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Rationale & Objective: Blood pressure (BP) control is essential for preventing cardiorenal complications in chronic kidney disease (CKD), but most patients fail to reach BP target. We assessed longitudinal patterns of antihypertensive drug prescription and systolic BP. Study Design: Prospective observational cohort study. Setting & Population: In total, 2,755 hypertensive patients with CKD stages 3-4, receiving care from a nephrologist, from the French CKD–Renal Epidemiology and Information Network (CKD-REIN cohort study). Exposure: Patient factors, including sociodemographic characteristics, medical history, and laboratory data, and provider factors, including number of primary care physician and specialist encounters. Outcomes: Changes in antihypertensive drug-class prescription during follow-up: add-on or withdrawal. Analytical Approach: Hierarchical shared-frailty models to estimate hazard ratios (HR) to deal with clustering at the nephrologist level and linear mixed models to describe systolic BP trajectory. Results: At baseline, median age was 69 years, and mean estimated glomerular filtration rate was 33 mL/min/1.73 m². In total, 66% of patients were men, 81% had BP ≥ 130/80 mm Hg, and 75% were prescribed ≥2 antihypertensive drugs. During a median 5-year follow-up, the rate of changes of antihypertensive prescription was 50 per 100 person-years, 23 per 100 for add-ons, and 25 per 100 for withdrawals. After adjusting for risk factors, systolic BP, and the number of antihypertensive drugs, poor medication adherence was associated with increased HR for add-on (1.35, 95% confidence interval [CI], 1.01-1.80), whereas a lower education level was associated with increased HR for withdrawal (1.23, 95% CI, 1.02-1.49) for 9-11 years versus ≥12 years. More frequent nephrologist visits (≥4 vs none) were associated with higher HRs of add-on and withdrawal (1.52, 95% CI, 1.06-2.18; 1.57, 95% CI, 1.12-2.19, respectively), whereas associations with visit frequency to other physicians varied with their specialty. Mean systolic BP decreased by 4 mm Hg following drug add-on but tended to increase thereafter. Limitations: Lack of information on prescriber and drug dosing. Conclusions: In patients with CKD and poor BP control, changes in antihypertensive drug prescriptions are common and relate to clinician preferences and patients’ tolerability. Sustainable reduction in systolic BP after add-on of a drug class is infrequently achieved. Plain-Language Summary: Blood pressure (BP) control remains unattained in most patients with chronic kidney disease (CKD), raising questions about how antihypertensive treatment is managed. Our study highlights dynamic, yet heterogeneous patterns of antihypertensive drug prescriptions in patients with CKD stages 3-4 receiving care from a nephrologist over 5 years of follow-up. Modifiable factors such as high body mass index and poor medication adherence were associated with higher hazard of adding-on an antihypertensive drug class, independently of baseline BP and antihypertensive treatment. Similarly, lower education level was associated with antihypertensive drug withdrawn, as was more frequent visits to primary care physicians, underlining the importance of coordinated care. Sustainable reduction in systolic BP after add-on of a drug class is infrequently achieved and may be related to drug withdrawal and poor treatment adherence.

Background: Chronic kidney disease is common, affecting up to 13 % of the global population, and is predicted to become the fifth leading cause of 'life years lost' by 2040. Individuals with end-stage kidney disease commonly develop complications such as protein-energy wasting and cachexia which further worsens their prognosis. The syndrome of ‘renal cachexia’ is poorly understood, under-diagnosed and even if recognised has limited treatment options. Objective: To explore the lived experience of renal cachexia for individuals with end-stage kidney disease and the interrelated experiences of their carers. Design: This interpretive phenomenological study was designed to facilitate an in-depth exploration of how patients and carers experience of renal cachexia. To improve and document the quality, transparency, and consistency of patient and public involvement in this study the Guidance for Reporting Involvement of Patients and the Public-Short Format was followed. Setting: The study was conducted across two nephrology directorates, within two healthcare trusts in the United Kingdom. Participants: Seven participants who met the inclusion criteria were recruited for this study, four patients (three female, one male) and three carers (two male, one female). Methods: We employed a purposive sampling strategy. Data collection was conducted between July 2022 and December 2023. Interviews were semi-structured, audio-recorded, transcribed verbatim and analysed in six steps by two researchers using interpretive phenomenological analysis. Ethical approval was approved by the Office for Research Ethics Committees Northern Ireland (Reference: 22/NI/0107). Results: Analysis generated six group experiential themes: the lived experience of appetite loss, functional decline and temporal coping, weight loss a visual metaphor of concern, social withdrawal and vulnerability, the emotional toll of eating challenges and psychological strain amidst a lack of information about cachexia. Conclusion: This is the first qualitative study exploring the lived experience of renal cachexia for patients and carers. Our study highlights that psycho-social and educational support is urgently needed. Additionally, healthcare professionals need better information provision to help them to recognise and respond to the needs of this population. Further research is required to develop models of holistic support which could help patients and carers cope with the impact of renal cachexia and optimally manage this syndrome within the family unit. Registration: N/A.

