Humoral Response to the Third Dose of BNT162b2 COVID-19 Vaccine among Hemodialysis Patients.

BACKGROUND: Hemodialysis patients are at high risk for severe COVID-19 disease. Despite a high early seropositivity rate, dialysis patients mount a dampened immune response following two doses of an mRNA vaccine. This study aimed to evaluate the serologic response to a booster dose of BNT162b2 vaccine, 6 months after the second dose, among hemodialysis patients. METHODS: This prospective study included 80 hemodialysis patients and 56 healthcare workers serving as controls. Serologic samples were evaluated before and ∼3 weeks after the third vaccine dose. The primary outcomes were the seropositivity rate and the log-transformed anti-SARS-COV-2 S1 (RBD) IgG as a continuous variable after the third dose. Secondary outcomes were the proportion of participants with "high response," defined as antibody levels >1,000 AU/mL, and "robust response," defined as antibody levels >4,160 AU/mL, according to prespecified cutoff values associated with neutralizing antibodies. Univariate and multivariate analyses were conducted to identify predictors of antibody response. RESULTS: Among 80 hemodialysis patients, seropositivity rates improved from 78% (62/80) before the third dose, up to 96% (77/80) after the booster dose. The S1-RBD log-transformed antibody level increased significantly following the third dose from 2.15 ± 0.75 to 3.99 ± 0.83 compared with 2.65 ± 0.4 to 4.31 ± 0.42 in the control group. Among the hemodialysis patients, 88% (70/80) became "high responders" (>1,000 AU/mL), and of these, 79% (63/80) mounted a "robust response" (>4,160 AU/mL). Baseline antibody level, dialysis therapy, and hypoalbuminemia were independent predictors of impaired antibody response. CONCLUSIONS: A third dose of BNT162b2 COVID-19 vaccine, 6 months after the standard two-dose vaccination regimen, substantially improved humoral response in hemodialysis patients.

Occlusive Mesenteric Ischemia in Chronic Dialysis Patients.

BACKGROUND: Among dialysis patients, occlusive mesenteric vascular disease has rarely been reported. OBJECTIVES: To report on the experience of one center with regard to diagnosing and treating this complication. METHODS: The retrospective case-series involved six patients (3 females, 3 males; age 52-88 years; 5/6 were smokers) on chronic hemodialysis at a single center. All patients with symptoms suggestive of occlusive mesenteric disease and a subsequent angiographic intervention were included. Demographic, clinical, and laboratory data were collected from patient charts for the period before and after angioplasty and stenting of the mesenteric vessels. A Wilcoxon signed-rank test was used to compare the relevant data before and after the intervention. RESULTS: All participants had variable co-morbidities and postprandial abdominal pain, food aversion, and weight loss. CT angiography was limited due to heavy vascular calcifications. All underwent angioplasty with stenting of the superior mesenteric artery (4 patients) or the celiac artery (2 patients). All procedures were successful in resolving abdominal pain, malnutrition, and inflammation. Weight loss before was 15 ± 2 kg and weight gain after was 6 ± 2 kg. C-reactive protein decreased from 13.4 ± 5.2 mg/dl to 2.2 ± 0.4 mg/dl (P < 0.05). Serum albumin increased from 3.0 ± 0.2 g/dl to 3.9 ± 0.1 g/dl (P < 0.05). Two patients underwent a repeat procedure (4 years, 5 months, respectively). Follow-up ranged from 0.5-7 years. CONCLUSIONS: Occlusive mesenteric ischemia occurs among dialysis patients. The diagnosis requires a high degree of suspicion, and it is manageable by angiography and stenting of the most involved mesenteric artery.

Cessation of Bezafibrate in patients with chronic kidney disease improves renal function.

