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2.
Diabetes Obes Metab ; 26(5): 1908-1918, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38418407

RESUMO

AIM: The risk of cardiorenal events remains high among patients with diabetes and chronic kidney disease (CKD), despite the prescription of recommended treatments. We aimed to determine whether the attainment of a combination of nephroprotection targets at baseline (glycated haemoglobin <7.0%, urinary albumin-creatinine ratio <300 mg/g, blood pressure <130/80 mmHg, renin-angiotensin system inhibition) was associated with better cardiorenal outcomes and lower mortality. MATERIALS AND METHODS: From the prospective French CKD-REIN cohort, we studied 1260 patients with diabetes and CKD stages 3-4 (estimated glomerular filtration rate: 15-60 ml/min/1.73 m2); 69% were men, and at inclusion, mean ± SD age: 70 ± 10 years; estimated glomerular filtration rate: 33 ± 11 ml/min/1.73 m2. The median follow-up was 4.9 years. RESULTS: In adjusted Cox regression models, the attainment of two nephroprotection targets was consistently associated with a lower risk of cardiorenal events [hazard ratio 0.70 (95% confidence interval 0.57-0.85)], incident kidney failure with replacement therapy [0.58 (0.43-0.77)], four major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure) [0.75 (0.57-0.99)] and all-cause mortality [0.59 (0.42-0.82)] when compared with the attainment of zero or one target. For patients with a urinary albumin-creatinine ratio ≥300 mg/g, those who attained at least two targets had lower hazard ratios for cardiorenal events [0.61 (0.39-0.96)], four major adverse cardiovascular events [0.53 (0.28-0.98)] and all-cause mortality [0.35 (0.17-0.70)] compared with those who failed to attain any targets. CONCLUSIONS: These findings suggest that the attainment of a combination of nephroprotection targets is associated with better cardiorenal outcomes and a lower mortality rate in people with diabetic kidney disease.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Nefropatias Diabéticas , Insuficiência Cardíaca , Insuficiência Renal Crônica , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Nefropatias Diabéticas/complicações , Estudos de Coortes , Estudos Prospectivos , Creatinina , Insuficiência Cardíaca/complicações , Albuminas , Doenças Cardiovasculares/etiologia , Taxa de Filtração Glomerular
3.
Ther Apher Dial ; 28(3): 341-353, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38163858

RESUMO

The most common kidney replacement therapy (KRT) worldwide is hemodialysis (HD), and only 5%-10% of patients are prescribed peritoneal dialysis (PD) as KRT. Despite PD being a different method, these patients also present particular complications, such as oxidative stress, gut dysbiosis, premature aging, and mitochondrial dysfunction, leading to an inflammation process and high cardiovascular mortality risk. Although recent studies have reported nutritional strategies in patients undergoing HD with attempts to mitigate these complications, more information must be needed for PD patients. Therefore, this review provides a comprehensive analysis of recent studies of nutritional intervention to mitigate inflammation in PD patients.


Assuntos
Inflamação , Diálise Peritoneal , Humanos , Diálise Peritoneal/métodos , Inflamação/prevenção & controle , Inflamação/etiologia , Estresse Oxidativo , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações
4.
Clin Nutr ESPEN ; 59: 343-354, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38220396

RESUMO

Vitamin E is a lipid-soluble nutrient found mainly in vegetable oils and oilseeds. It is divided into eight homologous compounds; however, only α-tocopherol exhibits vitamin activity. Many advantages are related to these compounds, including cellular protection through antioxidant and anti-inflammatory activity, and improving lipid metabolism. Physiopathology of many diseases incepts with reduced antioxidant defense, characterized by an increased reactive oxygen species production and activation of transcription factors involved in inflammation, such as nuclear factor-kappa B (NF-κB), that can be linked to oxidative stress. Moreover, disorders of lipid metabolism can increase the risk of cardiovascular diseases. In addition, intestinal dysbiosis plays a vital role in developing chronic non-communicable diseases. In this regard, vitamin E can be considered to mitigate those disorders, but data still needs to be more conclusive. This narrative review aims to elucidate the mechanisms of action of vitamin E and if supplementation can be beneficial in a disease scenario regarding non-communicable diseases.