Introduction: Adjusting drug dose levels based on equations that standardize the estimated glomerular filtration rate (eGFR) to a body surface area (BSA) of 1.73 m2 can pose challenges, especially for patients with extremely high or low body mass index (BMI). The objective of the present study of patients with CKD and diabetes was to assess the impact of deindexing creatinine-based equations on estimates of kidney function and on the frequency of inappropriate prescriptions of oral antidiabetic drugs (OADs).Methods: The prospective CKD-REIN cohort is comprised of patients with eGFR 1.73 m2. Deindexing the kidney function estimates led to higher eGFRs, especially in BMI group 3. The proportion of patients with at least one inappropriate prescription differed greatly when comparing indexed and deindexed estimates. The magnitude of the difference increased with the BMI: when comparing BMI group 1 with BMI group 3, the difference was respectively −4% and −10% between deindexed 2021 CKD-EPI and indexed CKD-EPI. Metformin and sitagliptin were the most frequent inappropriately prescribed OADs.Conclusion: We highlight significant differences between the BSA-indexed and deindexed versions of equations used to estimate kidney function, emphasizing the importance of using deindexed estimates to adjust drug dose levels - especially in patients with an extreme BMI.

Depression is common in patients with chronic kidney disease (CKD). Experimental studies suggest the role of urea toxicity in depression. We assessed both the incidence of antidepressant prescriptions and depressive symptoms (measured by CESD (Center for Epidemiologic Depression) scale) in 2505 patients with CKD (Stage 3–4) followed up over 5 years in the Chronic Kidney Disease Renal Epidemiology and Information Network (CKD-REIN) cohort. We used a joint model to assess the association between the serum urea level and incident antidepressant prescriptions, and mixed models for the association between the baseline serum urea level and CESD score over the 5-year follow-up. Among the 2505 patients, 2331 were not taking antidepressants at baseline. Of the latter, 87 started taking one during a median follow-up of 4.6 years. After adjustment for confounding factors, the hazard ratio for incident antidepressant prescription associated with the serum urea level (1.28 [95%CI, 0.94,1.73] per 5 mmol/L increment) was not significant. After adjustment, the serum urea level was associated with the mean change in the CESD score (β = 0.26, [95%CI, 0.11,0.41] per 5 mmol/L increment). Depressive symptoms burden was associated with serum urea level unlike depression events. Further studies are needed to draw firm conclusions and better understand the mechanisms of depression in CKD.

Abstract 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.

Highlights • Cryoglobulinemia is frequent in SLE, but mostly asymptomatic. • Sixty-six percent of SLE patients tested positive for cryoglobulins, and 15% of the SLE patients with cryoglobulinemia developed a cryoglobulinemic vasculitis. • Features of the cryoglobulinemic vasculitis mainly involved skin, joints, and general signs. Severe manifestations of vasculitis were rare.

Abstract We assessed the risks of bleeding, acute kidney injury (AKI), and kidney failure associated with the prescription of antithrombotic agents (oral anticoagulants and/or antiplatelet agents) in patients with moderate‐to‐advanced chronic kidney disease (CKD). CKD‐REIN is a prospective cohort of 3022 nephrology outpatients with CKD stages 2–5 at baseline. We used cause‐specific Cox proportional hazard models to estimate hazard ratios (HRs) for bleeding (identified through hospitalizations), AKI, and kidney failure. Prescriptions of oral antithrombotics were treated as time‐dependent variables. At baseline, 339 (11%) patients (65% men; 69 [60–76] years) were prescribed oral anticoagulants only, 1095 (36%) antiplatelets only, and 101 (3%) both type of oral antithrombotics. Over a median (interquartile range [IQR]) follow‐up period of 3.0 (IQR, 2.8–3.1) years, 152 patients experienced a bleeding event, 414 patients experienced an episode of AKI, and 270 experienced kidney failure. The adjusted HRs (95% confidence interval [95% CI]) for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants only, and antiplatelet + oral anticoagulant were, respectively, 0.74 (95% CI, 0.46–1.19), 2.38 (95% CI, 1.45–3.89), and 3.96 (95% CI, 2.20–7.12). An increased risk of AKI risk was associated with the prescription of oral anticoagulants (adjusted HR, 1.90, 95% CI, 1.47–2.45) but not the prescription of antiplatelets (HR, 1.24, 95% CI, 0.98–1.56). Kidney failure was not associated with the prescription of oral antithrombotics of any type. This study confirms the high risk of AKI associated with oral anticoagulants prescription in patients with CKD and also highlights the potential aggravating effect of combining vitamin K antagonist (VKA) and antiplatelets on the risk of bleeding.

