Nathalie Thilly

Low-protein diet in chronic kidney disease: from questions of effectiveness to those of feasibility

A low-protein diet (LPD) as a therapeutic measure in chronic kidney disease (CKD) was suggested by Beale as early as 1869 [1], and the first attempt to evaluate experimentally LPD in humans was fulfilled by Smith in 1926 [2]. In the mid 1960s, Giordano and Giovannetti were the first to show that LPD, supplemented with essential amino acids to achieve neutral nitrogen balance, was able to reduce almost all uraemic signs and symptoms [3, 4]. By lowering blood urea and other nitrogenous waste products, LPD has favourable effects on secondary hyperparathyroidism [5], peripheral resistance to insulin [6], hyperlipidaemia [7], hypertension and acid– base disorders [8]. For instance, Goraya et al. [8] have shown that a vegetarian diet in CKD patients Stage II (60–90 mL/min) significantly decreased the 8-h urine net acid excretion, potential renal acid load, urine albumin-to-creatinine ratio, urine N-acetyl-β-D-glucosaminidase-to-creatinine ratio and the urine transforming growth factor-β-to-creatinine ratio at 30 days, as compared with a control group. They also showed a 30-day greater decrease in systolic blood pressure, plasma and urine excretion of potassium, aldosterone, endothelin and urine excretion of sodium in the vegetarian group. As maintenance dialysis is generally initiated when uraemic symptoms begin, the need to start it may be deferred by LPD [9]. For instance, Walser et al. [10] found that dialysis can be safely deferred by LPD for a median of 1 year after patients reach a glomerular filtration rate (GFR) level of 10 mL/min among non-diabetics and 15 mL/min among diabetics. In the 1980s, the rapid development of kidney replacement therapies led to an enormous increase in expenditure, but mortality and morbidity remained high for patients receiving dialysis. This observation further raised the interest of health providers and researchers in interventions for slowing the deterioration of kidney function in order to delay end-stage renal disease (ESRD). Since that time, many experimental and observational studies have addressed the question of the ability of LPD (protein intake ≤0.8 g/kg/day), or very LPD (protein intake ≤0.3 g/kg/day), to retard the progression of CKD towards ESRD. Fouque et al. [11] identified 46 studies conducted between 1975 and 1991 that addressed this issue in non-diabetic CKD patients, and Pan et al. [12] identified 26 studies published up to 2008 in diabetic CKD patients. Despite the many studies performed over more than 30 years, the effectiveness of LPD in preventing ESRD among diabetic or nondiabetic CKD patients remains uncertain, with largely conflicting results. The Modification of Diet in Renal Disease (MDRD) was the largest randomized clinical trial to test the hypothesis that LPD slows the progression of kidney disease among 1840 patients with various stages of CKD. The primary results published in 1994 were not conclusive with regard to the effectiveness of this intervention [13]. However, following secondary analyses undertaken later, the authors concluded that ‘the balance of evidence is more consistent with the hypothesis of a beneficial effect of protein restriction than with the contrary hypothesis of no beneficial effect’ [14]. Five metaanalyses of studies of the effects of LPD on CKD progression in diabetic and non-diabetic patients have been performed since the early 1990s, four in favour of a beneficial effect [9, 11, 15, 16] and one not [12]. The reasons for the discrepancies between the results of studies conducted to evaluate LPD are of particular interest. Comparison of their designs reveals great heterogeneity:

Anxiety symptoms and coping strategies in the perinatal period.

BackgroundThe aim of the present study was to explore the prospective relationship between anxiety symptoms and coping strategies during late pregnancy and early postpartum.MethodsParticipants completed the Hospital Anxiety Depression-Anxiety subscale and Carver’s Brief COPE at two time points, namely during the last trimester of pregnancy (N = 400) and at two months postpartum (N = 158).ResultsAntenatally, 18.8% of pregnant women presented severe anxiety symptoms while 20.2% of women presented severe anxiety symptoms after birth. Carvers proposed coping styles allowed to significantly distinguish between anxious and non anxious women during these two periods. Anxious women used significantly more inappropriate coping and less adaptive coping responses, such as self-blame and denial of reality, which remained associated with anxiety in the perinatal period. Our results also indicated a decrease in adaptive coping in women without anxiety after birth (e.g. acceptance, positive reframing).ConclusionOur findings confirm that antenatal and postnatal anxiety symptoms occur frequently and that inappropriate and/or non functional coping may account for persisting anxiety after childbirth. Limitations: Data were based on self-reports and participating women were predominantly primiparous. A high drop-out rate at two months postpartum must also be acknowledged.

