Synergistic Effect of Inflammatory Cytokines and Body Adiposity on Insulin Resistance and Endothelial Markers in Patients With Stages 3-5 Chronic Kidney Disease.

BACKGROUND: High body adiposity, inflammatory cytokines, insulin resistance (IR), and the endothelial markers-soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1)-are among cardiovascular risk factors observed in chronic kidney disease (CKD). Synergistic interaction of inflammatory cytokines with adiposity on IR, sICAM-1, and sVCAM-1 has not been reported in nondialysis-dependent CKD (NDD-CKD) patients. Thus the study aim was to evaluate the interaction of inflammatory cytokines on the association of body adiposity with the cardiometabolic risk factors-IR, sICAM-1, and sVCAM-1-in NDD-CKD patients. Cytokines association with estimated glomerular filtration rate (eGFR) and body adiposity was also examined. DESIGN AND METHODS: A cross-sectional study was conducted in an interdisciplinary outpatient Nephrology Clinic. SUBJECTS AND MEASUREMENTS: NDD-CKD adults with eGFR ≤60 mL/minute/1.73 m2 under regular treatment. Inflammatory cytokines, homeostasis model assessment of insulin resistance (HOMA-IR), sICAM-1, sVCAM-1, eGFR (by CKD-Epidemiology collaboration equation)-EPI equation, and body composition assessed by dual-energy X-ray absorptiometry and anthropometry were evaluated. Synergistic effects of inflammatory markers with body adiposity on studied cardiometabolic risk factors were assessed by interaction and mediation analysis. RESULTS: The study cohort comprised 241 NDD-CKD patients (54.8% men; eGFR = 29.4 ± 12.9 mL/minute/1.73 m2). Variables evaluated: Inflammatory cytokines were not associated with eGFR and not different among CKD stages. Percentage of total body adiposity (%TBA) was independently associated with tumor necrosis factor-alpha (TNFα) and HOMA-IR. Waist-to-height ratio was independently associated with TNFα, interleukin-8, monocyte chemoattractant protein-1 (MCP1), and HOMA-IR. Interaction analysis showed TNFα, interleukin-8, and MCP1 as independent mediators of the effects of high percentage of total body adiposity and waist-to-height ratio on HOMA-IR (P < .0001). Body adiposity did not associate with sICAM-1 and sVCAM-1. TNFα (ß = 0.40) and MCP1 (ß = 0.31) were independently associated with sVCAM-1 (P < .01). CONCLUSIONS: In NDD-CKD patients, inflammatory cytokines synergistically mediated the effects of body adiposity, enhancing the cardiometabolic risk. Inflammation was associated with sVCAM-1, but not with eGFR.

Sarcopenia and its components in adult renal transplant recipients: prevalence and association with body adiposity.

Sarcopenia is a progressive and generalised skeletal muscle disorder associated with adverse outcomes. Ageing causes primary sarcopenia, while secondary causes include chronic kidney disease (CKD), long-term use of glucocorticoids and obesity. The aim of the present study was to evaluate the prevalence of sarcopenia using guidelines recommended by the European Working Group on Sarcopenia in Older People (EWGSOP, 2010; EWGSOP2, 2018) and the Foundation of the National Institutes of Health (FNIH) and analyse the relationship between sarcopenia and body adiposity in adult renal transplant recipients (RTR). This was a cross-sectional study of adult RTR (BMI ≥ 18·5 kg/m2). Body composition was evaluated by dual-energy X-ray absorptiometry (DXA) and anthropometry. Glomerular filtration rate was estimated (eGFR) by CKD-Epidemiology Collaboration equation. The prevalence of sarcopenia in adult RTR (n 185; 57 % men, 50 (se 0·82) years and eGFR 55·80 (se 1·52) ml/min) was 7 % (FNIH), 11 % (EWGSOP2) and 17 % (EWGSOP). Low muscle mass, muscle function and physical performance affected, respectively, up to 28, 46 and 10 % of the participants. According to EWGSOP and EWGSOP2, body adiposity evaluated by anthropometry and DXA (percentage trunk fat) was lower in participants with sarcopenia. Conversely, according to the FNIH criteria, RTR with sarcopenia presented higher waist:height ratio. The present study suggests that adult RTR sarcopenia prevalence varies according to the diagnostic criteria; low muscle mass, low muscle function and low physical performance are common conditions; the association of body adiposity and sarcopenia depends on the criteria used to define this syndrome; and the FNIH criteria detected higher adiposity in individuals with sarcopenia.