Assuntos
Doenças não Transmissíveis , Vitamina E , Humanos , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Estresse Oxidativo , alfa-Tocoferol
5.
Clin Kidney J ; 17(1): sfad248, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38186868

RESUMO

Background: Kynurenine is a protein-bound uremic toxin. Its circulating levels are increased in chronic kidney disease (CKD). Experimental studies showed that it exerted deleterious cardiovascular effects. We sought to evaluate an association between serum kynurenine levels and adverse fatal or nonfatal cardiovascular events and all-cause mortality in CKD patients. Methods: The CKD-REIN study is a prospective cohort of people with CKD having an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m². Baseline frozen samples of total and free fractions of kynurenine and tryptophan were measured using a validated liquid chromatography tandem mass spectrometry technique. Cause-specific Cox models were used to estimate hazard ratios (HRs) for each outcome. Results: Of the 2406 included patients (median age: 68 years; median eGFR: 25 ml/min/1.73 m2), 52% had a history of cardiovascular disease. A doubling of serum-free kynurenine levels was associated with an 18% increased hazard of cardiovascular events [466 events, HR (95%CI):1.18(1.02,1.33)], independently of eGFR, serum-free tryptophan level or other uremic toxins, cardioprotective drugs, and traditional cardiovascular risk factors. Serum-free kynurenine was significantly associated with non-atheromatous cardiovascular events [HR(95%CI):1.26(1.03,1.50)], but not with atheromatous cardiovascular events [HR(95%CI):1.15(0.89,1.50)]. The association of serum-free kynurenine with cardiovascular mortality was also independently significant [87 events; adjusted HR(95%CI):1.64(1.10,2.40)]. However, the association of serum-free kynurenine with all-cause mortality was no more significant after adjustment on serum-free tryptophan [311 events, HR(95%CI):1.12(0.90, 1.40)]. Conclusions: Our findings imply that serum-free kynurenine, independently of other cardiovascular risk factors (including eGFR), is associated with fatal or nonfatal cardiovascular outcomes, particularly non-atheromatous cardiovascular events; in patients with CKD. Strategies to reduce serum kynurenine levels should be evaluated in further studies.

6.
J Ren Nutr ; 34(1): 19-25, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37321431

RESUMO

OBJECTIVES: The aim of the present study was to assess the dietary intake and nutritional status of patients with chronic kidney disease (CKD) stage 4-5 according to the presence of diabetes. METHODS: This observational and cross-sectional study included adult patients with CKD stage 4-5 referred to a nephrology unit, between October 2018 and March 2019. Daily dietary intake was evaluated by 24-hour dietary inquiry and urine excretion. Nutritional status was assessed by measuring body composition using bioimpedance analysis and muscle function using handgrip strength. Undernutrition was considered using the protein energy wasting score. RESULTS: A total of 75 CKD patients were included, 36 (48%) of whom had diabetes; median age (interquartile range) was 71 (60-80) years. The median weight-adjusted dietary energy intake (DEI) was 22.6 (19.1-28.2) kcal/kg/day and the mean weight-adjusted dietary protein intake (DPI) was 0.86 ± 0.19 g/kg/day. There was no significant difference in DEI and DPI between patients with diabetes and those without, except for weight-adjusted DPI which was significantly lower in diabetic patients (P = .022). In univariate analysis, diabetes was associated with weight-adjusted DPI (coefficient [95% confidence interval] -0.237 [-0.446; -0.004] kcal/kg/day; P = .040), but this association did not remain significant in multivariate analysis. Nutritional status did not differ significantly between diabetic and nondiabetic patients except for lean tissue mass, which was lower in diabetic patients (P = .046). The proportion of patients with protein energy wasting was not significantly different between diabetic and nondiabetic patients (13.9% vs. 10.2%, respectively). CONCLUSIONS: In the present cohort, DPI and DEI were not significantly different between diabetic and nondiabetic CKD patients. Diabetes was not found to be associated with dietary intakes in CKD stage 4-5 patients.


