respiratory rate, VE, and oxygen uptake per kilogram of FFM (VO2/kg FFM) were higher in patients (20 (7), 10.4 (1.4) 1/min and 5.5 (0.8) ml/kg FFM/min) than in controls (13 (4), 7.0 (1.2), and 4.2 (0.5), respectively.) The error standard deviation for replicated measures of OCB was 0.5 ml O2/l VE in controls and 0.8 ml O2/l VE in patients with coefficients of variation of 24% in controls and 28% in patients. The mean OCB in patients was 2.9 (1.4) ml O2/l VE and 2.1 (0.7) ml O2/l VE in controls. OCB, expressed as ml/min (VO2resp) was 28.5 (11.7) in patients and 14.0 (3.6) in controls. REE was higher in patients (125.9 (14.0)% predicted) than in controls (99.0 (9.4)%). The estimated non-respiratory component of REE was 112.1 (14.9)% for patients and 93.0 (10.0)% for controls. CONCLUSIONS: In clinically stable patients with cystic fibrosis the OCB at rest is increased but is not the sole explanation for increased metabolic rate. This contrasts with the finding in COPD where the increase in REE is largely explained by increased OCB. This study also showed poor repeatability and OCB measurements similar to earlier studies, which indicates that the technique is not suitable for longitudinal studies.     

维持性血液透析患者的静息能量消耗特点

目的 探讨维持性血液透析(MHD)患者的静息能量消耗特点.方法 选择我院行MHD的终末期肾脏疾病(ESRD)患者50例,采用呼吸间接测热法测量患者实际的静息能量消耗(REE)值,与国际上通用的健康成人的Harris-Benedict公式的计算值比较,使用Spearman相关、配对t检验、吻合比例进行统计分析.结果 MH...     

In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients.

BACKGROUND: The beneficial effects of statins in reducing cardiovascular events have been attributed predominantly to their lipid-lowering effects, recent studies suggest that these effects might be due to their anti-inflammatory properties. We here investigate the in vivo and in vitro effects of simvastatin on cytokine production in pre-dialysis chronic renal failure patients. METHODS: Our clinical study has been designed as a randomized double-blind placebo controlled study. A total of 55 chronic kidney disease (CKD) patients at stages 3 and 4 (mean creatinine clearance 45 ml/min, range 15-60) were randomly assigned to receive simvastatin 40 mg/day or placebo, added to their ongoing treatment, for 6 months. Blood samples were obtained at baseline, and after 3 and 6 months of observation for the determination of lipids, inflammatory markers and renal function. For the in vitro studies, the effect of increasing doses of simvastatin on cytokine production [namely interleukin (IL)-6 and IL-8] in human cultured monocytes from 10 healthy subjects (HS) and 15 CKD patients stimulated by lipopolysaccharide (LPS) was investigated. RESULTS: A significant reduction in total cholesterol from 221+/-44 mg/dl to 184+/-41 mg/dl (3 months) and to 186+/-39 mg/dl (6 months) (P<0.02) and low-density lipoprotein cholesterol from 139+/-40 mg/dl to 104+/-29 mg/dl (3 months) and to 100+/-31 mg/dl (6 months) (P<0.001) was observed in the 28 patients treated with simvastatin. In this group, C-reactive protein (CRP) levels significantly decreased from 2.6 mg/l [interquartile range (IQR 4.9)] to 2.0 mg/l (IQR 1.9) (P = 0.03) at 6 months (P<0.05). A parallel reduction of IL-6 levels from 5.1 pg/ml (IQR 3.8) to 3.5 pg/ml (IQR 3.1) (P = 0.001) at 6 months was also observed. No significant reduction in inflammatory markers [CRP from 5.1 mg/l (IQR 1.9) to 5.4 mg/l (IQR 1.3) (P = NS) at 6 months] or plasma lipids [LDL-cholesterol from 127+/-32 mg/dl to 131+/-21 mg/dl (6 months)] was observed in the 27 patients of the placebo group. In the in vitro studies, the average value for cell-associated IL-6 and IL-8 was higher in CKD (155+/-95 pg/ml monocytes for IL-6 and 722+/-921 pg/ml monocytes for IL-8) vs HS (137+/-87 pg/ml monocytes and 186+/-125 pg/ml monocytes) (P<0.01) and was not affected by simvastatin alone. LPS resulted in a significant increase in cytokine production (IL-6: 1954+/-321 pg/ml monocytes for CKD and 1451+/-237 pg/ml monocytes for HS; P<0.001); the simultaneous addition of increasing doses of simvastatin to these cultures induced a dose-dependent inhibition of IL-6 and IL-8 production in stimulated peripheral blood mononuclear cells in all groups. CONCLUSIONS: These results indicate that simvastatin in commonly used doses has an in vitro and in vivo anti-inflammatory effect in CKD patients, and may play an important role in counteracting the mechanisms involved on the pathogenesis of cardiovascular disease.     