Vitamin D status in renal transplant recipients living in a low-latitude city: association with body fat, cardiovascular risk factors, estimated glomerular filtration rate and proteinuria.

Recent evidence suggests that vitamin D deficiency is associated with CVD, impaired kidney function and proteinuria. To date, no study has evaluated these associations in renal transplant recipients (RTR) adjusting for body adiposity assessed by a 'gold standard' method. This study aimed to evaluate the vitamin D status and its association with body adiposity, CVD risk factors, estimated glomerular filtration rate (eGFR) and proteinuria in RTR, living in Rio de Janeiro, Brazil (a low-latitude city (22°54'10"S)), taking into account body adiposity evaluated by dual-energy X-ray absorptiometry (DXA). This cross-sectional study included 195 RTR (114 men) aged 47·6 (sd 11·2) years. Nutritional evaluation included anthropometry and DXA. Risk factors for CVD were hypertension, diabetes mellitus, dyslipidaemia and the metabolic syndrome. eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration equation. Serum 25-hydroxyvitamin D (25(OH)D) concentration was used to define vitamin D status as follows: 10 % (n 19) had vitamin D deficiency (30 ng/ml). Percentage of body fat (DXA) was significantly associated with vitamin D deficiency independently of age, sex and eGFR. Lower 25(OH)D was associated with higher odds of the metabolic syndrome and dyslipidaemia after adjustment for age, sex and eGFR, but not after additional adjustment for body fat. Hypertension and diabetes were not related to 25(OH)D. Lower serum 25(OH)D was associated with increasing proteinuria and decreasing eGFR even after adjustments for age, sex and percentage of body fat. This study suggests that in RTR of a low-latitude city hypovitaminosis D is common, and is associated with excessive body fat, decreased eGFR and increased proteinuria.

Can renal nutrition education improve adherence to a low-protein diet in patients with stages 3 to 5 chronic kidney disease?

OBJECTIVE: Low adherence is frequently observed in patients with chronic kidney disease (CKD) who are following a low-protein diet. We have evaluated whether a specific nutrition education program motivates patients with CKD who do not yet receive dialysis to reduce their protein intake and whether such a program improves adherence to a low-protein diet over and above standard dietary counseling. DESIGN AND METHODS: This was a randomized controlled clinical trial conducted at the CKD outpatient clinic at Pedro Ernesto University Hospital, Rio de Janeiro, Brazil. SUBJECTS: This study included adult patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) who were receiving conservative treatment. Participants had received their first referrals to a renal dietitian. INTERVENTION: Patients were randomized to a normal counseling group (individualized dietary program: 0.6 to 0.75 g protein/kg/day or 0.6 to 0.8 g/kg/day for patients with diabetes and 25 to 35 kcal/kg/day with sodium restriction) or an intense counseling group (same dietary program plus nutrition education materials). The nutrition education material included 4 different actions to improve patient knowledge and understanding of the low-protein and low-sodium diet. Both groups were followed by means of individual monthly visits to the outpatient clinic for 4 months. MAIN OUTCOME MEASURE: We looked for a change in protein intake from baseline values as well as the adherence rate, assessed as a 20% decrease of the initial protein intake (by 24-hour food recall). RESULTS: Eighty-nine patients completed the study (normal counseling n = 46; intense counseling n = 43). The number of patients who adhered to a low-protein diet was high but did not differ between groups (in the last visit 69% vs. 48%; P = .48; intense vs. normal counseling, respectively). The reduction in protein intake from baseline values was greater for the intense counseling group compared with the normal counseling group (at the last visit, -20.7 g/day [-30.9%] vs. -10.5 g/day [-15.1%], intense vs. normal counseling, respectively; P = .04). CONCLUSION: An intense nutrition education program contributed to reducing protein intake in patients with stage 3 to 5 CKD over and above our standard dietary counseling. Nutritional education programs are effective in increasing patient adherence to protein intake recommendations.

Annual variation in body fat is associated with systemic inflammation in chronic kidney disease patients Stages 3 and 4: a longitudinal study.