Assuntos
Diabetes Mellitus , Insuficiência Renal Crônica , Adulto , Humanos , Idoso , Estado Nutricional , Proteínas Alimentares , Estudos Transversais , Força da Mão , Insuficiência Renal Crônica/complicações , Diabetes Mellitus/epidemiologia , Ingestão de Alimentos
7.
J Ren Nutr ; 34(1): 68-75, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37619675

RESUMO

BACKGROUND: Patients with chronic kidney disease (CKD) have reduced expression of erythroid nuclear factor-related factor 2 (NRF2) and increased nuclear factor κB (NF-κB). "Food as medicine" has been proposed as an adjuvant therapeutic alternative in modulating these factors. No studies have investigated the effects of sulforaphane (SFN) in cruciferous vegetables on the expression of these genes in patients with CKD. OBJECTIVE: The study aimed to evaluate the effects of SFN on the expression of NRF2 and NF-κB in patients on hemodialysis (HD). DESIGN AND METHODS: A randomized, double-blind, crossover study was performed on 30 patients on regular HD. Fourteen patients were randomly allocated to the intervention group (1 sachet/day of 2.5 g containing 1% SFN extract with 0.5% myrosinase) and 16 patients to the placebo group (1 sachet/day of 2.5 g containing corn starch colored with chlorophyll) for 2 months. After a washout period of 2 months, the groups were switched. NRF2 and NF-κB mRNA expression was evaluated by real-time quantitative polymerase chain reaction, and tumor necrosis factor alpha and interleukin-6 levels were quantified by enzyme-linked immunosorbent assay. Malondialdehyde was evaluated as a marker of lipid peroxidation. RESULTS: Twenty-five patients (17 women, 55 [interquartile range = 19] years and 55 [interquartile range = 74] months on HD) completed the study. There was no significant difference concerning the expression of mRNA NRF2 (P = .915) and mRNA NF-κB (P = .806) after supplementation with SFN. There was no difference in pro-inflammatory and oxidative stress biomarkers. CONCLUSION: 150 µmol of SFN for 2 months had no antioxidant and anti-inflammatory effect in patients with CKD undergoing HD.


Assuntos
Isotiocianatos , NF-kappa B , Insuficiência Renal Crônica , Sulfóxidos , Humanos , Feminino , NF-kappa B/genética , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estudos Cross-Over , Estresse Oxidativo , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/etiologia , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia , Suplementos Nutricionais
8.
Nutr Rev ; 82(4): 572-577, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-37354557

RESUMO

Diet therapy for hyperkalemia in people with chronic kidney disease (CKD) has shifted considerably in recent years with the observations that reported potassium intake is weakly, or not at all, associated with plasma potassium levels in this population. One of the lingering debates is whether dietary potassium presents a risk of hyperkalemia in the postprandial state. Although there is general agreement about the need for additional research, the commentary by Varshney et al contends that the available research sufficiently demonstrates that high-potassium plant foods do not pose a risk of postprandial hyperkalemia. Others argue that this remains unsettled science. Although the traditional approach of providing people with CKD lists of high-potassium foods to limit or avoid may be unnecessary, those at high risk of hyperkalemia should be encouraged to consume balanced meals and control portions, at least until some of the key research gaps in this area are resolved. This editorial critiques the analyses offered by Varshney et al and explains the rationale for a more cautious approach to care.


Assuntos
Hiperpotassemia , Insuficiência Renal Crônica , Humanos , Hiperpotassemia/etiologia , Hiperpotassemia/prevenção & controle , Dieta Baseada em Plantas , Dieta , Insuficiência Renal Crônica/complicações , Potássio
9.
Nephrol Dial Transplant ; 39(4): 669-682, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37935529

