Outcomes for clinical trials involving adults with chronic kidney disease: a multinational Delphi survey involving patients, caregivers and health professionals.

BACKGROUND: Many outcomes of high priority to patients and clinicians are infrequently and inconsistently reported across trials in chronic kidney disease (CKD), which generates research waste and limits evidence-informed decision making. We aimed to generate consensus among patients/caregivers and health professionals on critically important outcomes for trials in CKD prior to kidney failure and the need for kidney replacement therapy, and to describe the reasons for their choices. METHODS: This was an online two-round international Delphi survey. Adult patients with CKD (all stages and diagnoses), caregivers and health professionals who could read English, Spanish or French were eligible. Participants rated the importance of outcomes using a Likert scale (7-9 indicating critical importance) and a Best-Worst Scale. The scores for the two groups were assessed to determine absolute and relative importance. Comments were analysed thematically. RESULTS: In total, 1399 participants from 73 countries completed Round 1 of the Delphi survey, including 628 (45%) patients/caregivers and 771 (55%) health professionals. In Round 2, 790 participants (56% response rate) from 63 countries completed the survey including 383 (48%) patients/caregivers and 407 (52%) health professionals. The overall top five outcomes were: kidney function, need for dialysis/transplant, life participation, cardiovascular disease and death. In the final round, patients/caregivers indicated higher scores for most outcomes (17/22 outcomes), and health professionals gave higher priority to mortality, hospitalization and cardiovascular disease (mean difference >0.3). Consensus was based upon the two groups yielding median scores of ≥7 and mean scores >7, and the proportions of both groups rating the outcome as 'critically important' being >50%. Four themes reflected the reasons for their priorities: imminent threat of a health catastrophe, signifying diminishing capacities, ability to self-manage and cope, and tangible and direct consequences. CONCLUSION: Across trials in CKD, the outcomes of highest priority to patients, caregivers and health professionals were kidney function, need for dialysis/transplant, life participation, cardiovascular disease and death.

Prevalence of mild cognitive impairment in automated peritoneal dialysis patients.

BACKGROUND: Cognitive deterioration decreases quality of life, self-care and adherence to treatment, increasing mortality risk. There is scarce information of cognitive impairment in peritoneal dialysis (PD) and data are controversial. Our aim was to determine the frequency and associated factors of cognitive impairment in patients on automated PD (APD). METHODS: In this cross-sectional study, 71 patients on APD underwent clinical, biochemical and cognitive function evaluation by means of the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Cognitive function was also evaluated in healthy controls. RESULTS: Participants mean age was 42 ± 16 years, 79% were men and dialysis vintage was 17 months ( interquartile range 7-32). In APD patients, cognitive impairment was present in 7% (mild deterioration) and 68% according to the MMSE and MoCA, respectively, and 4 and 37% in the healthy controls. Patients with cognitive impairment (according to MoCA) were older, with less education, had diabetes more frequently and higher serum glucose as well as lower serum creatinine, phosphorus and sodium concentrations than patients with normal cognitive function. In multiple linear regression analysis, predictors for the MoCA score (R2 = 0.63, P = 0.002) were education {B = 0.54 [95% confidence interval (CI) 0.20-0.89]; P = 0.003}, age [B = -0.11 (95% CI -0.21 to -0.01); P = 0.04], serum sodium [B = 0.58 (95% CI 0.05-1.11); P = 0.03] and creatinine concentration [B = 3.9 (95% CI 0.03-0.83); P = 0.03]. CONCLUSIONS: In this sample of APD patients, the prevalence of cognitive impairment by the MoCA was 65% and was associated with older age, lower education level and lower serum concentrations of sodium and creatinine.

Clinical Taste Perception Test for Patients With End-Stage Kidney Disease on Dialysis.

