Prevalence and trends of Clostridioides difficile infection among persons requiring maintenance hemodialysis: A systematic review and meta-analysis.

OBJECTIVE: Clostridioides difficile infection (CDI) is among the most common cause of healthcare-associated infections. Persons requiring maintenance hemodialysis (MHD) are at increased risk of CDI and associated mortality compared to persons not requiring MHD. Given the clinical impact of CDI among persons requiring MHD, we aimed to quantify the burden of CDI and trends over time in this patient population. STUDY DESIGN: A systematic review and meta-analysis of studies reporting rates of CDI among persons requiring MHD in MEDLINE, Embase, Web of Science Core Collection, CINAHL, and Cochrane Central Register of Controlled Trials were performed. Searches were conducted on May 17, 2021, and March 4, 2022. RESULTS: In total, 2,408 titles and abstracts were identified; 240 underwent full text review. Among them, 15 studies provided data on rates of CDI among persons requiring MHD, and 8 of these also provided rates among persons not requiring MHD. The pooled prevalence of CDI among persons requiring MHD was 19.14%, compared to 5.16% among persons not requiring MHD (odds ratio [OR], 4.35; 95% confidence interval [CI], 2.07-9.16; P = .47). The linear increase in CDI over time was significant, increasing an average of 31.97% annually between 1993 and 2017 (OR, 1.32; 95% CI, 1.1-1.58; P < .01). The linear annual increase was similar among persons requiring and not requiring MHD (OR, 1.28; 95% CI, 1.13-1.45; P = .11). CONCLUSIONS: Persons requiring MHD have a 4-fold higher risk of CDI compared to persons not requiring MHD, and rates of CDI are increasing over time in both groups.

Long-term immunogenicity and safety of the hepatitis B vaccine HepB-CpG (HEPLISAV-B) compared with HepB-Eng (Engerix-B) in adults with chronic kidney disease.

BACKGROUND: Hepatitis B virus (HBV) infection remains a significant global burden, especially for patients with chronic kidney disease (CKD) receiving hemodialysis. Three doses of HepB-CpG (HEPLISAV-B® vaccine) induced a superior immune response compared with 4 double doses of HepB-Eng (Engerix-B®) in a phase 3 trial (HBV-17) in adults with CKD. Here we report the long-term immunogenicity and safety of HepB-CpG and HepB-Eng in eligible participants of HBV-17 who enrolled in this optional 34-month follow-up trial (HBV-19). METHODS: HBV-19 is a multicenter, open-label, phase 3b trial of adults with CKD who previously received a complete series of HepB-CpG or HepB-Eng in the HBV-17 trial. Participants were assigned to seroprotection categories at enrollment on the basis of their antibody response to hepatitis B surface antigen (anti-HBs) in HBV-17. The objective was to evaluate the durability of seroprotection (defined as an anti-HBs concentration ≥ 10mIU/mL) induced by HepB-CpG and HepB-Eng. Participants whose anti-HBs concentration was below 10mIU/mL received additional HepB-CpG or HepB-Eng doses. RESULTS: 147 participants were enrolled; 66.7 % were men, median age was 65.0 years, and 83.7 % were white. The durability of seroprotection in participants with CKD was similar in those who received HepB-CpG and those who received HepB-Eng. Antibody concentrations ≥ 100mIU/mL persisted for longer in HepB-CpG than HepB-Eng recipients, among those with anti-HBs ≥ 100mIU/mL post vaccination. The geometric mean anti-HBs concentration in the HepB-CpG group was significantly higher than in the HepB-Eng group over time (P ≤ 0.0001). The safety profiles were similar between the vaccine groups. CONCLUSIONS: Due to the higher antibody levels induced by HepB-CpG in participants with CKD, seroprotection against HBV may be expected to persist longer than that induced by HepB-Eng. CLINICALTRIALS: gov: NCT01282762.

Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection: An Analysis of the DARE-19 Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Patients who were hospitalized with coronavirus disease 2019 (COVID-19) infection are at high risk of AKI and KRT, especially in the presence of CKD. The Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial showed that in patients hospitalized with COVID-19, treatment with dapagliflozin versus placebo resulted in numerically fewer participants who experienced organ failure or death, although these differences were not statistically significant. We performed a secondary analysis of the DARE-19 trial to determine the efficacy and safety of dapagliflozin on kidney outcomes in the overall population and in prespecified subgroups of participants defined by baseline eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The DARE-19 trial randomized 1250 patients who were hospitalized (231 [18%] had eGFR <60 ml/min per 1.73 m2) with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. Dual primary outcomes (time to new or worsened organ dysfunction or death, and a hierarchical composite end point of recovery [change in clinical status by day 30]), and the key secondary kidney outcome (composite of AKI, KRT, or death), and safety were assessed in participants with baseline eGFR <60 and ≥60 ml/min per 1.73 m2. RESULTS: The effect of dapagliflozin versus placebo on the primary prevention outcome (hazard ratio, 0.80; 95% confidence interval, 0.58 to 1.10), primary recovery outcome (win ratio, 1.09; 95% confidence interval, 0.97 to 1.22), and the composite kidney outcome (hazard ratio, 0.74; 95% confidence interval, 0.50 to 1.07) were consistent across eGFR subgroups (P for interaction: 0.98, 0.67, and 0.44, respectively). The effects of dapagliflozin on AKI were also similar in participants with eGFR <60 ml/min per 1.73 m2 (hazard ratio, 0.71; 95% confidence interval, 0.29 to 1.77) and ≥60 ml/min per 1.73 m2 (hazard ratio, 0.69; 95% confidence interval, 0.37 to 1.29). Dapagliflozin was well tolerated in participants with eGFR <60 and ≥60 ml/min per 1.73 m2. CONCLUSIONS: The effects of dapagliflozin on primary and secondary outcomes in hospitalized participants with COVID-19 were consistent in those with eGFR below/above 60 ml/min per 1.73 m2. Dapagliflozin was well tolerated and did not increase the risk of AKI in participants with eGFR below or above 60 ml/min per 1.73 m2.

Hypothyroidism-induced Acute Kidney Injury and Hyponatremia.

Thyroid hormones affect every organ system in the body including renal development and physiology, and electrolyte and water homeostasis. These effects happen as a consequence of the combination of direct effects of thyroid hormones on renal tubules and hemodynamic effects of thyroid hormones. As a consequence, both hypothyroidism and hyperthyroidism significantly affect renal function. This case describes a patient with hypothyroidism-related acute kidney injury without rhabdomyolysis, and no additional precipitating factor. While there are many case reports describing hypothyroidism-related rhabdomyolysis leading to acute kidney injury, there are only a handful of case reports on hypothyroidism-related acute kidney injury without rhabdomyolysis.

Inpatient Dialysis Planning During the COVID-19 Pandemic: A Single-Center Experience and Review of the Literature.

BACKGROUND: COVID-19 has created havoc in healthcare systems worldwide, including shortages in equipment and supplies for dialysis in the acute setting. METHODS: We compared our planning and experience at a tertiary care academic medical center to recommendations in the literature. RESULTS: Published literature and our experience underscored the need to plan for adequate dialysis equipment, particularly for continuous renal replacement therapy in the ICU setting, adequate nursing, and flexible scheduling of chronic patients to accommodate the surge in acute patients. We discovered other "shortages" not mentioned in the literature: shortages in the number of portable reverse osmosis (RO) machines needed to prepare dialysis water, inadequate number of rooms in units designated for COVID-19 patients with plumbing for dialysis, and lack of temperature blending valves on sinks that necessitated using cold water only, and damaging the RO membranes. We identified the need for cooperation between nephrology and critical care medicine, hospital-based and community nephrologists and community dialysis units as well as nephrologists at other hospitals in the region. We turned to guidance from the hospital ethics committee. CONCLUSION: Planning for an expected surge in hospitalized patients requiring RRT demands coordination between critical care, dialysis and nursing services as well as community and hospital providers to make certain there are adequate dialysis resources. Our experience suggests that continuous dialysis is in greatest demand early in the illness, and that plans to increase supplies should be put in place. But, planning should also focus on unforeseen hospital-specific infrastructure shortages that can develop over time and hamper intermittent dialysis delivery to all patients who require treatment.