RESUMO

BACKGROUND: The trajectories of haemoglobin in patients with chronic kidney disease (CKD) have been poorly described. In such patients, we aimed to identify typical haemoglobin trajectory profiles and estimate their risks of major adverse cardiovascular events (MACE). METHODS: We used 5-year longitudinal data from the CKD-REIN cohort patients with moderate to severe CKD enrolled from 40 nationally representative nephrology clinics in France. A joint latent class model was used to estimate, in different classes of haemoglobin trajectory, the competing risks of (i) MACE + defined as the first event among cardiovascular death, non-fatal myocardial infarction, stroke or hospitalization for acute heart failure, (ii) initiation of kidney replacement therapy (KRT) and (iii) non-cardiovascular death. RESULTS: During the follow-up, we gathered 33 874 haemoglobin measurements from 3011 subjects (median, 10 per patient). We identified five distinct haemoglobin trajectory profiles. The predominant profile (n = 1885, 62.6%) showed an overall stable trajectory and low risks of events. The four other profiles had nonlinear declining trajectories: early strong decline (n = 257, 8.5%), late strong decline (n = 75, 2.5%), early moderate decline (n = 356, 11.8%) and late moderate decline (n = 438, 14.6%). The four profiles had different risks of MACE, while the risks of KRT and non-cardiovascular death consistently increased from the haemoglobin decline. CONCLUSION: In this study, we observed that two-thirds of patients had a stable haemoglobin trajectory and low risks of adverse events. The other third had a nonlinear trajectory declining at different rates, with increased risks of events. Better attention should be paid to dynamic changes of haemoglobin in CKD.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Insuficiência Renal Crônica , Acidente Vascular Cerebral , Humanos , Terapia de Substituição Renal , Hemoglobinas
10.
Artigo em Inglês | MEDLINE | ID: mdl-37950574

RESUMO

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) is associated with an elevated risk of neurocognitive disorders (NCDs). It remains unclear whether CKD-related NCDs have specific cognitive pattern or are earlier-onset phenotypes of the main NCDs (vascular NCDs and Alzheimer's disease). METHODS: We used the Mini Mental State Examination score (MMSE) to assess cognitive pattern in 3003 CKD patients (stage 3 to 4) followed up over 5 years in the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort. After normalizing MMSE scores to a 0-to-100 scale, the associations between the baseline estimated glomerular filtration rate (eGFR, using the CKD-EPI-creatinine formula) and changes in each MMSE domain score were assessed in linear mixed models. RESULTS: Patients (age: 67±13 years old; males: 65%, mean eGFR: 33±12 ml/min/1.73 m²) had a good baseline cognitive functions: the mean MMSE score was 26.9/30 ±2.9. After adjustment for age, sex, educational level, depression (past or present), cardiovascular risk factors, cerebrovascular disease, a lower baseline eGFR (per 10 ml/min/1.73 m²) was associated with a 0.53-point decrement (p<0.001; 95%CI [-0.98,-0.08]) for orientation, a 1.04-point decrement (p=0.03; 95%CI [-1.96,-0.13]) for attention and calculation, a 0.78-point decrement (p=0.003; 95%CI [-1.30,-0.27]) for language, and a 0.94-point decrement (p=0.02; 95%CI [-1.75,-0.13]) for praxis. Baseline eGFR was not, however, associated with significant changes over time in MMSE domain scores. CONCLUSION: A lower eGFR in CKD patients was associated with early impairments in certain cognitive domains: praxis, language and attention domains before an obvious cognitive decline. Early detection of NCD in CKD patients must be perform before clinically cognitive decline using preferably tests assessing executive, attentional functions and language than memory test. This could lead to a better management of cognitive impairment and their consequences on CKD management.