Abstract Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), their mechanisms of action are unclear. A reduced production of uremic toxins could contribute to the benefits of LPDs. Aromatic amino-acids (AA) are precursors of major uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS). We hypothesize that a low aromatic amino acid diet (LA-AAD, namely a low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the decreased production of uremic toxins. Kidney failure was chemically induced in mice with a diet containing 0.25% (w/w) of adenine. Mice received three different diets for six weeks: normoproteic diet (NPD: 14.7% proteins, aromatic AAs 0.019%), LPD (5% proteins, aromatic AAs 0.007%) and LA-AAD (14% proteins, aromatic AAs 0.007%). Both LPD and LA-AAD significantly reduced proteinuria, kidney fibrosis and inflammation. While LPD only slightly decreased plasma free PCS and free IS compared to NPD; free fractions of both compounds were significantly decreased by LA-AAD. These results suggest that a LA-AAD confers similar benefits of a LPD in delaying the progression of CKD through a reduction in some key uremic toxins production (such as PCS and IS), with a lower risk of malnutrition.

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.

Numerous studies have shown that chronic renal failure, whatever the treatment, is an important risk factor during the SARS-Cov2 pandemic. We present the incidence of COVID-19 infection, and its lethality, in France according to data from the French Language Peritoneal Dialysis Registry (RDPLF), during the period of the epidemic peak between March 1 and May 15, 2020. Of the 3,104 patients treated with PD during this period, from 156 centers, 59 contracted COVID-19, ie 1.8%, a percentage significantly lower than that observed in center hemodialysis. Diabetes was found in 64% of infected patients while it was only present in 36% of uncontaminated patients. The mode of contamination was attributed to a hospital stay in 19% of the cases, a family infection in 17% of the cases, treatment in nursing homes in 15% of the cases, unknown in 44% of the cases. Sixty-two percent of the infected patients were on assisted PD, without identifying the source of contamination. The mortality rate was high at 40%, comparable to other countries in PD. A comparison with hemodialysis could only be made after adjustment for comorbidities and patient profiles: data on hemodialysis are not available in the RDPLF. Home peritoneal dialysis decreases the risk of Covid-19 contamination, but associated comorbidities and age are the source of high mortality. Non-autonomous patients have a higher risk of contamination.

Background and AimsLittle is known about the effects of probiotics on inflammation in the context of chronic kidney disease (CKD). We investigated the association between probiotic intake and inflammation in patients with moderate-to-advanced CKD.MethodsWe performed a cross-sectional study of 888 patients with stage 3–5 CKD and data on serum C-reactive protein (CRP) levels and a concomitant food frequency questionnaire. We estimated the odds ratios (ORs) [95% confidence interval (CI)] for various CRP thresholds (>3, >4, >5, >6, and >7 mg/L) associated with three intake categories (no yoghurt, ordinary yoghurt, and probiotics from yoghurts or dietary supplements) and two frequency categories (daily or less than daily).ResultsThe 888 study participants (median age: 70; men: 65%) had a median estimated glomerular filtration rate of 28.6 mL/min/1.73 m2 and a median [interquartile range] CRP level of 3.0 [1.6, 7.0] mg/L. Fifty-seven percent consumed ordinary yoghurt and 30% consumed probiotic yoghurt. The median intake frequency for yoghurt and probiotics was 7 per week. Relative to participants not consuming yoghurt, the ORs [95% CI] for CRP > 6 or >7 mg/L were significantly lower for participants consuming ordinary yoghurt (0.58 [0.37, 0.93] and 0.57 [0.35, 0.91], respectively) and for participants consuming probiotics (0.54 [0.33, 0.9] and 0.48 [0.28, 0.81], respectively), independently of age, sex, body mass index, CKD stage, cardiovascular disease, and fibre, protein and total energy intakes. The ORs were not significantly lower for CRP thresholds >3, >4, and >5 mg/L and were not significantly greater in daily consumers than in occasional consumers.ConclusionWe observed independent associations between the consumption of yoghurt or probiotics and lower levels of inflammation in patients with CKD. There was no evidence of a dose-effect relationship.Clinical Trial Registration[https://www.clinicaltrials.gov/ct2/show/NCT03381950], identifier [NCT03381950].

