Kidney biopsy in very elderly patients: indications, therapeutic impact and complications.

BACKGROUND: Few data is available on the risk/benefit balance of native kidney biopsy (KB) in very elderly patients. METHODS: Multicenter retrospective cohort study in the Aix-Marseille area: the results of KB and medical charts of all patients over 85 years biopsied between January 2010 and December 2018 were reviewed. RESULTS: 104 patients were included. Median age was 87 years. Indications for KB were: acute kidney injury (AKI) in 69.2% of patients, nephrotic syndrome (NS) with AKI in 13.5%, NS without AKI in 12.5%, and proteinuria in 4.8%. Median serum creatinine was 262 µmol/L, 21% of patients required dialysis at the time of KB. Significant bleeding occurred in 7 (6.7%) patients, requiring blood cell transfusion in 4 (3.8%), and radiological embolization in 1 (1%). The most frequent pathological diagnoses were: non-diabetic glomerular diseases (29.8%, including pauci-immune crescentic glomerulonephritis in 9.6%), hypertensive nephropathy (27.9%), acute interstitial nephritis (16.3%), renal involvement of hematological malignancy (8.7%), and acute tubular necrosis (6.7%). After KB, 51 (49%) patients received a specific treatment: corticosteroids (41.3%), cyclophosphamide (6.7%), rituximab (6.7%), bortezomib (3.8%), other chemotherapies (3.8%). Median overall survival was 31 months. CONCLUSIONS: KB can reveal a diagnosis with therapeutic impact even in very elderly patients. Severe bleeding was not frequent in this cohort, but KB may have not been performed in more vulnerable patients.

Hydroxychloroquine and azithromycin tolerance in haemodialysis patients during COVID-19 infection.

BACKGROUND: Haemodialysis patients are at risk of developing severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: coronavirus disease 2019 (COVID-19). In March 2020, hydroxychloroquine (HCQ) and azithromycin (AZI) were proposed as potential treatments of COVID-19, but with warnings concerning their possible toxicity. No data are available regarding the toxicity of this treatment in haemodialysis patients. METHODS: We report the use of HCQ and AZI in a cohort of COVID-19 haemodialysis patients with focus on safety concerns. RESULTS: Twenty-one patients received 200 mg HCQ thrice daily during 10 days, and AZI 500 mg on Day 1, and 250 mg on the four following days. HCQ plasma concentrations were within the recommended range (0.1-1.0 µg/mL) in all patients except one, in which maximum concentration was 1.1 µg/mL. HCQ concentration raised until the third day and remained stable thereafter. No cardiac event occurred in spite of progressive lengthening of corrected QT interval (QTc) during the treatment. One patient experienced a long QTc syndrome (QTc >500 ms) without any arrhythmia episode, although HCQ concentration was in the target range. Five (23.8%) patients experienced hypoglycaemia, a well-known HCQ side-effect. SARS-CoV-2 RNA remained detectable in nasopharyngeal swabs for a long time in haemodialysis patients (mean time 21 days). CONCLUSIONS: HCQ and AZI are safe in haemodialysis patients at these doses but can lead to long QTc syndrome and hypoglycaemia. HCQ concentrations were not correlated with side effects. We recommend monitoring of the QTc length throughout treatment, as well as glycaemia. SARS-CoV-2 could persist for longer in haemodialysis patients than in the general population.

Haemodialysis patients with diabetes eat less than those without: A plea for a permissive diet.