Bezafibrate (BzF) is eliminated by renal excretion and dosage must be reduced in patients with chronic kidney disease (CKD). There is a concern that BzF causes a further deterioration in renal function in patients with CKD. This study assessed whether BzF discontinuation or dose reduction in CKD patients improves renal function. 117 CKD patients treated with BzF between 2009 and 2014 were studied for demographics, comorbid conditions and laboratory variables. Data compared 2 groups: an intervention group of 64 patients where recommendations regarding BzF administration was implemented and a control group of 37 patients. Follow-up was maintained for 12 months. In the intervention group, estimated glomerular filtration rate (eGFR) increased from 38 to 42 mL/min/1.73 m2 (p = 0.01); blood urea levels decreased from 81 to 77 mg/dL (p = 0.04). Serum creatinine decreased by more than 0.2 mg/dL in 45% of the intervention group, as compared to 19% of the control group (p < 0.01). Improvement in eGFR was seen exclusively in patients who stopped BzF completely (eGFR increased from 38 to 44 mL/min/1.73 m2). In the intervention group, TG level increased from 183 to 220 mg/dL (p < 0.001). BzF cessation in approximately 50% of patients with CKD was associated with an increase in eGFR.

The Quandary of Oral Anticoagulation in Patients With Atrial Fibrillation and Chronic Kidney Disease.

Compared to patients with normal renal function, the prevalence of atrial fibrillation (AF) in chronic kidney disease (CKD) is increased, as is consequently the stroke prevalence in these patients. This increased risk of stroke in patients with CKD is caused not only by the increased prevalence of AF, but also by associated co-morbidities, and inherent platelet and vascular dysfunction. Paradoxically, imbalance in the same factors also increases the bleeding risk, imposing a dilemma as to whether anticoagulation should be prescribed or deferred, particularly in patients with end-stage renal disease (ESRD), in whom the bleeding diathesis and thromboembolic predisposition are most recalcitrant. Unfortunately, it is in this vulnerable population, in whom therapeutic options are most limited, that evidence-based studies relating to stroke prophylaxis are scarce, discordant and based only on registry observations. Pending randomized controlled studies on this issue, we will review important epidemiologic data and major recent registry-based studies that the clinician has to weigh when making the best decision on the issue of the prophylactic use of warfarin in patients with CKD with AF, focusing on patients with end-stage renal disease.

An intradialytic increase in serum interleukin-6 levels is associated with an increased mortality in hemodialysis patients.

BACKGROUND: The inflammatory marker interleukin-6 (IL-6) increases early in the inflammatory cascade. The aim of this study was to evaluate whether an increase in serum IL-6 levels during a hemodialysis (HD) session is associated with mortality. METHODS: 57 adult patients treated with HD for more than 1 month were prospectively studied over a 3-year follow-up period. Demographic and clinical data were collected and blood samples were drawn before and after a midweek HD session. Events of death and censoring were recorded. RESULTS: During the 3-year follow-up, 50.8% of the patients died. In univariate Cox regression analysis, an increase in IL-6 levels during HD was associated with an increased mortality (HR 1.41 per pg/ml; 95% CI 1.06 to 1.88; P = .017). In multivariate Cox models, the only independent predictors of all-cause mortality were: an increase in IL-6 levels during dialysis (HR 1.46 per pg/ml; 95% CI 1.08 to 1.98; P = .014), higher baseline C-reactive protein (CRP) levels and older age. When predictors of an increase in serum IL-6 levels during HD were introduced into the model, mortality was still significantly associated with IL-6 elevation during dialysis (HR 1.47 per pg/ml, 95% CI 1.01 to 2.14; P = .045). CONCLUSIONS: A rise in serum IL-6 levels during a single HD session is associated with a higher mortality among HD patients, independent of predialysis CRP or IL-6 levels. The results may imply the presence of an intradialytic inflammatory response that affects survival in HD patients.

The very old on hemodialysis: 8 years' experience in a single unit.

BACKGROUND: Elderly patients constitute a significant proportion of chronically dialyzed patients. This study evaluated mortality rates and predictors of mortality among very old patients receiving chronic hemodialysis (HDx). METHODS: A single-center retrospective analysis was carried out on patients >84 years of age who started chronic dialysis between 2004 and 2012. Univariate and multivariate analyses determined which parameters predicted survival. RESULTS: Twenty-nine hemodialyzed patients (19 males) were studied. Mean age was 88 ± 3 years. Median survival time was 38 months (range 4-96). One-year and 2-year survival probability was 80 and 65%, respectively. The most common cause of death was complicated peripheral vascular disease. Multivariate analysis revealed the following: for each 1 g/dl decrease in serum albumin level, the hazard ratio for patient death was 2.63 (p = 0.017), and for each weekly HDx treatment time decrease of 1 h, the hazard ratio for patient death was 1.40 (p = 0.006). CONCLUSION: Very elderly patients can be hemodialyzed with cautious optimism.