11.
Am J Kidney Dis ; 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37951340

RESUMO

RATIONALE & OBJECTIVE: Adverse drug reactions (ADRs) are common in patients with chronic kidney disease (CKD). The impact of kidney function decline on serious ADR risk has been poorly investigated. We comprehensively describe ADRs and assess the relationship between estimated glomerular filtration rate (eGFR) and serious ADR risk. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,033 participants in French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study, a nationwide sample of nephrology outpatients with moderate to advanced CKD. PREDICTORS: Demographic and biological data (including eGFR), medication prescriptions. OUTCOME: ADRs (preventable or not) were prospectively identified from hospital discharge reports, medical records, and patient interviews. Expert pharmacologists used validated tools to adjudicate ADRs. ANALYTICAL APPROACH: Restricted cubic splines in fully adjusted cause-specific Cox proportional hazard models were used to evaluate the relationship between eGFR and the risk of serious ADRs (overall and by subtype). RESULTS: During a median follow-up period of 4.7 years, 360 patients experienced 488 serious ADRs. Kidney and urinary disorders (n=170) and hemorrhage (n=170) accounted for 70% of serious ADRs. The most common medications classes were antithrombotics and renin-angiotensin system inhibitors. The majority of those serious ADRs were associated with hospitalization (n=467), with 32 directly or indirectly associated with death and 22 associated with a life-threatening event. More than 27% of the 488 serious ADRs were preventable or potentially preventable. The eGFR is a major risk factor for serious ADRs. The risk of acute kidney injury was 2.2% higher and risk of bleeding ADRs was 8% higher for each 1mL/min/1.73m2 lower baseline eGFR. LIMITATIONS: The results cannot be extrapolated to patients who are not being treated by a nephrologist. CONCLUSIONS: ADRs constitute a major cause of hospitalization in CKD patients for whom lower eGFR level is a major risk factor. PLAIN-LANGUAGE SUMMARY: Patients with chronic kidney disease (CKD) have complex clinical presentations, take multiple medications, and often receive inappropriate prescriptions. Using data from a large, prospective CKD cohort, we found a high incidence of serious adverse drug reactions (ADRs). The 2 most common serious ADRs were drug-induced acute kidney injury and bleeding. A large proportion of serious ADRs required hospital admission, and 11% led to death or were life threatening. Lower kidney function was a major risk factor for serious ADRs. Many of these serious ADRs were determined to be partly preventable through greater adherence to prescription guidelines. This report enhances our understanding of the potential toxicity of drugs taken by patients with moderate to advanced CKD. It emphasizes the importance of monitoring kidney function when prescribing drugs, particularly for high-risk medications such as antithrombotic agents.

12.
Nephrol Ther ; 19(4): 233-250, 2023 08 03.
Artigo em Francês | MEDLINE | ID: mdl-37533268

RESUMO

Launched in 2013 supported by the Program "Cohorts ­ Investments for the Future", the CKD-REIN (Chronic Kidney Disease ­ Renal Epidemiology and Information Network) study is a prospective cohort that included and followed for 5 years more than 3000 patients with moderate or advanced chronic kidney disease (CKD), from 40 nationally representative nephrology clinics. A large amount of data was collected on CKD and its treatments, patient social characteristics and reported outcomes, and nephrology practices and services. A total of 170,000 blood and urine samples were collected and stored in a central biobank. Coordinated with the CKD outcomes and practice pattern study (CKDopps) and collaborating with the international Network of CKD cohorts (iNETCKD), CKD-REIN contributes to the understanding of CKD and the positioning of France with respect to CKD epidemiology and care in the world. This review highlights major findings from the cohort, and their potential implications for clinical practices and the health system, grouped into the following themes: (1) the complexity of patients with CKD; (2) adherence to clinical guidelines; (3) treatment practices and drug risk; (4) acute on chronic kidney disease; (5) CKD metabolic complications; (6) prediction of kidney failure; (7) sex differences in CKD; (8) patient perspective on CKD; (9) transition to kidney failure and replacement therapy; (10) conservative care.


Lancée en 2013 grâce au Programme « Cohortes ­ Investissements d'Avenir ¼, l'étude CKD-REIN (Chronic Kidney Disease ­ Renal Epidemiology and Information Network) est une cohorte prospective qui a inclus et suivi pendant cinq ans plus de 3 000 patients avec une maladie rénale chronique (MRC) modérée ou avancée, dans 40 consultations de néphrologie, représentatives nationalement. Un grand nombre de données ont été collectées sur la MRC et ses traitements, les caractéristiques sociales et la santé perçue des patients, les pratiques et l'organisation des services de néphrologie. Une biothèque de 170 000 échantillons de sang et d'urine a été constituée et stockée dans une biobanque centrale. Coordonnée avec l'étude Chronic Kidney Disease outcomes and practice pattern study (CKDopps) et collaborant avec l'International Network of CKD cohorts (iNET-CKD), CKD-REIN contribue à l'avancée des connaissances et au positionnement de la France dans le domaine de l'épidémiologie de la MRC et des pratiques dans le monde. Cette revue fait le point des faits marquants de la cohorte, et de leur implication potentielle pour la clinique et le système de santé, regroupés par thème : (1) la complexité des patients avec une MRC ; (2) l'adhésion aux recommandations cliniques ; (3) les pratiques thérapeutiques et le risque médicamenteux ; (4) l'insuffisance rénale aiguë dans la MRC ; (5) l'évolution des complications métaboliques ; (6) la prédiction de la défaillance rénale ; (7) les différences hommes-femmes ; (8) le point de vue des patients sur la MRC ; (9) la transition vers la défaillance rénale et le traitement de suppléance ; (10) le traitement conservateur.