OBJECTIVE: The aim of this study was to validate a direct taste perception test (TPT) and evaluate its performance in patients on dialysis. METHODS: This cross-sectional study was carried out in a tertiary-care hospital. A TPT was validated on 112 healthy subjects and applied on 43 patients on hemodialysis and 32 patients on peritoneal dialysis. All participants were presented a 10-mL sample to identify and rate intensity of primary tastes: sweet (sucrose 2%), sour (citric acid 0.1%), bitter (caffeine 0.06%), salty (sodium chloride 0.5%), and umami (sodium glutamate 0.25%). The internal consistency and repeatability of TPT was assessed by Cronbach's alpha and intraclass correlation coefficient. Chi-square and Mann-Whitney U tests were used to compare groups. RESULTS: TPT had Cronbach's alpha of 0.77. Intraclass correlation coefficient was 0.74 for sweet, P < .0001; 0.57 for salty, P = .001; 0.62 for sour, P < .0001; 0.78 for bitter, P < .0001; and 0.76 for umami, P < .0001. Compared with controls, patients on peritoneal dialysis were less able to identify sweet and umami tastes (P < .05) and marginally (P = .06) sour taste, whereas patients on hemodialysis were marginally (P = .06) less able to identify sweet and salty tastes. Bitter was not differently identified between groups. According to the visual analog scale (0-10), all patients on dialysis perceived sour taste less intensely than control subjects (P < .05). CONCLUSIONS: This TPT for patients on dialysis had adequate reliability to identify five primary tastes in a clinical setting. Except for bitter taste, perception of all the primary tastes was altered in patients on dialysis compared with control subjects. A broader use of this test would help identify taste alterations and implement strategies for malnutrition.

Interactions Between Diet Quality and Interleukin-6 Genotypes Are Associated With Metabolic and Renal Function Parameters in Mexican Patients With Type 2 Diabetes Mellitus.

OBJECTIVE: The aim of this study was to evaluate the interaction between diet quality and interleukin (IL)-6 genotypes and its association with metabolic and renal function parameters in Mexican patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: Using an analytical cross-sectional design, 219 patients with T2DM (92 men; age 62 ± 10 years) were evaluated for selected metabolic and renal function parameters. Diet quality according to the Healthy Eating Index was evaluated and classified as good diet or poor diet in all patients. IL-6 serum concentrations and genotypes and haplotypes for IL6-597G > A (rs180097), -572G > C (rs180096), and -174G > C (rs180095) polymorphisms were determined. RESULTS: Eighty-two percent of patients reported having a poor diet. Carriers of alleles -572C and -174C showed higher high-density lipoprotein cholesterol levels (44 ± 12 vs. 40 ± 9 mg/dL; P = .01) and lower total cholesterol levels (184 ± 33 vs. 197 ± 42 mg/dL; P = .03) than did those homozygous for G/G. Neither IL6 genotypes nor haplotypes were significantly associated with serum concentrations of IL-6. Some significant interactions between IL6 genotypes/haplotypes and diet quality were associated with body mass index, waist circumference, high-density lipoprotein cholesterol levels, and estimated glomerular filtration rate. CONCLUSIONS: Interactions between diet quality and IL6 genotypes/haplotypes were associated with the main metabolic and renal function parameters in Mexican patients with T2DM. It will be important to consider genetic profiles in designing dietary portfolios and nutritional interventions for the management of such patients.

Frequency and Risk Factors of Kidney Alterations in Children and Adolescents who Are Overweight and Obese in a Primary Health-care Setting.