Regression of left ventricular hypertrophy in patients with primary aldosteronism/low-renin hypertension on low-dose spironolactone.

BACKGROUND: The incidence of left ventricular hypertrophy (LVH) in primary aldosteronism (PA) is higher than in essential hypertension. LVH is an independent cardiovascular risk factor. Treatment of PA with mineralocorticoid receptor blockers (MRBs) improves LVH. Previous studies included relatively small groups, low incidence of LVH and used high MRB dose. We tested the hypothesis that long-term regression of LVH in PA/low-renin hypertension may be achieved with low-dose MRB. METHODS: Forty-eight patients (male/female 28/20, age 61.4 years, range 47-84) had PA (low renin, high aldosterone and high aldosterone/renin ratio, n=24) or low-renin hypertension (low renin, normal aldosterone and high aldosterone/renin ratio, n=24). All had either LVH or concentric remodelling. All had an echocardiogram both at baseline and at 1 year after the initiation of spironolactone. A subgroup of 29 patients had an echocardiogram at baseline, 1 year (range 0.5-1.5) and 3 years (range 1.8-7). RESULTS: At baseline, spironolactone was commenced in all patients. The dose was 33.3±13.7 and 29.0±11.7 mg/day at 1 year and 3 years, respectively. A total of 73% of the patients received ≤37.5 mg/day. Introduction of spironolactone enabled the reduction of other antihypertensive medications (from 2.6±1.2 to 1.5±1.0 at 1 year). At 1 year, systolic and diastolic blood pressure decreased (149.3±14.1 to 126.2±12.0 mmHg, P<0.001, and 88.2±9.8 to 78.3±7.1 mmHg, P<0.001, respectively). At baseline, LVH was present in 39 of the 48 (81%) patients, and concentric remodelling, i.e. increased relative wall thickness (RWT) with a normal left ventricular mass index (LVMI), in 36 (75%). At 1 year, LVMI decreased in 44 of the 48 (92%) patients (142.9±25.4 versus 117.7±20.4 g/m2, P<0.001). LVH normalized in 16 of the 39 (41%) patients. RWT normalized in 36% of the patients. The changes in blood pressure and LVMI did not correlate. At 3 years, LVH decreased further and normalized in 57% of the patients. CONCLUSIONS: In patients with PA/low-renin hypertension, long-term regression of LVH may be achieved with low-dose MRB.

Changes in inflammatory markers during a hemodialysis session and their relation to vascular access type.

PURPOSE: In an attempt to better understand the relationship between vascular access and inflammation we assessed the effect of vascular access on inflammatory markers changes during hemodialysis (HD) session. METHODS: Fifty HD patients were included: 23 patients with central venous catheters (CVC) and 27 patients with arteriovenous fistulas (AVF). Blood samples for high sensitivity C-reactive protein (hsCRP), Interleukin 6 (IL-6), and Tumor Necrosis Factor α (TNF α) were collected before and after HD session. The outcome was the change in the inflammatory markers during the dialysis. RESULTS: Predialysis hsCRP levels were high in 70% of patients, without differences between the groups. Predialysis values were also similar in the two groups for IL-6 and TNF α. There was no increase in hsCRP values following HD and no difference between the change from baseline values in the CVC and AVF groups (-0.01±0.09 mg/dL and -0.01±0.13 mg/dL, respectively [P=.95]). IL-6 values increased during the HD session in the AVF group and non-significantly decreased in the CVC group. The change from baseline values was statistically significantly greater in the AVF group compared to the CVC group (0.76±1.44 ng/mL and -0.52±1.66 ng/mL, respectively, P=.006). TNF α values were significantly decreased in the CVC group and were not changed in the AVF group. The decrease from baseline values was not different between the groups. CONCLUSIONS: Chronic inflammation is present in most HD patients. No increase in pro-inflammatory parameters was seen after a HD session in patients treated via CVC or AVF.

Fatalities and severe metabolic disorders associated with the use of sodium phosphate enemas: a single center's experience.

