Difference in Antihypertensive Medication Pattern in the First Year Compared to More than a Year of Maintenance Hemodialysis: A Northern India Tertiary Care Experience

Introduction There is a high prevalence of hypertension in maintenance hemodialysis patients. Information regarding prevalent pattern of antihypertensive medications will help modify it to prevent future cardiovascular morbidity and mortality. Materials and Methods In this cross-sectional study, patients on maintenance hemodialysis, aged ≥18 years visiting Nephrology outpatient department (OPD) from April 2019 to May 2020 were included. The patients were divided into two groups based on their dialysis vintage, ≤12 months and >12 months. Their antihypertensive medication patterns and two-dimensional (2D) echocardiography (ECHO) findings were compared. Independent t-test was used to compare continuous variables. One-way analysis of variance was used to study the antihypertensive drug-dosing pattern in both the groups. Results Out of 250 patients, 131 had a dialysis vintage of ≤12 months, whereas 119 had a vintage of >12 months. There was no significant difference in the number of antihypertensive agents used in either of the vintage groups. Calcium channel blockers (87.02 and 89.07%, respectively, in ≤12 and >12 months' vintage groups) and β blockers (64.12 and 65.54%, respectively, in ≤12 and >12 months' vintage groups) were the commonly used antihypertensive agents. Metoprolol use was higher in ≤12 months' group, whereas carvedilol usage was higher in >12 months' group (p = 0.028). Mean pill burden was more than five in both the groups. Concentric left ventricular hypertrophy was significantly more common in >12 months' group. Renin–angiotensin system (RAS) blocking agent use was limited to 3% of patients. Conclusion This study shows a high antihypertensive pill burden in dialysis patients likely due to underlying chronic volume overload in addition to the perceived efficacy of certain class of drug in a frequent dosing pattern. Low use of RAS blocking agent was also underlined. This study highlights the need to bring about changes in the antihypertensive prescription pattern in line with the existing evidence.

Allograft Vesicoureteral Reflux after Kidney Transplantation

Allograft vesicoureteral reflux (VUR) is a leading urological complication of kidney transplantation. Despite the relatively high incidence, there is a lack of consensus regarding VUR risk factors, impact on renal function, and management. Dialysis vintage and atrophic bladder have been recognized as the most relevant recipient-related determinants of post-transplant VUR, whilst possible relationships with sex, age, and ureteral implantation technique remain debated. Clinical manifestations vary from an asymptomatic condition to persistent or recurrent urinary tract infections (UTIs). Voiding cystourethrography is widely accepted as the gold standard diagnostic modality, and the reflux is generally graded following the International Reflux Study Committee Scale. Long-term transplant outcomes of recipients with asymptomatic grade I-III VUR are yet to be clarified. On the contrary, available data suggest that symptomatic grade IV-V VUR may lead to progressive allograft dysfunction and premature transplant loss. Therapeutic options include watchful waiting, prolonged antibiotic suppression, sub-mucosal endoscopic injection of dextranomer/hyaluronic acid copolymer at the site of the ureteral anastomosis, and surgery. Indication for specific treatments depends on recipient’s characteristics (age, frailty, compliance with antibiotics), renal function (serum creatinine concentration < 2.5 vs. ≥ 2.5 mg/dL), severity of UTIs, and VUR grading (grade I-III vs. IV-V). Current evidence supporting surgical referral over more conservative strategies is weak. Therefore, a tailored approach should be preferred. Properly designed studies, with adequate sample size and follow-up, are warranted to clarify those unresolved issues.

Antibody Response and Safety After mRNA-1273 SARS-CoV-2 Vaccination in Peritoneal Dialysis Patients – the Vienna Cohort

BackgroundDialysis patients are at high risk for a severe clinical course after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Safety and early immune responses after mRNA-based vaccination have been reported mostly in patients on hemodialysis (HD), whereas reports of peritoneal dialysis (PD) patients remain rare.MethodsIn this retrospective observational study, 39 PD patients had received two doses of the mRNA-1273 Moderna® vaccine. We analyzed SARS-CoV-2 Spike (S) antibody titers 4 weeks after each dose of mRNA-1273 and report local and systemic side effects in PD patients that occurred within one week after each mRNA-1273 dose. Using a quantile regression model we examined factors that might influence SARS-CoV-2 S antibody levels in PD patients.ResultsFour weeks after the first dose of mRNA-1273 vaccine 33 of 39 (84.6%) PD patients seroconverted and presented with 6.62 U/mL (median; IQR 1.57-22.5) anti-SARS-CoV-2 S antibody titers. After the second dose, 38 of 39 (97.4%) PD patients developed anti-SARS-CoV-2 S antibodies and titers increased significantly (median 968 U/mL; IQR 422.5-2500). Pain at the injection site was the most common local adverse event (AE) (71%). Systemic AEs occurring after the first dose were mostly fatigue (33%) and headache (20%). No severe systemic AEs were reported after the first injection. After the second dose the incidence and the severity of the systemic AEs increased. The most common systemic AEs were: fatigue (40.5%), headache (22.5%), joint pain (20%), myalgia (17.5%) and fever (13%). Lower Davies Comorbidity Score (p=0.04) and shorter dialysis vintage (p=0.017) were associated with higher antibody titers after the first dose. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose (p=1.53x10-05).ConclusionsPeritoneal dialysis patients in this cohort had a high seroconversion rate of 97.4%, showed high antibody titers after full vaccination and tolerated the anti-SARS-CoV-2 mRNA-1273 vaccine well without serious adverse events.