Renal cachexia is an important consideration in the person-centred care that is needed in end-stage renal disease (ESRD). However, given that clinical guidelines relating to renal cachexia are largely absent, this is an unmet care need. To inform guidelines and future renal service planning, there is an urgency to understand individuals' experiences of renal cachexia and the interrelated experiences of the carers in their lives. We report here the protocol for an interpretative phenomenological study which will explore this lived experience. A purposive sampling strategy will recruit individuals living with ESRD who have cachexia and their carers. A maximum of 30 participants (15 per group) dependent on saturation will be recruited across two nephrology directorates, within two healthcare trusts in the United Kingdom. Individuals with renal cachexia undergoing haemodialysis will be recruited via clinical gatekeepers and their carers will subsequently be invited to participate in the study. Participants will be offered the opportunity to have a face-to-face, virtual or telephone interview. Interviews will be audio-recorded, transcribed verbatim and analysed using interpretative phenomenological analysis. NVivo, will be used for data management. Ethical approval for this study was granted by the Office for Research Ethics Committees Northern Ireland (REC Reference: 22/NI/0107). Scientific evidence tends to focus on measurable psychological, social and quality of life outcomes but there is limited research providing in-depth meaning and understanding of the views of individuals with renal disease who are experiencing renal cachexia. This information is urgently needed to better prepare healthcare providers and in turn support individuals with ESRD and their carers. This study will help healthcare providers understand what challenges individuals with ESRD, and their carers face in relation to cachexia and aims to inform future clinical practice guidelines and develop supportive interventions which recognise and respond to the needs of this population.

Introduction: We describe the characteristics of patients with moderate/advanced chronic kidney disease (CKD) according to receipt of lipid-lowering therapy (LLT), and whether they achieved low-density lipoprotein cholesterol (LDL-C) targets for high- and very high-risk patients. Methods: CKD-REIN (NCT03381950), a prospective cohort study conducted in 40 nephrology clinics in France, enrolled 3033 patients with moderate (stage G3) or advanced (stage G4/G5) CKD (2013−2016) who had not been on chronic dialysis or undergone kidney transplantation. Data were collected from patients’ interviews and medical records. Patients were followed up at 1 year. Results: Among 2542 patients (mean [SD] age 67 [13] years, 34% women) with LDL-C measurements at baseline (mean [SD] LDL-C 2.7 [1.1] mmol/l; cholesterol 4.8 [1.3] mmol/l), 63% were on LLT; 24% were at high (CKD stage G3, no cardiovascular disease [CVD] or diabetes) and 74% at very high (CKD stage G3 with diabetes or CVD, or CKD stage G4/5) cardiovascular risk. Among high-risk patients, 45% of those on statin and/or ezetimibe achieved the LDL-C treatment target (

Abstract Background Weight loss and homeostatic disturbances of both energy and protein balances are characteristics of several illnesses including cancer, heart failure, and chronic kidney disease (CKD). Different definitions have been used to describe this deleterious process. The term protein‐energy wasting (PEW) has been proposed for CKD patients by the International Society of Renal Nutrition and Metabolism. Methods We searched the publication in Medline from February 2008 to September 2018 using PEW or cachexia in their title. Results Since its inception, the term PEW has been exceptionally successful, highlighted by 327 original publications referenced in PubMed over 10 years. Using this classification, several studies have confirmed that PEW is among the strongest predictors of mortality in CKD patients [hazard ratio of 3.03; confidence interval of 1.69–5.26 in 1068 haemodialysis patients and 1.40 (1.04–1.89) in 1487 non‐dialysed patients across PEW stages 0 to 4]. Based on this classification, prevalence of PEW is 28% to 54% among 16 434 adults undergoing maintenance dialysis. PEW prevalence increases when renal function declines, that is, from 5% is a mandatory criterion for cachexia but supportive for PEW. Conclusions The recent understanding of cachexia physiopathology during CKD progression suggests that PEW and cachexia are closely related and that PEW corresponds the initial state of a continuous process that leads to cachexia, implicating the same metabolic pathways as in other chronic diseases. Despite the success of the definition of PEW, using a more uniform term such as ‘kidney disease cachexia’ could be more helpful to design future research through collaborative groups of researchers with focus on cachexia.

Note editor : retraction of case report https://doi.org/10.25796/bdd.v3i1.54503 Dear Editor-in-chief, By this letter we would like to retract our case report entitled « First viral replication of Covid-19 identified in the peritoneal dialysis fluid of a symptomatic patient» that we submitted to your journal one week ago. We indeed wanted to inform the renal community of a potential presence of Covid-19 virus in the peritoneal dialysis fluid in patients undergoing peritoneal dialysis treatment. However, the patient general status impaired and he was transferred to an intensive care unit for acute myocardial insufficiency. During this stay, he was re-checked for a number of other organs alterations. A total of 7 RT-PCR SARS-Cov2 tests , validated by the National Reference Center, were done : 2 by nasopharyngeal swabs, 1 in bronchoalveolar lavage, 3 peritoneal dialysate and one in stool. A serological test was also performed. All tests were found negative. The CT scan was analyzed again by a specialized radiologist and although a COVID-19 pulmonary disease was likely, it was not possible to rule out a pulmonary edema secondary to an acute myocarditis of different origin. Therefore, based on these later information, and after careful discussion with the virologists, we think that the first positive PCR result was erroneous, without clear explanation for this. Until new cases appear, the fact that two subsequent peritoneal dialysate carefully processed were negative indicates that we cannot reliably prove a peritoneal dialysate contamination by COVID-19 virus in our patient. We deeply apologize for this premature publication. M.Nouvier and D.Fouque for the authors