We report our experience with severe complications of sodium phosphate enemas. Eleven elderly patients received Fleet enemas for constipation. Three patients received 500 to 798 mL, and 8 received a standard 250-mL dose. Most presented within 24 hours with hypotension and volume depletion, extreme hyperphosphatemia (phosphorus level, 5.3-45.0 mg/dL), and severe hypocalcemia (calcium level, 2.0-8.7 mg/dL). Hypernatremia and hypokalemia were seen in most patients. Acute renal failure was present in all patients. Two patients required urgent hemodialysis. Five patients died (45%). One patient was autopsied. Calcium-phosphate deposition within the renal tubular lumens was found. Following an educational campaign, the use of Fleet enemas was reduced in our hospital by 96%. Sodium phosphate enemas, even in standard doses, may lead to severe metabolic disorders associated with a high mortality and morbidity. Their use should be limited to low-risk patients only.

Lanthanum, constipation, bafflying X-rays and a perforated colonic diverticulum.

Lanthanum carbonate (LC) is used as a phosphate binder in dialysed patients. Abdominal pain and constipation are known side effects of its use. Furthermore, in radiological studies, LC tablets are seen as intense radio-opaque deposits within the entire gastrointestinal tract-findings which can lead to diagnostic misinterpretations. An elderly patient on peritoneal dialysis and taking LC presented with peritonitis, secondary to a perforated colonic diverticulum. The possible association between the use of LC, worsening constipation and complications arising from colonic diverticular disease, are discussed.

Inhibition of mitochondrial function reduces DNA repair in human mononuclear cells.

BACKGROUND: Mitochondria provide ATP and Ca(2+) needed for DNA repair, but also produce reactive oxygen species (ROS), which may damage DNA. AIM: To investigate the effect of mitochondrial function inhibition on DNA repair. METHOD: Five mitochondrial inhibitors acting at various sites of electron transport were studied. Human peripheral blood mononuclear cells, spontaneous and H(2)O(2)-induced DNA repair, as well as %-double-stranded-DNA, were measured. RESULTS: All mitochondrial inhibitors suppressed spontaneous and H(2)O(2)-induced DNA repair. However, their effect on %-double-stranded-DNA differed, which is partly related to ROS suppression. CONCLUSION: Mitochondrial inhibition may enhance efficacy and reduce toxicity of radiation and cytotoxic drugs therapy.

Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta-analysis.

BACKGROUND: In patients with euvolemic and hypervolemic hyponatremia, the effect of vasopressin antagonists is yet undefined. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING & POPULATION: In- and outpatients with euvolemic or hypervolemic hyponatremia. SELECTION CRITERIA FOR STUDIES: We included all RCTs regardless of publication status or language. INTERVENTION: Vasopressin antagonists with or without fluid restriction versus placebo or no treatment with or without fluid restriction. OUTCOMES: Response rate defined as normalization of serum sodium level or significant increase in serum sodium level at 3-7 days (primary) and later, change from baseline serum sodium level at 3-7 days and later, adverse events, rate of rapid sodium level correction, and rate of hypernatremia. RESULTS: 15 RCTs were identified. Vasopressin antagonist treatment significantly increased response rate both early (RR, 3.15; 95% CI, 2.27-4.37; 11 trials) and late (RR, 2.27; 95% CI, 1.79-2.89; 4 trials). Response rates were high in trials assessing mostly euvolemic patients and those assessing mostly hypervolemic patients, with greater effect estimate in the former. Change from baseline serum sodium level was significantly increased both early (weighted mean difference, 5.27 mEq/L; 95% CI, 4.27-6.26, 13 trials) and late (weighted mean difference, 3.49 mEq/L; 95% CI, 2.56-4.41, 8 trials). Although there was an increased rate of rapid sodium correction (RR, 2.52; 95% CI, 1.26-5.08, 8 trials) with vasopressin antagonists, hypernatremia rates were not significantly higher (RR, 2.21; 95% CI, 0.61-7.96; 5 trials), adverse events were not increased, and there were no reports of osmotic demyelination syndrome. LIMITATIONS: Significant heterogeneity in the primary outcome. CONCLUSIONS: Vasopressin antagonists are effective for the treatment of hypervolemic and euvolemic hyponatremia.

Retrospective comparison of mechanical percutaneous thrombectomy of hemodialysis arteriovenous grafts with the Arrow-Trerotola device and the lyse and wait technique.