Resting energy expenditure and nitrogen loss after surgery in chronically undernourished patients

Chronically undernourished patients (n=10) undergoing elective abdominal surgery were assessed with regard to their energy expenditure and urinary nitrogen loss. These measurements were made for 1 week after the surgery, and stress factors for each parameter were computed. The responses of the chronically undernourished patients were compared to those of relatively well nourished patients (n=10) undergoing comparable surgeries. It was found that the postoperative resting energy expenditure (REE) of the chronically undernourished patients was not significantly elevated when compared to their preoperative values (mean±SEM): 1210.66±88.13, 1354.91±86.61, 1215.09±89.68, and 1188.23±86.61 kcal/day preoperatively and on postoperative days 1, 4, and 8, respectively. On the other hand, the postoperative REE of the controls was significantly elevated (p<0.05) over their baseline values: 1357.18±70.81, 1574.66±100.35, 1502.89±109.44, and 1477.23±83.52; kcal/day, respectively, for the same days. The stress factors for the controls were higher than those for the undernourished (1.16 versus 1.12, 1.11 versus 1.00, and 1.09 versus 0.98 on postoperative days 1, 4, and 8, respectively). The urinary nitrogen excretion in both groups (for the 4 days) was not significantly elevated over baseline (6.23±0.87, 7.72±0.71, 8.36±0.87, and 8.04±1.56 grams/day in the undernourished; and 7.59±1.03, 9.57±1.33, 9.49±1.03, and 8.67±0.76 grams/day in the controls. The stress factors for nitrogen excretion were slightly higher in the undernourished group. The data from this study show that the postoperative REE of chronically undernourished subjects is lower than that of well nourished controls. The nitrogen loss, however, is similar in the two groups.

---

Resumen Pacientes con desnutrición crónica (n=10) sometidos a cirugía abdominal electiva fueron valorados en cuanto al gasto energético y las pérdidas urinarias de nitrógeno. Se hicieron mediciones una semana después de la cirugía y se calcularon los factores de estrés para cada parámetro. Los datos de los pacientes con desnutrición crónica fueron comparados con los de pacientes relativamente bien nutridos (n=10) sometidos a operaciones comparables. Se encontró que el gasto energético en reposo (REE) de los pacientes con desnutrición crónica no aparece significativamente elevado al compararlo con los valores preoperatorios (1210.66±88.13, 1354.91±86.61, 1215.09 ±89.68, 1188.23±86.61, kcal/día; preoperatorío, días 1, 4, y 8 postoperatorios respectivamente, media ± s.c.m.). Por el contrario, el gasto energético en reposo postoperatorio de los controles apareció significativamente elevado (p<0.05) sobre los niveles bases (1357.18±70.81, 1574.66±100.35, 1502.89±109.44, y 1477.23±83.52 kcal/día; preoperatorio, días 1, 4, y 8 postoperatorios, respectivamente, media ± s.c.m.). Los factores de estrés para los controles resultaron más altos que para los desnutridos (1.16 vs. 1.12, 1.11 vs. 1.00, y 1.09 vs. 0.98; días 1, 4, y 8 postoperatorios, respectivamente). La excreción de nitrógeno urinario (g/día) no resultó significativamente elevada frente al valor de base (6.73±0.87, 7.77±0.71, 8.36±0.87, y 8.04±1.56 en el desnutrido) y 7.59±1.03, 9.57±1.33, 9.49±1.03, y 8.67±0.76 en los controles. Datos preoperatorios y para los días postoperatorios 1, 4, y 8 respectivamente, media ± s.c.m.). Los factores de estrés para la excreción de nitrógeno resultaron ligeramente más altos en el grupo de los pacientes desnutridos. Los datos del presente estudio muestran que el gasto energético postoperatorio de los pacientes con desnutrición crÔnica es menor que el de los controles en buen estado de nutrición. Sin embargo, las pérdidas de nitrógeno son similares en los dos grupos.

