Search

Patients on maintenance hemodialysis (MHD), which are at high risk of infection by SARS-CoV-2 virus and death due to COVID-19, have been prioritized for vaccination. However, because they were excluded from pivotal studies and have weakened immune responses, it is not known whether these patients are protected after the “standard” two doses of mRNA vaccines. To answer this, anti-spike receptor binding domain (RBD) IgG and interferon gamma-producing CD4+ and CD8+ specific-T cells were measured in the circulation 10-14 days after the second injection of BNT162b2 vaccine in 106 patients receiving MHD (14 with history of COVID-19) and compared to 30 healthy volunteers (four with history of COVID-19). After vaccination, most (72/80, 90%) patients receiving MHD naïve for the virus generated at least one type of immune effector, but their response was weaker and less complete than that of healthy volunteers. In multivariate analysis, hemodialysis and immunosuppressive therapy were significantly associated with absence of both anti-RBD IgGs and anti-spike CD8+ T cells. In contrast, previous history of COVID-19 in patients receiving MHD correlated with the generation of both types of immune effectors anti-RBD IgG and anti-spike CD8+ T cells at levels similar to healthy volunteers. Patients receiving MHD naïve for SARS-Cov-2 generate mitigated immune responses after two doses of mRNA vaccine. Thus, the good response to vaccine of patients receiving MHD with a history of COVID-19 suggest that these patients may benefit from a third vaccine injection., Graphical abstract

The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication.

The level of protection achieved by the standard two doses of COVID-19 mRNA vaccines in patients receiving maintenance hemodialysis (MHD) remains unclear. To study this we used the French Renal Epidemiology and Information Network (REIN) Registry to compare the incidence and severity of 1474 cases of COVID-19 diagnosed in patients receiving MHD after none, one or two doses of vaccine. Vaccination significantly reduce COVID-19 incidence and severity but 11% of patients infected after two doses still died. Lack of vaccinal protection in patients naïve for SARS-CoV-2 could be due to defective Tfh response [38% patients with negative spike-specific CD4+ T cell interferon gamma release assay] and failure to generate viral neutralizing titers of anti-spike receptor binding domain (RBD) IgGs (63% patients with titer at or under 997 BAU/ml, defining low/no responders) after two doses of vaccine. To improve protection, a third dose of vaccine was administered to 75 patients [57 low/no responders, 18 high responders after two doses] from the ROMANOV cohort that prospectively enrolled patients receiving MHD vaccinated with BNT162b2 (Pfizer). Tolerance to the third dose was excellent. High responders to two doses did not generate more anti-RBD IgGs after three doses but had more side effects. Importantly, 31 (54%) of low/no responders to two doses reached neutralizing titers of anti-RBD IgGs after three doses. A positive interferon gamma release assay and/or suboptimal titer of anti-RBD IgGs after two doses were the only predictive variables for response to three doses in multivariate analysis. Thus, the standard scheme of vaccination insufficiently protects patients receiving MHD. Anti-RBD IgG and specific CD4+ T cell response after two doses can guide personalized administration of the third dose, which improves the humoral response of SARS-CoV-2 naïve patients receiving MHD., Graphical abstract

Wasting has been associated with increased cardiovascular and all-cause mortality in chronic kidney disease (CKD). We investigated whether serum zinc-alpha2-glycoprotein (ZAG), a potent cachectic and lipid-mobilizing factor that is increased in patients with CKD, predicts clinical outcomes in patients on chronic hemodialysis. We quantified serum ZAG at baseline in a prospective cohort of 252 patients undergoing maintenance hemodialysis. Serum ZAG concentrations were inversely associated with serum albumin, creatinine, and triglycerides and, conversely, positively associated with age. Although ZAG is strongly linked to protein energy wasting (PEW) in patients with cancer, higher ZAG concentrations were not associated with PEW in our cohort. During a mean study follow-up of 954 days, 49 patients died and 62 patients experienced a cardiovascular event. Kaplan-Meier analysis revealed a significant correlation between serum ZAG concentrations and all-cause mortality and cardiovascular events. In separate multivariable Cox regression models, serum ZAG concentrations remained significantly associated with all-cause mortality and cardiovascular events after adjustment for demographic factors (age, sex, and dialysis vintage), metabolic parameters (serum albumin, prealbumin, triglycerides, cholesterol, normalized protein catabolic rate, and body mass index), and cardiovascular risk factors (diabetes, dyslipidemia, history of cardiovascular disease, smoking, and diuretic use as a proxy of residual renal function). Thus, serum ZAG appears to be a strong and independent predictor of mortality and cardiovascular events in patients with end-stage renal disease. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.