The COVID-19 pandemic is characterized by a disease with mainly respiratory tropism and varying severity. Viral excretion of COVID-19 has been described in both urine and stool with the risk of contamination by stool. No viral replication in the peritoneal dialysis fluid has been reported to date. We report an observation demonstrating the presence of the virus in the peritoneal dialysis drainage fluid of a COVID-19 patient. This underlines the importance in COVID-19 patients of considering dialysis fluid as a possible source of contamination.

The uremic syndrome is a metabolic disorder characterized by the impairment of renal handling of several solutes, the resulting accumulation of toxic products and the activation of some adaptive but detrimental mechanisms which all together contribute to the progression of renal damage. In moderate to advanced renal failure, the dietary manipulation of nutrients improves metabolic abnormalities and may contribute to delay the time of dialysis initiation. This commentary focuses on the physiopathological rationale and the clinical application of the very low-protein diet supplemented with ketoanalogs for the management of chronic kidney disease. Keywords: Low-protein diet, Ketoanalogs, Renal failure, Chronic kidney disease

Abstract Background Surveys using traditional measures of nutritional status indicate that muscle wasting is common among persons with end-stage kidney disease (ESKD). Up to 75% of adults undergoing maintenance dialysis show some evidence of muscle wasting. ESKD is associated with an increase in inflammatory cytokines and can result in cachexia, with the loss of muscle and fat stores. At present, only limited data are available on the classification of wasting experienced by persons with ESKD. Individuals with ESKD often exhibit symptoms of anorexia, loss of lean muscle mass and altered energy expenditure. These symptoms are consistent with the syndrome of cachexia observed in other chronic diseases, such as cancer, heart failure, and acquired immune deficiency syndrome. While definitions of cachexia have been developed for some diseases, such as cardiac failure and cancer, no specific cachexia definition has been established for chronic kidney disease. The importance of developing a definition of cachexia in a population with ESKD is underscored by the negative impact that symptoms of cachexia have on quality of life and the association of cachexia with a substantially increased risk of premature mortality. The aim of this study is to determine the clinical phenotype of cachexia specific to individuals with ESKD. Methods A longitudinal study which will recruit adult patients with ESKD receiving haemodialysis attending a Regional Nephrology Unit within the United Kingdom. Patients will be followed 2 monthly over 12 months and measurements of weight; lean muscle mass (bioelectrical impedance, mid upper arm muscle circumference and tricep skin fold thickness); muscle strength (hand held dynamometer), fatigue, anorexia and quality of life collected. We will determine if they experience (and to what degree) the known characteristics associated with cachexia. Discussion Cachexia is a debilitating condition associated with an extremely poor outcome. Definitions of cachexia in chronic illnesses are required to reflect specific nuances associated with each disease. These discrete cachexia definitions help with the precision of research and the subsequent clinical interventions to improve outcomes for patients suffering from cachexia. The absence of a definition for cachexia in an ESKD population makes it particularly difficult to study the incidence of cachexia or potential treatments, as there are no standardised inclusion criteria for patients with ESKD who have cachexia. Outcomes from this study will provide much needed data to inform development and testing of potential treatment modalities, aimed at enhancing current clinical practice, policy and education.

Reducing protein intake is recommended for slowing chronic kidney disease (CKD) progression, but assessment of its true effectiveness is sparse. Methods: Using the Maroni formula, we assessed dietary protein intake (DPI) from 24-hour urinary urea excretion in 1594 patients (67% men and 33% women) with CKD, 784 of whom also had 7-day food records. Cause-specific hazard ratios (HRs) and 95% confidence intervals for the competing risks of DPI-associated end-stage renal disease (ESRD) or death were estimated in 1412 patients with baseline glomerular filtration rate ≥15 ml/min per 1.73 m2, measured by 51Cr-EDTA renal clearance (mGFR). Results: Overall, mean DPI estimated from urea excretion was 1.09 ± 0.30 g/kg of body weight per day (range = 0.34−2.76); 20% of patients had values > 1.3 g/kg per day, and 1.9% had values < 0.6 g/kg per day. Urea excretion and food records produced similar estimates of mean DPI. The lower the mGFR, the lower the mean DPI. Over a median follow-up of 5.6 years, there were 319 ESRD events and 189 pre-ESRD deaths. After adjusting for relevant covariates, each 0.1 g/kg daily higher baseline urea excretion−based DPI or food record−based DPI was associated with an HR for ESRD of 1.05 (95% confidence interval 1.01−1.10) or 1.09 (95% confidence interval 1.04−1.14), respectively. HRs were stronger in patients with baseline mGFR < 30 ml/min per 1.73 m2. There was no association with mortality. The mean age of the patients was 59 ± 15 years, and mean body mass index was 26.6 ± 5.2 kg/m2. Conclusion: In this prospective observational study, the lower the baseline DPI, the slower the progression toward ESRD. Most importantly, the absence of threshold for the relation between DPI and ESRD risk indicates that there is no optimal DPI in the range observed in this cohort.

