Impact of COVID-19 on maintenance peritoneal dialysis patients and providers: A review.

The COVID-19 pandemic exerted complex pressures on the nephrology community. Despite multiple prior reviews on acute peritoneal dialysis during the pandemic, the effects of COVID-19 on maintenance peritoneal dialysis patients remain underexamined. This review synthesizes and reports findings from 29 total cases of chronic peritoneal dialysis patients with COVID-19, encompassing 3 case reports, 13 case series, and 13 cohort studies. When available, data for patients with COVID-19 on maintenance hemodialysis are also discussed. Finally, we present a chronological timeline of evidence regarding the presence of SARS-CoV-2 in spent peritoneal dialysate and explore trends in telehealth as they relate to peritoneal dialysis patients during the pandemic. We conclude that the COVID-19 pandemic has underscored the efficacy, flexibility, and utility of peritoneal dialysis.

Novel Aspects of the Immune Response Involved in the Peritoneal Damage in Chronic Kidney Disease Patients under Dialysis.

Chronic kidney disease (CKD) incidence is growing worldwide, with a significant percentage of CKD patients reaching end-stage renal disease (ESRD) and requiring kidney replacement therapies (KRT). Peritoneal dialysis (PD) is a convenient KRT presenting benefices as home therapy. In PD patients, the peritoneum is chronically exposed to PD fluids containing supraphysiologic concentrations of glucose or other osmotic agents, leading to the activation of cellular and molecular processes of damage, including inflammation and fibrosis. Importantly, peritonitis episodes enhance peritoneum inflammation status and accelerate peritoneal injury. Here, we review the role of immune cells in the damage of the peritoneal membrane (PM) by repeated exposure to PD fluids during KRT as well as by bacterial or viral infections. We also discuss the anti-inflammatory properties of current clinical treatments of CKD patients in KRT and their potential effect on preserving PM integrity. Finally, given the current importance of coronavirus disease 2019 (COVID-19) disease, we also analyze here the implications of this disease in CKD and KRT.

Extension of Tablo TrEatmeNt Duration (XTEND) study: successful 24 h prolonged therapy with Tablo in critical patients.

BACKGROUND: The Tablo® Hemodialysis System (Tablo) is an all in one, easy-to-learn device featuring integrated water purification, on demand dialysate production and two-way wireless data transmission and is approved for use in the acute, chronic, and home settings. Prior reports have demonstrated Tablo's ability to achieve clinical goals, seamlessly integrate into hospitals and reduce cost across a wide range of treatment times. Extension of the Tablo cartridge to 24 h allows prolonged therapy and even greater flexibility for prescribers in the acute setting. The objective is to report on the first ever experience with Tablo prolonged therapy between 12 and 24 h in critically ill patients treated at a single-center ICU. METHODS: Nursing staff were trained during a single training session on Tablo prolonged therapy. After a run-in period of five treatments, Tablo data were collected via real-time transmission to a cloud-based, HIPAA compliant platform and reviewed by site staff. Dialysis treatment delivery, clinically significant alarms, and clotting events were recorded. Sub-group analysis between COVID-19 positive and negative patients were reported. RESULTS: One hundred (100) consecutive Tablo prolonged treatments had a median prescribed treatment time of 24 h and a median achieved treatment time of 21.3 h. Median cartridge usage was 1.3 per treatment. The dialysis treatment time was delivered in 91% of treatments, with 6% ending early due to an alarm, and 3% ending due to clotting. Clinically significant alarms occurred at a median rate of 0.5 per treatment hour with a resolution time of 18 s. Median blood pump stoppage time related to these alarms was 2.3 min per treatment. Blood pump stoppage time was higher in the COVID-19 subgroup when compared to the non-COVID-19 subgroup. CONCLUSION: Tablo successfully achieves prescribed treatment time with minimal therapy interruptions from alarms or cartridge changes. This data demonstrates the effectiveness of Tablo in achieving personalization of treatments necessary for unstable patients and enabling successful delivery of extended therapy with minimal clotting. Tablo's prolonged therapy meets the needs of critically patients, including COVID-19 positive patients, requiring renal replacement therapy for greater than 12 h.

The case for increased peritoneal dialysis utilization in low- and lower-middle-income countries.