OBJECTIVE: Obesity is clearly associated to kidney disease in adult population; however, there is scarce evidence in children and adolescents. The aim was to compare frequency of renal damage according to the presence of overweight-obesity in children and adolescents, as well as to compare nutritional and biochemical risk factors, according to the presence of kidney alterations. METHODS: Cross-sectional study; 172 children and adolescents, 6-16 years old, without malnutrition, diabetes mellitus, hypertension and independent comorbid conditions associated to obesity or kidney disease, as well as transitory causes of microalbuminuria (MA) from a Primary Health-Care Unit were included. Clinical, biochemical, anthropometric and dietetic evaluations were measured in all subjects; subsequently they were classified as normal weight, overweight and obesity groups according to sex- and age-adjusted body mass index (BMI). Glomerular filtration rate (GFR, estimated by Schwartz equation) and albuminuria (albumin/creatinine ratio) were determined. Presence of kidney alterations was measured as decreased GFR (<90 mL/min/1.73m2), hyperfiltration (>170 mL/min/1.73m2) and MA (30-300 mg/g). RESULTS: Compared with controls, subjects with overweight-obesity had significantly (P<.05) abdominal obesity (0 vs 69%), hypertension (19 vs 26%), hypertriglyceridemia (11 vs 47%), high low-density lipoprotein cholesterol (2 vs 8%) and low high-density lipoprotein cholesterol (HDL-cholesterol; 2 vs 28%), hyperuricemia (11 vs 28%) and hyperinsulinemia (8 vs 70%). Hyperfiltration and MA were present in 5 and 4 subjects with overweight/obesity, respectively, whereas decreased GFR was present in only 1 subject with obesity. Normal weight subjects had no kidney alterations. In multivariate analysis, kidney alterations were significantly predicted by higher BMI and lower HDL-cholesterol. CONCLUSIONS: Kidney alterations were observed only in subjects with overweight (3.6%) and obesity (9.9%), who additionally, displayed cardiometabolic and kidney disease risk factors more frequently than normal weight subjects.

Prevalence of Pica in Patients on Dialysis and its Association With Nutritional Status.

OBJECTIVE: Pica could be strongly implicated in nutritional status of patients on dialysis; however, very scarce data are currently available. The objective of this study was to evaluate the prevalence of pica and its association with nutritional status in dialysis patients. DESIGN AND METHODS: This is a cross-sectional study in a tertiary care teaching hospital. Four-hundred patients on dialysis, without previous pica diagnosis or transplant, pregnancy, mental illness, or infection, were included in the study. Pica, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, was classified as no pica, ice pica, or hard pica. Dialysis Malnutrition Score, 24-hour dietary recall, and biochemical measurements were obtained from patients. As part of statistical analysis, point prevalence and 95% confidence interval of pica were calculated. Comparisons between groups were performed by means of analysis of variance, Kruskal-Wallis test, χ2, or Fisher exact tests, as appropriate. A multivariate analysis was performed by multinomial logistic regression. RESULTS: Prevalence of pica was 42% (ice pica, 46%; soil, 29%; two substances, 14%; red brick, 5%; paper, 3%; soap, 2%; and cattle pasture, 1%). Comparing patients with pica (hard pica and ice pica) versus no pica, subjects with pica were of younger age (25 ± 7, 27 ± 9, 30 ± 11 years, respectively), were more frequently educated <9 years (57%, 46%, 30%, respectively), and had longer dialysis duration (36 ± 19, 32 ± 18, 27 ± 16 months, respectively). Patients with pica achieved the recommended calorie and macronutrients intake target less frequently than those without pica (40-64% vs. 66-77%, P <.05). Malnutrition was present in 74% of the whole sample: (1) 67% in no pica group, (2) 80% in ice pica group, and (3) 89% in hard pica group (P = .001). In the multivariate analysis (R2, 0.27; P < .0001), malnutrition, C-reactive protein, and lower educational level significantly predicted both ice and hard pica. CONCLUSIONS: A worse nutritional status was observed in patients with pica, who additionally were younger, had lower educational level, longer dialysis duration, and worse macronutrient intake routine than patients without pica. Malnutrition, C-reactive protein, and lower educational level significantly predicted both ice and hard pica.

Economic evaluation of treatments for patients with localized prostate cancer in Europe: a systematic review.