We used high-resolution quantitative computed tomography to study the microarchitecture of bone in patients with chronic kidney disease on dialysis. We compared bone characteristics in 56 maintenance hemodialysis (21 women, 14 post-menopausal) and 23 peritoneal dialysis patients (9 women, 6 post-menopausal) to 79 healthy men and women from two cohorts matched for age, body mass index, gender, and menopausal status. All underwent dual-energy X-ray absorptiometry of the spine and hip to measure areal bone mineral density, and high-resolution peripheral quantitative computed tomography of the radius and tibia to measure volumetric bone mineral density and microarchitecture. When compared to their matched healthy controls, patients receiving hemodialysis and peritoneal dialysis had a significantly lower areal bone mineral density in the hip. Hemodialysis patients had significantly lower total, cortical, and trabecular volumetric bone mineral density at both sites. Hemodialysis patients had significantly lower trabecular volumetric bone mineral density and microarchitecture at the tibia than the peritoneal dialysis patients. Overall, peritoneal dialysis patients were less affected, their cortical thickness at the distal tibia being the only significant difference versus controls. Thus, we found more severe trabecular damage at the weight-bearing tibia in hemodialysis compared to peritoneal dialysis patients, but this latter finding needs confirmation in larger cohorts.

The incidence of malnutrition disorders in chronic kidney disease (CKD) appears unchanged over time, whereas patient-care and dialysis techniques continue to progress. Despite some evidence for cost-effective treatments, there are numerous caveats to applying these research findings on a daily care basis. There is a sustained generation of data confirming metabolic improvement when patients control their protein intake, even at early stages of CKD. A recent protein-energy wasting nomenclature allows a simpler approach to the diagnosis and causes of malnutrition. During maintenance dialysis, optimal protein and energy intakes have been recently challenged, and there is no longer an indication to control hyperphosphatemia through diet restriction. Recent measurements of energy expenditure in dialysis patients confirm very low physical activity, which affects energy requirements. Finally, inflammation, a common state during CKD, acts on both nutrient intake and catabolism, but is not a contraindication to a nutritional intervention, as patients do respond and improve their survival as well as do noninflamed patients.

The recent research findings concerning syndromes of muscle wasting, malnutrition, and inflammation in individuals with chronic kidney disease (CKD) or acute kidney injury (AKI) have led to a need for new terminology. To address this need, the International Society of Renal Nutrition and Metabolism (ISRNM) convened an expert panel to review and develop standard terminologies and definitions related to wasting, cachexia, malnutrition, and inflammation in CKD and AKI. The ISRNM expert panel recommends the term ‘protein–energy wasting’ for loss of body protein mass and fuel reserves. ‘Kidney disease wasting’ refers to the occurrence of protein–energy wasting in CKD or AKI regardless of the cause. Cachexia is a severe form of protein–energy wasting that occurs infrequently in kidney disease. Protein–energy wasting is diagnosed if three characteristics are present (low serum levels of albumin, transthyretin, or cholesterol), reduced body mass (low or reduced body or fat mass or weight loss with reduced intake of protein and energy), and reduced muscle mass (muscle wasting or sarcopenia, reduced mid-arm muscle circumference). The kidney disease wasting is divided into two main categories of CKD- and AKI-associated protein–energy wasting. Measures of chronic inflammation or other developing tests can be useful clues for the existence of protein–energy wasting but do not define protein–energy wasting. Clinical staging and potential treatment strategies for protein–energy wasting are to be developed in the future.

International audience; Dialysis patients exhibit an inverse, L- or U-shaped association between blood pressure and mortality risk, in contrast to the linear association in the general population. We prospectively studied 9333 hemodialysis patients in France, aiming to analyze associations between predialysis systolic, diastolic, and pulse pressure with all-cause mortality, cardiovascular mortality, and nonfatal cardiovascular endpoints for a median follow-up of 548 days. Blood pressure components were tested against outcomes in time-varying covariate linear and fractional polynomial Cox models. Changes throughout follow-up were analyzed with a joint model including both the time-varying covariate of sequential blood pressure and its slope over time. A U-shaped association of systolic blood pressure was found with all-cause mortality and of both systolic and diastolic blood pressure with cardiovascular mortality. There was an L-shaped association of diastolic blood pressure with all-cause mortality. The lowest hazard ratio of all-cause mortality was observed for a systolic blood pressure of 165 mm Hg, and of cardiovascular mortality for systolic/diastolic pressures of 157/90 mm Hg, substantially higher than currently recommended values for the general population. The 95% lower confidence interval was approximately 135/70 mm Hg. We found no significant correlation for either systolic, diastolic, or pulse pressure with myocardial infarction or nontraumatic amputations, but there were significant positive associations between systolic and pulse pressure with stroke (per 10-mm Hg increase: hazard ratios 1.15, 95% confidence interval 1.07 and 1.23; and 1.20, 1.11 and 1.31, respectively). Thus, whereas high pre-dialysis blood pressure is associated with stroke risk, low pre-dialysis blood pressure may be both harmful and a proxy for comorbid conditions leading to premature death.