Peritoneal dialysis (PD) has several advantages compared to haemodialysis (HD), but there is evidence showing underutilization globally, especially in low-income and lower-middle-income countries (LLMICs) where kidney replacement therapies (KRT) are often unavailable, inaccessible, and unaffordable. Only 11% of all dialysis patients worldwide use PD, more than 50% of whom live in China, the United States of America, Mexico, or Thailand. Various barriers to increased PD utilization have been reported worldwide including patient preference, low levels of education, and lower provider reimbursement. However, unique but surmountable barriers are applicable to LLMICs including the excessively high cost of providing PD (related to PD fluids in particular), excessive cost of treatment borne by patients (relative to HD), lack of adequate PD training opportunities for doctors and nurses, low workforce availability for kidney care, and challenges related to some PD outcomes (catheter-related infections, hospitalizations, mortality, etc.). This review discusses some known barriers to PD use in LLMICs and leverages data that show a global trend in reducing rates of PD-related infections, reducing rates of modality switches from HD, and improving patient survival in PD to discuss how PD use can be increased in LLMICs. We therefore, challenge the idea that low PD use in LLMICs is unavoidable due to these barriers and instead present opportunities to improve PD utilization in LLMICs.

SARS-CoV-2 in Spent Dialysate from Chronic Peritoneal Dialysis Patients with COVID-19.

Background: To date, it is unclear whether SARS-CoV-2 is present in spent dialysate from patients with COVID-19 on peritoneal dialysis (PD). Our aim was to assess the presence or absence of SARS-CoV-2 in spent dialysate from patients on chronic PD who had a confirmed diagnosis of COVID-19. Methods: Spent PD dialysate samples from patients on PD who were positive for COVID-19 were collected between March and August 2020. The multiplexed, real-time RT-PCR assay contained primer/probe sets specific to different SARS-CoV-2 genomic regions and to bacteriophage MS2 as an internal process control for nucleic acid extraction. Demographic and clinical data were obtained from patients' electronic health records. Results: A total of 26 spent PD dialysate samples were collected from 11 patients from ten dialysis centers. Spent PD dialysate samples were collected, on average, 25±13 days (median, 20; range, 10-45) after the onset of symptoms. The temporal distance of PD effluent collection relative to the closest positive nasal-swab RT-PCR result was 15±11 days (median, 14; range, 1-41). All 26 PD effluent samples tested negative at three SARS-CoV-2 genomic regions. Conclusions: Our findings indicate the absence of SARS-CoV-2 in spent PD dialysate collected at ≥10 days after the onset of COVID-19 symptoms. We cannot rule out the presence of SARS-CoV-2 in spent PD dialysate in the early stage of COVID-19.

Novel Use of Premixed Dialysate Bags during Water Supply Interruption in Acute Hospital Setting.

Patients on dialysis are exposed to large amounts of water during conventional intermittent hemodialysis; hence, there are strict regulations regarding the quality of water used to prepare dialysate. Occasionally, water systems fail due to natural disasters or structural supply issues, such as water-main breaks or unplanned changes in municipal or facility water quality. It is critical to regularly monitor and immediately recognize such a failure and take steps to avoid exposing the patients to contaminants. In addition to the recognition of the problem, the ability to pivot and continue to provide safe treatment to inpatients who are dependent on dialysis is essential, both from an ultrafiltration and a clearance standpoint. At our hospital, an unforeseen water disruption occurred and we were able to continue to provide KRT with premade, bagged dialysate to mitigate the effect on our patients on dialysis. This is a novel method using available machines and dialysate, which we normally stock for continuous KRT, for short dialysis sessions. The methodology is similar to that which has been widely used for short daily home hemodialysis with low dialysate flow rate. Because this situation occurred in the midst of the SARS-CoV-2 pandemic, we had to be mindful of dialysate volumes and staffing time. Here, we present our investigation into the cause of the water-system failure and how we quickly implemented the alternative dialysis method. Short dialysis with low-flow dialysate will not deliver the same Kt/V per session as standard dialysis; however, this method was successfully implemented and tailored with adjustments for patients requiring higher clearance for specific indications, such as severe hyperkalemia.

Protocol for Local On-Site Dialysate Production for Continuous Renal Replacement Therapy during the COVID-19 Pandemic.

AKI frequently occurs in patients with COVID-19, and kidney injury severe enough to require RRT is a common complication among patients who are critically ill. During the surge of the pandemic, there was a high demand for dialysate for continuous RRT, and this increase in demand, coupled with vulnerabilities in the supply chain, necessitated alternative approaches, including internal production of dialysate. Using a standard hemodialysis machine and off-the-shelf supplies, as per Food and Drug Administration guidelines, we developed a method for on-site dialysate production that is adaptable and can be used to fill multiple bags at once. The use of a central reverse osmosis unit, dedicated hemodialysis machine, sterile bags with separate ports for fill and use, and frequent testing will ensure stability, sterility, and-therefore-safety of the produced dialysate. The dialysate made in house was tested and it showed both stability and sterility for at least 30 hours. This detailed description of our process for generating dialysate can serve as a guide for other programs experiencing similar vulnerabilities in the demand versus supply of dialysate.