Assuntos
Nefrologia , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , França/epidemiologia , Serviços de Informação
14.
Nephrol Dial Transplant ; 38(6): 1341-1344, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37253537
15.
Biochimie ; 213: 22-29, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37142118

RESUMO

Indoxyl sulfate (IS) is a uremic toxin produced by the gut microbiota that commonly accumulates in patients with chronic kidney disease (CKD) and can be harmful. Resveratrol is a polyphenol with properties that attenuate oxidative stress and inflammation. This study aims to evaluate the effect of resveratrol against the damage caused by IS in RAW 264.7 murine macrophages. Cells were treated with 0, 250, 500 and 1000 µmol/L of IS, in the presence of 50 µmol/L of resveratrol. The mRNA and protein expressions of erythroid-related nuclear factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) were measured using rt-PCR and Western blot analysis, respectively. Malondialdehyde (MDA) and reactive oxygen species (ROS) levels were also analyzed. As a result, it was demonstrated that resveratrol induces the activation of the Nrf2 pathway that enhances cytoprotective response. IS upregulated the NF-κB expression and downregulated the Nrf2 expression. In contrast, resveratrol treatment significantly reduced the MDA and ROS production and inhibited the IS-induced expression of NF-κB in macrophage-like RAW 264.7. In conclusion, resveratrol can mitigate inflammation and oxidative stress caused by uremic toxins produced by the gut microbiota, such as IS.


Assuntos
Indicã , NF-kappa B , Humanos , Camundongos , Animais , Resveratrol/farmacologia , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Indicã/toxicidade , Toxinas Urêmicas , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Inflamação/tratamento farmacológico , Macrófagos/metabolismo
16.
Toxins (Basel) ; 15(4)2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37104214

RESUMO

Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by the kidney's tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription and serum concentrations of various UTs. We studied a randomly selected sub-group of participants in the CKD-REIN cohort (adult patients with a confirmed diagnosis of CKD and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) with available frozen samples collected at baseline. PPI prescription was recorded at baseline. Serum concentrations of 10 UTs were measured using a validated liquid chromatography tandem mass spectrometry technique. Multiple linear regression was performed, with the log UT concentration as the dependent variable. Of the 680 included patients (median age: 68 years; median eGFR: 32 mL/min/1.73 m2), 31% had PPI prescriptions at baseline. Patients using PPIs had higher levels of certain UTs in comparison to other patients, including total and free indoxyl sulfate (IS), total and free p-cresylsulfate, total and free p-cresylglucuronide (PCG), phenylacetylglutamine (PAG), free kynurenine, and free hippuric acid. After adjustment for baseline co-morbidities, number of co-prescribed drugs, and laboratory data, including eGFR, associations between PPI prescription and elevated serum concentrations of free and total IS, free and total PCG, and PAG remained significant. Our results indicate that PPI prescription is independently associated with serum UT retention. These findings are interesting to better understand the factors that may modulate serum UT concentration in CKD patients, however, they will need to be confirmed by longitudinal studies.


Assuntos
Insuficiência Renal Crônica , Uremia , Adulto , Humanos , Idoso , Toxinas Urêmicas , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Transversais , Indicã
17.
Sci Rep ; 13(1): 3952, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36894586

RESUMO

We investigated the shape of the relationship between longitudinal uric acid (UA) and the hazard of kidney failure and death in chronic kidney disease (CKD) patients, and attempted to identify thresholds associated with increased hazards. We included CKD stage 3-5 patients from the CKD-REIN cohort with one serum UA measurement at cohort entry. We used cause-specific multivariate Cox models including a spline function of current values of UA (cUA), estimated from a separate linear mixed model. We followed 2781 patients (66% men, median age, 69 years) for a median of 3.2 years with a median of five longitudinal UA measures per patient. The hazard of kidney failure increased with increasing cUA, with a plateau between 6 and 10 mg/dl and a sharp increase above 11 mg/dl. The hazard of death had a U-shape relationship with cUA, with a hazard twice higher for 3 or 11 mg/dl, compared to 5 mg/dl. In CKD patients, our results indicate that UA above 10 mg/dl is a strong risk marker for kidney failure and death and that low UA levels below 5 mg/dl are associated with death before kidney failure.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Masculino , Humanos , Idoso , Feminino , Ácido Úrico , Insuficiência Renal Crônica/complicações , Modelos de Riscos Proporcionais , Fatores de Risco
18.
Clin Nutr ; 42(4): 443-457, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36857954

RESUMO

Increased life expectancy is posing unprecedented challenges to healthcare systems worldwide. These include a sharp increase in the prevalence of chronic kidney disease (CKD) and of impaired nutritional status with malnutrition-protein-energy wasting (PEW) that portends worse clinical outcomes, including reduced survival. In older adults with CKD, a nutritional dilemma occurs when indications from geriatric nutritional guidelines to maintain the protein intake above 1.0 g/kg/day to prevent malnutrition need to be adapted to the indications from nephrology guidelines, to reduce protein intake in order to prevent or slow CKD progression and improve metabolic abnormalities. To address these issues, the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Renal Nutrition group of the European Renal Association (ERN-ERA) have prepared this conjoint critical review paper, whose objective is to summarize key concepts related to prevention and treatment of both CKD progression and impaired nutritional status using dietary approaches, and to provide guidance on how to define optimal protein and energy intake in older adults with differing severity of CKD. Overall, the authors support careful assessment to identify the most urgent clinical challenge and the consequent treatment priority. The presence of malnutrition-protein-energy wasting (PEW) suggests the need to avoid or postpone protein restriction, particularly in the presence of stable kidney function and considering the patient's preferences and quality of life. CKD progression and advanced CKD stage support prioritization of protein restriction in the presence of a good nutritional status. Individual risk-benefit assessment and appropriate nutritional monitoring should guide the decision-making process. Higher awareness of the challenges of nutritional care in older adult patients with CKD is needed to improve care and outcomes. Research is advocated to support evidence-based recommendations, which we still lack for this increasingly large patient subgroup.


Assuntos
Desnutrição , Insuficiência Renal Crônica , Humanos , Idoso , Estado Nutricional , Dieta com Restrição de Proteínas , Qualidade de Vida , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Rim , Caquexia , Desnutrição/terapia
19.
J Ren Nutr ; 33(4): 508-519, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36796502

RESUMO

An expert advisory board discussed the prevention and treatment of chronic kidney disease (CKD), with a focus on dietary options. This is timely, given the uptake of value based models for kidney care in the United States. Timing of dialysis start is influenced by patients' clinical status and complex patient-clinician interactions. Patients value personal freedom and quality of life and may want to delay dialysis, whilst physicians are sometimes more concerned with clinical outcomes. Kidney-preserving therapy can prolong the dialysis-free period and preserve residual kidney function, thus patients are asked to adjust their lifestyle and diet, to follow a low- or very low-protein diet, with or without ketoacid analogues. Multi-modal approaches include pharmacotherapies, management of symptoms, and a gradual, individualized dialysis transition. Patient empowerment is vital, including CKD education and involvement in decision making. These ideas may help patients, their families, and clinical teams to improve the management of CKD.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Estados Unidos , Qualidade de Vida , Insuficiência Renal Crônica/terapia , Diálise Renal , Dieta com Restrição de Proteínas , Assistência ao Paciente , Falência Renal Crônica/terapia
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