Allograft function and muscle mass evolution after kidney transplantation.

BACKGROUND: Advanced chronic kidney disease is associated with muscle wasting, but how glomerular filtration rate (GFR) recovery after kidney transplantation is associated with muscle mass is unknown. METHODS: We took advantage of the simultaneous measurement of GFR (using iohexol plasma clearance; ioGFR) and creatinine excretion rate (a surrogate marker of muscle mass; CER) performed 3 months after transplantation and at a later time point at our institution to investigate the interplay between allograft function, muscle mass, and outcome in kidney transplant recipients. RESULTS: Between June 2005 and October 2019, 1319 successive kidney transplant recipients (mean age 50.4 ± 14.6; 38.7% female) underwent GFR measurement at our institution 3 months after kidney transplantation. CER (CER3 ) and ioGFR (ioGFR3 ) were 7.7 ± 2.6 µmol/min and 53 ± 17.1 mL/min/1.73 m2 , respectively. Multivariable analysis identified female gender, older donor and recipient age, reduced body mass index, coronary disease, dialysis history, proteinuria, and reduced ioGFR3 as independent predictors of low CER3 (ioGFR3 : ß coefficient 0.19 [95% confidence interval 0.14 to 0.24]). A total of 1165 patients had a subsequent CER measurement after a median follow-up of 9.5 months. Of them, 373 (32%) experienced an increase in CER > 10%, while 222 (19%) showed a CER decrease of more than 10%. Multivariable analysis adjusted for CER3 and other confounders identified ioGFR3 as an independent predictor of CER at follow-up (ß coefficient 0.11 [95% confidence interval 0.07 to 0.16]). In multivariable Cox analysis, reduced CER at 3 months or at follow-up were consistently associated with mortality (hazard ratio [95% confidence interval] at 3 months: 0.82 [0.74 to 0.91]; at follow-up: 0.79 [0.69 to 0.99]) but not with graft loss. CONCLUSIONS: Glomerular filtration rate recovery is a determinant of muscle mass variation after kidney transplantation. Early interventions targeting muscle mass gain may be beneficial for kidney transplant recipients.

Dialysis monitor and low-cost haemodialysis / Générateur de dialyse et hémodialyse à bas coût.

An experimental model of a hemodialysis monitor has been developed to perform ultrafiltration control, and urea and creatinine clearance tests. This model allowed us to develop an original device that separates the used dialysate from fresh dialysate and to define the characteristics of an industrial prototype which ultimate objective is to reduce the costs of haemodialysis treatment in low and middle-income countries.

Acetate-free bicarbonate dialysate: Which acid in the dialysis buffer? / Nouveaux dialysats : quel acide dans le bain de dialyse ?

The mix of bicarbonate and divalent cations requires a small amount of acid to avoid insoluble precipitation in the dialysate buffer. Small doses of acetic acid (3­7 mmol/L) are commonly used. Acetic acid may be replaced by hydrochloric acid or citric acid to achieve acetate-free haemodialysis. Hydrochloric acid theoretically avoids metabolic side effects of acetate. However, additional cost generated by technical constraints probably slowed its generalization. Citric acid has been proposed as a more biocompatible acidifier than acetic acid. By binding calcium, citric acid inhibits both coagulation and complement activation and may reduce the treatment-induced inflammatory response. However, results of the study are conflicting, especially regarding impact on calcium and phosphate metabolism and acid-base metabolism. On the basis of current findings, systematic replacement of acetic acid by citric acid cannot be proposed for all the patients.

Course of chronic kidney disease in French patients.

BACKGROUND: In 1998, a French survey showed that the referral of patients with chronic kidney disease to a nephrologist was delayed, resulting in many emergency initiations of dialysis. In 2009, the ORACLE study aimed to describe the renal course of dialysis patients from their first nephrology visit to their first dialysis session. METHODS: The ORACLE study was a multicentre retrospective study of all patients who started chronic dialysis. Data were collected at the first nephrology visit and at the first dialysis session. RESULTS: In total, 720 patients were included (69 centres). At the first nephrology visit, the mean Cockcroft-Gault (CG) indicator was 31.8 mL/min (22.7 in 1998) and 52.4% of patients (73% in 1998) had a CG <30. The mean time between the first nephrology visit and the first dialysis session was 48 months (35 months in 1998). CONCLUSION: In 2009, most patients were referred a long time before dialysis initiation, which likely allowed them to benefit from the impact of nephrology care on early outcomes when on dialysis. However, 34.2% of the dialysis sessions were still initiated under emergency conditions.

Hemodialysis without systemic anticoagulation: a prospective randomized trial to evaluate 3 strategies in patients at risk of bleeding.