Efficacy and safety of sofosbuvir in the treatment of hep C among patients on hemodialysis: a systematic review and meta-analysis.

Hepatitis C virus (HCV) infection among maintenance hemodialysis patients is implicated in increased morbidity and mortality compared to uninfected patients. Sofosbuvir (SOF)-based regimens may not be optimal among patients requiring hemodialysis. Several studies, however, provide evidence that use of SOF among HCV-positive patients with renal impairment, is effective and safe. We searched Pubmed and Embase to identify studies reporting the efficacy and safety of SOF-based regimens for the treatment of HCV-positive patients on maintenance hemodialysis and performed a random effects meta-analysis. The overall pooled estimate of the efficacy of SOF-based therapy was 95% (95% CI 91-98%). The efficacy of the SOF-based regimen was 92% (95% CI 80-99%), 98% (95% CI 96-100%), and 100% (95% CI 95-100%) for the following doses: 400 mg on alternate days, 400 mg daily, and 200 mg daily, respectively. The most frequent adverse event was fatigue with a pooled prevalence of 16% (95% CI 5-29%), followed by anemia 15% (95% CI 3-31%), and nausea or vomiting 14% (95% CI 4-27%). Anemia was more prevalent in treatment regimens containing ribavirin (46%, 95% CI 33-59%) compared to ribavirin-free regimens (3%, 95% CI 0-9%). This study suggests that SOF-based regimens in the treatment of HCV infection among hemodialysis patients are both effective and safe.

Clinical and Economic Benefits of Antimicrobial Stewardship Programs in Hemodialysis Facilities: A Decision Analytic Model.

BACKGROUND AND OBJECTIVES: Infections caused by multidrug-resistant organisms and Clostridium difficile are associated with substantial morbidity and mortality as well as excess costs. Antimicrobial exposure is the leading cause for these infections. Approximately 30% of antimicrobial doses administered in outpatient hemodialysis facilities are considered unnecessary. Implementing an antimicrobial stewardship program in outpatient hemodialysis facilities aimed at improving prescribing practices would have important clinical and economic benefits. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We developed a decision analytic model of antimicrobial use on the clinical and economic consequences of implementing a nationwide antimicrobial stewardship program in outpatient dialysis facilities. The main outcomes were total antimicrobial use, infections caused by multidrug-resistant organisms and C. difficile, infection-related mortality, and total costs. The analysis considered all patients on outpatient hemodialysis in the United States. The value of implementing antimicrobial stewardship programs, assuming a 20% decrease in unnecessary antimicrobial doses, was calculated as the incremental differences in clinical end points and cost outcomes. Event probabilities, antimicrobial regimens, and health care costs were informed by publicly available sources. RESULTS: On a national level, implementation of antimicrobial stewardship programs was predicted to result in 2182 fewer infections caused by multidrug-resistant organisms and C. difficile (4.8% reduction), 629 fewer infection-related deaths (4.6% reduction), and a cost savings of $106,893,517 (5.0% reduction) per year. The model was most sensitive to clinical parameters as opposed to antimicrobial costs. CONCLUSIONS: The model suggests that implementation of antimicrobial stewardship programs in outpatient dialysis facilities would result in substantial reductions in infections caused by multidrug-resistant organisms and C. difficile, infection-related deaths, and costs.

The positive effects of an antimicrobial stewardship program targeting outpatient hemodialysis facilities.