---

Résumé Les dépenses énergétiques et l'excrétion urinaire azotée ont été mesurées pendant une semaine, après une intervention chirurgicale chez dix patients en état de dénutrition chronique et ont été comparées à celles de dix patients dont l'état nutritionnel était normal. La dépense énergétique de base (DEB) des patients en état de dénutrition chronique n'était pas significativement plus élevée comparée aux valeurs préopératoires [respectivement, en préopératoire, et aux jours postopératoires 1, 4, et 8: 1210.66±88.13, 1354.91±86.61, 1215.09±89.68, 1188.23±86.61 kcal/jour: valeurs (moyenne ± écart-type de la moyenne)]. Les dépenses énergétiques des témoins étaient significativement plus élevées (p<0.05) par rapport à la DEB [respectivement en préopératoire, et aux jours postopératoires 1, 4, et 8: 1357.18±70.81, 1574.66±100.35, 1502.89±109.44, 1477.23±83.52 kcal/jour: valeurs (moyenne ± écart-type de la moyenne)]. Des facteurs de stress en cause dans la dépense énergétique ont été retrouvés plus souvent (mais non significativement) chez les témoins que chez les patients en dénutrition [respectivement, pour les jours postopératoires 1, 4, et 8: 1.16 vs. 1.12, 1.11 vs. 1.00, et 1.09 vs. 0.98, (valeur moyenne ± écart-type de la moyenne)]. L'excrétion azotée (g/jour) n'était pas plus élevée par rapport à la valeur de base (valeur moyenne ± écart-type de la moyenne, respectivement, en préopératoire, et aux jours postopératoires 1, 4, et 8: 6.23±0.87, 7.72±0.71, 8.36±0.87, et 8.04±1.09) chez les patients dénutris comparés à celle des témoins (valeur moyenne ± écart-type de la moyenne, respectivement, en préopératoire, et aux jours postopératoires 1, 4, et 8: 7.59±1.03, 9.57±1.33, 9.49±1.03, et 8.67 ±0.76). Des facteurs de stress en cause dans l'excrétion urinaire d'azote ont été retrouvés plus souvent (mais non significativement) chez les patients en état de dénutrition chronique. Les résultats de cette étude montrent que les dépenses énergétiques post-opératoires chez les patients en état de dénutrition chronique étaient plus basses que chez les patients dont l'état nutritionnel est satsifaisant. L'excrétion d'urée urinaire, par contre, était similaire dans les deux groupes.

     

Efficacy and tolerance of treatment with recombinant-human erythropoietin in chronic renal failure (pre-dialysis) patients

Recombinant-human erythropoietin (r-HuEPO) was administered to 24 anaemic pre-dialysis patients with end-stage renal disease. R-HuEPO was injected i.v. three times weekly during the first two months (correction phase). Fixed dosages of 50 U/kg, 100 U/kg, and 150 U/kg were used, and each dose group consisted of eight patients. During the subsequent six months r-HuEPO was given once weekly and the dose was adjusted to maintain a stable haemoglobin value (maintenance phase). The mean +/- SD haemoglobin increased from 9.3 +/- 0.6 to 11.1 +/- 1.3 g/dl with 50 U/kg, from 7.9 +/- 1.4 to 11.8 +/- 1.7 g/dl with 100 U/kg and from 8.4 +/- 1.0 to 12.1 +/- 1.1 g/dl with 150 U/kg of r-HuEPO. The two highest dose groups showed a marked reticulocytosis and a transient thrombocytosis. During the maintenance phase haemoglobin remained stable (11.9 +/- 1.1 g/dl) at a mean dose of 199 +/- 139 U/kg of r-HuEPO per week. Blood pressure did not increase, but in nine of eighteen previously hypertensive patients antihypertensive medication was increased. One hypertensive patient developed seizures. No accelerated progression of renal failure could be demonstrated. All patients reported an improved sense of well-being. R-HuEPO is an important new therapeutic agent for the treatment of anaemia of end-stage renal failure that is also effective in pre-dialysis patients.     

Glucose-added dialysis fluid prevents asymptomatic hypoglycaemia in regular haemodialysis.

BACKGROUND: Hypoglycaemia (HG) has been demonstrated during chronic haemodialysis (HD). These events may become more frequent with the current use of glucose-free bicarbonate dialysis solution, the standard formula in most dialysis facilities in the last decade. On the other hand, HG-related symptoms are unusual among patients during or just after dialysis sessions. The aim of this study was to evaluate the occurrence of HG in diabetic (DM) and non-diabetic (NDM) end-stage renal failure patients during HD using dialytic solution without and with glucose. METHODS: Forty-two chronic renal failure patients-21 DM and 21 NDM-randomly selected among the 97 in our dialysis unit were submitted to an HD session with glucose-free bicarbonate solution (phase 1). Serum glucose was measured at 30, 60, 150 and 240 min. In eight patients (four DM and four NDM) glucose was also measured in fluid leaving the dialyser at 30, 60 and 150 min. After a week, all procedures were repeated in the same patients, this time with a 90 mg/dl glucose-added bicarbonate solution (phase 2). We compared the glucose levels and the number of symptomatic and asymptomatic HG events in each group in phases 1 and 2, using bivariate analysis methods with confidence limit of 0.95%. RESULTS: Data were expressed as mean+/-SD. No patient presented any clinical evidence of HG. For all patients, the mean plasma glucose level (mg/dl) was significantly higher in phase 2 than in phase 1 (138.2+/-96.3 vs 120.7+/-75.9; P=0.0392). This occurred in DM (171.1+/-104.5 vs 132.5+/-71.0; P=0.0067), but not in NDM (101.3+/-19.4 vs 95.2+/-21.2; P=0.06). With glucose-free HD solution, 10 patients (five DM, five NDM) presented 18 measures of glycaemia under 70 mg/dl, and with glucose-added solution, only one (DM) presented two measures under 70 mg/dl-P=0.0045 (number of patients); P=0.0003 (number of HG measures). Among DM patients, values for HG measures in phase 1 (49.1+/-16.2 mg/dl) were significantly lower than in phase 2 (65.0+/-1.4 mg/dl)-P=0.0139. For all patients, glucose was lost in HD fluid leaving the dialyser at lower values in phase 2 (5.2+/-2.9 g/h) than in phase 1 (16.7+/-10.9 g/h)-P<0.0001. CONCLUSIONS: Asymptomatic HG was frequent during HD when glucose-free dialysis solution was used. Glucose was lost in dialytic fluid leaving the dialyser in significantly lower amounts when using glucose-added solution than glucose-free solution. Glucose-added dialysis solution at 90 mg/dl significantly reduced the number and severity of HG episodes and although it caused higher mean glycaemia in DM patients during HD, its use seems advisable in all patients.     

The safety of gadolinium in patients with stage 3 and 4 renal failure.

BACKGROUND: Although there is a well-documented risk of acute renal failure (ARF) with the iodinated contrast agents, intravenous gadolinium-based contrast agents are considered non-nephrotoxic and have been widely used for magnetic resonance imaging (MRI). However, debate continues regarding the safety issue of gadolinium, especially in patients with kidney failure. Therefore, we aimed to evaluate the safety of gadolinium in patients with stage 3 and 4 renal failure as well as risk factors for nephrotoxicity. METHOD: We retrospectively analysed 473 patients with chronic renal failure who underwent angiographic MRI procedures in our centre from February 1999 to March 2005 in whom gadolinium was used as the sole contrast agent at a dose of 0.2 ml/kg. Among them, 91 patients with stage 3 or 4 renal failure according to K/DOQI definition, who had available data in their files, were enrolled in the study. The ARF was defined as an increase of at least 0.5 mg/dl in serum creatinine level over baseline after using gadolinium. RESULTS: Eleven of 91 (52 males, 39 females; median age 59 years; median estimated glomerular filtration rate (eGFR) 33 ml/min/1.73 m2) patients developed ARF (12.1%). The median eGFR was lower in patients with ARF than in those who did not develop ARF. The risk factors for ARF were baseline eGFR, older age, diabetic nephropathy and low baseline haemoglobin and albumin levels. Baseline eGFR and diabetic nephropathy were determined as the independent risk factors in regression analysis. CONCLUSIONS: An ARF can occur after gadolinium-based contrast agents in patients with moderate to severe chronic renal failure. Risk factors for ARF after gadolinium toxicity include diabetic nephropathy and low GFR.