Dialysis Therapy for Volume Overload: A Feasible Option to Reduce Heart Failure Hospitalizations in Advanced Heart Failure.

BACKGROUND: Advanced heart failure (HF) carries a high rate of recurrent HF hospitalizations and a very high mortality rate. Mechanical devices and heart transplantation are limited to a select few. Dialysis may be a good alternative for advanced HF patients with volume overload despite maximal pharmacological therapy. OBJECTIVES: To assess the net clinical outcome of peritoneal dialysis or hemodialysis in patients with advanced HF. METHODS: We analyzed all advanced HF patients who were referred for dialysis due to volume overload in our institution. Patients were followed for complications, HF hospitalizations, and survival. RESULTS: We assessed 35 patients; 10 (29%) underwent peritoneal dialysis and 25 (71%) underwent hemodialysis; 71% were male; median (interquartile range) age was 74 (67-78) years. Estimated glomerular filtration rate was 20 (13-32) ml/min per 1.73 m2. New York Heart Association functional capacity was III. Median follow-up time was 719 days (interquartile range 658-780). One-year mortality rate was 8/35 (23%) and overall mortality rate was 16/35 (46%). Three patients (9%) died during the first year due to line or peritoneal dialysis related sepsis, and 6 (17%) died during the entire follow-up. The median number of HF hospitalizations was significantly reduced during the year on dialysis compared to the year prior to dialysis (0.0 [0.0-1.0] vs. 2.0 [0.0-3.0], P < 0.001). CONCLUSIONS: Dialysis is reasonably safe and significantly reduced HF hospitalization in advanced HF patients. Dialysis could be a good alternative for advanced HF patients with intractable volume overload.

Ambulatory monitoring unmasks hypertension among kidney transplant patients: single center experience and review of the literature.

BACKGROUND: Disagreements between clinic and ambulatory blood pressure (BP) measurements are well-described in the general population. Though hypertension is frequent in renal transplant recipients, only a few studies address the clinic-ambulatory discordance in this population. We aimed to describe the difference between clinic and ambulatory BP in kidney transplant patients at our institution. METHODS: We compared the clinic and ambulatory BP of 76 adult recipients of a kidney allograft followed at our transplant center and investigated the difference between these methods, considering confounding by demographic and clinical variables. RESULTS: Clinic systolic BP (SBP) and diastolic BP (DBP) were 128 ± 13/79 ± 9 mmHg. Awake SBP and DBP were 147 ± 18/85 ± 10 mmHg. The clinic-minus-awake SBP and DBP differences were - 18 and - 6 mmHg, respectively. The negative clinic-awake ΔSBP was more pronounced at age > 60 years (p = 0.026) and with tacrolimus use compared to cyclosporine (p = 0.046). Sleep SBP and DBP were 139 ± 21/78 ± 11 mmHg. A non-dipping sleep BP pattern was noted in 73% of patients and was associated with tacrolimus use (p = 0.020). CONCLUSIONS: Our findings suggest pervasive underestimation of BP when measured in the kidney transplant clinic, emphasizes the high frequency of a non-dipping pattern in this population and calls for liberal use of ambulatory BP monitoring to detect and manage hypertension.

Impact of tozinameran (BNT162b2) mRNA vaccine on kidney transplant and chronic dialysis patients: 3-5 months follow-up.

BACKGROUND: Determining the humoral immunogenicity of tozinameran (BNT162b2) in patients requiring chronic renal replacement therapy, and its impact on COVID-19 morbidity several months after vaccination, may guide risk assessment and changes in vaccination policy. METHODS: In a prospective post-vaccination cohort study with up to 5 months follow-up we studied outpatient dialysis and kidney transplant patients and respective healthcare teams. Outcomes were anti S1/S2 antibody responses to vaccine or infection, and infection rate during follow-up. RESULTS: One hundred seventy-five dialysis patients (40% women, 65 ± 15 years), 252 kidney transplant patients (33% women, 54 ± 14 years) and 71 controls (65% women, 44 ± 14 years) were followed. Three months or longer after vaccination we detected anti S1/S2 IgG antibodies in 79% of dialysis patients, 42% of transplant recipients and 100% of controls, whereas respective rates after infection were 94%, 69% and 100%. Predictors of non-response were older age, diabetes, history of cancer, lower lymphocyte count and lower vitamin-D levels. Factors associated with lower antibody levels in dialysis patients were modality (hemodialysis vs peritoneal) and high serum ferritin levels. In transplant patients, hypertension and higher calcineurin or mTOR inhibitor drug levels were linked with lower antibody response. Vaccination was associated with fewer subsequent infections (HR 0.23, p < 0.05). Moreover, higher antibody levels (particularly above 59 AU/ml) were associated with fewer events, with a HR 0.41 for each unit increased in log10titer (p < 0.05). CONCLUSIONS: Dialysis patients, and more strikingly kidney transplant recipients, mounted reduced antibody response to COVID-19 mRNA vaccination. Lesser humoral response was associated with more infections. Measures to identify and protect non-responsive patients are required.

Nontuberculous mycobacteria infections of peritoneal dialysis patients: A multicenter study.

OBJECTIVES: Nontuberculous mycobacteria (NTM) infections pose a diagnostic challenge in peritoneal dialysis (PD) patients. In this study, we sought to identify findings that are suggestive of NTM infection in PD adult patients. METHODS: All patients with NTM exit-site infection (ESI) with/without tunnel infection and peritonitis identified during the last decade in eight medical centers in Israel were included. Clinical, microbiological, and outcome data were collected and analyzed. RESULTS: Thirty patients were identified; 16 had ESI (53%) and 14 had peritonitis (47%). Median age was 65 years (interquartile range 52-76). Abdominal pain and cloudy PD fluid were reported in all patients with peritonitis, whereas exit-site discharge and granulation tissue were common in patients with ESI. Fourteen patients (47%) had negative cultures prior NTM diagnosis, and isolation of diphtheroids or Corynebacterium spp. was reported in 9 of 30 patients (30%). Antimicrobial treatment prior to diagnosis was documented in 13 of 30 patients (43%). Delayed diagnosis was frequent. Treatment regimens and duration of therapy varied widely. In 26 of 30 (87%) patients, catheter was removed and 19 of 30 patients (63%) required permanent transition to hemodialysis. Two patients with peritonitis (2 of 14, 14%) and seven with ESI (7 of 16, 44%) were eligible for continuation of PD. CONCLUSIONS: Culture negative peritonitis, isolation of diphtheroids or Corynebacterium spp., previous exposure to antibiotics, and/or a refractory infection should all prompt consideration of PD-related NTM infection and timely workup. Catheter removal is recommended aside prolonged antimicrobial therapy. In select patients with ESI, continuation of PD may be feasible.

Implementation of guidelines for metabolic syndrome control in kidney transplant recipients: results at a single center.

BACKGROUND: Cardiovascular disease is a leading cause of death among kidney transplant recipients. Metabolic syndrome increases the risk for cardiovascular events and decreases graft survival. Lately, guidelines for management of the metabolic syndrome, primarily hypertension, diabetes mellitus (DM) and hypercholesterolemia have dramatically changed in an attempt to decrease cardiovascular risks among kidney transplant recipients. In the present study we examined whether these guideline changes had impact on our management of post-transplantation patients and the subsequent treatment outcomes for these diseases. METHODS: Data were obtained from kidney transplant clinic files from two follow-up (FU) periods-between 1994-1997 and between 2008-2011. Demographic data, monitoring and screening frequency for cardiovascular risk factors, immunosuppression regimen, treatment for hypertension, diabetes and hyperlipidemia, treatment outcomes and graft function changes were compared between the two follow-up periods. RESULTS: There was a significant increase in the percentage of patients undergoing transplantation due to renal failure secondary to diabetes and/or hypertension. Patient monitoring and screening during the second FU period were less frequent, but more targeted, reflecting changes in clinic routines. Blood pressure was better controlled in the second FU period (p < 0.01), as was hypercholesterolemia (p < 0.001). High fasting glucose levels were more prevalent among patients in the second group (p < 0.005), although more patients received treatment for DM (p < 0.001). Significantly, fewer patients experienced deterioration of kidney functions during the second FU period (p < 0.001). CONCLUSIONS: We found that guideline changes had impact on clinical practice, which translated to better control of the metabolic syndrome. DM control is challenging. Overall, stability of kidney function improved.

Major bleeding caused by warfarin in a genetically susceptible patient.

A 90-year-old woman was hospitalized for gastrointestinal bleeding. Although she had been receiving only warfarin 5 mg/day, her international normalized ratio (INR) was 66. Warfarin was discontinued, and her INR fell to 3.7 after transfusion of fresh-frozen plasma. However, it rose again spontaneously to 7.5. Eleven days after the last dose of warfarin had been administered, it was still detectable in the patient's plasma, indicating that impaired warfarin clearance may have caused an enhanced anticoagulation effect. Genetic analysis of the cytochrome P450 (CYP) isoenzyme 2C9, which mediates the major deactivating pathway of S-warfarin, revealed that the patient was a compound heterozygote carrying two variant alleles: CYP2C9*2 and CYP2C9*3. The patient's enhanced sensitivity to warfarin 5 mg/day can be ascribed to decreased clearance of S-warfarin secondary to genetic alteration of the gene encoding CYP2C9, resulting in a life-threatening complication.

Carbapenem-resistant Klebsiella pneumoniae is associated with poor outcome in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) units have become a source of resistant bacteria. One of the most alarming developments is the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Risk factors and outcomes of CRKP isolation in HD patients have not been previously studied. METHODS: A nested case-control study was conducted in maintenance HD patients between January 1st 2006 and June 30th 2009. CRKP-positive patients were matched with randomly selected CRKP-negative HD patients. Demographics, clinical and laboratory data were collected for 24 months prior to the specimen collection. Multivariate analyses identified independent risk factors for CRKP. A prospective follow-up determined CRKP-associated outcome. RESULTS: Demographics associated with CRKP acquisition in HD patients were age between 65 and 75 and having no living offspring. Clinical conditions associated with CRKP were previous hospitalization, temporary HD catheter and previous isolation of vancomycin-resistant enterococcus. CRKP-related outcome was poor: median survival of one month and a hazard ratio [95% CI] of 5.9 [3.2-11.0] for mortality. CONCLUSIONS: Temporary HD catheters and previous treatment for VRE may predict subsequent CRKP isolation. A microbiological diagnosis of CRKP in HD patients is highly associated with imminent mortality. Meticulous measures to control the spread of CRKP bacteria among HD patients appear particularly warranted.

Treatment of chronic hepatitis B virus infection via oral immune regulation toward hepatitis B virus proteins.

OBJECTIVES: Hepatitis B virus (HBV) is a noncytopathic virus, and hepatocellular injury is mediated by a defective host antiviral immune response. We have previously shown that antiviral immunity can be modulated through oral feeding of viral proteins. The aims of this study were to determine the safety and efficacy of treatment of patients with chronic HBV by means of p.o. administration of HBV envelope proteins. METHODS: A total of 42 chronic HBV patients were treated p.o. with HBV envelope proteins (HBsAg+preS1+preS2), three times/wk for 20-30 wk, and followed for an additional 20 wk. Patients were monitored for HBV-DNA levels, liver enzymes, and liver histology. HBV-directed T cell immune modulation was assessed in vitro by HBV specific T cell-proliferation, cytotoxicity, IFN gamma, and IL10 ELISPOT assays, and reverse transcription-polymerase chain reaction cytokines assay. RESULTS: Favorable response in one of the primary endpoints was achieved in 28/42 patients (66.6%) by means of p.o. immune regulation. A significant decrease in viral load was observed in 15 patients (35.7%). HBsAg/HBcAg biopsy scores improved in 41% and 57.1% of patients, respectively. Histological improvement in liver necroinflammatory score was noted in 12/40 patients (30%). In all, 80% showed biochemical response. Five of 19 HBeAg positive patients (26.3%) became negative for HBeAg. A favorable augmentation in anti-HBV specific T cell response, with increased HbsAg specific T cell proliferation (78%), cytotoxicity (75%), and IFN gamma positive T cell clones (62.9%) was noted. In addition, a decrease in the IL10 gamma positive T cell clones was achieved (48.1%). Natural killer T (NKT) lymphocytes increased significantly in all treated patients. CONCLUSIONS: Immune regulation of the anti-HBV immune response via p.o. administration of HBV envelope proteins alleviated the immune-mediated liver injury while augmenting the effective antiviral immunity.