U-Shaped Association of the Heart Rate Variability Triangular Index and Mortality in Hemodialysis Patients With Atrial Fibrillation

Background: Atrial fibrillation (AF) is common in hemodialysis patients and contributes to increased mortality. We aimed to examine heart rate variability triangular index (HRVI) in hemodialysis patients with AF as it has recently been reported to predict mortality in AF patients without kidney disease.Methods: A total of 88 patients on hemodialysis with a medical history of AF or newly diagnosed AF underwent 24-h electrocardiography recordings. The primary endpoint of cardiovascular mortality was recorded during a median follow up of 3.0 years. Risk prediction was assessed by Cox regression, both unadjusted and adjusted for the Charlson Comorbidity Index and the Cardiovascular Mortality Risk Score.Results: Median age was 76 years, median dialysis vintage was 27 months. Altogether, 22 and 44 patients died due to cardiovascular and non-cardiovascular causes. In 55% of patients AF was present during the recording. Kaplan-Meier plots of HRVI quartiles suggested a non-linear association between HRVI, cardiovascular, and all-cause mortality which was confirmed in non-linear Cox regression analysis. Adjusted linear Cox regression revealed a hazard ratio of 6.2 (95% CI: 2.1–17.7, p = 0.001) and 2.2 (95% CI: 1.3–3.8, p = 0.002) for the outer quartiles (combined first and fourth quartile) for cardiovascular and all-cause mortality, respectively. Patients in the first quartile were more likely to have sinus rhythm whereas patients in the fourth quartile were more likely to have AF.Conclusions: We found a U-shaped association between HRVI and mortality in hemodialysis AF patients. The results might contribute to risk stratification independent of known risk scores in hemodialysis AF patients.

Association between the psoas muscle index and hospitalization for pneumonia in patients undergoing hemodialysis

Background Although muscle mass loss and pneumonia are common and crucial issues in hemodialysis (HD) patients, few reports have focused on their association, which remains unclear. This study assessed the association between skeletal muscle mass and the incidence of pneumonia in HD patients using the psoas muscle index (PMI). Methods This retrospective study included 330 patients on HD who were treated at a single center between July 2011 and June 2012. The observation period was between July 2011 and June 2021. Demographic, clinical, and HD data were collected, and the associations between PMI and hospitalization due to bacterial pneumonia were evaluated using Cox proportional hazards models adjusted for patients’ background data. Additionally, the correlation between patient characteristics and PMI was evaluated using multivariable linear regression. Results Among 330 patients (mean age, 67.3 ± 13.3; 56.7% male; median dialysis vintage 58 months, (interquartile range [IQR] 23–124), 79 were hospitalized for pneumonia during the observation period (median observation period was 4.5 years [IQR 2.0–9.1]). The multivariable Cox proportional analysis, which was adjusted for age, sex, dialysis vintage, diabetes mellitus, and stroke history and considered death as a competing risk, indicated that decreased PMI/(standard deviation) was closely associated with the development of pneumonia (hazard ratio: 0.67, 95% confidence interval: 0.47–0.95, p = 0.03). Conclusions Skeletal muscle mass was associated with the development of pneumonia in patients on HD and could be a useful marker for the risk of pneumonia.