BACKGROUND: Antimicrobial stewardship programs are effective in optimizing antimicrobial prescribing patterns and decreasing the negative outcomes of antimicrobial exposure, including the emergence of multidrug-resistant organisms. In dialysis facilities, 30%-35% of antimicrobials are either not indicated or the type of antimicrobial is not optimal. Although antimicrobial stewardship programs are now implemented nationwide in hospital settings, programs specific to the maintenance dialysis facilities have not been developed. OBJECTIVE: To quantify the effect of an antimicrobial stewardship program in reducing antimicrobial prescribing.Study design and settingAn interrupted time-series study in 6 outpatient hemodialysis facilities was conducted in which mean monthly antimicrobial doses per 100 patient months during the 12 months prior to the program were compared to those in the 12-month intervention period. RESULTS: Implementation of the antimicrobial stewardship program was associated with a 6% monthly reduction in antimicrobial doses per 100 patient months during the intervention period (P=.02). The initial mean of 22.6 antimicrobial doses per 100 patient months decreased to a mean of 10.5 antimicrobial doses per 100 patient months at the end of the intervention. There were no significant changes in antimicrobial use by type, including vancomycin. Antimicrobial adjustments were recommended for 30 of 145 antimicrobial courses (20.6%) for which there were sufficient clinical data. The most frequent reasons for adjustment included de-escalation from vancomycin to cefazolin for methicillin-susceptible Staphylococcus aureus infections and discontinuation of antimicrobials when criteria for presumed infection were not met. CONCLUSIONS: Within 6 hemodialysis facilities, implementation of an antimicrobial stewardship was associated with a decline in antimicrobial prescribing with no negative effects.

Targeting Regulatory T Cells for Transplant Tolerance: New Insights and Future Perspectives.

BACKGROUND: Organ transplantation is considered the ultimate therapy for end-stage organ disease. While pharmacologic immunosuppression is the mainstay of therapeutic strategies to prolong the survival of the graft, long-term use of immunosuppressive medications carries the risk of organ toxicity, malignancies, serious opportunistic infections, and diabetes. Therapies that promote recipient tolerance in solid organ transplantation are able to improve patient outcomes by eliminating the need for long-term immunosuppression. SUMMARY: Establishing tolerance to an allograft has become an area of intense study and would be the ideal therapy in clinical practice. The discovery of a subset of T cells naturally committed to perform immunoregulation has led to further investigation into their role in the immunopathogenesis of transplantation. Evidence suggests that regulatory T cells (Tregs) are fundamentally involved in promoting allograft tolerance. Efforts to characterize specific markers for Tregs, while challenging, have identified Foxp3 gene expression as a crucial step in promoting the tolerance-inducing features of Tregs. A number of approaches, including those based on targeting the glycogen synthase kinase 3ß signaling pathway or activating the melanocortinergic pathway, have been tested as a way to promote Treg lineage commitment and maintenance as well as to facilitate immune tolerance. In order to be effective in clinical practice, Tregs must be allospecific and possess a specific phenotype to avoid suppression of other aspects of the immune system or increasing the risk of malignancy or infections. Multiple experimental and clinical studies have demonstrated the impact of currently used immunosuppressants on the immunoregulatory activities of Tregs and their Foxp3 expression status. Pharmacological induction of tolerogenic Tregs for inducing transplant tolerance, including epigenetic therapies, is in the ascendant. KEY MESSAGES: Therapies that promote Treg function and survival may represent a novel strategy for achieving immune tolerance in transplant patients.

Evaluating Infection Prevention Strategies in Out-Patient Dialysis Units Using Agent-Based Modeling.

Patients receiving chronic hemodialysis (CHD) are among the most vulnerable to infections caused by multidrug-resistant organisms (MDRO), which are associated with high rates of morbidity and mortality. Current guidelines to reduce transmission of MDRO in the out-patient dialysis unit are targeted at patients considered to be high-risk for transmitting these organisms: those with infected skin wounds not contained by a dressing, or those with fecal incontinence or uncontrolled diarrhea. Here, we hypothesize that targeting patients receiving antimicrobial treatment would more effectively reduce transmission and acquisition of MDRO. We also hypothesize that environmental contamination plays a role in the dissemination of MDRO in the dialysis unit. To address our hypotheses, we built an agent-based model to simulate different treatment strategies in a dialysis unit. Our results suggest that reducing antimicrobial treatment, either by reducing the number of patients receiving treatment or by reducing the duration of the treatment, markedly reduces overall colonization rates and also the levels of environmental contamination in the dialysis unit. Our results also suggest that improving the environmental decontamination efficacy between patient dialysis treatments is an effective method for reducing colonization and contamination rates. These findings have important implications for the development and implementation of future infection prevention strategies.