Chronic kidney disease: appropriateness of therapeutic management and associated factors in the AVENIR study.

RATIONALE, AIMS AND OBJECTIVES The nephrology literature contains little information about the global patterns of medication used in the management of patients with chronic kidney disease (CKD). This study aims to evaluate the appropriateness of nephrological therapeutic management of CKD patients compared with current guidelines and to investigate associations between patient characteristics and the quality of therapeutic management. METHODS All adult CKD patients who were starting dialysis in Lorraine (France) between 1 January 2005 and 31 December 2006 and who had been referred to a nephrologist no less than 1 month previously were enrolled. Demographic, clinical, biological and therapeutic data were collected retrospectively from medical records covering the period from the first nephrology consultation to initiation of dialysis. Outcomes of interest were the appropriateness of the therapeutic management of five aspects of CKD: hypertension/proteinuria, anaemia, bone disease, metabolic acidosis and dyslipidemia. Therapeutic care was given a global rating (high, moderate or poor), depending on the number of aspects being managed appropriately. Relationships between the global rating and demographic and clinical characteristics of patients were explored. RESULTS During predialysis nephrology follow-up, 93.1% of the 420 patients enrolled were receiving antihypertensive therapy; 67.1% were taking a renin-angiotensin system inhibitor. Other prescriptions included: erythropoiesis-stimulating agents (67.4%), iron (48.3%), phosphate binders (38.1%), vitamin D (21.1%), bicarbonates (15.5%) and statins (36.2%). Hypertension/proteinuria was managed appropriately in 72.4% of cases, anaemia in 56.2%, bone disease in 16.7%, metabolic acidosis in 60.2% and dyslipidemia in 61.4%. The global quality of care was high in 22.1% of cases, moderate in 65.7% and poor in 12.2%. After adjustment, the more nephrology consultations a patient had before dialysis, the higher the quality of his or her care. CONCLUSION The quality of therapeutic care delivered to CKD patients in nephrology setting was suboptimal when assessed in terms of adherence to guidelines.

Effect of gender on the association between weight status and health-related quality of life in adolescents.

BackgroundSome studies have investigated the association between body mass index (BMI) and health-related quality of life (HRQoL) among adolescents, but their results have been discrepant and few paid attention to the role of gender. The present investigation aimed to assess the relationship between weight status and HRQoL in adolescents and to verify whether it was similar in boys and girls.MethodsFive thousand two hundred and twenty six adolescents aged 14 to 18 years were included in the PRomotion de l’ALIMentation et de l’Activité Physique (PRALIMAP) trial, a 2x2x2 factorial cluster randomized trial performed in 24 high schools in France. Sociodemographic, anthropometric and HRQoL data were collected. BMI was categorized in four classes (thin, normal-weight, overweight, obese). Linear regression models were used to estimate the association between weight status and HRQoL, adjusting for confounders.ResultsThe mean age of adolescents was 15.7±0.6 years and their mean BMI was 21.6 ±3.5 kg/m2; 55% were girls. Boys were more often overweight and obese than were girls (overweight: 15.6% vs 14.2%, obese: 4.8% vs 3.3%), and girls were more likely to be thin (5.5% vs 4.5%, p=0.0042). All HRQoL scores were higher for boys (p=<0.0001). Weight status was not associated with physical and social scores neither in boys nor in girls. Conversely, it was associated with mental score, but differently in girls than boys. As compared with normal-weight girls, thin girls had better mental HRQoL (β=+6.17, p=0.0010), and overweight and obese girls had lower mental HRQoL (β=−3.89 and β=−5.90, respectively, p<0.001). Mental HRQoL was lower for thin, overweight and obese boys than for normal-weight boys (β= −4.97, β= −1.68 and β= −3.17, respectively, p<0.0001).ConclusionsGender can modify the association between weight status and HRQoL in adolescents. Body image could be an important target of public health programs to improve subjective health during adolescence.