BACKGROUND: Our objective was to assess the efficiency of treatments in patients with localized prostate cancer, by synthesizing available evidence from European economic evaluations through systematic review. METHODS: Articles published 2000-2015 were searched in MEDLINE, EMBASE and NHS EED (Prospero protocol CRD42015022063). Two authors independently selected studies for inclusion and extracted the data. A third reviewer resolved discrepancies. We included European economic evaluations or cost comparison studies, of any modality of surgery or radiotherapy treatments, regardless the comparator/s. Drummond's Checklist was used for quality assessment. RESULTS: After reviewing 8,789 titles, 13 European eligible studies were included: eight cost-utility, two cost-effectiveness, one cost-minimization, and two cost-comparison analyses. Of them, five compared interventions with expectant management, four contrasted robotic with non robotic-assisted surgery, three assessed new modalities of radiotherapy, and three compared radical prostatectomy with brachytherapy. All but two studies scored ≥8 in the quality checklist. Considering scenario and comparator, three interventions were qualified as dominant strategies (active surveillance, robotic-assisted surgery and IMRT), and six were cost-effective (radical prostatectomy, robotic-assisted surgery, IMRT, proton therapy, brachytherapy, and 3DCRT). However, QALY gains in most of them were small. For interventions considered as dominant strategies, QALY gain was 0.013 for active surveillance over radical prostatectomy; and 0.007 for robotic-assisted over non-robotic techniques. The highest QALY gains were 0.57-0.86 for radical prostatectomy vs watchful waiting, and 0.72 for brachytherapy vs conventional radiotherapy. CONCLUSIONS: Currently, relevant treatment alternatives for localized prostate cancer are scarcely evaluated in Europe. Very limited available evidence supports the cost-effectiveness of radical prostatectomy over watchful waiting, brachytherapy over radical prostatectomy, and new treatment modalities over traditional procedures. Relevant disparities were detected among studies, mainly based on effectiveness. These apparently contradictory results may be reflecting the difficulty of interpreting small differences between treatments regarding QALY gains.

Prevalence of pre-diabetes in young Mexican adults in primary health care.

BACKGROUND: Pre-diabetes in young people is frequently unrecognized or not treated on time, with the consequent loss of opportunity for diabetes prevention. In Mexico, there is scarce information about the prevalence of pre-diabetes in young adults. OBJECTIVE: To determine the prevalence and risk factors for pre-diabetes in young Mexican adults in primary health care. METHODS: In a cross-sectional study, 288 subjects, aged 18-30 years, from a primary care unit were included. Pre-diabetes was diagnosed (according to the criteria of the American Diabetes Association) as impaired fasting glucose (8-12 hours fasting plasma glucose level: 100-125 mg/dl) or impaired glucose tolerance (140-199 mg/dl after a 2-hour oral glucose tolerance test). RESULTS: Prevalence of pre-diabetes was 14.6% [95% confidence interval (CI): 10.7-19.2], whereas that of diabetes was 2.4% (95% CI: 1.0-4.9). A high proportion of patients had history of obesity, diabetes, hypertension and consumption of tobacco and alcohol. Pre-diabetic patients were older than normoglycaemics (pre-diabetic patients: 26±4 years versus normoglycaemic subjects: 24±3 years, P = 0.003) and had higher body mass index (BMI; pre-diabetic patients: 29.4±6.8 kg/m(2) versus normoglycaemic subjects: 26.8±5.8 kg/m(2); P = 0.009), particularly in the case of men (pre-diabetic men: 29.3±7.0 kg/m(2) versus normoglycaemic men: 26.4±5.1 kg/m(2); P = 0.03). Although waist circumference showed a trend to be higher among pre-diabetics, no significant differences were found according to gender (among males: pre-diabetics: 99.5±18.8 cm versus normoglycaemics: 93.3±14.4 cm, P = 0.09; among females: pre-diabetics: 91.5±13.8 cm versus normoglycaemics: 85.8±15.9 cm, P = 0.16). Only age and BMI were significantly associated with the presence of pre-diabetes. CONCLUSIONS: Almost 15% of these young adults had pre-diabetes. Many modifiable and non-modifiable risk factors were present in these patients, but only age and a higher BMI were independent variables significantly associated with pre-diabetes. Timely interventions in primary health care are needed to prevent or delay the progression to diabetes.

Service Utilization Patterns and Direct Medical Costs of Hospitalization in Patients With Renal Failure Before and After Initiating Home Peritoneal Dialysis.