Short daily hemodialysis rapidly improves nutritional status in hemodialysis patients.BackgroundMalnutrition is a common problem in maintenance hemodialysis patients and is associated with increased mortality and morbidity. Interventions such as oral or intravenous nutritional supplements have often failed to improve nutritional status. We studied the effect of a daily dialysis program on nutritional parameters.MethodsEight patients treated with standard hemodialysis (SHD) 4 to 5 hours three times per week were converted to daily hemodialysis (DHD) 2 to 2.5 hours six times per week. Serum albumin, prealbumin, and total cholesterol were evaluated every three months. Anthropometry and dietary evaluation were performed every six months.ResultsSerum albumin rose from 39.0 ± 2.6 to 42.0 ± 3.1 and 43.0 ± 2.6 g/L, prealbumin from 0.36 ± 0.04 to 0.41 ± 0.05 and 0.42 ± 0.1 g/L, total cholesterol from 1.7 ± 0.4 to 1.9 ± 0.4 and 1.8 ±0.3 g/L at baseline and at 6 and 12 months, respectively, after switching patients to DHD. Daily protein intake increased from 1.29 ± 0.20 g/kg/day to 1.48 ± 0.60 and 1.90 ± 0.70 (P < 0.05). These changes were accompanied by a dry body weight increase of 2.4 ± 1.6kg (P < 0.005) at month 6 and 4.2 ± 2.8kg at one year (P < 0.05). Lean body mass increased from 47.7 ± 4.9kg to 49.1 ± 5.9 (P < 0.05) and 50.5 ± 6.2 (P < 0.05).ConclusionsDaily hemodialysis appears to be a suitable method to improve nutritional status in maintenance dialysis patients.

bolic hormone that mediates most of the growth effects of ance in CAPD patients with protein-energy malnutrition. growth hormone. This study tested the hypothesis that recomrhIGF-1 administration may be an effective method for treating binant human IGF-1 (rhIGF-1) will induce an anabolic remalnutrition in maintenance dialysis patients. sponse in malnourished patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods. Six CAPD patients with protein-energy malnutrition underwent nitrogen balance studies in a clinical research Many adult patients undergoing either maintenance center for 35 days each. Throughout the study, patients were hemodialysis or chronic peritoneal dialysis show evimaintained on their same CAPD regimen prior to hospitalizadence for protein-energy malnutrition [1‐3]. The incition, and were fed a constant protein and energy intake that was similar to their diet prior to hospitalization. The first 15 dence of malnutrition in chronic peritoneal dialysis pahospital days were a baseline period; during the subsequent tients is reported to range from approximately 18 to 20-day period, patients were given subcutaneous injections of 56% [4, 5]. Many factors may engender malnutrition in rhIGF-1 (100 mg/kg/12 h), except for one patient who received maintenance peritoneal dialysis patients [6]. Inadequate 50 mg/kg/12 h for the first five days, followed by 100 mg/kg/12 intake of protein and energy is considered to be an imh for the following 15 days. Results. During the treatment with rhIGF-1, serum IGF-1 portant factor. Evidence also suggests that resistance to increased by about 100% (P 5 0.03), and nitrogen balance the anabolic effects of growth factors may contribute to became strongly positive (12.0 g/day, P 5 0.015 vs. baseline). the propensity for protein-energy malnutrition in mainThis anabolic effect was observed within hours after commenc- tenance dialysis patients. Because malnutrition is an iming the rhIGF-1 treatment and was largely caused by a 20% portant risk factor for morbidity and mortality in both decrease in peritoneal dialysate effluent nitrogen. There was a proportionate reduction in urine nitrogen and serum urea maintenance hemodialysis and chronic peritoneal dialnitrogen. This decrease in nitrogen output was sustained during ysis patients [7], this issue appears to be of considerable the entire 20 day of treatment with rhIGF-1. Serum phosphorus clinical importance. decreased significantly during the first several days of rhIGF-1 With the availability of growth factors manufactured treatment, whereas serum calcium increased significantly dur- by recombinant DNA techniques, a number of studies ing the rhIGF-1 treatment. Serum potassium and albumin did not change during the rhIGF-1 injections. There was no change have examined the nutritional effects of these comin body weight and body composition, as assessed by anthro- pounds in malnourished patients. In the past years, the pometry during the baseline or treatment phases of the study. most commonly used anabolic agent evaluated has been Some patients exhibited minor possible adverse events that recombinant growth hormone (rhGH). This hormone induces an anabolic response that has been observed in both acutely catabolic patients without renal disease and 1 The current address of Dr. Fouque is Department of Nephrology, %

Renal blood flow measurement by positron emission tomography using 15O-labeled water.BackgroundOnly few noninvasive methods have the potential to quantitate renal blood flow (RBF) in humans. Positron emission tomography (PET) is a clinical imaging method that can be used to measure the tissue blood flow noninvasively. The purpose of this study was to validate PET measurement of RBF using 15O-labeled water (H215O), a tracer that allows repeated measurements at short time intervals.MethodsRBF was measured in six pigs by PET and by radioactive microspheres (MS). Three measurements were performed in each pig at baseline (BL), during vascular expansion and dopamine infusion (DA; 20 μg · kg-1 · min-1 intravenously), and during angiotensin II (Ang II) infusion (50 ng · kg-1 · min-1 intravenously). RBF was estimated from aortic and renal tracer kinetics using a model adapted from the blood flow model described by Kety and Smith.ResultsPET and MS values correlated strongly (y = 0.79x + 42, r = 0.93, P < 0.0001) over the RBF range from 100 to 500 mL · min-1 · 100 g-1. Pharmacologically induced changes were significant and were measured equally well by PET and MS: 38 and 39%, respectively, below BL (P < 0.005 and P < 0.05) under Ang II, and 47 and 48%, respectively, above BL (P < 0.005 and P < 0.01) under DA. A Bland and Altman representation showed a low average difference of -17 ± 45 mL · min-1 · 100 g-1 (mean ± SD).ConclusionTo our knowledge, this study provides the first validation of RBF measurement by PET using H215O over a large range of RBF values (100 to 500 mL · min-1 · 100 g-1), which correspond to RBF values in both healthy subjects and in patients suffering from chronic renal failure.

Twenty-five years of experience with out-center hemodialysis. Background Out-center hemodialysis (HD) offers patients a better quality of life, a greater independence, and a better rehabilitation opportunity. A lower mortality than with other modalities of dialysis has been reported. In addition, in France the charges paid depend on the modality of dialysis, out-center HD being the less expensive, and savings are also accomplished through fewer patient transports, which are additionally reimbursed. We present a 25-year experience of out-center HD. Methods We retrospectively studied the clinical records of 471 patients treated between 1974 and 1997 in a single nonprofit organization operating regional home HD (H-HD) and facilities for self-care HD (SC-HD). Survival results were analyzed according to: ( a ) causes of end-stage renal disease, ( b ) age at the start of HD, ( c ) period of start of HD, ( d ) modality of HD (H-HD, SC-HD), and ( e ) a subgroup of 174 patients defined at risk because they were contraindicated for transplantation. Results The mean age at the start of HD increased from 31.2 ± 9.7 (mean ± SD) years in 1974 to 52.6 ± 13.5 years in 1997. Causes of the end of treatment were: ( a ) transplantation (63%), ( b ) transfer (20%), and ( c ) death (17%). The overall survival was 90% at 5 years, 77% at 10 years, 62% at 15 years, and 45% at 20 years, and, for the group at risk, 78%, 62%, 46%, and 31%, respectively. Cox proportional hazard analyses showed that risk factors were older age, diabetes, and renal vascular diseases. Conclusion If adequate choice is given, out-center HD offers a reliable and safe modality of dialysis with better survival results than survival in full-care in-center HD. In addition, out-center HD ensures a striking financial benefit as compared with the higher costs if the same patients were treated with full-care in-center HD. These modalities should be encouraged for all HD patients who are able to be treated by out-center modalities.

Pharmacokinetics of recombinant human insulin-like growth factor-1 in dialysis patients. Six maintenance hemodialysis (MHD), six continous ambulatory peritoneal dialysis (CAPD) and six normal adults underwent pharmacokinetic studies of insulin-like growth factor-1 (IGF-1). Each subject received two separate subcutaneous injections of recombinant human IGF-1 (rhIGF-1) (50 or 100 µg/kg) in random order separated by 7 to 21 days. Two different responses were observed. With the 50 µg/kg dose, serum IGF-1 levels and the pharmacokinetic parameters were not different between the three groups. With the 100 µg/kg dose, peak serum IGF-1 concentrations were significantly greater in the MHD and CAPD patients than in normals. However, by 12 to 14 hours after injection, serum IGF-1 was not different in the three groups. Although the T max , area under the curve and serum clearance of IGF-1 were similar in the three groups, the half-life and volume of distribution of rhIGF-1 was significantly decreased in both MHD and CAPD patients. These data indicate that IGF-1 pharmacokinetics are abnormal in maintenance dialysis patients.

Impaired metabolic response to recombinant insulin-like growth factor 1 in dialysis patients. The acute metabolic effects of recombinant human insulin-like growth factor-1 (rhIGF-1) were studied after an overnight fast in six maintenance hemodialysis (MHD) patients, six chronic peritoneal dialysis (PD) patients and six normal subjects. Each subject received a subcutaneous injection of rhIGF-1, 50 or 100 µg/kg body wt, given in random order on two occasions separated by 7 to 21 days. After the rhIGF-1 injection, plasma insulin, C-peptide, Cortisol, amino acids and glucose decreased. The magnitude of the decrease was greater with the larger rhIGF-1 dose. The fall in plasma insulin, C-peptide and many amino acid concentrations was less and the decrease in glucose was similar in the MHD and CAPD patients as compared to normals. With 50 µg rhIGF-1/kg, plasma insulin and C-peptide decreased more quickly and often to a greater magnitude in normal individuals. With 100 µg rhIGF-1/kg, the decrease in plasma insulin, C-peptide and amino acids in the MHD and CAPD patients was almost as frequent as in the normal subjects, but the magnitude of the fall was often significantly less. This impaired response occurred in both MHD and CAPD patients even though, with the 100 µg rhIGF-1/kg dose, their plasma IGF-1 was significantly higher than in normals during most of the first four hours after injection. These results provide the first in vivo evidence for resistance to the metabolic effects of rhIGF-1 in patients with advanced renal failure.

The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend that serum parathyroid hormone (PTH) concentration of patients with chronic kidney disease (CKD) should be measured regularly and maintained within target ranges that are defined according to the stage of CKD (e.g., 150–300 pg/ml in patients with CKD stage 5). The quality of the PTH assay is of paramount importance, as it contributes to the therapeutic decision. Indeed, when the PTH concentration is above these target values, drugs that decrease PTH secretion, such as active vitamin D compounds or calcimimetic agents, may be given and the doses are then adapted according to the evolution of the PTH concentration. By contrast, if the PTH concentration is below the target range, any treatment that may decrease PTH secretion is stopped to avoid adynamic bone disease and associated extra-skeletal calcifications. The aim of this article is to discuss the main features and pitfalls related to PTH measurement in the setting of CKD.

Acute leptin regulation in end-stage renal failure: The role of growth hormone and IGF-1. Background Leptin, a recently discovered peptide involved in nutrient intake and energy expenditure, has been shown to be abnormally regulated in certain conditions such as obesity. In chronic renal failure, leptin appears to be increased. However, little is known about leptin regulation during chronic renal failure (CRF). Methods We measured serum leptin in eight well nourished, chronic hemodialysis patients (seven males, one female) receiving anabolic factors for three days as either recombinant insulin-like growth factor-1 (rhIGF-1) or a combination of recombinant growth hormone (rhGH) plus recombinant IGF-1, in a random cross-over trial. Results Serum leptin values were in the range of normal volunteers matched for body mass index. As reported in other conditions, serum leptin was strongly correlated with patients dry body wt ( P = 0.01) and body fat ( P = 0.0001). Both treatments affected serum leptin in a rapid and opposite manner. RhIGF-1 decreased serum leptin from 11.2 ± 20.8 (sd) to 4.3 ± 3.8 μg/liter ( P = 0.011), whereas the combination of rhGH + rhIGF-1 increased serum leptin from 7.4 ± 9.4 to 21.0 ± 32.9 μg/liter ( P = 0.011). Regression analyses indicated a linear regression between serum leptin and insulin variations after treatment. Conclusions This study shows for the first time that both rhIGF-1 and rhGH acutely regulate serum leptin in dialysis patients. Whether leptin changes are explained by the concomitant insulin variation should be further studied under renal failure conditions.