Prognostic factors for acute ischemic stroke in patients undergoing hemodialysis

Background Acute ischemic stroke (AIS) is a critical complication in patients undergoing dialysis. Although the improvement of AIS management is an urgent requirement, few studies have evaluated the prognostic factors of AIS in these patients. This study aimed to assess the relationship between clinical factors in patients undergoing dialysis and the prognosis of AIS. Methods Among 1267 patients who were hospitalized for AIS in Sendai City Hospital from January 2015 to June 2020, 81 patients undergoing hemodialysis were retrospectively enrolled. Multivariate analysis was performed to evaluate the effect of baseline characteristics, dialysis factors, and neurological severity of patients at admission [National Institutes of Health Stroke Scale (NIHSS) score] on in-hospital mortality, physical disability, and the need for rehabilitation transfer. Results A higher NIHSS score was a critical risk factor for each outcome and the only significant factor for in-hospital mortality [odds ratio (OR)/point 1.156, 95% confidence interval (CI) 1.054–1.267]. The risk factors of physical disability were NIHSS score (OR/point 1.458, 95% CI 1.064–1.998), older age (OR/year 1.141, 95% CI 1.022–1.274), diabetic nephropathy (OR 7.096, 95% CI 1.066–47.218), and higher premorbid modified Rankin scale (mRS) score (OR/grade 2.144, 95% CI 1.155–3.978); while those of rehabilitation transfer were a higher NIHSS score (OR/point 1.253, 95% CI 1.080–1.455), dialysis vintage (OR/year 1.175, 95% CI 1.024–1.349), and intradialytic hypotension before onset (OR 5.430, 95% CI 1.320–22.338). Conclusions Along with neurological severity, dialysis vintage, intradialytic hypotension, and diabetic nephropathy could worsen the prognosis of patients with AIS undergoing hemodialysis.

Pilot study to investigate differences in middle molecules, oxidative stress and markers of peripheral vascular disease in patients treated by high flux haemodialysis and haemodiafiltration

Background Dialysis patients have an increased risk of mortality. Recently treatment with haemodiafiltration (HDF) has been reported to reduce mortality, particularly cardiovascular mortality, compared to standard high-flux haemodialysis (HD). However, why HDF may offer a survival advantage remains to be determined. So, we conducted a pilot study to explore differences in middle-molecules, inflammation and markers of vascular disease in patients treated by HD and HDF. Methods Observational cross-sectional study measuring serum β2-microglobulin (β2M), Advanced Glycosylation End Products (AGEs) by skin autofluorescence (SAF), oxidative stress with ischaemia modified albumin ratio (IMAR) and peripheral vascular disease assessment using Ankle-Brachial Index (ABI), and arterial stiffness using Cardio-Ankle Vascular Index (CAVI). Results We studied 196 patients, mean age 69.1 ± 12.4 years, 172 (87.8%) treated by HD and 24 (12.2%) by HDF. Age, body mass index, co-morbidity and dialysis vintage were not different between HD and HDF groups. Middle molecules; β2M (31±9.9 vs 31.2±10 ug/mL) and SAF (2.99±0.72 vs 3.0±0.84 AU), ABI (1.06±0.05 vs 1.07±0.10) and CAVI (9.34±1.55 vs 9.35±1.23) were not different, but IMAR was higher in the HD patients (38.4±14.8 vs 31.3 ± 17.4, P = 0.035) Conclusions In this pilot observational study, we found patients treated by HDF had lower oxidative stress as measured by IMAR, with no differences in middle molecules. Lower oxidative stress would be expected to have diverse protective effects on the cardiovascular system Although we found no differences in ABI and CAVI, future studies are required to determine whether reduced oxidative stress translates into clinically relevant differences over time.

Pregnancy and delivery in women receiving maintenance hemodialysis in Japan: analysis of potential risk factors for neonatal and maternal complications

Introduction Average dialysis vintage in Japan is among the longest in the world, providing a unique opportunity to characterize pregnancy under conditions of long dialysis vintage. In 2017, we carried out a nationwide survey following up on a similar survey in 1996, in which we investigated the prevalence and outcomes of pregnancy in women undergoing dialysis and assessed risk factors associated with neonatal and maternal complications. Methods The target population was women aged 15–44 years undergoing maintenance dialysis between 2012 and 2016. The survey was conducted in 2693 dialysis units. Results A response was obtained from 951 dialysis units, yielding a target population of 1992 women of childbearing age receiving hemodialysis or peritoneal dialysis. Pregnancy occurred only among women receiving hemodialysis, with 25 pregnancies (1.26% in 5 years) being reported for 20 women. Detailed information about 19 pregnancies (mean age 34.6 ± 5.7 years at conception, mean dialysis vintage 8.4 ± 7.3 years) indicated 4 spontaneous abortions, 1 elective abortion, no neonatal deaths, and 14 surviving infants, including 5 full-term (≥ 37 weeks at birth), 2 late preterm (34–36), and 3 extremely preterm (< 28) cases. Neonatal complications occurred in the offspring of 3 mothers who had end-stage renal disease (ESRD) caused by primary glomerulonephritis and serum albumin levels (sAlb) ≤ 3.2 mg/dL in the first trimester. These mothers had started dialysis at 12, 17, and 30 years of age. ESRD caused by diabetic nephropathy or primary glomerulonephritis, age at conception ≥ 38 years, and sAlb ≤ 3.2 mg/dL were associated with maternal complications, although not significantly. Conclusions In this study, the pregnancy rate of Japanese women with ESRD was 0.25% per year. The study generates the hypothesis that ESRD caused by diabetic nephropathy and age at conception ≥ 38 years are potential risk factors for maternal complications but not for neonatal complications in dialysis patients, and that hypoalbuminemia is a potential risk factor for both kinds of complications. Graphic Abstract

Risk Factors for Low Humoral Response to BNT-162b2 In Hemodialysis Patients

IntroductionMaintenance Hemodialysis (HD) patients are at higher risk of both infection and mortality associated with the new coronavirus 2. Immunization through large-scale vaccination is the cornerstone of infection prevention in this population. This study aims to identify risk factors for low response to the BNT-162b2 (Pfizer BioNTech) vaccine in a HD cohort.Materials and MethodsObservational prospective study of a HD group followed in a Portuguese Public Founded Hemodialysis Center who received BNT-162b2 vaccination. Specific anti-Spike IgG was evaluated as arbitrary units per milliliter (AU/mL) on two separate occasions: 3 weeks after the first dose and 3 weeks after the second. IgG titers, Non-Responders (NR), and Weak-Responders (WR) after each dose were evaluated against risk factors that included demographic, clinical and analytical variables.ResultsHumoral response evaluated by IgG anti-Spike levels showed a strong correlation with Charlson comorbidity index (CCI) and intact parathormone (iPTH) after each inoculation (1st dose: ρ=−0.64/0.54; 2nd dose: ρ=−0.66/0.63, respectively; p<0.01 throughout). After completing both doses: 1) NR were associated with female sex (p<0.01), lower albumin and iPTH (p=0.01); 2) WR showed higher CCI, older age, lower iPTH and lower albumin (p=<0.01, p=0.03, p<0.01, p=0.05, respectively) and, consistently, associated with CCI over 8, age over 75, iPTH under 150 ng/L, female sex, dialysis vintage under 24 months and central venous catheter (CVC) over arteriovenous fistula (p=0.01, p=0.03, p<0.01, p=0.01, p=0.01, p<0.01, respectively). A binary regression model using CCI, sex (male) and CVC was statistically significant in prediction of WR after the 2nd dose with OR (95% CI): 1.81 (1.06-3.08); 0.05 (0.01-0.65); 13.55 (1.06-174.18), respectively (p=0.01).ConclusionOlder age, higher CCI, lower iPTH and albumin, CVC as vascular access and recent hemodialysis initiation (less than 2 years) associate with lower response to vaccination in our study. A higher comorbidity burden is suggested as a more significant surrogate marker for low immunogenicity rather than age alone. Identifying HD patients as a population at high-risk for low response to vaccination is essential for proper policy-making, facilitating the implementation of adequate and individualized contingency protocols.What is already known about this subjectMaintenance hemodialysis patients have lower humoral response to BNT-162b2 COVID-19 vaccine when compared to the general population.Maintenance dialysis patients are at high risk of exposure to coronavirus 2 in addition to a more severe disease course.What this study addsWe suggest Charlson commorbidity index, older age, intact parathormone, central venous catheter as vascular access and lower dialysis vintage as possible surrogate markers of immunogenicity in HD patients.There is a low humoral response after a single dose of the vaccine (50%) that can be increased after the second (86%).What impact this may have on practice or policyStrict Protocols for follow-up measures in HD patients, including closer humoral titers assessment, risk stratification, adequate isolation, and surveillance of symptoms might be necessary in order to improve this population survival/life expectancy.Screening HD patients, seroconversion rates may be improved by giving extra inoculations for patients at risk for low response.

Underdiagnosis of Major Depressive Episodes in Hemodialysis Patients: The Need for Screening and Patient Education

This article aims to identify the reasons why patients with major depressive episode (MDE) do not seek treatment for their mental disorder. 89 out of 208 persons screened were diagnosed with major depressive episode using the Mini-International Neuropsychiatric Interview. 85 individuals with untreated depression filled out the following questionnaires: Beck Depression Inventory, List of Explanations of Well-Being (LEWB), Brief Measure to Assess Perception of Self-Influence on the Course of the Disease, Coping Inventory for Stressful Situations, Brief Method of Evaluating Coping with Disease, and Metacognitions Questionnaire. There were 43 women (50.6%) and 42 men (49.4%), aged 24 to 93 years (Mean (M) = 68.26 years; Standard Deviation (SD) = 14.19 years), with dialysis vintage ranging from 1 month to 33 years (M = 70.63 months; SD = 75.26 months). Among study patients, 70.6% declared that depression was the cause of their poor well-being, 75.3% attributed their depressive symptoms to kidney failure, and 49.4%, more specifically, to hemodialysis. A total of 64.7% of patients had a low perception of self-influence on the course of their kidney disease, and 58.5% presented a coping style focused on emotions. The most frequent dysfunctional metacognitive beliefs were negative beliefs about not controlling one’s own thoughts. This attitude was related to the low perception of self-influence on the course of the disease, maladaptive coping styles, and dysfunctional metacognitive beliefs.