OBJECTIVES: This study aimed to determine the hospital service utilization patterns and direct healthcare hospital costs before and during peritoneal dialysis (PD) at home. METHODS: A retrospective cohort study of patients with kidney failure (KF) was conducted at a Mexican Social Security Institute hospital for the year 2014. Cost categories included inpatient emergency room stays, inpatient services at internal medicine or surgery, and hospital PD. The study groups were (1) patients with KF before initiating home PD, (2) patients with less than 1 year of home PD (incident), and (3) patients with more than 1 year of home PD (prevalent). Costs were actualized to international dollars (Int$) 2023. RESULTS: We found that 53% of patients with KF used home PD services, 42% had not received any type of PD, and 5% had hospital dialysis while waiting for home PD. The estimated costs adjusting for age and sex were Int$5339 (95% CI 4680-9746) for patients without home PD, Int$17 556 (95% CI 15 314-19 789) for incident patients, and Int$7872 (95% CI 5994-9749) for prevalent patients; with significantly different averages for the 3 groups (P < .001). CONCLUSIONS: Although the use of services and cost is highest at the time of initiating PD, over time, using home PD leads to a significant reduction in use of hospital services, which translates into institutional cost savings. Our findings, especially considering the high rates of KF in Mexico, suggest a pressing need for interventions that can reduce healthcare costs at the beginning of renal replacement therapy.

Pica is associated with lower willingness to change negative habits of diet and exercise, inadequate lifestyle, and less healthful food consumption in dialysis.

Background: In dialysis patients, on the one hand unwillingness to change negative lifestyle patterns is associated with worse nutritional status and unhealthy lifestyle, whereas on the other, pica may be highly prevalent. However, it is not known whether pica is associated with unwillingness to change negative lifestyle behaviors, as well as with consumption of different types of foods. This study aimed to investigate this issue. Methods: This is a cross-sectional study in dialysis patients. Lifestyle was assessed using the self-administered Instrument to Measure Lifestyle Questionnaire (IMEVID). Pica diagnosis was established according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. A food frequency questionnaire was performed and self-reported willingness to change was determined by a trans-theoretical model staging inventory. Results: Compared with patients without pica, those with pica (particularly hard pica) had lower willingness to change unhealthy behavior in the case of diet (22% vs. 46% in precontemplation/contemplation stages, respectively) and exercise (43% vs. 62% in precontemplation/contemplation stages, respectively). Patients with hard pica had significantly (p < 0.05) lower scores in almost all dimensions of the lifestyle questionnaire than those in the no pica group: diet (23.9 vs. 26.8, respectively), physical activity (5.5 vs. 7, respectively), knowledge of disease (5.7 vs. 6.4, respectively), emotion management (6.6 vs. 8, respectively) and adherence to treatment (13.4 vs. 14.7, respectively), but not in the consumption of tobacco and alcohol. Compared to patients with no pica, those with hard pica ate vegetables and fruits less frequently, and dairy products, fried foods and soda more frequently. Conclusions: Pica was more frequently observed in patients with lower willingness to change negative habits of diet and exercise, in those who had more unhealthy behaviors in diet, exercise and emotion management dimensions and adherence to treatment, as well as in those who ate less frequently healthful foods and more frequently unhealthy foods.

Dietary counseling, meal patterns, and diet quality in patients with type 2 diabetes mellitus with/without chronic kidney disease.