The effect of N-acetylcysteine on plasma total homocysteine levels in hemodialysis: a randomized, controlled study.

BACKGROUND: The chronic hemodialysis population has an accelerated rate of cardiovascular morbidity and death. Furthermore, elevated levels of the putative atherothrombotic risk factor homocysteine are almost ubiquitous in this population. Attempts to normalize elevated plasma total homocysteine (tHcy) levels in dialysis patients using pharmacological-dose vitamin therapy or other strategies generally have been unsuccessful. Preliminary uncontrolled evidence suggests that N-acetylcysteine (NAC) may be an effective tHcy-lowering agent. We designed a randomized placebo-controlled study to determine the effect of prolonged oral NAC therapy on lowering tHcy levels in vitamin-replete chronic hemodialysis patients. METHODS: Thirty-eight subjects were treated before intervention with a standard dialysis vitamin supplement to ensure a uniform vitamin-replete state. They were then block randomized to treatment with NAC, 1.2 g twice a day, for 4 weeks or matched placebo. RESULTS: There were no significant baseline differences between the two groups, although differences in pyridoxal 5'-phosphate (active form of vitamin B(6)) levels approached significance (P = 0.06). In a paired analysis, there was no statistically significant difference between the NAC and placebo groups. NAC was very well tolerated in hemodialysis patients. CONCLUSION: This randomized placebo-controlled trial found that chronic oral NAC therapy did not significantly reduce tHcy levels in hemodialysis patients. Although a larger sample size theoretically could have increased the statistical significance between groups, implications of the potentially very modest reduction in tHcy levels are not yet known. Finally, based on this limited study, NAC appears to be a safe and well-tolerated therapy in the hemodialysis population.

A multicenter, prospective, randomized, comparative evaluation of dual- versus triple-lumen catheters for hemodialysis and apheresis in 485 patients.

BACKGROUND: The purpose of this study is to compare a new temporary triple-lumen catheter (TLC) for dialysis that has a third lumen devoted to fluid and medication administration or blood sampling with a marketed dual-lumen catheter (DLC). METHODS: Four hundred eighty-five patients referred for acute hemodialysis or apheresis were randomly assigned to either a TLC or DLC in a multicenter, prospective, randomized trial. RESULTS: Analysis of blood flow rates was completed on 464 patients (228 patients, DLC; 236 patients, TLC) with a total of 1,681 hemodialysis (808 treatments, DLC; 873 treatments, TLC) and 82 apheresis treatments (37 treatments, DLC; 45 treatments, TLC). During hemodialysis, a median achieved flow rate (AFR) of 267 mL/min was realized for both groups (P = 0.58). During apheresis, a median AFR of 72.5 mL/min (range, 50 to 150 mL/min) was achieved in the DLC group, and 87 mL/min (range, 60 to 150 mL/min), in the TLC group (P = 0.14). Three hundred ninety-three patients (193 patients, DLC; 200 patients, TLC) had blood and catheter tip cultures performed on removal, and catheter-related bloodstream infection (CRBSI) status was determined. Thirty-one patients (7.9%) had a CRBSI: 16 patients (8.3%), DLC; and 15 patients (7.5%), TLC (P= 0.77). Incidence densities of CRBSI were 12.4/1,000 DLC-days and 10.2/1,000 TLC-days (P = 0.59). The CRBSI incidence of 18.2/1,000 catheter-days for femoral sites was significantly greater than the 7/1,000 catheter-days for jugular sites (P = 0.02) and 6.6/1,000 catheter-days for combined jugular and subclavian sites (P = 0.01). In multivariate analysis, antibiotic use was the only factor related to CRBSI (odds ratio, 0.30; 95% confidence interval, 0.12 to 0.76). There were no statistically significant differences in rates of other complications between the 2 catheters. CONCLUSION: Results show that the new TLC is similar to the marketed DLC.

Anemia and bone disease of chronic kidney disease: pathogenesis, diagnosis, and management.