OBJECTIVE: In this clinical trial, we aimed to compare three means of performing chronic hemodialysis in patients with contra-indication to systemic heparinization. METHODS: This open-label monocentric randomized « n-of-one ¼ trial, conducted in a single tertiary care center, recruited chronic hemodialysis patients with a contra-indication to systemic heparinization for at least 3 consecutive sessions. All patients underwent hemodialysis with an AN69ST dialyzer, and were administered three alternative dialysis procedures in a random sequence: intermittent saline flushes, constant saline infusion, or pre-dialysis heparin coating of the membrane. The primary outcome was the need to interrupt the dialysis session because of clotting events due to either (i) a complete coagulation of the circuit; (ii) a partial coagulation of the circuit; (iii) a>50% rise over baseline in the venous pressure. RESULTS: At the end of the inclusion period (May, 2007 to December, 2008), the number of patients to include (n=75) was not reached: only 46 patients were included and underwent randomization. The study was terminated, and statistical analysis took into account 224 hemodialysis sessions performed in 44 patients with analyzable data. Heparin adsorption was associated with a significant reduction of the need to interrupt the dialysis session because of clotting events: odds ratio 0.3 (CI 95% 0.2 to 0.6; p<0.001, versus intermittent saline flushes). Heparin adsorption was also associated with higher odds for performing >3 h dialysis sessions and for having complete blood restitution. There were no significant effects of the dialysis procedure on weight loss, online ionic dialysance, and adverse events. CONCLUSION: Heparin-coated AN69ST dialysis membrane is a safe and effective method to avoid or delay per-dialytic clotting events in patients with contra-indication to systemic anticoagulation. However, results are not generalizable safely to patients with active bleeding, since weak heparinemia, not assessed in this study, may occur. TRIAL REGISTRATION: ClinicalTrials.gov NCT00473109.

[Prepare: cross-sectional study on management of chronic kidney disease by nephrologists before dialysis in France]. / PREPARE - étude transversale observationnelle sur la prise en charge de l'insuffisance rénale chronique en néphrologie avant le stade d'épuration extrarénale en France.

There are few epidemiologic data on Chronic Kidney Disease management before replacement therapy. The two objectives of the PREPARE study were (1) to describe the characteristics of these patients and accordance to clinical practice guidelines (2) to study nephrologists preference for renal replacement therapy in case of progression to end stage renal disease. PREPARE is a non-interventional cross-sectional study. All the French nephrologists had been solicited to collect information about CKD outpatients not on dialysis, not transplanted, with glomerular filtration rate lower than 60mL/min/1,73m(2), followed on any day between 23 and 27 November 2009. Three hundred and eight investigators included 2089 patients, 59% of them were male, they were on average 69 years old, 15, 37 and 48% had respectively a CKD stage V, stage IV and stage III, the nephropathy was the most often (43%) vascular. The most frequently reported cardiovascular risk factors were hypertension (88%), hypercholesterolemia (53%), diabetes (37%). The average time between diagnosis of nephropathy and the first nephrology consultation was too long 1,5 years. The implementation measures of nephroprotection and treatment of complications of CKD were generally satisfactory. However, preparation for replacement therapy was often too late, haemodialysis was more likely scheduled instead of peritoneal dialysis and without preparation for renal transplantation. PREPARE can therefore highlight the qualities of the current management of CKD by nephrologists in France. Nevertheless, PREPARE also shows weaknesses in preparation for replacement therapy. One can suggest that they could be reduced by systematic access of patients with risk of progression to stage V, as soon as the stage IV, to structured multidisciplinary care.

Calcium balance in haemodialysis--do not lower the dialysate calcium concentration too much (con part).

The debate on the most adequate dialysate calcium concentration for intermittent haemodialysis therapy is ongoing. There is probably no one optimal concentration. In general, one would like to maintain a neutral calcium balance in adult haemodialysis patients. However, a slightly negative balance may be preferable to avoid soft-tissue calcium accumulation in face of net calcium loss from the bone with ageing. The problem with measurements of calcium balance is that they are generally imprecise, as are estimations of total body calcium and its distribution in various compartments, unless done with labour-intensive methods and great care. The choice of the dialysate calcium will depend on several factors, including parathyroid and vitamin D status, type and severity of concomitant bone disease, presence or absence of arterial calcification, dietary habits, drug treatment and dialysis modality. Ideally the dialysate calcium would be adapted to each patient's needs. This is not feasible, however, in most dialysis settings and neither is it cost-effective. From a practical point of view, a relatively high dialysate calcium concentration in the range of of 1.50-1.75 mmol/L (3.0-3.5 mEq/L) should probably be preferred in haemodialysis patients with high serum PTH levels who are not prescribed calcium-based phosphate binders or high doses of active vitamin D sterols, and in those who are receiving a calcimimetic. In those who are treated with high doses of calcium-based binders and/or active vitamin D derivatives or who have a very low serum PTH level, the optimal dialysate calcium concentration is probably lower, in the range of 1.25-1.50 mmol/L (2.50-3.0 mEq/L). In the present pro/con debate about the optimal dialysate calcium concentration used for the haemodialysis session, we have accepted to defend the viewpoint that a low calcium concentration may do more harm than benefit in many patients. This viewpoint is opposite to that taken by Gotch. He argues that since calcitriol and other active vitamin D derivatives have become available virtually all haemodialysis patients are in positive calcium balance. We would like to take issue with this statement and warn against the indiscriminate use of a low calcium dialysate in all patients receiving haemodialysis therapy.

[Disturbances of mineral metabolism in a French hemodialysis unit]. / Les anomalies du métabolisme phosphocalcique dans un service d'hémodialyse associatif : DOPPS et recommandations NKF-K/DOQI.

Recent data from DOPPS in the field of the mineral metabolism showed that there is a relative homogeneity between most of the countries and continents studied. In reference to the American recommendations (NKF-K/DOQI 2003) the majority of the patients are apart from the desired targets. Approximately 70% of the patients have a relative biological hypoparathyroidism (PTHi<150 pg/ml) or a hyperparathyroidism (PTHi > 300 pg/ml). Only 4.7-5.5% of the patients are in the standard targets, for the four criteria which are: the calcemia, the phosphatemia, serum calcium-phosphorus product and PTH. Many open questions remained to explain why such an overall homogeneity, and why there is such an important inadequacy with the recommendations. In the present work we compared the data of our hemodialysis patients with data from DOPPS I and DOPPS II.

AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: a potential target for N-acetylcysteine treatment in dialysis patients.

UNLABELLED: AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: A potential target forN-acetylcysteine treatment in dialysis patients. BACKGROUND: Oxidative stress largely contributes to hemodialysis-associated lethal complications, thus explaining the urgent need of antioxidant-based therapeutic strategies in hemodialysis patients. We previously identified advanced oxidation protein products (AOPP) in the uremic plasma as exquisite markers of oxidative stress and potent mediators of monocyte activation. The present study was aimed at searching whether (1) AOPP can also trigger activation of polymorphonuclear neutrophils (PMN), and (2) whether AOPP-induced activation could be inhibited by N-acetylcysteine (NAC), a widely used compound which has been shown to prevent oxidative injury to kidney. METHODS: Both human serum albumin (HAS) AOPP (i.e., HOCl-modified HSA in vitro preparations and AOPP extracted from plasma of hemodialysis patients) were tested for their capacity to trigger phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase (MPO)-dependent activities as measured by lucigenin- and luminol-amplified chemiluminescence (CL), respectively, as compared to receptor-dependent [opsonized zymosan or receptor-independent phorbol myristate acetate (PMA)]. The effect of PMN priming by platelet-activating factor (PAF), and the effect of NAC on normal monocyte and on normal or hemodialysis patient's (N = 16) PMN oxidative responses were compared. RESULTS: HSA-AOPP triggered in a HOCl dose-dependent manner both NADPH-oxidase- and MPO-dependent CL of PMN. This latter was further enhanced by PAF priming. Plasma-derived AOPP obtained from hemodialysis patients also triggered PMN respiratory burst. NAC significantly reduced HSA-AOPP-mediated responses of normal monocyte and of normal and uremic PMN but had no significant effect on opsonized zymosan- or PMA-induced CL responses. CONCLUSION: This dual potential of NAC to inhibit phagocyte oxidative responses induced by HSA-AOPP without affecting those mediated by compounds mimicking pathogens supports the proposal of a therapeutic trial with NAC aimed at reducing oxidative stress-related inflammation in hemodialysis patients.

Octogenarians reaching end-stage renal disease: cohort study of decision-making and clinical outcomes.

The fate of octogenarians reaching end-stage renal disease (ESRD) is poorly defined, and implicit dialysis rationing may be practiced in this age group. The main objectives of this study were to analyze the characteristics of pre-ESRD octogenarians offered dialysis or not and to identify factors influencing mortality while on dialysis, to improve prognosis assessment and decision-making. In this single-center cohort, 146 consecutive pre-ESRD octogenarians were referred to a nephrology unit over a 12-yr period (1989 to 2000). Main outcome measures were baseline characteristics of patients offered dialysis and conservative therapy and overall and 1-yr survival according to effective treatment. A therapeutic decision was made for 144 patients. Octogenarians who were not proposed dialysis (n = 37) differed from those who were proposed dialysis (n = 107) mainly in terms of social isolation (43.3% versus 14.7%; P = 0.03), late nephrologic referral (51.4% versus 28.9%; P = 0.01), Karnofsky score (55 +/- 18 versus 63 +/- 20; P = 0.03), and diabetic status (22.2% versus 6.5%, P = 0.008). Six patients refused the dialysis proposal. During the 12-yr observation period, 99 patients died (68.7%). Median survival was 28.9 mo (95% CI, 24 to 38) in patients undergoing dialysis, compared with 8.9 mo (95% CI, 4 to 10) in patients treated conservatively (P < 0.0001). In multivariable piecewise Cox analysis, independent predictors of death within 1 yr on dialysis were poor nutritional status, late referral, and functional dependence. Included in a survivor function, these covariates predict groups with low and high 1-yr mortality risk. Beyond 1 yr on dialysis, the only independent predictor of death was the presence of peripheral vascular disease. It is concluded that beside a patient's individual refusal, late referral, social isolation, low functional capacity, and diabetes may have oriented medical decision toward withholding dialysis in a significant proportion of pre-ESRD octogenarians. Although most patients on dialysis experienced a substantial prolongation of life, identification of mortality predictors in this age group should improve the process of decision-making regarding the expected benefit of renal replacement therapy.