BACKGROUND: Aim to this study is to investigate the association of Dietary Counseling, Meal Patterns, and Diet Quality (DietQ) in Patients with Type 2 Diabetes Mellitus (T2DM) with/without chronic kidney disease (CKD) in primary healthcare. METHODS: Cross-sectional study acquired data on dietary counseling and meal patterns by direct interview with a food-frequency questionnaire and one 24-h food-recall. The Healthy Eating Index (HEI) was used to classify DietQ ["good" DietQ (GDietQ, score ≥ 80) and "poor" DietQ (PDietQ, score < 80)]. PARTICIPANTS/SETTING: This study included 705 patients with T2DM: 306 with normal kidney function; 236 with early nephropathy, and 163 with overt nephropathy (ON). STATISTICAL ANALYSES PERFORMED: Multivariate linear-regression models for predicting HEI and χ2 tests for qualitative variables and one-way ANOVA for quantitative variables were employed. Mann-Whitney U and independent Student t were performed for comparisons between GDietQ and PDietQ. RESULTS: Only 18 % of the population was classified as GDietQ. Patients with ON and PDietQ vs. with GDietQ received significantly less dietary counseling from any health professional in general (45 % vs 72 %, respectively), or from any nutrition professional (36 % vs. 61 %, respectively). A better HEI was significantly predicted (F = 42.01; p = 0.0001) by lower HbA1C (ß -0.53, p = 0.0007) and better diet diversity (ß 8.09, p = 0.0001). CONCLUSIONS: Patients with more advanced stages of CKD had less nutritional counseling and worse dietary patterns, as well as more frequent PDietQ. Our findings reinforce the need for dietitians and nutritionists in primary healthcare to provide timely nutritional counseling.

Gut Microbiome Is Related to Cognitive Impairment in Peritoneal Dialysis Patients.

Gut microbiota disturbances may influence cognitive function, increasing uremic toxins and inflammation in dialysis patients; therefore, we aimed to evaluate the association of the gut microbiota profile with cognitive impairment (CI) in patients on automated peritoneal dialysis (APD). In a cross-sectional study, cognitive function was evaluated using the Montreal Cognitive Assessment in 39 APD patients and classified as normal cognitive function and CI. The gut microbiota was analyzed using the 16S rRNA gene sequencing approach. All patients had clinical, biochemical and urea clearance evaluations. Eighty-two percent of patients were men, with a mean age of 47 ± 24 years and 11 (7-48) months on PD therapy; 64% had mild CI. Patients with CI were older (53 ± 16 vs. 38 ± 14, p = 0.006) and had a higher frequency of diabetes mellitus (56% vs. 21%, p = 0.04) and constipation (7% vs. 48%, p = 0.04) and lower creatinine concentrations (11.3 ± 3.7 vs. 14.9 ± 5.4, p = 0.02) compared to normal cognitive function patients. Patients with CI showed a preponderance of S24_7, Rikenellaceae, Odoribacteraceae, Odoribacter and Anaerotruncus, while patients without CI had a greater abundance of Dorea, Ruminococcus, Sutterella and Fusobacteria (LDA score (Log10) > 2.5; p < 0.05). After glucose and age adjustment, Odoribacter was still associated with CI. In conclusion, patients with CI had a different gut microbiota characterized by the higher abundance of indole-producing and mucin-fermenting bacteria compared to normal cognitive function patients.

Association of KLOTHO gene variants with metabolic and renal function parameters in Mexican patients living with type 2 diabetes.

Objective: Type 2 diabetes (T2D) and high blood pressure are the main causes of chronic kidney disease (CKD) in adulthood. Both metabolic and oxidative stresses driven by hyperglycemia as well as genetic factors have been suggested as pathogenic causes of renal failure. Some single nucleotide variants (SNVs) on gene coding KLOTHO (KL) have been implicated in several clinical scenarios including hypertension, diabetes, and cardiovascular disease. The aim of this study was to analyze the association of rs1207568 (-395G > A), rs953614 (+ 1062T > G) and rs564481 (+ 1818 C > T) SNVs with metabolic and renal function parameters in Mexican patients living with type 2 diabetes. Methods: A cross-sectional study was conducted in 637 Mexican patients with T2D, and/or hypertension without previous diagnosis of CKD. Anthropometric, metabolic, and renal function parameters were determined. Patients were genotyped for rs1207568, rs953614 and rs564481 SNVs and associations under a dominant genetic model were analyzed by logistic regression. Results: For rs9536314, G-allele showed to be protective for hypo-HDL-C, albuminuria, and CKD. Carriers of minor allele of rs564481 had low odds for high glucose levels. No differences in genotype nor allele frequencies between the patients and the reference population were observed. Conclusion: In Mexican patients living with type 2 diabetes, KL variant rs9536314 was found associated with low odds of hypo-HDL cholesterol, albuminuria and presence of CKD. Meanwhile the consensus of soluble KLOTHO measurement is reached, genetic variants in the KL gene could be considered as genetic markers for CKD susceptibility in patients at high-risk of vascular complications.

Association of CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T Polymorphisms with Tacrolimus Dose, Serum Concentration, and Biochemical Parameters in Mexican Patients with Kidney Transplant.

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.

Urinary concentration of Cathepsin D as a relievable marker of preeclampsia.

BACKGROUND: The early and accurate diagnosis of preeclampsia is crucial to avoid serious complications for both the mother and baby. However, the current diagnostic methods are limited, and there is a need for new diagnostic biomarkers. Previous studies have shown that cathepsin D (CTD) participates in the pathophysiology of preeclampsia and is present in urine samples, making it a potential biomarker for the disease. This study aimed to compare urinary and serum levels of CTD in preeclamptic and normotensive women and analyze its potential role as a diagnostic biomarker in preeclampsia. METHODS: The study included thirty-nine patients with preeclampsia and twelve normotensive pregnant women as controls. Biomarkers were determined using Multiplex Assay kit, and serum prolactin (Prl) and urinary TNF-α levels were also evaluated. Statistical analysis was conducted using the Mann-Whitney U test. RESULTS: We found that urinary and serum CTD levels were significantly higher in the preeclampsia group than in the normotensive group, suggesting that CTD could be a diagnostic biomarker for preeclampsia. No significant differences were found in the levels of serum prolactin or urinary TNF-α between the two groups. CONCLUSIONS: The study provides evidence that non-invasive biological samples such as urine can be used to improve new therapeutic strategies for the early management of preeclampsia.

Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Gut microbiota disturbances and protein-energy wasting in chronic kidney disease: a narrative review.

Protein-energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality, and lower quality of life. It is a complex syndrome, in which inflammation and retention of uremic toxins are two main factors. Causes of inflammation and uremic toxin retention in CKD are multiple; however, gut dysbiosis plays an important role, serving as a link between those entities and PEW. Besides, there are several pathways by which microbiota may influence PEW, e.g., through effects on appetite mediated by microbiota-derived proteins and hormonal changes, or by impacting skeletal muscle via a gut-muscle axis. Hence, microbiota disturbances may influence PEW independently of its relationship with local and systemic inflammation. A better understanding of the complex interrelationships between microbiota and the host may help to explain how changes in the gut affect distant organs and systems of the body and could potentially lead to the development of new strategies targeting the microbiota to improve nutrition and clinical outcomes in CKD patients. In this review, we describe possible interactions of gut microbiota with nutrient metabolism, energy balance, hunger/satiety signals and muscle depletion, all of which are strongly related to PEW in CKD patients.

Association of Serum Fibroblast Growth Factor 23 and FGF23 Gene Variants with Chronic Kidney Disease in Patients with Type 2 Diabetes and Essential Hypertension.

INTRODUCTION: Fibroblast growth factor 23 (FGF23) gene variants could influence the production of FGF23 in subjects at risk for chronic kidney disease (CKD). Our purpose was to analyze the association of serum levels of FGF23 and two FGF23 gene variants with metabolic and renal function parameters in Mexican patients with Type 2 Diabetes (T2D) and/or essential hypertension (HTN). MATERIALS/METHODS: The study included 632 individuals diagnosed with T2D and/or HTN, of which 269 (43%) were diagnosed with CKD. FGF23 serum levels were determined and FGF23 gene variants rs11063112 and rs7955866 were genotyped. Genetic association analysis included binary and multivariate logistic regressions adjusted for age and sex. RESULTS: Patients with CKD were older, had higher systolic blood pressure, uric acid, and glucose levels than those without CKD. Also, patients with CKD had higher FGF23 levels (106 vs. 73 pg/mL p = 0.003). No correlation of any gene variants with FGF23 levels was found, but minor allele for rs11063112 and haplotype rs11063112A-rs7955866A were associated with low probability of CKD (Odds Ratio [OR] = 0.62 and 0.58, respectively). Conversely, the haplotype rs11063112T-rs7955866A was associated with increased FGF23 levels and risk for CKD (OR = 6.90). CONCLUSIONS: In addition to the traditional risk factors, levels of FGF23 are higher in Mexican patients with diabetes and/or essential hypertension and CKD, compared to those without renal damage. In contrast, the two minor alleles of two variants of the FGF23 gene, rs11063112 and rs7955866, as well as the haplotype carrying these two alleles, were found to be protective against renal disease in this Mexican patients' sample.

Can the implementation of clinical practice guidelines improve clinical competence of physicians and kidney function of patients with type 2 diabetes mellitus?

Background: There are many clinical practice guidelines (CPGs) in Nephrology; however, there is no evidence that their availability has improved the clinical competence of physicians or the outcome of patients with chronic kidney disease (CKD). This study was aimed to evaluate the effect of implementation of CPGs for early CKD on family physicians (FP) clinical competence and subsequently on kidney function preservation of type 2 diabetes mellitus (DM2) patients at a primary healthcare setting. Methods: A prospective educative intervention (40-h) based on CPGs for Prevention, Diagnosis and Treatment of Early CKD was applied to FP; a questionnaire to evaluate clinical competence was applied at the beginning and end of the educative intervention (0 and 2 months), and 12 months afterwards. DM2 patients with CKD were evaluated during 1-year of follow-up with estimated glomerular filtration rate (eGFR) and albuminuria. Results: After educative intervention, there was a significant increase in FP clinical competence compared to baseline; although it was reduced after 1 year, it remained higher compared to baseline. One-hundred thirteen patients with early nephropathy (58 stage 1, 55 stage 2) and 28 with overt nephropathy (23 stage 3, 5 stage 4) were studied. At final evaluation, both groups maintained eGFR [(mean change) early 0.20 ± 19 pNS; overt 0.51 ± 13 mL/min pNS], whereas albuminuria/creatinuria (early -67 ± 155 p < 0.0001; overt -301 ± 596 mg/g p < 0.0001), systolic blood pressure (early -10 ± 18 p < 0.05; overt -8 ± 20 mmHg p < 0.05), and total cholesterol (early -11 ± 31 p < 0.05; overt -17 ± 38 mg/dL p < 0.05) decreased. Diastolic blood pressure, waist circumference and LDL-cholesterol were also controlled in early nephropathy patients. Conclusions: CPGs for Prevention, Diagnosis and Treatment of CKD, by means of an educative intervention increases FP clinical competence and improves renal function in DM2 patients with CKD.

Willingness to change diet and exercise behavior is associated with better lifestyle in dialysis patients close to a kidney transplant.

BACKGROUND & AIMS: Evidence suggests that multiple-behavior interventions (with a specialist) have a greater impact on public health than single-behavior interventions, particularly in a chronic patient. However, there is little understanding of some very basic principles concerning multiple health behavior change, especially in situations such as kidney transplantation, which requires a great willingness to change negative lifestyle behaviors to achieve intermediate and long-term success. We compared healthy lifestyles and nutritional status according to the willingness to change dietary and exercise behavior in dialysis patients from a living donor kidney transplant program. METHODS: 400 dialysis patients had a dietetic, anthropometric, protein-energy wasting [subjective global assessment (SGA)] and biochemical evaluation. Lifestyle was evaluated with an adapted instrument to measure lifestyle in chronic disease. Willingness to change behaviors was evaluated by the trans-theoretical model; 2 groups were formed: willingness to change dietary and exercise behaviors and unwillingness to change. RESULTS: Willingness to change dietary behavior was 50% and exercise 25%. Patients with willingness to change dietary and exercise behaviors had better healthy lifestyle scores, and higher frequency of healthy food consumption. Healthy lifestyle score (R2 = 0.37, p < 0.0001) was predicted by older age, higher educational degree, shorter time on dialysis, and the highest willingness to change dietary and exercise behaviors. CONCLUSIONS: Willingness to change dietary and exercise behaviors was associated with healthy lifestyle, as well as with higher frequency of healthy food consumption and with lower frequency of unhealthy food consumption.