Anemia and metabolic bone disease accompany chronic kidney disease (CKD), and worsen as CKD progresses. It is likely that both processes contribute to the increased morbidity and mortality seen in CKD. This paper briefly reviews the pathogenesis and diagnosis of anemia and bone disease in CKD, and summarizes recent consensus guidelines for treatment.

Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for early acute kidney injury.

Based on information to date, although limitations in the accuracy of NGAL in predicting AKI persist, the preponderance of published studies demonstrate that NGAL, when measured in the plasma and in the urine, is a reliable biomarker for the subsequent development of clinically apparent AKI. If very early detection of AKI, via the measurement of plasma or urinary NGAL, can be followed by effective treatment to abort the development or limit the severity of AKI, and therefore decrease the rate of RRT, length of hospitalization stay, and/or mortality risk, NGAL measurement will become a critically important diagnostic tool in critical care medicine, pediatrics, and surgery.

Lupus nephritis mimicking pyelonephritis in pregnancy.

BACKGROUND: Systemic lupus erythematosis (SLE) is a multisystemic autoimmune connective tissue disorder that presents with a wide range of clinical manifestations including renal involvement. Routine prenatal care includes assessment of renal function. CASE: A 29-year-old nullipara presented at 17 weeks with fever, vomiting, and costovertebral angle tenderness 1 week after being treated for a presumed urinary tract infection. On presentation, new-onset hypertension was noted. Inpatient evaluation established a diagnosis of SLE with lupus nephritis. The pregnancy ended with intrauterine fetal demise. CONCLUSION: SLE is a disease with complex and protean clinical manifestations. It should appear on the differential when more common disease processes are ruled out. Routine prenatal care can detect otherwise silent and undiagnosed renal disease, and with early intervention improve prognosis.

Complications of therapeutic plasma exchange: a prospective study of 1,727 procedures.

The type and number of complications was prospectively examined in 1,727 successive TPE treatments in 174 patients over 66 months at a single center. Most treatments were prescribed for thrombotic thrombocytopenic purpura (TTP; 42%), recurrent focal segmental glomerulosclerosis (FSGS; 22%), or myasthenia gravis (MG; 13%). About 57% of treatments used albumin-saline as the replacement solution and 43% used fresh-frozen plasma (FFP), almost all for TTP. There were 889 complications; 614 treatments (36% of the total) involved a complication. Most complications were minor; there were no deaths. Three treatments (0.2%) were discontinued due to a complication, and 2 (0.1%) required transfer to a higher acuity hospital bed. The most common complications were fever (7.7% of treatments), urticaria (7.4%), and hypocalcemic symptoms (7.3%). 42% of treatments with FFP involved a complication, compared to 30% of treatments using albumin-saline (P < 0.0001). The most common complications with FFP were urticaria (17%) and pruritus (13%); these occurred more commonly than in patients receiving albumin-saline. The most common complications with albumin-saline replacement were hypocalcemic symptoms (8.2%) and mild hypotension (8.1%). Mild and severe hypotension was significantly (P < 0.0001) more common with albumin-saline replacement. TPE is associated with a number of minor complications. Complications occur more commonly with FFP replacement compared to albumin-saline replacement. Pruritus and urticaria occur more commonly with FFP, and hypotension occurs more commonly with albumin-saline.

Dialysis in pregnant women with chronic kidney disease.

Pregnancy occurs uncommonly in women with chronic kidney disease (CKD) and fetal outcome tends to be poor, with high rates of prematurity and mortality. Dialysis, by complementing residual renal function, may improve fetal outcome in pregnant women with CKD. Although there are no prospective or randomized trials that examine the relationship between dialysis and fetal outcome, there is evidence that increased solute clearance, by early initiation of or intensification of dialysis, is beneficial for the health of the fetus. Case reports and observational studies from the United States, Belgium, and Saudi Arabia suggest that there is a relationship between successful pregnancy and the amount of dialysis received. Unfortunately, in these reports, measures of residual renal function and dialysis adequacy are lacking or incomplete. Nonetheless, compared to nonpregnant patients with CKD, in pregnant women with CKD it is reasonable to begin dialysis at a higher level of residual renal function in the hope of improving fetal outcome.