OBJECTIVE: The purpose of our study was to determine whether pharmacologic thrombolysis with urokinase in the lyse and wait (L&W) technique compared with mechanical declotting using the Arrow-Trerotola percutaneous thrombectomy device is more efficient, safer, or less expensive in treating thrombosed hemodialysis grafts. MATERIALS AND METHODS: The files of 157 patients who underwent arteriovenous graft declotting from 2000 to 2007 at one tertiary care center were reviewed. The study group included 83 women and 74 men with a mean age of 68 +/- 12 years (range, 27-95 years). A total of 563 procedures were performed: 427 with the L&W technique and 136 with mechanical percutaneous thrombectomy using the percutaneous thrombectomy device. The two types of procedures were compared for success rate, complications, average patency time, and cost. RESULTS: There were no statistically significant differences between the pharmacologic and mechanical procedures in immediate success rate (99% and 98%, respectively) or average patency time (5.44 months and 5.40 months, respectively). The L&W technique was considerably less expensive. CONCLUSION: Given its lower cost and equal efficacy and safety, L&W appears to be preferable to mechanical thrombolysis with a percutaneous thrombectomy device for initial arteriovenous hemodialysis graft declotting.

Effects of histone deacetylase inhibitors on rat mesangial cells.

Glomerular mesangial cells (MCs) proliferate and produce extracellular matrix proteins in many progressive renal diseases. Recently, histone deacetylase inhibitors (HDIs) were shown to have antiproliferative and antifibrogenic effects in some in vitro and in vivo models. Using the [(3)H]-thymidine incorporation test, we have found that the HDI trichostatin A (TSA) effectively inhibits MC growth at nontoxic nanomolar concentrations. Similarly, the HDI valproic acid also inhibited MCs proliferation. Cell-cycle analysis indicated an arrest in G(0)/G(1) phase in response to TSA, which was accompanied by elevation in synthesis of the cyclin-dependent kinase inhibitors (CDKIs) p21/Waf1 and p27/Kip1. TSA treatment suppressed alpha-smooth muscle actin, transforming growth factor-beta1, and collagen protein synthesis by MCs and induced myofibroblast-like appearance of proliferating MCs. In the in vivo model of the anti-Thy1.1-induced glomerulonephritis, TSA and valproic acid treatments significantly suppressed proteinuria. Collectively, these data suggest a therapeutic potential for HDIs in the treatment of mesangial proliferative diseases and glomerulosclerosis.

Endovascular interventions of juxtaanastomotic stenoses and thromboses of hemodialysis arteriovenous fistulas.

PURPOSE: To assess the primary and secondary patency rates for juxtaanastomotic stenoses, with or without superimposed thromboses, of arteriovenous hemodialysis fistulas treated with angioplasty and to compare it with National Kidney Foundation Dialysis Outcomes Quality Initiative treatment guidelines for stenosed and occluded arteriovenous fistulas (50% primary patency rate at 12 months). MATERIALS AND METHODS: This study was a retrospective analysis, covering a period of 5(1/2) years. Forty-three hemodialysis patients were referred due to secondary fistula dysfunction, and angiography was diagnostic of a juxtaanastomotic lesion. Interventions consisted of standard angioplasty techniques along with thrombolysis and/or thrombectomy and intravascular stent placement as needed. Follow-up was performed at the attending dialysis center, and repeat angiography was performed as clinically required. RESULTS: Immediate postprocedural angiography demonstrated an angiographic success rate of 98%. Clinical success, with at least one session of normal dialysis, occurred in 95% of interventions. Primary patency rates at 12 months for the stenosed and stenosed/thrombosed fistulas were 56% and 64%, respectively. Secondary patency rates at 12 months were 64% and 63%, respectively. Half of the stenosed fistulas were patent at 1.5 years, 28% were patent at 4 years, and 13% remained patent at 6 years. No major complications were documented. Four minor complications, which did not require therapy, were noted. CONCLUSIONS: The results achieved are comparable to those reported for interventions at nonjuxtaanastomotic sites and exceed those quoted by the National Kidney Foundation Dialysis Outcomes Quality Initiative guidelines. Angioplastic interventions in a juxtaanastomatic area of arteriovenous fistulas are safe, promote prolonged patency, and postpone the need for surgical intervention or creation of a new fistula.