Predialysis therapeutic care and health-related quality of life at dialysis onset (The pharmacoepidemiologic AVENIR study)

BackgroundTo determine the impact of the quality of pre-dialysis nephrological care on health-related quality of life (HRQoL) at dialysis onset, which has not been well evaluated.MethodsAll adults who began a dialysis treatment in the administrative region of Lorraine (France) in 2005 or 2006, were enrolled in this prospective observational study.HRQoL was measured using the Kidney Disease Quality of Life V36 questionnaire, which enables calculation of two generic (physical and mental) and three specific dimensions (Symptoms/problems, Effects and Burden of kidney disease). The specific dimensions were scored from 0 to 100 (worst to best possible functioning). Pre-dialysis nephrological care was measured using three indicators: quality of therapeutic practices (evaluated across five main aspects: hypertension/proteinuria, anemia, bone disease, metabolic acidosis and dyslipidemia), time since referral to a nephrologist and number of nephrology consultations in the year preceding dialysis treatment.ResultsTwo thousand and eighty-three (67.4%) patients were referred to a nephrologist more than 1 month before dialysis initiation and completed the HRQoL questionnaire. Quality of therapeutic practices was significantly associated with the Mental component. Time since referral to a nephrologist was associated with Symptoms/problems and the Effects of kidney disease dimensions, but no relationship was found between the number of nephrology consultations and HRQoL.ConclusionsHRQoL at dialysis onset is significantly influenced by the quality of pre-dialysis nephrological care. Therefore, disease management should be emphasized.

Evaluation and determinants of underprescription of erythropoiesis stimulating agents in pre-dialysis patients with anaemia.

Background: Inadequate anaemia correction (haemoglobin (Hb) <11 g/dl without receiving an erythropoiesis-stimulating agent (ESA) is common in pre-dialysis patients, but little is known about its determinants. We used data from the French end-stage renal disease (ESRD) registry to investigate these determinants and the patients’ anaemia status 1 year after starting dialysis. Methods: Pre-dialysis anaemia care was studied in 6,271 incident ESRD patients from 13 regions, who were first treated between 2003 and 2005. Data included pre-dialysis Hb measure and ESA use, patient’s condition and modalities of dialysis initiation. Anaemia status at 1 year was studied in 925 patients from four regions who started dialysis in 2003 and 2004, were still on dialysis one year later, and had completed the annual registry data form. Results: Overall, 34.7% of the patients had inadequate pre-dialysis anaemia correction, with variations across regions from 21.1 to 43.2%. Inadequate anaemia correction decreased from 38.0% in 2003 to 33.2% in 2005. It was less likely in patients with diabetic or polycystic kidney disease and more likely in those with malignancy, unplanned haemodialysis, and low glomerular filtration rate or low serum albumin at dialysis initiation. One year after starting dialysis, inadequate correction concerned only 2.6% of the patients. Hb level had risen from 10.3 g/dl in pre-dialysis to 11.7 g/dl, but remained lower in those with inadequate pre-dialysis correction. Conclusion: Despite improvement over time, inadequate correction with ESAs remains high in pre-dialysis patients in contrast with those on dialysis. As the timing of dialysis initiation is uncertain, continuous management of anaemia is requested.

Determinants and patterns of renin-angiotensin system inhibitors' prescription in the first year following kidney transplantation.

Abstract:  The benefit of prescribing angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin‐II receptor antagonists (ARB) to kidney transplant recipients remains controversial. We investigated determinants and prescribing patterns of ACEi/ARB during the first year following kidney transplantation. All recipients of a first kidney transplant performed at the university hospital of Nancy (France) between January 1997 and June 2004 were included. Determinants of ACEi/ARB prescription were identified by Cox models among various recipient characteristics (at transplantation and during follow‐up), donor characteristics and transplant parameters. Of 491 patients, 28.9% started using ACEi/ARB during the year after transplantation, and 26.9% were taking them at one yr. Recipient determinants of ACEi/ARB use were male sex (HR: 1.82, p = 0.003), pre‐transplant hypertension (HR: 2.27, p = 0.0002) and ACEi/ARB administration (HR: 1.85, p = 0.002), post‐transplant proteinuria (HR: 1.62, p < 0.0001) and anemia (HR: 4.08, p < 0.0001). Glomerular filtration rate level was not associated with ACEi/ARB use. Post‐transplant hypercholesterolemia (HR: 0.42, p = 0.013) and higher donor age (HR: 0.98, p = 0.015) were associated with a lower likelihood of ACEi/ARB use. Fewer HLA mismatches (HR: 1.16, p = 0.029) and shorter cold ischemia duration (HR: 1.02, p = 0.045) were also independent predictors of ACEi/ARB use. Regardless of recipient characteristics, nephrologists were more likely to prescribe ACEi/ARB after kidney transplantation when the transplant parameters were favorable.

Prognostic value of serum PIIINP, MMP1 and TIMP1 levels in hypertensive patients: a community-based prospective cohort study

The purpose of this study was to examine the prognostic value of serum ECM biomarkers in hypertensive patients with no history of cardiovascular events. In a community‐based cohort study of 125 hypertensive patients free of cardiovascular events, we collected clinical data and blood samples to assess serum levels of amino‐terminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase type 1(MMP1) and tissue inhibitor of MMPs type 1(TIMP1). Left ventricular hypertrophy (LVH) was assessed using the ECG Cornell product. Patients were followed up for death or cardiovascular hospitalisation. We used Cox regression models to assess the prognostic value of ECM biomarkers. The sample included 60.8% women; the mean (±SD) age was 62.9 (±11.4) years. Patients were followed up for a median of 5.5 years, during which 23 events (five deaths) occurred. PIIINP (3.2 ± 1.0 vs. 2.6 ± 0.8 μg/L, P = 0.001) and TIMP1 (886 ± 168 vs. 751 ± 202 μg/L, P < 0.001) levels were higher in the presence of LVH than with no LVH. Basal MMP1 serum levels were significantly associated with CV events (MMP1: HR, 1.06; 95%CI [1.02–1.09]). Adjusting for confounders did not modify this result. Cardiac fibrosis, as assessed with serum ECM biomarkers, might develop early in hypertensive patients and is predictive of cardiovascular events or death.

Patterns and Predictors of Kidney Function Decline in the Last Year prior to Dialysis

Background: Establishing a comprehensive characterization of kidney function decline before dialysis is necessary to predict dialysis onset and prepare patients for replacement therapy. Aims: To investigate kidney function as measured by pattern and rate of decline in glomerular filtration rate (GFR) over the year preceding dialysis and to identify factors associated with a nonlinear GFR decline. Methods: We enrolled patients beginning dialysis in Lorraine (France) in 2005 and 2006, who were referred to a nephrologist more than 4 months before dialysis and had received more than 3 predialysis serum creatinine tests. From medical records, we retrospectively collected demographic and clinical data, as well as biological data during nephrologist follow-up, limited to 1 year before dialysis. A curve of GFR evolution by time was drawn for each patient and his linearity was evaluated graphically and confirmed by R2 > 0.7. Factors associated with a nonlinear decline in GFR were identified by logistic regression. Results: A total of 342 patients were included; the mean length of predialysis nephrologist care was 10.0 ± 9.7 months and the median number of serum creatinine tests per patient was 9 . Among these patients, 185 (54.1%) showed a linear decline in GFR and 157 (45.9%) a nonlinear decline. Patients with cardiovascular disease were 2.6 times more likely to show a nonlinear than linear decline in GFR (p < 0.0001). Conclusion: For patients with a linear decline in GFR, but not those with a nonlinear decline, date of dialysis onset can be estimated.

Performing both propensity score and instrumental variable analyses in observational studies often leads to discrepant results: a systematic review

OBJECTIVES Propensity score (PS) and instrumental variable (IV) are analytical techniques used to adjust for confounding in observational research. More and more, they seem to be used simultaneously in studies evaluating health interventions. The present review aimed to analyze the agreement between PS and IV results in medical research published to date. STUDY DESIGN AND SETTING Review of all published observational studies that evaluated a clinical intervention using simultaneously PS and IV analyses, as identified in MEDLINE and Web of Science. RESULTS Thirty-seven studies, most of them published during the previous 5 years, reported 55 comparisons between results from PS and IV analyses. There was a slight/fair agreement between the methods [Cohens kappa coefficient = 0.21 (95% confidence interval: 0.00, 0.41)]. In 23 cases (42%), results were nonsignificant for one method and significant for the other, and IV analysis results were nonsignificant in most situations (87%). CONCLUSION Discrepancies are frequent between PS and IV analyses and can be interpreted in various ways. This suggests that researchers should carefully consider their analytical choices, and readers should be cautious when interpreting results, until further studies clarify the respective roles of the two methods in observational comparative effectiveness research.