AIM: The main cause of malnutrition in haemodialysis patients is a spontaneous decline in energy and protein intakes. This study aims to report the dietary energy intake (DEI), dietary protein intake (DPI), and dietary micronutrient intake in a French HD population, to report factors associated with a low DPI and DEI, and to analyze if nutritional intake was correlated with nutritional status. METHODS: We conducted an observational cross-sectional study in a haemodialysis population of 87 adult patients in July 2014. Daily nutritional oral intake, handgrip strength, body composition measured by bioimpedancemetry, and biological and dialysis parameters were obtained from medical records. Statistical analyses of parameters associated with DEI and DPI were performed. RESULTS: The median age (interquartile range) of the population was 77.3 [71.1; 84.8] years, 57.5% were men, and 52.9% had diabetes mellitus. Median weight-adjusted DEI was 18.4 [15.7;22.3] kcal/kg per day (1308 [1078; 1569] kcal/day), and median weight-adjusted DPI was 0.80 [0.66; 0.96] g/kg per day (57.5 [47.1; 66.8] g/day). In multivariate analysis, weight-adjusted DEI was statistically lower in patients with diabetes (coefficient [95%CI] -3.81[-5.21;-2.41] kcal/kg per day; P = 0.01) but was not associated with the others parameters. When DEI was not adjusted for weight, diabetes was no longer associated with DEI, but female gender (-178[-259;-961] kcal/day; P = 0.03) and a higher Charlson comorbidity index (-30[-44;-15]; P = 0.04) were associated with a lower calorie intake. Results for DPI were similar except that the Charlson comorbidity index did not reach significance. CONCLUSIONS: Diabetes is an important factor associated with low dietary intake in haemodialysis patients. Restrictive regimens should be prescribed cautiously in haemodialysis patients, especially in those with diabetes.

The "Dose-Effect" Relationship Between 25-Hydroxyvitamin D and Muscle Strength in Hemodialysis Patients Favors a Normal Threshold of 30 ng/mL for Plasma 25-Hydroxyvitamin D.

OBJECTIVE: Muscle strength is weakened in maintenance hemodialysis patients. Strength is both a measure of a functional parameter and of frailty as it is independently associated with mortality. In the general population, observational studies show that plasma 25-hydroxyvitamin D (25[OH]D) is positively correlated with muscle strength and function. We analyzed the determinants of muscle strength measured by handgrip and 25(OH)D in a maintenance hemodialysis population. METHODS: In this observational cross-sectional study, data from all hemodialysis patients from our nephrology department were recorded in July 2014. Daily nutritional oral intake, handgrip strength, body composition measured by bioimpedancemetry analysis, as well as biological and dialysis parameters, were obtained from medical files. We used a linear regression model to assess nutritional, biological, and dialysis parameters as well as body composition associated with handgrip strength. RESULTS: The median age (interquartile range) of the 130 included patients was 77.3 (69.5-84.7) years, 57.7% were men, and 50.8% had diabetes mellitus. Median handgrip strength value (interquartile range) was 14.3 (10.6-22.2) kg. In univariate analyses, the factors associated with handgrip strength were age, gender, albumin, transthyretin, predialysis creatinine and urea, normalized protein nitrogen appearance, lean mass, and muscle mass measured by bioimpedancemetry analysis as well as phase angle, and 25(OH)D. In multivariate analyses, lower age, male gender, higher albumin, higher muscle mass, and 25(OH)D level ≥ 30 ng/mL were independently correlated with muscle strength measured by handgrip. CONCLUSIONS: This study found a positive correlation between plasma 25(OH)D and muscle strength measured by handgrip in hemodialysis patients. We report a "dose-effect" relationship between 25(OH)D and handgrip strength under 30 ng/mL, which is no more present above 30 ng/mL. Prospective randomized studies are needed to prove that supplementation with cholecalciferol, leading to 25(OH)D levels ≥ 30 ng/mL, improves muscle strength in hemodialysis patients.

Remission of C3 glomerulopathy with rituximab as only immunosuppressive therapy.

C3 glomerulopathy (C3GP) is a membranoproliferative glomerulonephritis without immunoglobulin deposits. Activation of the alternative pathway of the complement system is central in its pathogenesis. The presence of a C3 nephritic factor (C3Nef), or deficient factor H or I is associated with C3 GP. The treatment is not codified. Here we describe a case of a Caucasian male with a dense deposit disease (a form of C3GP) revealed by nephritic syndrome. C3Nef was present. We treated him with rituximab as the sole immunosuppressive regimen and obtained a complete remission on proteinuria. The effect was sustained at more than 2 years with only two courses of treatment and an excellent tolerance. Rituximab could be proposed as a treatment of C3GP associated with antibodies interfering with complement alternative pathway.