Peritoneal dialysis for acute kidney injury: Equations for dosing in pandemics, disasters, and beyond.

BACKGROUND: Peritoneal dialysis (PD) is a viable option for renal replacement therapy in acute kidney injury (AKI), especially in challenging times during disasters and pandemics when resources are limited. While PD techniques are well described, there is uncertainty about how to determine the amount of PD to be prescribed toward a target dose. The aim of this study is to derive practical equations to assist with the prescription of PD for AKI. METHODS: Using established physiological principles behind PD clearance and membrane transport, a primary determinant of dose delivery, equations were mathematically derived to estimate dialysate volume required to achieve a target dose of PD. RESULTS: The main derivative equation is VD = (1.2 × std-Kt/V × TBW)/(tdwell + 4), where VD is the total dialysate volume per day, std-Kt/V is the desired weekly dose, TBW is the total body water, and tdwell is the dwell time. VD can be expressed in terms of dwell volume, vdwell, by VD = (0.3 × std-Kt/V × TBW) - (6 × vdwell). Two further equations were derived which directly describe the mathematical relationship between tdwell and vdwell. A calculator is included as an Online Supplementary Material. CONCLUSIONS: The equations are intended as a practical tool to estimate solute clearances and guide prescription of continuous PD. The estimated dialysate volume required for any dose target can be calculated from cycle duration or dwell volume. However, the exact target dose of PD is uncertain and should be adjusted according to the clinical circumstances and response to treatment. The equations presented in this article facilitate the adjustment of PD prescription toward the targeted solute clearance.

ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention.

GUIDELINE 1: A pathophysiological taxonomy: A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing individualized dialysis or when planning modality transfer (e.g. to automated peritoneal dialysis (PD) or haemodialysis) in the context of shared and informed decision-making with the person on PD, taking individual circumstances and treatment goals into account. (practice point). GUIDELINE 2A: Identification of fast peritoneal solute transfer rate (PSTR): It is recommended that the PSTR is determined from a 4-h peritoneal equilibration test (PET), using either 2.5%/2.27% or 4.25%/3.86% dextrose/glucose concentration and creatinine as the index solute. (practice point) This should be done early in the course dialysis treatment (between 6 weeks and 12 weeks) (GRADE 1A) and subsequently when clinically indicated. (practice point). GUIDELINE 2B: Clinical implications and mitigation of fast solute transfer: A faster PSTR is associated with lower survival on PD. (GRADE 1A) This risk is in part due to the lower ultrafiltration (UF) and increased net fluid reabsorption that occurs when the PSTR is above the average value. The resulting lower net UF can be avoided by shortening glucose-based exchanges, using a polyglucose solution (icodextrin), and/or prescribing higher glucose concentrations. (GRADE 1A) Compared to glucose, use of icodextrin can translate into improved fluid status and fewer episodes of fluid overload. (GRADE 1A) Use of automated PD and icodextrin may mitigate the mortality risk associated with fast PSTR. (practice point). GUIDELINE 3: Recognizing low UF capacity: This is easy to measure and a valuable screening test. Insufficient UF should be suspected when either (a) the net UF from a 4-h PET is <400 ml (3.86% glucose/4.25% dextrose) or <100 ml (2.27% glucose /2.5% dextrose), (GRADE 1B) and/or (b) the daily UF is insufficient to maintain adequate fluid status. (practice point) Besides membrane dysfunction, low UF capacity can also result from mechanical problems, leaks or increased fluid absorption across the peritoneal membrane not explained by fast PSTR. GUIDELINE 4A: Diagnosing intrinsic membrane dysfunction (manifesting as low osmotic conductance to glucose) as a cause of UF insufficiency: When insufficient UF is suspected, the 4-h PET should be supplemented by measurement of the sodium dip at 1 h using a 3.86% glucose/4.25% dextrose exchange for diagnostic purposes. A sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at 1 h indicates UF insufficiency. (GRADE 2B). GUIDELINE 4B: Clinical implications of intrinsic membrane dysfunction (de novo or acquired): in the absence of residual kidney function, this is likely to necessitate the use of hypertonic glucose exchanges and possible transfer to haemodialysis. Acquired membrane injury, especially in the context of prolonged time on treatment, should prompt discussions about the risk of encapsulating peritoneal sclerosis. (practice point). GUIDELINE 5: Additional membrane function tests: measures of peritoneal protein loss, intraperitoneal pressure and more complex tests that estimate osmotic conductance and 'lymphatic' reabsorption are not recommended for routine clinical practice but remain valuable research methods. (practice point). GUIDELINE 6: Socioeconomic considerations: When resource constraints prevent the use of routine tests, consideration of membrane function should still be part of the clinical management and may be inferred from the daily UF in response to the prescription. (practice point).