Abstract Background A balanced diet is essential to slowing the progression of chronic kidney disease (CKD) and managing the symptoms. Currently, no tool is available to easily and quickly assess energy and macronutrient intake in patients with non end-stage CKD. We aimed to develop and evaluate the validity and reproducibility of a new short 49-item food frequency questionnaire (SFFQ) adapted to patients with CKD. Methods The CKD-REIN study is a prospective cohort that enrolled 3033 patients with moderate or advanced CKD from a national sample of nephrology clinics. A sub-sample of 201 patients completed the SFFQ twice, at a one-year interval and were included in the reproducibility study. During this interval, 127 patients also completed six 24-h recalls and were included in the validity study. Main nutrient and dietary intakes were computed. Validity was evaluated by calculating crude, energy-adjusted and de-attenuated correlation coefficients (CC) between FFQ and the mean of the 24-h recall results. Bland-Altman plots were performed and cross-classification into quintiles of consumption of each nutrient and food group was computed. Reproducibility between the two SFFQs was evaluated by intraclass CC (ICC). Results Regarding validity, CC ranged from 0.05 to 0.79 (unadjusted CC, median: 0.40) and 0.10 to 0.59 (de-attenuated CC, median: 0.35) for food group and nutrient intakes, respectively. Five of the most important nutrients of interest in CKD, i.e. protein, calcium, phosphorus, potassium, and sodium had de-attenuated CC of 0.46, 0.43, 0.39, 0.32, and 0.12, respectively. The median of classification into the same or adjacent quintiles was 68% and 65% for food and nutrient intakes, respectively, and ranged from 63% to 69% for the five nutrients mentioned before. Bland-Altman plots showed good agreement across the range of intakes. ICC ranged from 0.18 to 0.66 (median: 0.46). Conclusions The CKD-REIN SFFQ showed acceptable validity and reproducibility in a sample of patients with CKD, notably for CKD nutrients of importance. It can now be used in large-scale epidemiological studies to easily assess the relations between diet and CKD outcomes as well as in clinical routine. It may also serve as a basis for the development of FFQs in international CKD cohort networks.

Background: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD. Methods: Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation. Results: Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function. Conclusions: These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients.

Regardless of the primary disease responsible for kidney failure, patients suffering from chronic kidney disease (CKD) have in common multiple impairments of both the innate and adaptive immune systems, the pathophysiology of which has long remained enigmatic. CKD-associated immune dysfunction includes chronic low-grade activation of monocytes and neutrophils, which induces endothelial damage and increases cardiovascular risk. Although innate immune effectors are activated during CKD, their anti-bacterial capacity is impaired, leading to increased susceptibility to extracellular bacterial infections. Finally, CKD patients are also characterized by profound alterations of cellular and humoral adaptive immune responses, which account for an increased risk for malignancies and viral infections. This review summarizes the recent emerging data that link the pathophysiology of CKD-associated immune dysfunctions with the accumulation of microbiota-derived metabolites, including indoxyl sulfate and p-cresyl sulfate, the two best characterized protein-bound uremic retention solutes.