Comparative safety and efficiency of five percutaneous kidney biopsy approaches of native kidneys: a multicenter study.

BACKGROUND: Renal biopsy (RB) is necessary for the diagnosis, prognosis, and therapy guidance of native kidney diseases. Few studies have compared outcomes of RB procedures. We retrospectively compared the safety and efficiency of five biopsy procedures. METHODS: The number of glomeruli on light microscopy (LM) and on immunofluorescence (IF) and serious adverse events following RB performed in five nephrology units (C1-C5) were collected. C1 performed ultrasound (US) assessment before RB and used a 14-gauge core-cutting needle biopsy gun, C2 US guidance and a 14-gauge needle, C3 tomodensitometry guidance and a 14-gauge needle, C4 US guidance and a 16-gauge needle, and C5 tomodensitometry guidance and a 16-gauge needle. RESULTS: RB was performed in 943 adults between January 2006 and July 2010. Serious adverse events occurred in 1.5% of biopsies. The complication rate was not different between nephrology units. The mean number of glomeruli on biopsy was 14.2 ± 8.6 with LM and 4.4 ± 3.3 on IF. It was different according to the nephrology unit for LM (p = 0.01) and for IF (p < 0.001). The number of failed biopsies was influenced by the nephrology unit and radiological guidance technique, favoring real-time US guidance. Failed biopsies using US or tomodensitometry assessment before RB was certainly due to kidney imprecise localization since it was often non-renal tissue sampling. At least 10 glomeruli were found in 69% of biopsies on LM. This rate varied according to the nephrology unit (p = 0.004) and was higher when 14-gauge needles were used in comparison with 16-gauge needles. CONCLUSION: RB is safe regardless of the technical procedure, but radiological guidance and needle size influence the efficiency of biopsies.

Presence of specific SARS-COV2 antibodies in hemodialysis patients and their caregivers after the first wave of COVID-19.

Hemodialysis (HD) patients are at risk for severe COVID-19 and cannot comply with social distancing. SARS-COV2 seroprevalence in French patients and caregivers after the first wave of COVID-19 is unknown. SeroCOVIDial is a prospective study conducted between June and December 2020. SARS-COV2 seroprevalence was evaluated by a rapid serological test (BIOSYNEX) in HD patients and caregivers, and the presence or not of anti-SARS-COV2 neutralizing or non-neutralizing antibodies in patients was also determined by ELISA and seroneutralization. In June 2020, 451 HD patients and 238 caregivers were included. Overall SARS-COV2 seroprevalence was 8.4% (patients) and 6.7% (caregivers), and was 87.1% (patients) and 90.0% (caregivers) in participants with a previously documented SARS-COV2 infection. Overall seroprevalence reached 13.8% (patients) and 12.6% (caregivers) following the second epidemic wave. During the follow-up, 38 (8.4%) patients died (9 of COVID-19). Among the 44 (10.6%) patients who became infected, only two were seropositive at M0. The levels of anti-SARS-COV2 antibodies decreased over time in patients and caregivers. The BIOSYNEX test showed 82.9% sensitivity and 97.7% specificity. Prevalence of anti-SARS-COV2 antibodies was low in HD patients and caregivers after the first epidemic wave but rose after the second wave. A rapid serological test showed good performances and could be useful for future monitoring of anti-SARS-COV2 antibodies.

Increased expression of adenosine A2A receptors in patients with spontaneous and head-up-tilt-induced syncope.

BACKGROUND: Adenosine may play a role in the triggering of neurocardiogenic syncope, but no information on adenosine receptors is available at the present time. OBJECTIVE: The purpose of this study was to investigate whether adenosine A2A receptors expression is altered in patients with neurocardiogenic syncope. METHODS: Adenosine plasma levels (APLs), the expression of A2A receptors, were measured (mean +/- standard error of the mean) during tilt testing. Expression of receptors was assessed on mononuclear cells using a selective receptor ligand. RESULTS: At baseline, the APLs of 16 patients with a positive test were higher than those of 17 patients with a negative test and of those of a control group (2.10 +/- 0.30 vs. 0.40 +/- 0.05 and 0.41 +/- 0.06 muM, respectively; P <.0001). The number of receptors was higher in patients tested positive than in patients tested negative or in the control group (122 +/- 10 vs. 38 +/- 4 and 44 +/- 4 fmol/g of proteins, respectively; P <.0001). No difference was found in the affinity or synthesis among the three groups. CONCLUSION: This study showed an increased number and an up-regulation of adenosine A2A receptors in patients with spontaneous syncope and a positive head-up tilt, which in the context of high APLs may play a role in the recurrence of syncopal episodes.

Influence of the dialysis membrane on markers of tissue ischemia.

BACKGROUND: Hemodialysis (HD) is often accompanied by adverse effects, such as tissue ischemia. We have already observed an increase in plasma adenosine (ADO) levels during HD sessions, which may be the result of tissue ischemia. Here we evaluate the influence of the dialysis membrane on two sensitive and early markers of ischemia: ADO and ischemia-modified albumin (IMA). METHODS: We included in the study 50 patients with end-stage renal failure, 39 hemodialyzed (mean age 61+/-24 years; 24 male; membranes: 23 synthetic and 16 cellulose based) and 11 undialyzed (mean age 55+/-12 years; 6 male), and 10 healthy subjects (mean age 47+/-11 years; 4 male). We compensated for hemoconcentration during HD by measuring either the IMA to albumin (Alb) or the ADO to Alb ratio. RESULTS: Under basal conditions, the IMA to Alb ratio was not significantly different in patients and controls and HD did not significantly modify this ratio. Conversely, the ADO to Alb ratio (mean+/-SD in micromol/g) was higher in patients before HD compared with either undialyzed patients or controls (before HD: 0.077+/-0.02; undialyzed patients: 0.026+/-0.11; controls: 0.022+/-0.01). During HD, there was a significant increase in the ADO to Alb ratio (before HD: 0.077+/-0.02; after HD: 0.09+/-0.029; p<.01). We found no significant difference in the IMA to Alb or ADO to Alb ratio using either synthetic or cellulose-based membranes. CONCLUSIONS: We concluded that ADO is a more sensitive marker of ischemia than IMA and that, under our HD conditions, the ischemia caused by HD was very weak, independent of the dialysis membrane.

Relationship between A2A adenosine receptor expression and intradialytic hypotension during hemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is a common complication of hemodialysis sessions (HDSs). Adenosine may contribute to the drop in blood pressure during IDH events because it has hypotensive effects. As A(2A) adenosine receptor expression is essential for blood pressure control, we compared the expression of A(2A) receptors (Bmax, K(D), and messenger ribonucleic acid [mRNA] levels) in peripheral blood mononuclear cells from IDH and non-IDH patients and from controls. We also evaluated adenosine plasma levels (APLs). METHODS: We included 10 hemodialyzed patients with at least three IDH events per month. We also included 11 hemodialyzed patients with no history of IDH events and 10 healthy subjects as controls. RESULTS: IDH patients had higher Bmax values than non-IDH patients (mean before HDS, +86%; after HDS, +112%), whereas non-IDH patients had lower Bmax values than controls (mean -72%). K(D) values were not significantly different between patients and controls. The levels of mRNA increased significantly during HDS but without an increase in receptor expression on the cell membranes. APLs were higher in hemodialyzed patients than in controls. CONCLUSION: We found that A(2A) receptors are more expressed in IDH patients than in non-IDH patients, whereas APL was high in all patients. Both high APL and a relative increase in A(2A) receptor expression may favor IDH events.

[Fluid overload and arterial hypertension in hemodialysis patients]. / Évaluation et traitement de la surcharge hydrosodée et de l'hypertension artérielle en hémodialyse.

The water sodium overload is a factor of morbi-mortality and its treatment is one of the markers of adequacy of the hemodialysis treatment. Its first clinical assessment was improved by tools such as echocardiography and ultrasonography of the inferior vena cava, the per-dialytic curve of plasma volume, measuring BNP or proBNP and by impedancemetry. The combination of the evaluation of these parameters and of the clinical situation allows one to assess the extracellular overload, the state of the blood volume and the potential of plasma refilling. The latter is a key factor of the per-dialytic hemodynamic tolerance. It is itself a determining factor in weight can be achieved at the end of the session. Getting the "dry" weight can require modifications of the prescriptions of the hemodialysis sessions, a filling by albumin even a drugs support. Finally, the overload treatment is the central part of the treatment of arterial hypertension, which has to benefit however often from antihypertensive treatment the profit of which is demonstrated.

[Experiment of self blood pressure measurement at home in haemodialysis patients in a hospital unit]. / Expérience de l'automesure tensionnelle à domicile chez des patients hémodialysés dans une unité hospitalière.

We analyzed, by home blood pressure (BP) self-measurement and conventional predialytic measurement of BP, a cohort of haemodialysis patients in two hospital units between 2008 and 2010. All patients who already own a BP self-measurement device were included in this study. BP was recorded by the two methods for one week. The number of patients with a validated self-measurement device was 69 of 350 (21%) and 60 patients were included in analyses. These patients were divided into 23 (38%) permanent uncontrolled hypertensive (elevated BP at home and in hospital), 13 (22%) masked hypertensive (normal BP in hospital and elevated at home), eight (13%) white coat hypertensive (elevated BP in hospital and normal at home), and 16 (27%) permanent controlled normotensive (normal BP in hospital and at home). Patient compliance with all the self BP measurements was 95%. We did not find in this cohort the factors associated with masked hypertension in the general population such as being male, smoking and high body mass index. These results obtained in an in-hospital dialysis unit should be extrapolated with caution to all haemodialysis patients. However it is, to our knowledge, the first study on home BP self-measurement published in patients undergoing haemodialysis in France. A significant proportion of patients have masked hypertension. This should alert clinicians because of the poor cardiovascular prognosis associated with masked hypertension.

Influence of haemodialysis and left ventricular failure on peripheral A(2A) adenosine receptor expression.

BACKGROUND: Haemodialysis (HD) sometimes accelerates left ventricular failure (LVF). As adenosine (ADO) is strongly implicated in cardiovascular functions, particularly via A(2A) receptor activation and as changes of peripheral A(2A) receptors mirror changes occurring in the cardiovascular system, we examined the influence of HD and LVF on both ADO plasma concentration and the expression of A(2A) receptors (i.e. Bmax, K(D) and mRNA amount) of peripheral blood mononuclear cells. METHODS: This cross-sectional study included 61 chronic renal failure (CRF) patients: 41 without LVF (24 haemodialysed and 17 undialysed) and 20 with LVF (9 haemodialysed and 11 undialysed). Ten LVF patients without CRF and 10 healthy subjects were also examined. RESULTS: (i) Bmax values of CRF patients without LVF were significantly decreased in undialysed patients compared with haemodialysed patients, and compared with controls (69 +/- 25 vs 98 +/- 33 vs 180 +/- 60 fmol/mg of protein, P < 0.05). Bmax values of CRF patients with LVF were lower in undialysed patients than in haemodialysed patients (60 +/- 27 vs 101 +/- 27 fmol/mg of protein, P < 0.05). Bmax values of LVF patients without CRF were lower than in controls (51 +/- 19 vs 180 +/- 60 fmol/mg of protein). (ii) A(2A) mRNA expression was increased in haemodialysed patients compared with controls (20.2 +/- 0.75 vs 17.6 +/- 1.3, P < 0.05). (iii) ADO plasma levels were high in haemodialysed patients and further increased during the HD sessions. CONCLUSION: The number of A(2A) receptors was decreased by CRF with or without LVF. However, this decrease was less important in haemodialysed patients. The changes in peripheral A(2A) receptor expression suggest a significant inflammatory response to HD and heart or kidney failure. Whether these changes do reflect alterations in cardiomyocytes needs further investigation.