Home Hemodialysis: Core Curriculum 2021.

In the early days of dialysis, because of a lack of existing in-center infrastructure, home hemodialysis (HHD) was frequently used to expand dialysis programs. Recently, HHD has been thrust into the spotlight of kidney care programs once again. Patients and policymakers are demanding more choices for the management of kidney failure while controlling for cost. Perhaps it is not surprising that the kidney community's interest in HHD has been revived, especially during the COVID-19 pandemic. To meet this increased interest and demand, nephrologists and dialysis providers must embrace new technologies and improve their understanding of HHD systems. This installment of AJKD's Core Curriculum in Nephrology seeks to inform the reader about factors that can improve success in the training and retention of HHD patients. Benefits, pitfalls, and challenges of HHD are outlined. The features of novel and commonly used HHD equipment are also summarized. Examples of prescriptions and prescription adjustments to meet the needs of patients will also be reviewed. Finally, considerations related to medical management of HHD patients and their dialysis access at home are also included. HHD is an important tool for the management and rehabilitation of patients with kidney failure, which allows for patient-centered care and increased patient choice.

Image-guided tunneled peritoneal dialysis catheter placement.

Patients with end-stage renal disease (ESRD) often will ultimately require dialysis to survive. One type of dialysis is peritoneal dialysis (PD), which utilizes the vessel-rich peritoneum as a semi-permeable membrane to filter blood. In order to perform PD, a tunneled catheter must be placed through the abdominal wall and into the peritoneal space, with ideal positioning of the catheter within the most dependent portion of the pelvis, represented by the rectouterine or rectovesical space in women and men, respectively. There are several approaches to PD catheter insertion, including open surgical, laparoscopic surgical, blind percutaneous, and image-guided with the use of fluoroscopy techniques. Interventional radiology (through the use of image-guided percutaneous techniques) is an infrequently utilized resource to place PD catheters, and offers real-time imaging confirmation of catheter positioning with similar outcomes to more invasive surgical catheter insertion approaches. Although the vast majority of dialysis patients receive hemodialysis instead of peritoneal dialysis in the United States, some countries have moved towards a "Peritoneal Dialysis First" initiative, prioritizing initial PD, as it is less burdensome on healthcare facilities as it can be performed at home. In addition, the outbreak of the COVID-19 pandemic has produced shortages of medical supplies and delays in care delivery worldwide, while simultaneously generating a shift away from in-person medical visits and appointments. This shift may be met with more frequent utilization of imaged-guided PD catheter placement, reserving surgical and laparoscopic placement for complex patients who may require omental periprocedural revisions. This literature review outlines a brief history of PD, the various techniques of PD catheter insertion, patient selection criteria, and new COVID-19 considerations, in anticipation for the increased demand for PD in the United States.

Angiogenic Role of Mesothelium-Derived Chemokine CXCL1 During Unfavorable Peritoneal Tissue Remodeling in Patients Receiving Peritoneal Dialysis as Renal Replacement Therapy.

Peritoneal dialysis (PD) is a valuable 'home treatment' option, even more so during the ongoing Coronavirus pandemic. However, the long-term use of PD is limited by unfavourable tissue remodelling in the peritoneal membrane, which is associated with inflammation-induced angiogenesis. This appears to be driven primarily through vascular endothelial growth factor (VEGF), while the involvement of other angiogenic signaling pathways is still poorly understood. Here, we have identified the crucial contribution of mesothelial cell-derived angiogenic CXC chemokine ligand 1 (CXCL1) to peritoneal angiogenesis in PD. CXCL1 expression and peritoneal microvessel density were analysed in biopsies obtained by the International Peritoneal Biobank (NCT01893710 at www.clinicaltrials.gov), comparing 13 children with end-stage kidney disease before initiating PD to 43 children on chronic PD. The angiogenic potential of mesothelial cell-derived CXCL1 was assessed in vitro by measuring endothelial tube formation of human microvascular endothelial cells (HMECs) treated with conditioned medium from human peritoneal mesothelial cells (HPMCs) stimulated to release CXCL1 by treatment with either recombinant IL-17 or PD effluent. We found that the capillary density in the human peritoneum correlated with local CXCL1 expression. Both CXCL1 expression and microvessel density were higher in PD patients than in the age-matched patients prior to initiation of PD. Exposure of HMECs to recombinant CXCL1 or conditioned medium from IL-17-stimulated HPMCs resulted in increased endothelial tube formation, while selective inhibition of mesothelial CXCL1 production by specific antibodies or through silencing of relevant transcription factors abolished the proangiogenic effect of HPMC-conditioned medium. In conclusion, peritoneal mesothelium-derived CXCL1 promotes endothelial tube formation in vitro and associates with peritoneal microvessel density in uremic patients undergoing PD, thus providing novel targets for therapeutic intervention to prolong PD therapy.

SARS-CoV-2 Antibody Response After a Third Dose of the BNT162b2 Vaccine in Patients Receiving Maintenance Hemodialysis or Peritoneal Dialysis.

RATIONALE & OBJECTIVE: Recent studies showed that antibody titers after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the dialysis population are diminished as compared with the general population, suggesting the possible value of a third booster dose. We characterized the humoral response after 3 doses of the BNT162b2 vaccine in patients treated with either maintenance hemodialysis (HD) or peritoneal dialysis (PD). STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 69 French patients (38 HD and 31 PD) treated at a single center who received 3 doses of the BNT162b2 vaccine. FINDINGS: Humoral response was evaluated using plasma levels of anti-SARS-CoV-2 spike protein S1 immunoglobulin measured after the second dose and at least 3 weeks after the third dose of the BNT162b2 vaccine. Patients (median age 68 years [interquartile range (IQR), 53-76 years], 65% men) had a median anti-S1 antibody level of 284 [IQR, 83-1190] AU/mL after the second dose, and 7,554 [IQR, 2,268-11,736] AU/mL after the third dose. Three patients were nonresponders (anti-S1 antibody level < 0.8 AU/mL), and 12 were weak responders (anti-S1 antibody level 0.8-50 AU/mL) after the second vaccine dose. After the third dose, 1 of the 3 initial nonresponders produced anti-spike antibody, and all the 12 initial weak responders increased their antibody levels. Patients with a greater increase in anti-S1 antibody levels after a third dose had lower antibody levels after the second dose, and a longer time interval between the second and the third dose. Adverse events did not seem to be more common or severe after a third vaccine dose. LIMITATIONS: Observational study, small sample size. Relationship between antibody levels and clinical outcomes is not well understood. CONCLUSIONS: A third dose of the BNT162b2 vaccine substantially increased antibody levels in patients receiving maintenance dialysis and appeared to be as well tolerated as a second dose.

Humoral and Cellular Responses to mRNA-1273 and BNT162b2 SARS-CoV-2 Vaccines Administered to Hemodialysis Patients.

RATIONALE & OBJECTIVE: Patients with kidney failure who are receiving maintenance dialysis have a higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and worse clinical outcomes after coronavirus disease 2019 (COVID-19) than the general population. Therefore, immunization against SARS-CoV-2 with effective vaccines is an important component of health-maintenance strategies for these patients. This study evaluated the humoral and cellular responses to messenger RNA (mRNA) SARS-CoV-2 vaccines in this population. STUDY DESIGN: Observational prospective multicenter cohort study. SETTING & PARTICIPANTS: 205 patients treated at 3 dialysis units at the Hospital Clínic of Barcelona (Spain) were vaccinated from February 3 to April 4, 2021, and followed until April 23, 2021. EXPOSURE: Immunization with either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccine. OUTCOME: Seroconversion, defined as the detection of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG), and the identification of activated CD4+T cells 3 weeks after completing vaccination. Anti-S1-RBD IgG levels were also analyzed as a secondary outcome. ANALYTICAL APPROACH: Univariate and multivariable logistic and multiple linear regression models were used to evaluate the associations between vaccination and study outcomes. RESULTS: We found that 97.7% of 175 vaccinated patients who were seronegative at baseline developed a response (humoral, cellular, or both); 95.4% of these patients seroconverted, while 62% of those tested for cellular immunity had a positive response. Greater age and immunosuppressive treatment were associated with lower antibody levels. LIMITATIONS: Mandatory vaccine administration by health authorities. Anti-S1-RBD IgG levels were reported up to 150U/mL and cellular immune responses were characterized qualitatively. Antibody assay and cellular response assessment may not be comparable with previously published laboratory approaches. CONCLUSIONS: Immunization with mRNA vaccines generated a humoral and cellular immune response in a high proportion of patients with kidney failure receiving maintenance dialysis. These findings as well as the high risk of infection and poor clinical outcomes among these patients make their vaccination a health priority.

COVID-19 Among US Dialysis Patients: Risk Factors and Outcomes From a National Dialysis Provider.

RATIONALE & OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, patients receiving maintenance dialysis are a highly vulnerable population due to their comorbidities and circumstances that limit physical distancing during treatment. This study sought to characterize the risk factors for and outcomes following COVID-19 in this population. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Maintenance dialysis patients in clinics of a midsize national dialysis provider that had at least 1 patient who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from February to June 2020. PREDICTORS: Demographics, dialysis characteristics, residence in a congregated setting, comorbid conditions, measurements of frailty, and use of selected medications. OUTCOMES: COVID-19, defined as having a positive SARS-CoV-2 test result, and all-cause mortality among those with COVID-19. ANALYTICAL APPROACH: Logistic regression analyses conducted to identify clinical characteristics associated with COVID-19 and risk factors associated with mortality among patients following COVID-19. RESULTS: 438 of 7948 (5.5%) maintenance dialysis patients developed COVID-19. Male sex, Black race, in-center dialysis (vs home dialysis), treatment at an urban clinic, residence in a congregate setting, and greater comorbidity were associated with contracting COVID-19. Odds of COVID-19 were 17-fold higher for those residing in a congregated setting (odds ratio [OR], 17.10 [95% CI, 13.51-21.54]). Of the 438 maintenance dialysis patients with COVID-19, 109 (24.9%) died. Older age, heart disease, and markers of frailty were associated with mortality. LIMITATIONS: No distinction was detected between symptomatic and asymptomatic SARS-CoV-2 positivity, with asymptomatic screening limited by testing capacity during this initial COVID-19 surge period. CONCLUSIONS: COVID-19 is common among patients receiving maintenance dialysis, particularly those residing in congregate settings. Among maintenance dialysis patients with COVID-19, mortality is high, exceeding 20%.

Frequency of Comorbidities in Admitting COVID-19 Pneumonia Patients in a Tertiary Care Setup: An Observational Study.

Background The novel coronavirus disease 2019 (COVID-19) is a highly infectious and pandemic disease with a variable mode of action. Patients with underlying illnesses such as diabetes, hypertension, and other diseases are more prone to infection. An understanding of the different comorbidities that place patients at the highest risk of COVID-19 pneumonia and other fatal complications associated with COVID-19 is necessary for healthcare professionals. This study aimed to determine the frequency of different comorbid illnesses among COVID-19 patients admitted to a tertiary care hospital in Karachi, Pakistan. Methodology All patients diagnosed with COVID-19 who required admission for the care of their symptoms were included in this observational, cross-sectional study conducted from May 1 to July 30, 2020. The patients were treated at a specialized COVID-19 isolation ward built at the Dow University of Health Sciences at the Ojha campus. The patients were referred from the emergency department, medical and allied wards, and COVID-19 screening units. A detailed history and clinical examination were performed, and comorbidities were evaluated. Results A total of 212 patients were admitted during the study with a mean age of 52 ± 16 years. The study population consisted of 120 (56.6%) males and 92 (43.39%) females, and the most common comorbidities were uncontrolled diabetes with hypertension (n = 56; 26.4%), controlled diabetes (n = 22; 10.37%), obstructive airway disease (n = 16; 7.5%), and interstitial lung disease (n = 14; 6.6%). A total of 48 (22.64%) patients had no comorbidities. Conclusions Most COVID-19-positive patients with pneumonia were male, and common comorbidities included uncontrolled diabetes, hypertension, and obstructive and restrictive lung disease. The presence of comorbidities was associated with a marked increase in the risk of morbidity and mortality. Further studies are warranted to confirm these findings.

End-Stage Renal Disease Patients on Chronic Hemodialysis Fare Better With COVID-19: A Retrospective Cohort Study From the New York Metropolitan Region.

Introduction Several comorbid conditions have been identified as risk factors in patients with coronavirus disease 2019 (COVID-19). However, there is a dearth of data describing the impact of COVID-19 infection in patients with end-stage renal disease on hemodialysis (ESRD-HD). Methods This retrospective case series analyzed 362 adult patients consecutively hospitalized with confirmed COVID-19 illness between March 12, 2020, and May 13, 2020, at a teaching hospital in the New York City metropolitan area. The primary outcome was severe pneumonia as defined by the World Health Organization. Secondary outcomes were the (1) the Combined Outcome of Acute respiratory distress syndrome or in-hospital Death (COAD), and (2) need for high levels of oxygen supplementation (HiO2). Results Patients with ESRD-HD had lower odds for poor outcomes including severe pneumonia [odds ratio (OR) 0.4, confidence interval (CI) 0.2-0.9, p=.04], HiO2 [OR 0.3, CI (0.1-0.8), p=.02] and COAD [OR 0.4, CI (0.2-1.05), p=.06], when compared to patients without ESRD. In contrast, higher odds for severe pneumonia, COAD and HiO2 were seen with advancing age. African Americans were over-represented in the hospitalized patient cohort, when compared to their representation in the community (35% vs 18%). Hispanics had higher odds for severe illness and HiO2 when compared to Caucasians. Conclusions Patients with ESRD-HD had a milder course of illness with a lower likelihood of severe pneumonia and a lesser need for aggressive oxygen supplementation when compared to patients not on chronic dialysis. The lower odds of severe illness in ESRD-HD patients might have a pathophysiologic basis and need to be further explored.

Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States.

RATIONALE & OBJECTIVE: Underlying kidney disease is an emerging risk factor for more severe coronavirus disease 2019 (COVID-19) illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing chronic kidney disease (CKD) and investigated the association between the degree of underlying kidney disease and in-hospital outcomes. STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 4,264 critically ill patients with COVID-19 (143 patients with pre-existing kidney failure receiving maintenance dialysis; 521 patients with pre-existing non-dialysis-dependent CKD; and 3,600 patients without pre-existing CKD) admitted to intensive care units (ICUs) at 68 hospitals across the United States. PREDICTOR(S): Presence (vs absence) of pre-existing kidney disease. OUTCOME(S): In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/cardiac arrest, thromboembolic events, major bleeds, and acute liver injury (secondary). ANALYTICAL APPROACH: We used standardized differences to compare patient characteristics (values>0.10 indicate a meaningful difference between groups) and multivariable-adjusted Fine and Gray survival models to examine outcome associations. RESULTS: Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median of 4 [IQR, 2-9] days for maintenance dialysis patients; 7 [IQR, 3-10] days for non-dialysis-dependent CKD patients; and 7 [IQR, 4-10] days for patients without pre-existing CKD). More dialysis patients (25%) reported altered mental status than those with non-dialysis-dependent CKD (20%; standardized difference=0.12) and those without pre-existing CKD (12%; standardized difference=0.36). Half of dialysis and non-dialysis-dependent CKD patients died within 28 days of ICU admission versus 35% of patients without pre-existing CKD. Compared to patients without pre-existing CKD, dialysis patients had higher risk for 28-day in-hospital death (adjusted HR, 1.41 [95% CI, 1.09-1.81]), while patients with non-dialysis-dependent CKD had an intermediate risk (adjusted HR, 1.25 [95% CI, 1.08-1.44]). LIMITATIONS: Potential residual confounding. CONCLUSIONS: Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies in this vulnerable population.

Successful treatment of two Japanese ESRD cases with severe COVID-19 pneumonia.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious and deadly disease, spreading worldwide. There are limited data about the clinical course of end-stage renal disease (ESRD) patients infected with COVID-19. However, previous cohort studies showed a high mortality rate of ESRD patients infected with COVID-19. We report here two Japanese ESRD patients confirmed with severe COVID-19 pneumonia. Case 1 was a 60-year-old man with ESRD due to diabetic nephropathy who were infected with COVID-19 and exhibited acute respiratory distress syndrome (ARDS) requiring mechanical ventilation and intensive care unit (ICU) admission. He was treated with tocilizumab and intravenous immunoglobulin (IVIG). After 6 days of treatment in ICU, he was extubated. Case 2 was a 68-year-old woman undergoing maintenance hemodialysis for 17 years who also exhibited ARDS due to COVID-19. Her clinical course resembles case 1. Our experience of these two cases indicates that anti-cytokine therapy might be effective for severe COVID-19 pneumonia in ESRD patients.