High serum levels of gut-derived uremic toxins, especially p-cresyl sulfate (pCS), indoxyl sulfate (IS) and indole acetic acid (IAA), have been linked to adverse outcomes in patients with chronic kidney disease (CKD). Sevelamer carbonate could represent an interesting option to limit the elevation of gut-derived uremic toxins. The aim of the present study was to evaluate the adsorptive effect of sevelamer carbonate on different gut-derived protein-bound uremic toxins or their precursors in vitro, and its impact on the serum levels of pCS, IS and IAA in patients with CKD stage 3b/4. For the in vitro experiments, IAA, p-cresol (precursor of pCS) and indole (precursor of IS), each at a final concentration of 1 or 10 µg/mL, were incubated in centrifugal 30 kDa filter devices with 3 or 15 mg/mL sevelamer carbonate in phosphate-buffered saline at a pH adjusted to 6 or 8. Then, samples were centrifuged and free uremic toxins in the filtrates were analyzed. As a control experiment, the adsorption of phosphate was also evaluated. Additionally, patients with stage 3b/4 CKD (defined as an eGFR between 15 and 45 mL/min per 1.73 m2) were included in a multicenter, double-blind, placebo-controlled, randomized clinical trial. The participants received either placebo or sevelamer carbonate (4.8 g) three times a day for 12 weeks. The concentrations of the toxins and their precursors were measured using a validated high-performance liquid chromatography method with a diode array detector. In vitro, regardless of the pH and concentration tested, sevelamer carbonate did not show adsorption of indole and p-cresol. Conversely, with 10 µg/mL IAA, use of a high concentration of sevelamer carbonate (15 mg/mL) resulted in a significant toxin adsorption both at pH 8 (mean reduction: 26.3 ± 3.4%) and pH 6 (mean reduction: 38.7 ± 1.7%). In patients with CKD stage 3b/4, a 12-week course of treatment with sevelamer carbonate was not associated with significant decreases in serum pCS, IS and IAA levels (median difference to baseline levels: −0.12, 0.26 and −0.06 µg/mL in the sevelamer group vs. 1.97, 0.38 and 0.05 µg/mL in the placebo group, respectively). Finally, in vitro, sevelamer carbonate was capable of chelating a gut-derived uremic toxin IAA but not p-cresol and indole, the precursors of pCS and IS in the gut. In a well-designed clinical study of patients with stage 3b/4 CKD, a 12-week course of treatment with sevelamer carbonate was not associated with significant changes in the serum concentrations of pCS, IS and IAA.

Uremic retention solutes (URS) are associated with cardiovascular complications and poor survival in chronic kidney disease. The better understanding of the origin of a certain number of these toxins enabled the development of new strategies to reduce their production. URS can be classified according to their origins (i.e., host, microbial, or exogenous). The discovery of the fundamental role that the intestinal microbiota plays in the production of many URS has reinstated nutrition at the heart of therapeutics to prevent the accumulation of URS and their deleterious effects. The intestinal microbiota is personalized and is strongly influenced by dietary habits, such as the quantity and the quality of dietary protein and fibers. Herein, this review out lines the role of intestinal microbiota on URS production and the recent discoveries on the effect of diet composition on the microbial balance in the host with a focus on the effect on URS production.

Zinc-α2-glycoprotein (ZAG), a potent cachectic factor, is increased in patients undergoing maintenance dialysis. However, there is no data for patients before initiation of renal replacement therapy. The purpose of the present study was to assess the relationship between plasma ZAG concentration and renal function in patients with a large range of glomerular filtration rate (GFR). Plasma ZAG concentration and its relationship to GFR were investigated in 71 patients with a chronic kidney disease (CKD) stage 1 to 5, 17 chronic hemodialysis (HD), 8 peritoneal dialysis (PD) and 18 non-CKD patients. Plasma ZAG concentration was 2.3-fold higher in CKD stage 5 patients and 3-fold higher in HD and PD patients compared to non-CKD controls (P

Exercise programs have been recommended as nutritional interventions in hemodialysis (HD) patients to minimize loss of muscle mass, improve physical and functional capacity, inflammation thus controlling or preventing cardiovascular diseases (CVD), which accounts for 50% of mortality in dialysis patients. Therefore the purpose of this study was to analyze the effects of a resistance exercise (RE) program on biochemical parameters, inflammation markers, and body composition in HD patients. Thirty- six HD patients (61.1% men, mean age 46.7±2.5yrs) were studied. The anthropometric and biochemical parameters are presented in Table. There were significant differences after 6 months of RE in albumin and CRP plasma levels and body composition parameters. The HD patients gained nearly 3kg of lean mass and lost about 3% of body fat. Parameters Before(n=30) After(n=30) BMI (kg/m2) 22.8±4.0 23.3±4.3 Arm muscular area (cm) 30.3±13.7 35.4±13.8* Body Fat (%) 31.5±5.6 28.4±5.9* Lean mass (kg) 42.4±10.0 45.5±11.0* Albumin (g/dL) 3.6±0.3 3.8±0.2* Globulin (g/dL) 3.2±0.3 2.8±0.5** Interleukin-6 (pg/mL) 81.3±9.4 78.7±10.4 TNF-α (pg/mL) 25.7±6.5 24.3±8.7 Creatinine (mg/dL) 12.5±3.6 12.2±3.7 CRP (pg/mL) 2.9±0.4 2.0±0.1* ⁎ p

Nutrition care is complex and encompasses evaluation and correction of protein-energy wasting plus many nutrition abnormalities such as hyperphosphatemia, abdominal obesity, and risk factors of cardiovascular disease. The purpose of this study was to test a nutritionally comprehensive algorithm for feasibility and functionality in a diverse group of HD patients. This was a prospective, observational study designed to test a nutrition algorithm for 1) clinical feasibility; 2) logical progression; 3) ability to collect data; and 4) effectiveness in improving outcomes. Patients included in this study were enrolled by renal dietitians (RD) working in HD units based in five different countries. To select study subjects, RD were asked to screen and consent patients in their facilities until 4 patients were identified as at nutrition risk per the algorithm’s screening tool. All data were collected via the algorithm including screening, assessment, nutrition related diagnosis, etiology of the nutrition diagnosis, nutrition related barriers, nutrition focused interventions, and outcome parameters. Statistics were performed using SPSS vs 20.0 and significance set at p

Chronic kidney disease (CKD) is associated with a large range of metabolic alterations among which insulin resistance and dyslipidemia. We hypothesize that a phenomenon of lipotoxicity and ectopic fat redistribution could be responsible for the insulin-resistance associated to CKD. C57BL/6 mice underwent a 5/6 nephrectomy and were compared to pair fed sham-operated mice. Insulin sensitivity was estimated through intra-peritoneal insulin (ipITT) and glucose tolerance (ipGTT) tests. Anthropometric (body weight, lean and fad pad mass) and metabolic parameters (glycemia, insulin, cholesterol, triglycerides) were measured. The phosphorylation of a key protein of insulin signaling pathway (protein kinase B, PKB/Akt) was studied by Western blot. The intra-muscular and intra-hepatic lipids were extracted using Chloroform-Methanol (2:1, v/v). The CKD mice exhibited a marked decrease in insulin sensitivity (−76%, p

Resting energy expenditure (REE) is the predominant component of total daily energy expenditure (TEE). Metabolic disorders and comorbities, such as inflammation and diabetes, can affect the REE in hemodialysis (HD) patients. The objective of this study was to evaluate the relationship between inflammation and REE estimated by TEE in HD patients. Twenty-five HD patients (54.5±11.7 years, 15 men, BMI, 24.4±4.7 kg/m2, urea clearance (Kt/Vsp) of 1.43±0.26 and 58.2±42.7 months on HD) were studied. TEE was measured during two days (one dialysis and one fx1 nondialysis day) by SWA (SenseWear Pro2 Armband, BodyMedia Inc, Pittsburgh, PA, USA). This monitor provides directly the TEE and the physical active energy expenditure (PAEE); the REE measurement was obtained by the subtraction of PAEE and thermic effect of food (approximately 10% of TEE) from TEE. C-reactive protein (CRP) was measured by immunoturbidimetric method. The REE was 1677.7±273.5 kcal/d for men and 1267.0±221.6 kcal/d for women (p〈0.0001). The CRP levels values were 0.27 ± 0.26 mg/dL and nine patients (36%) had CRP 〉0.3 mg/dL, compatible with chronic inflammation. A trend for high REE was observed in patients with inflammation (1865±216 kcal/d for men with CRP≥0.3 mg/dL and 1584±257kcal/d with CRP〈0.3 mg/dL (p= 0.05); 1361.4±181.5 kcal/d for women with CRP≥0.3 mg/dL and 1204.1±238.2kcal/d with CRP〈0.3 mg/dL (p = 0.27). CRP was positively correlated with REE (r=0.41; p=0.04). In conclusion, chronic mild inflammation can increase the REE in HD patients.

Chronic kidney disease (CKD) is associated with a large range of metabolic alterations. P-cresyl sulfate (PCS) has been identified as one of the main uremic toxins involved in the pathogenesis of accelerated atherosclerosis in CKD. The prebiotic soluble fibers have the property of selectively stimulate growth and activity of a limited number of beneficial bacteria in the colon. The aim of this study is to assess in mice the effects of prebiotics by the reduction of PCS intestinal production, on metabolic disturbances associated with CKD. Subtotally nephrectomized C57BL/6J wild-type mice were divided into two groups: CKD mice and CKD mice fed with 5% (w/w standard diet) of prebiotic arabinoxylane oligosaccharides (AXOS, WITAXOS SA,). Three weeks after initiation of prebiotics serum cholesterol total, triglycerides, glucose, PCS were measured. The insulin sensitivity was estimated by intra-peritoneal insulin tolerance test and glucose tolerance test. CKD mice treated with AXOS exhibited a significant decrease in serum total PCS (−74%, p=0.03). Prebiotic treatment reduced the loss of fat mass observed in CKD (+33%, p

Background: Chronic kidney disease (CKD) patients often have gastrointestinal symptoms which may result in malnutrition and a negative impact on their quality of life. Modulation of the gut microbiota can be a strategy to promote host health and homeostasis. Case report: The authors present a case of chronic diarrhea in a hemodialysis (HD) patient with an unknown etiology. After about one year and several failed interventions, synbiotic therapy was performed. The diarrhea episodes ceased after three months of daily supplementation and both biochemical and nutritional parameters improved. Synbyotic therapy promoted clinical benefits in this patient. Discussion: Therefore, this simple therapy may be a promising alternative in CKD and it should be tested in larger studies.