BACKGROUND: In dialysis patients, cross-sectional studies show that total and abdominal body fat associate with inflammatory markers. Whether this is true in earlier disease stages is unknown. We evaluated the cross-sectional and longitudinal (12-month interval) association between body fat markers and C-reactive protein (CRP) in pre-dialysis chronic kidney disease (CKD) patients. METHODS: We studied, over a period of 1 year, clinically stable CKD patients at Stages 3-4 who were under treatment in a single outpatient clinic. Fifty-seven patients were included and 44 concluded the observational period [males: 66%; age: 62.9±13.9 years; body mass index (BMI): 25.5±5.1 kg/m2; estimated glomerular filtration rate (eGFR): 34±12.3 mL/min/1.73 m2]. Total body fat (skinfold thicknesses), waist circumference (WC), laboratory measurements (serum creatinine, total cholesterol, albumin, high-sensitivity CRP and leptin) and food intake (24-h food recall) were assessed at baseline and after 12±2 months. RESULTS: Most patients had anthropometric parameters in the range of overweight/obesity and none had signs of protein-energy wasting. In univariate analysis, changes (delta: end-baseline) in CRP were associated (P<0.05) with changes in BMI (r=0.39) and WC (r=0.33). In multiple regression analysis, these associations remained significant (P<0.05) even after adjusted by potential confounders (sex, diabetes, baseline age and eGFR). CONCLUSIONS: During a follow-up of 12 months, changes in BMI and WC were directly associated with changes in CRP. Our results support the concept that interventions aimed at reducing weight and/or abdominal adiposity in pre-dialysis CKD patients may also translate into reduced systemic inflammation.

Osteosarcopenia in patients with non-dialysis dependent chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is associated with a reduction in bone mineral density (BMD), but less is understood regarding the relation between BMD and muscle mass, especially in non-dialysis dependent-CKD (NDD-CKD). The aim of this study was to explore the prevalence and association of low BMD (osteopenia and osteoporosis) with markers of muscle mass and function in patients with NDD-CKD. METHODOLOGY: This cross-sectional observational study included patients with NDD-CKD. Routine biochemical parameters including those related to mineral and bone metabolism were evaluated. Body composition was assessed by dual energy x-ray absorptiometry (DXA) for BMD (g/cm2), total and trunk body fat (%), total lean soft tissue (LST; kg), and appendicular skeletal muscle mass (ASM; kg) as the sum of the LST from the limbs. The latter two variables were used as markers of muscle mass, together with its height indexed values: ASM/height2 as ASM index (ASMI; kg/m2), and LST/height2 as LST index (LSTI, kg/m2). Muscle quality index (MQI) was calculated as handgrip strength (HGS)/mean ASMarms (kg/kg). Osteosarcopenia was defined according to referenced cut-points for patients presenting with low ASMI, HGS and BMD. RESULTS: Patients (n = 257, 57.6% males) had a mean age = 64.8 ± 12.9 years, estimated glomerular filtration rate (eGFR) = 30.1 ± 12.9 ml/min and body mass index (BMI) = 26.8 ± 4.8 kg/m2. Patients with low BMD (39.4%) presented with lower BMI, LST, LSTI, ASM and ASMI for both sexes. BMD was positively and significantly correlated with LST, LSTI, ASM, ASMI and HGS. Low ASM was associated with low BMD (odds-ratio-OR; 95% confidence interval-CI: males OR = 4.54, 2.02-10.21; females OR = 4.45, 1.66-11.93). Linear multiple regression analysis (adjusted for sex and eGFR) showed significant associations between T-score with HGS (R2 = 0.288, R2 adjusted = 0.272, standardized coefficient ß = 0.536, p < 0.0001) and also with MQI (R2 = 0.095, R2 adjusted = 0.075, standardized coefficient ß = 0.309, p = 0.024). Osteosarcopenia was present in about 7% of participants and similarly distributed between sexes. CONCLUSION: Low BMD was prevalent, and associated with low markers of muscle mass and quality, in NDD-CKD patients of both sexes. In view of the known significance of these conditions, targeted interventions are needed to optimize body composition and functional status of these patients.

Accuracy of surrogate methods to estimate skeletal muscle mass in non-dialysis dependent patients with chronic kidney disease and in kidney transplant recipients.

BACKGROUND & AIMS: Bioelectrical impedance analysis (BIA) and anthropometric predictive equations have been proposed to estimate whole-body (SMM) and appendicular skeletal muscle mass (ASM) as surrogate for dual energy X-ray absorptiometry (DXA) in distinct population groups. However, their accuracy in estimating body composition in non-dialysis dependent patients with chronic kidney disease (NDD-CKD) and kidney transplant recipients (KTR) is unknown. The aim of this study was to investigate the accuracy and reproducibility of BIA and anthropometric predictive equations in estimating SMM and ASM compared to DXA, in NDD-CKD patients and KTR. METHODS: A cross-sectional study including adult NDD-CKD patients and KTR, with body mass index (BMI) ≥18.5 kg/m2. ASM and estimated SMM were evaluated by DXA, BIA (Janssen, Kyle and MacDonald equations) and anthropometry (Lee and Baumgartner equations). Low muscle mass (LowMM) was defined according to cutoffs proposed by guidelines for ASM, ASM/height2 and ASM/BMI. The best performing equation as surrogate for DXA, considering both groups of studied patients, was defined based in the highest Lin's concordance correlation coefficient (CCC) value, the lowest Bland-Altman bias (<1.5 kg) combined with the narrowest upper and lower limits of agreement (LoA), and the highest Cohen's kappa values for the low muscle mass diagnosis. RESULTS: Studied groups comprised NDD-CKD patients (n = 321: males = 55.1%; 65.4 ± 13.1 years; eGFR = 28.8 ± 12.7 ml/min) and KTR (n = 200: males = 57.7%; 47.5 ± 11.3 years; eGFR = 54.7 ± 20.7 ml/min). In both groups, the predictive equations presenting the best accuracy compared to DXA were SMM-BIA-Janssen (NDD-CKD patients: CCC = 0.88, 95%CI = 0.83-0.92; bias = 0.0 kg; KTR: CCC = 0.89, 95%CI = 0.86-0.92, bias = -1.2 kg) and ASM-BIA-Kyle (NDD-CKD patients: CCC = 0.87, 95%CI = 0.82-0.90, bias = 0.7 kg; KTR: CCC = 0.89, 95%CI = 0.86-0.92, bias = -0.8 kg). In NDD-CKD patients and KTR, LowMM frequency was similar according to ASM-BIA-Kyle versus ASM-DXA. The reproducibility and inter-agreement to diagnose LowMM using ASM/height2 and ASM/BMI estimated by BIA-Kyle equation versus DXA was moderate (kappa: 0.41-0.60), in both groups. Whereas female patients showed higher inter-agreement (AUC>80%) when ASM/BMI index was used, male patients presented higher AUC (70-74%; slightly <80%) for ASM/height2 index. CONCLUSIONS: The predictive equations with best performance to assess muscle mass in both NDD-CKD patients and KTR was SMM-BIA by Janssen and ASM-BIA by Kyle. The reproducibility to diagnose low muscle mass, comparing BIA with DXA, was high using ASM/BMI in females and ASM/height2 in males in both groups.

[Chronic kidney diseases: common and harmful, but also preventable and treatable]. / Doença renal crônica: frequente e grave, mas também prevenível e tratável.

Chronic kidney disease (CKD) is a public health problem worldwide. In Brazil incidence and prevalence of end stage renal failure are increasing; prognosis is still poor and costs of disease treatment are very high. Regardless of the etiology, main outcomes in patients with CKD are its complications (anemia, metabolic acidosis, malnutrition and alteration in mineral metabolism), death (mainly due to cardiovascular causes) and loss of renal function. Recent studies indicate that these outcomes may be postponed with specific treatment if the CKD is diagnosed early and renoprotective and cardioprotective measures are implemented early in the course of the disease. The current definition and staging of CKD, as well as the discussion of the main preventive measures are addressed in this review.

Glomerular filtration rate estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in type 1 diabetes based on genomic ancestry.

BACKGROUND: Black individuals have a great risk of developing chronic kidney disease (CKD) that is associated with high morbimortality, so it is important to classify them into the correct renal function group. Some equations used to estimate glomerular filtration rate (eGFR) divide patients only into two categories: African Americans and non-African Americans. The CKD-EPI equation was tested only in African Americans, and not Black patients from other regions, and takes into consideration self-reported color-race instead of genomic ancestry (GA) to determine the use of the ethnic correction factor. So far, this equation has not been evaluated in admixed populations, such as the Brazilian, using the percentage of GA to decide to apply the correction factor. The purpose of our study was to compare, in patients with type 1 diabetes (T1D), the eGFR calculated without the use of the correction factor, with the values obtained using the correction factor in patients presenting 50% or more of African GA. METHODS: This cross-sectional, multicenter study enrolled 1279 patients from all geographic regions of Brazil. The CKD-EPI equation was used and CKD was defined as eGFR < 60 ml/min. GA were inferred using a panel of 46 AIM-INDEL, afterwards patients presenting an African GA ≥ 50% were selected. RESULTS: Initially, all patients with African GA ≥ 50% (n = 85) were considered as non-African Americans when calculating the eGFR and afterwards the ethnic correction factor was applied to recalculate the eGFR. CKD was present in 23 patients and 56.5% of them were redefined as having normal renal function after using the correction factor, mainly women [11 of the 13 patients (84.6%)], with GFR between 52-59.3 ml/min. CONCLUSIONS: More than half of the patients in the study were reclassified to a normal renal function group, showing that GA may be an important tool to decide between the use of the ethnic correction factor in the CKD-EPI equation in a highly admixed population of patients with T1D. A large-scale study involving GA and eGFR in comparison to reference methods should be conducted to better establish whether or not the ethnic correction factor should be used in highly admixed populations.

Obstructive sleep apnea in non-dialyzed chronic kidney disease patients: Association with body adiposity and sarcopenia.

OBJECTIVES: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease (CVD), the main cause of mortality in chronic kidney disease (CKD). Although the prevalence of OSA in patients with CKD has not been established, a few studies suggest that it is higher than in the general population, potentially increasing the risk for CVD. Obesity increases the risk, whereas sarcopenia has been suggested as a consequence of OSA in the general population. To our knowledge, these associations have not been adequately evaluated in patients with CKD. The aim of this study was to evaluate OSA frequency and its association with total and upper body adiposity and sarcopenia in non-dialyzed CKD patients. METHODS: This cross-sectional study included 73 patients with stages 3b-4 CKD (42 men, 62.9 ± 1.1 y of age). Glomerular filtration rate was estimated by the CKD-Epidemiology Collaboration equation. Patients were assessed for OSA by Watch-PAT200 (apnea-hypopnea index ≥5 events hourly; Itamar Medical), total body adiposity by dual-energy x-ray absorptiometry (DXA) and body mass index (BMI), upper body adiposity by anthropometric parameters and by trunk and visceral fat by DXA, and sarcopenia. RESULTS: OSA frequency was 67% (N = 49). Both total and upper body adiposity were associated with the presence and severity of OSA. In non-obese patients (BMI <30 kg/m2), upper body obesity increased significantly the frequency of OSA. OSA association with sarcopenia was blunted when BMI was included in regression model. CONCLUSIONS: Results from the present study suggest that in non-dialyzed CKD patients OSA is very common and associated with total and upper body obesity, but not with sarcopenia.

Agreement between anthropometry and bioelectrical impedance for measuring body fat in nonobese and obese nondialyzed chronic kidney disease patients.

OBJECTIVES: We investigated reproducibility and agreement between anthropometry (ANT) and bioelectrical impedance (BIA) in nonobese and obese nondialyzed chronic kidney disease (CKD) patients, and examined the factors influencing the agreement between these two methods. PATIENTS AND METHODS: One hundred and five clinically stable CKD patients, comprising stages 3 and 4 of CKD, had their body fat (BF) assessed by ANT and BIA. Patients were stratified into nonobese (body mass index [BMI] <25 kg/m(2), n = 48, 26 males, aged 64.5 +/- 13.6 years) and overweight/obese (BMI > or =25 kg/m(2), n = 57, 35 males, aged 63.1 +/- 12.1 years; +/-SD in all values) groups. RESULTS: In the nonobese group, BF as assessed by ANT was similar to body fat as assessed by BIA (11.4 +/- 3.8 kg vs 11.7 +/- 4.1 kg, respectively, no significance). The concordance correlation coefficient (CCC) was indicative of good reproducibility for males (0.67; 95% confidence interval [CI], 0.41 to 0.83) and females (0.88; 95% CI, 0.71 to 0.95), and the mean inter-method difference between ANT and BIA and limits of agreement were -0.9 (-6.8 to 4.9) kg for males, and 0.4 (-3.4 to 4.3) kg for females. In the overweight/obese group, a weak CCC was observed for males (0.46; 95% CI, 0.26 to 0.62) and females (0.53; 95% CI, 0.29 to 0.70), and the mean inter-method difference between both methods was 5.7 (-3.2 to 14.7) kg for males, and 6.4 (-1.8 to 14.7) kg for females. In the multiple regression analysis (adjusted r(2) = 0.42, n = 105), BMI, sex, body water, and age were independent determinants of the agreement between ANT and BIA. CONCLUSIONS: For nonobese patients, ANT and BIA can be applied equally well for assessing BF. For overweight/obese patients a weak agreement was observed. Body mass index, sex, body water, and age were the factors influencing the agreement between ANT and BIA.

Body adiposity predictors of vitamin D status in nondialyzed patients with chronic kidney disease: A cross-sectional analysis in a tropical climate city.

OBJECTIVES: The association of vitamin D status with high body adiposity is poorly investigated in the chronic kidney disease (CKD) population. The aim of the present study was to describe vitamin D status and to identify body adiposity predictors of vitamin D deficiency, in a nondialyzed CKD population inhabiting a tropical city. METHODS: This cross-sectional study included patients with CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min, regularly treated by an interdisciplinary team in an outpatient university clinic, set in a Brazilian city (latitude: 22°54'S; 43°12'W). Adiposity parameters analyzed were body mass index (BMI), total body adiposity (dual-energy x-ray absorptiometry [DXA] and body adiposity index [BAI]), and central body adiposity (DXA-trunk fat and waist-to-height ratio [WHtR]). Laboratory parameters included serum concentrations of 25-hydroxyvitamin D, phosphate, parathyroid hormone, and insulin (insulin resistance [IR evaluation: homeostasis model assessment; HOMA]). RESULTS: We studied 244 patients (54.9% men; n = 134) with median eGFR = 29.1 mL/min and BMI 26.1 kg/m2, comprising 58.2% (n = 142) with overweight/obesity. The vitamin D status was sufficient (≥30 ng/dL) in 43%, insufficient (20-30 ng/dL) in 37%, and deficient (<20 ng/dL) in 20%. Total body adiposity was the independent predictor of vitamin D deficiency (DXA: odds ratio [OR], 2.3; 95% confidence interval [CI], 1.1-5; P = 0.03; BAI: OR, 1.9; 95% CI, 1-3.8; P = 0.02), whereas BMI, DXA-trunk fat, and WHtR showed no correlation. Higher serum phosphorus and hyperparathyroidism were related (P < 0.05) to vitamin D deficiency. IR was not independently associated with 25-hydroxyvitamin D concentration. CONCLUSIONS: Just under half of the CKD population presented sufficient concentration of 25-hydroxyvitamin D. Total body adiposity, independent of age and eGFR, regardless if evaluated by DXA or BAI, was the predictor of vitamin D deficiency, which in turn was associated with higher serum phosphorus and hyperparathyroidism, but not with IR.

Is it possible to use modification of diet in renal disease (MDRD) equation in a Brazilian population?

BACKGROUND: Accurate assessment of kidney function level is the key to the identification and management of chronic kidney disease (CKD). Glomerular filtration rate (GFR) is the best measure of overall kidney function in health and disease. There is no consensus about the method to be used routinely to measure and/or estimate GFR. The objectives of this study were to assess which method correlates better with creatinine (Cr) clearance, extensively used in medical practice, as well as assessing the efficacy of the modification of diet in renal disease (MDRD) equation, in our population. METHODS: We studied 262 adult out-patients with stable CKD on conservative treatment. GFR was evaluated by Cr clearance, Cockcroft-Gault (CG) formula, the mean of urea and Cr clearances (total clearance (TCl)), the MDRD study equation, with and without the variable for African-Americans (MDRD1) and the simplified one (MDRDs). Data were analyzed by Pearson's correlation coefficient (r) and Bland & Altman plot analysis. RESULTS: Pearson's correlation showed that all methods where similar when compared to Cr clearance. A high correlation was observed between CG and MDRD equations, and TCl and MDRD equations showed the worst correlation. Among the MDRD equations, no differences were found. Bland-Altman plot analysis indicated a concordance among the studied methods. CONCLUSION: The CG formula could replace Cr clearance in our population, being simpler than and equally as sensitive as the MDRD equation.

Low molecular weight heparin in the treatment of puromycin-induced nephrosis.

Heparin may have a beneficial effect in proteinuric renal diseases, where negative charges of the glomerular capillary membrane are compromised. We evaluated the role of low molecular weight heparin (LMWH - 3000 Da) in puromycin aminonucleoside (PAN)-induced focal and segmental glomerulosclerosis in male Wistar rats: Controls (C) n=7, LMWH-treated group, n=9, subcutaneously (SC), 6 mg/kg every day. The PAN group (n=7) received 7 doses on weeks 0, 1, 2, 4, 6, 8, 10 (SC - 2mg/100g), and a group PAN+LMWH (n=6). After 12 weeks, cholesterol and triglycerides were higher in nephrotic groups, as well as proteinuria and urinary IgG. Kidney weight, glomerular volume, and glomerular sclerosis index were higher in the PAN-treated groups. Glomerular capillary length density (L(Vcap)) and glomerular capillary surface density (S(Vcap)) were lower in the PAN group, and mesangial fractional volume was higher. Fibronectin immunostaining was more intense in the PAN group, and collagens I and III were absent in the studied glomeruli. Thus, LMWH prevented mesangial expansion and capillaries changes, showing antiproliferative properties, despite worsening glomerular permeability changes in the PAN model. In conclusion, LMWH interferes in the complications of PAN model, but not through inhibition of the proteinuria.

Chronic renal failure in male and female rats.

Gender influences the progression of chronic renal failure (CRF). We studied male (M) and female (F) Wistar rats for 90 days: castrated (CMc,n=7;CFc,n=6) and non castrated controls (CM,n=9;CF,n=6); castrated (CRFMc,n=8; CRFFc,n=6) and non castrated animals submitted to 5/6 nephrectomy (CRFM,n=13;CRFF,n=6). Data are expressed as mean +/-SEM. Proteinuria (PTN) was higher in CRFM (554+/-69 mg/24h) compared to CRFMc (277+/-85 mg/24h), but not in females (CRFF=193+/-20mg/24h, CRFFc= 164+/-71 mg/24h). Mesangial fractional volume increased in all CRF animals. CRF animals showed an increase of glomerular sclerosis index (GSI) and tubulointerstitial damage (TID) but in a smaller proportion in male castrated animals; the opposite occurred with females: castration induced an increase of these parameters. CRF animals showed increased cortical and glomerular fibronectin (FN) rates. Castration decreased glomerular and cortical FN rates in CRFM but not in females. In conclusion, proteinuria was higher in CRFM and probably led to glomerular and interstitial damage, as well as to FN accumulation, castration seems to protect against development of PTN, TID and FN accumulation in males. Castrated female rats presented mesangial expansion, with no changes in PTN, TID and FN rates. It seems that female sex hormones do not protect against renal disease progression, instead, we suggest that male sex hormones lead to acceleration of CRF.

Bone disease in patients with chronic kidney disease under conservative management.

CONTEXT AND OBJECTIVE: Few studies have focused on bone disease in patients with chronic kidney disease under conservative treatment. The objective was to evaluate bone disease in patients with chronic kidney disease. DESIGN AND SETTING: Case series, at the Nephrology Division, Hospital Universitário Pedro Ernesto. METHODS: 131 patients with creatinine clearance from 10 to 60 ml/min/1.73 m(2) were followed up for at least one year. Serum creatinine, albumin, calcium, phosphorus, alkaline phosphatase, total CO2 (tCO2), intact parathyroid hormone (iPTH), and alkaline phosphatase were measured. Creatinine clearance was calculated from 24-hour urine creatinine measurements and protein ingestion estimates from urea assays. RESULTS: Patients presenting creatinine clearance < 30 ml/min/1.73 m(2) had higher iPTH values, but normal serum levels for calcium, phosphorus, alkaline phosphatase and tCO2. Patients presenting iPTH values of twice the normal upper limit (144 pg/ml) showed lower tCO2 values. Bone alkaline phosphatase was evaluated in 37 patients with creatinine clearance < 30 ml/min/1.73 m(2), showing correlation with alkaline phosphatase but not with parathyroid hormone. Bone biopsy on nine patients with creatinine clearance < 30 ml/min/1.73 m(2) and iPTH > 144 pg/ml showed osteitis fibrosa (4), mild lesion (4) and high turnover (1). CONCLUSION: The present data suggest the importance of early control for iPTH and metabolic acidosis, among patients under conservative management for chronic kidney disease, in order to prevent complications related to bone disease.

Nutritional profile of patients with chronic renal failure.

OBJECTIVE: A substantial number of patients with end-stage chronic renal failure (CRF) on dialysis have an inflammatory state that can be detected by elevation in serum levels of C-reactive protein (CRP). Hypoalbuminemia, which occurs in this population and always has been associated with malnutrition, seems to be a consequence of this inflammatory state. Data focusing on patients before dialysis treatment are lacking. DESIGN: Cross-sectional observational study. SETTING: Outpatients from the Nephrology Division of the University Hospital. PATIENTS: We investigated nutritional status and serum CRP in 27 patients (13 women) with advanced CRF on the occasion of their first visit. METHODS: Nutritional status was evaluated by anthropometric and serum measurements. Energy and protein intake were evaluated using a 24-hour recall questionnaire. RESULTS: Data are reported as mean +/- SD. Glomerular filtration rate was 18 +/- 5 mL/min. Anthropometric measurements showed normal body mass index in 75% of the patients, whereas the remaining patients were overweight; fat store was depleted in 60% of the patients. Serum albumin was 4.4 +/- 0.5 mg/dL and CRP was 0.47 +/- 0.63 mg/dL. Protein ingestion was 1.04 +/- 0.24 g/kg/d, and energy intake was 23.57 +/- 7.8 kcal/kg/d. CONCLUSION: Patients with advanced CRF without specific treatment, evaluated for the first time, showed fat store depletion. This alteration was not associated with inflammation or with visceral protein loss, but with low energy intake. These results support the idea that this population should be followed up by specialists from the early stage of CRF to prevent malnutrition.

Integrating medical abortion into a residency practice.

While changing residency services and curricula is difficult under the best of circumstances, adding something as controversial as medical abortion can provoke seemingly insurmountable resistance. This paper describes an innovative approach to adding medical abortion services. We first surveyed staff, faculty, residents, and colleagues to examine their reservations. These concerns were addressed in a structured manner, using a range of educational forums. While residents' participation in the service was voluntary, all patients were assured access to medical abortion.

Gender-related differences in kidney of rats with chronic renal failure.

Chronic renal failure is characterized by adaptive mechanisms secondary to the loss of functioning nephrons. Clinical and experimental studies suggest participation of gender-related hormones on renal function and progression of chronic renal failure. We evaluated the effect of castration on renal alterations in male and female Wistar control rats and after 30 days of chronic renal failure (CRF) induced by 5/6 nephrectomy. The CRF male group showed higher proteinuria. Glomerular hypertrophy was similar among groups. Podocyte morphology showed disorders of foot processes and thickening of the basement membrane in the CRF male group. The CRF female group showed fewer alterations compared to males. Castration changed the profile in CRF male animals and the filtration barrier was preserved. CRF males showed the presence of alfa-smooth muscle actin suggesting an early prefibrotic event in this group. After castration this phenomenon was not observed. Noteworthy, in females, castration exacerbated the presence of alfa-smooth muscle actin. In summary, proteinuria was higher in males and appeared early in the course of CRF, probably contributing to fibrotic events. Data were influenced by gender suggesting that male sex hormones aggravate renal alterations.

Waist-to-height ratio: an accurate anthropometric index of abdominal adiposity and a predictor of high HOMA-IR values in nondialyzed chronic kidney disease patients.

OBJECTIVE: Chronic kidney disease (CKD) is associated with metabolic disorders, including insulin resistance (IR), mainly when associated with obesity and characterized by high abdominal adiposity (AbAd). Anthropometric measures are recommended for assessing AbAd in clinical settings, but their accuracies need to be evaluated. The aim of this study was to evaluate the precision of different anthropometric measures of AbAd in patients with CKD. We also sought to determine the AbAd association with high homeostasis model assessment index of insulin resistance (HOMA-IR) values and the cutoff point for AbAd index to predict high HOMA-IR values. METHODS: A subset of clinically stable nondialyzed patients with CKD followed at a multidisciplinary outpatient clinic was enrolled in this cross-sectional study. The accuracy of the following anthropometric indices: waist circumference, waist-to-hip ratio, conicity index and waist-to-height ratio (WheiR) to assess AbAd, was evaluated using trunk fat, by dual x-ray absorptiometry (DXA), as a reference method. HOMA-IR was estimated to stratify patients in high and low HOMA-IR groups. The total area under the receiver-operating characteristic curves (AUC-ROC; sensitivity/specificity) was calculated: AbAd with high HOMA-IR values (95% confidence interval [CI]). RESULTS: We studied 134 patients (55% males; 54% overweight/obese, body mass index ≥ 25 kg/m(2), age 64.9 ± 12.5 y, estimated glomerular filtration rate 29.0 ± 12.7 mL/min). Among studied AbAd indices, WheiR was the only one to show correlation with DXA trunk fat after adjusting for confounders (P < 0.0001). Thus, WheiR was used to evaluate the association between AbAd with HOMA-IR values (r = 0.47; P < 0.0001). The cutoff point for WheiR as a predictor for high HOMA-IR values was 0.55 (AUC-ROC = 0.69 ± 0.05; 95% CI, 0.60-0.77; sensitivity/specificity, 68.9/61.9). CONCLUSIONS: WheiR is recommended as an effective and precise anthropometric index to assess AbAd and to predict high HOMA-IR values in nondialyzed patients with CKD.