Deployment of a New CRRT/PIRRT Device during the COVID-19 Pandemic Emergency: Organizational Challenges and Implementation Results.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to increased demand nationwide for dialysis equipment, including supplies and machines. To meet the demand in our institution, our surge plan included rapid mobilization of a novel continuous renal replacement treatment (CRRT) machine named SAMI. The SAMI is a push-pull filtration enhanced dialysis machine that can conjugate extremely high single-pass solute removal efficiency with very precise fluid balance control. MATERIAL AND METHODS: Machine assembly was conducted on-site by local biomedical engineers with remote assistance by the vendor. One 3-h virtual training session of 3 dialysis nurses was conducted before SAMI deployment. The SAMI was deployed in prolonged intermittent replacement therapy (PIRRT) mode to maximize patients covered per machine per day. Live on-demand vendor support was provided to troubleshoot any issues for the first few cases. After 4 weeks of the SAMI implementation, data on treatments with the SAMI were collected, and a questionnaire was provided to the nurse trainees to assess device usability. RESULTS: On-site installation of the SAMI was accomplished with remote assistance. Delivery of remote training was successfully achieved. 23 PIRRT treatments were conducted in 10 patients. 7/10 of patients had CO-VID-19. The median PIRRT dose was 50 mL/kg/h (IQR [interquartile range] 44 - 62 mL/kg/h), and duration of the treatment was 8 h (IQR 6.3 - 8 h). Solute control was adequate. The user response was favorable to the set of usability questions involving user interface, on-screen instructions, machine setup, troubleshooting, and the ease of moving the machine. CONCLUSION: Assembly of the SAMI and training of nurses remotely are possible when access to vendor employees is restricted during states of emergency. The successful deployment of the SAMI in our institution during the pandemic with only 3-h virtual training supports that operating the SAMI is simple and safe.

Adsorption of Uremic Toxins Using Ti3C2Tx MXene for Dialysate Regeneration.

The COVID-19 pandemic has become a major worldwide crisis. Although respiratory symptoms are a key feature of the disease, many people who are hospitalized with COVID-19 also suffer acute kidney injury, a condition that exacerbates patient mortality and may have to be treated through renal replacement therapy. Much of the focus on hospital capacity during the pandemic has centered on the availability of ventilators. However, supplies for dialysis treatment, including dialysate, have also run dangerously low in hospitals at the epicenter of the pandemic. Therefore, there is an urgent need to develop materials that can efficiently and rapidly regenerate dialysate, removing toxins and restoring electrolyte concentrations so that this vital resource remains readily available. In this work, Ti3C2Tx, a two-dimensional transition-metal carbide (MXene) that is known to efficiently adsorb urea, was used to remove creatinine and uric acid from an aqueous solution and dialysate, with a maximum adsorption capacity of 45.7 and 17.0 mg/g, respectively. We systematically analyzed and modeled the adsorption kinetics, isotherms, and thermodynamics, thus determining the rate-limiting step and adsorption mechanism. A fixed-bed column loaded with Ti3C2Tx was designed to further evaluate the adsorption performance under continuous fluid-flow conditions, mirroring conditions of continuous renal replacement therapy modalities. The maximum capacity and 50% breakthrough volume were calculated to further approach the practical application of Ti3C2Tx for removal of uremic toxins. Our findings suggest that Ti3C2Tx has the potential to be used as an efficient sorbent for the regeneration of dialysate, allowing for accelerated dialysate regeneration by removing filtered toxins and leading to more portable dialysis devices.

Urgent Peritoneal Dialysis in Patients With COVID-19 and Acute Kidney Injury: A Single-Center Experience in a Time of Crisis in the United States.

At Montefiore Medical Center in The Bronx, NY, the first case of coronavirus disease 2019 (COVID-19) was admitted on March 11, 2020. At the height of the pandemic, there were 855 patients with COVID-19 admitted on April 13, 2020. Due to high demand for dialysis and shortages of staff and supplies, we started an urgent peritoneal dialysis (PD) program. From April 1 to April 22, a total of 30 patients were started on PD. Of those 30 patients, 14 died during their hospitalization, 8 were discharged, and 8 were still hospitalized as of May 14, 2020. Although the PD program was successful in its ability to provide much-needed kidney replacement therapy when hemodialysis was not available, challenges to delivering adequate PD dosage included difficulties providing nurse training and availability of supplies. Providing adequate clearance and ultrafiltration for patients in intensive care units was especially difficult due to the high prevalence of a hypercatabolic state, volume overload, and prone positioning. PD was more easily performed in non-critically ill patients outside the intensive care unit. Despite these challenges, we demonstrate that urgent PD is a feasible alternative to hemodialysis in situations with critical resource shortages.

Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic.

With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic.