Effects of Delayed Graft Function on Transplant Outcomes: A Meta-analysis.

Delayed graft function (DGF) is a frequent complication of kidney transplantation, but its impact on long- and short-term transplant outcomes is unclear. We conducted a systematic literature search for studies published from 2007 to 2020 investigating the association between DGF and posttransplant outcomes. Forest plots stratified between center studies and registry studies were created with pooled odds ratios. Posttransplant outcomes including graft failure, acute rejection, patient mortality, and kidney function were analyzed. Of the 3422 articles reviewed, 38 papers were included in this meta-analysis. In single-center studies, patients who experienced DGF had increased graft failure (odds ratio [OR] 3.38; 95% confidence interval [CI], 1.85-6.17; P < 0.01), acute allograft rejection (OR 1.84; 95% CI, 1.30-2.61; P < 0.01), and mortality (OR 2.32; 95% CI, 1.53-3.50; P < 0.01) at 1-y posttransplant. Registry studies showed increased graft failure (OR 3.66; 95% CI, 3.04-4.40; P < 0.01) and acute rejection (OR 3.24; 95% CI, 1.88-5.59; P < 0.01) but not mortality (OR 2.27; 95% CI, 0.97-5.34; P = 0.06) at 1-y posttransplant. DGF was associated with increased odds of graft failure, acute rejection, and mortality. These results in this meta-analysis could help inform the selection process, treatment, and monitoring of transplanted kidneys at high risk of DGF.

Proximal aortic repair in dialysis patients: A national database analysis.

OBJECTIVES: Dialysis is a well-established risk factor for morbidity and mortality after cardiovascular procedures. However, little is known regarding the outcomes of proximal aortic surgery in this high-risk cohort. METHODS: Perioperative (in-hospital or 30-day mortality) and 10-year outcomes were analyzed for all the patients who underwent open proximal aortic repair with the diagnosis of nonruptured thoracic aortic aneurysm (aneurysm, n = 325) or type A aortic dissection (dissection, n = 461) from 1987 to 2015 using the US Renal Data System database. RESULTS: In patients with aneurysm, perioperative mortality was 12.6%. The 10-year mortality was 81% ± 3%. Age 65 years or more (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.03 to 1.78; P = .03), chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.01-2.82; P = .047), and Black race (HR, 1.46; 95% CI, 1.09-1.97; P = .01) were independently associated with worse 10-year mortality. In patients with dissection, perioperative mortality was 24.3% and 10-year mortality was 87.9% ± 2.2%. Age 65 years or more (HR, 1.49; 95% CI, 1.19-1.86; P < .001), congestive heart failure (HR, 1.39; 95% CI, 1.11-2.57; P = .004), and diabetes mellitus as the cause of dialysis (HR, 1.75; 95% CI, 1.2-2.57; P = .004) were independently associated with worse 10-year mortality. Black race (HR, 0.74; 95% CI, 0.6-0.92; P = .008) was associated with a better outcome. CONCLUSIONS: We described challenging perioperative and 10-year outcomes for dialysis patients undergoing proximal aortic repair. The present study suggests the need for careful patient selection in the elective repair of proximal aortic aneurysm for dialysis-dependent patients, whereas it affirms the feasibility of emergency surgery for acute type A aortic dissections.

Kidney nonprocurement in deceased donors with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is common in deceased organ donors and is associated with high rates of kidney discard by transplant centers. High discard rates may consequently drive nonprocurement of these kidneys by organ procurement organizations. We aimed to study the relationship between donor AKI and kidney nonprocurement. METHODS: Using U.S. registry data, we identified donors with at least one organ recovered from 2008 to 2018. We compared characteristics of donors with no kidneys procured across AKI stages, and used multivariable logistic regression to evaluate the relationship between AKI severity and kidney nonprocurement. RESULTS: Overall 14 543 kidneys from 7620 donors were not procured, among which 93% were from donors with AKI. For 6945 donors with no kidneys procured but an extrarenal organ recovered, most had stage 3 (51%), followed by stage 1 (27%) and stage 2 AKI (15%). Nonprocured stage 3 donors were the youngest and had the lowest Kidney Donor Risk Index of all nonprocured donors. Adjusted odds of kidney nonprocurement were 1.14 (95%CI 1.02-1.27) for stage 1, 1.25 (95%CI 1.12-1.41) for stage 2, and 10.37 (95%CI 9.30-11.56) for stage 3 donors, compared to non-AKI donors. Among donors with minimum creatinine <1.5 mg/dl, stage 2 and 3 AKI were still associated with significantly higher odds of nonprocurement. CONCLUSIONS: AKI severity is a strong risk factor for kidney nonprocurement. Efforts to address the organ shortage should focus on encouraging procurement and utilization of kidneys from deceased donors with severe AKI, given the large and rising prevalence of donor AKI and excellent transplant outcomes with these kidneys.

Optimizing Perioperative Renal Replacement Therapy for Patients Undergoing Cardiac Surgical Procedures Requiring Cardiopulmonary Bypass.

Coronary artery disease is highly prevalent in patients with end-stage renal disease (ESRD), and cardiovascular complications remain the most common cause of death in this patient population. Accordingly, many cardiac surgical procedures requiring cardiopulmonary bypass support are performed on these patients each year, with morbidity and mortality rates far exceeding patients without ESRD. Anuric patients lack the normal renal homeostatic functions which typically allow for physiologic protection from challenges during the operation, such as volume overload, hyperkalemia, and acidemia. Careful preoperative planning and coordination to provide pre-, intra-, and postoperative renal replacement therapies for such patients are imperative. Many different strategies have been reported in the literature. Zero-balance ultrafiltration is a newer strategy which utilizes convective ultrafiltration much like pre-filter continuous renal replacement therapy and utilizes pre-existing connections on the cardiopulmonary bypass pump performed by the perfusion team. This allows for control of potassium concentration throughout the operation with existing personnel and minimal additional equipment. Here, we describe the unique challenges caring for patients receiving renal replacement therapy undergoing cardiac surgical procedures requiring cardiopulmonary bypass.

Snapshots of nascent RNA reveal cell- and stimulus-specific responses to acute kidney injury.

The current strategy to detect acute injury of kidney tubular cells relies on changes in serum levels of creatinine. Yet serum creatinine (sCr) is a marker of both functional and pathological processes and does not adequately assay tubular injury. In addition, sCr may require days to reach diagnostic thresholds, yet tubular cells respond with programs of damage and repair within minutes or hours. To detect acute responses to clinically relevant stimuli, we created mice expressing Rosa26-floxed-stop uracil phosphoribosyltransferase (Uprt) and inoculated 4-thiouracil (4-TU) to tag nascent RNA at selected time points. Cre-driven 4-TU-tagged RNA was isolated from intact kidneys and demonstrated that volume depletion and ischemia induced different genetic programs in collecting ducts and intercalated cells. Even lineage-related cell types expressed different genes in response to the 2 stressors. TU tagging also demonstrated the transient nature of the responses. Because we placed Uprt in the ubiquitously active Rosa26 locus, nascent RNAs from many cell types can be tagged in vivo and their roles interrogated under various conditions. In short, 4-TU labeling identifies stimulus-specific, cell-specific, and time-dependent acute responses that are otherwise difficult to detect with other technologies and are entirely obscured when sCr is the sole metric of kidney damage.

Polyuria due to Pressure Natriuresis in Venoarterial Extracorporeal Membrane Oxygenation.

We report a case of a 40-year-old woman who developed profound polyuria (>25 L urine output) immediately after initiation of venoarterial (VA) extracorporeal membrane oxygenation (ECMO). Investigations into the cause determined the polyuria was due to marked natriuresis (>85 g of sodium excreted in 1 day). This natriuresis persisted despite low cardiac filling pressures and high-negative ECMO venous pressures, suggesting clinical hypovolemia due to pressure natriuresis from locally high pressures at the renal artery due to arterial ECMO inflow. As ECMO flows were decreased, polyuria and natriuresis resolved. To our knowledge, this is the first description of VA-ECMO-associated salt wasting.

Successful Use of Arteriovenous Graft for Hemodialysis Access After Left Ventricular Assist Device Placement.

Kidney replacement therapy is required in up to one-third of patients after left ventricular assist device (LVAD) placement. A subset of these patients requires long-term maintenance hemodialysis and therefore needs durable vascular access but the ideal access in such patients has not been established. We present a series of 3 patients in whom arteriovenous grafts (AVGs) were successfully used for long-term kidney replacement therapy after LVAD placement. The maximum time from AVG placement to first successful AVG use was 40 days, and the longest AVG use duration was more than 2 years. 2 patients required AVG excision due to infection but both had successful placement of a second AVG. Total time on kidney replacement therapy was 993, 1,055, and 956 days for the 3 cases, of which dialysis catheter use was required for only 23%, 6.5%, and 27%, respectively. These cases suggest that AVG placement is a viable option for dialysis access in patients with LVADs.

Post-acute COVID-19 syndrome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

Continuous renal replacement therapy and the COVID pandemic.

Severe COVID-19 illness and the consequent cytokine storm and vasodilatory shock commonly lead to ischemic acute kidney injury (AKI). The need for renal replacement therapies (RRTs) in those with the most severe forms of AKI is considerable and risks overwhelming health-care systems at the peak of a surge. We detail the challenges and considerations involved in the preparation of a disaster response plan in situations such as the COVID-19 pandemic, which dramatically increase demand for nephrology services. Taking careful inventory of all aspects of an RRT program (personnel, consumables, and machines) before a surge in RRT arises and developing disaster contingency protocol anticoagulation and for shared RRT models when absolutely necessary are paramount to a successful response to such a disaster.

Mortality and renal outcomes of patients with severe COVID-19 treated in a provisional intensive care unit.

COVID-19 has created an enormous health crisis and this spring New York City had a severe outbreak that pushed health and critical care resources to the limit. A lack of adequate space for mechanically ventilated patients induced our hospital to convert operating rooms into critical care areas (OR-ICU). A large number of COVID-19 will develop acute kidney injury that requires renal replacement therapy (RRT). We included 116 patients with COVID-19 who required mechanical ventilation and were cared for in our OR-ICU. At 90 days and at discharge 35 patients died (30.2%). RRT was required by 45 of the 116 patients (38.8%) and 18 of these 45 patients (40%) compared to 17 with no RRT (23.9%, ns) died during hospitalization and after 90 days. Only two of the 27 patients who required RRT and survived required RRT at discharge and 90 days. When defining renal recovery as a discharge serum creatinine within 150% of baseline, 68 of 78 survivors showed renal recovery (87.2%). Survival was similar to previous reports of patients with severe COVID-19 for patients cared for in provisional ICUs compared to standard ICUs. Most patients with severe COVID-19 and AKI are likely to recover full renal function.

Increased Mortality Associated with Hypermagnesemia in Severe COVID-19 Illness.

Background: Although electrolyte abnormalities are common among patients with COVID-19, very little has been reported on magnesium homeostasis in these patients. Here we report the incidence of hypermagnesemia, and its association with outcomes among patients admitted with COVID-19. Methods: We retrospectively identified all patients with a positive test result for SARS-CoV-2 who were admitted to a large quaternary care center in New York City in spring 2020. Details of the patients' demographics and hospital course were obtained retrospectively from medical records. Patients were defined as having hypermagnesemia if their median magnesium over the course of their hospitalization was >2.4 mg/dl. Results: A total of 1685 patients hospitalized with COVID-19 had their magnesium levels checked during their hospitalization, and were included in the final study cohort, among whom 355 (21%) had hypermagnesemia. Patients who were hypermagnesemic had a higher incidence of shock requiring pressors (35% vs 27%, P<0.01), respiratory failure requiring mechanical ventilation (28% vs 21%, P=0.01), AKI (65% vs 50%, P<0.001), and AKI severe enough to require renal replacement therapy (18% vs 5%, P<0.001). In an adjusted multivariable model, hypermagnesemia was observed more commonly with increasing age, male sex, AKI requiring RRT, hyperkalemia, and higher CPK. Survival probability at 30 days was 34% for the patients with hypermagnesemia, compared with 65% for patients without hypermagnesemia. An adjusted multivariable time to event analysis identified an increased risk of mortality with older age, need for vasopressors, higher C-reactive protein levels, and hypermagnesemia (HR, 2.03; 95% CI, 1.63 to 2.54, P<0.001). Conclusions: In conclusion, we identified an association between hypermagnesemia among patients hospitalized with COVID-19 and increased mortality. Although the exact mechanism of this relationship remains unclear, hypermagnesemia potentially represents increased cell turnover and higher severity of illness, which is frequently associated with more severe forms of AKI.

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.

High rate of renal recovery in survivors of COVID-19 associated acute renal failure requiring renal replacement therapy.

INTRODUCTION: A large proportion of patients with COVID-19 develop acute kidney injury (AKI). While the most severe of these cases require renal replacement therapy (RRT), little is known about their clinical course. METHODS: We describe the clinical characteristics of COVID-19 patients in the ICU with AKI requiring RRT at an academic medical center in New York City and followed patients for outcomes of death and renal recovery using time-to-event analyses. RESULTS: Our cohort of 115 patients represented 23% of all ICU admissions at our center, with a peak prevalence of 29%. Patients were followed for a median of 29 days (2542 total patient-RRT-days; median 54 days for survivors). Mechanical ventilation and vasopressor use were common (99% and 84%, respectively), and the median Sequential Organ Function Assessment (SOFA) score was 14. By the end of follow-up 51% died, 41% recovered kidney function (84% of survivors), and 8% still needed RRT (survival probability at 60 days: 0.46 [95% CI: 0.36-0.56])). In an adjusted Cox model, coronary artery disease and chronic obstructive pulmonary disease were associated with increased mortality (HRs: 3.99 [95% CI 1.46-10.90] and 3.10 [95% CI 1.25-7.66]) as were angiotensin-converting-enzyme inhibitors (HR 2.33 [95% CI 1.21-4.47]) and a SOFA score >15 (HR 3.46 [95% CI 1.65-7.25). CONCLUSIONS AND RELEVANCE: Our analysis demonstrates the high prevalence of AKI requiring RRT among critically ill patients with COVID-19 and is associated with a high mortality, however, the rate of renal recovery is high among survivors and should inform shared-decision making.

Rule Out Acute Kidney Injury in the Emergency Department With a Urinary Dipstick.

INTRODUCTION: The identification of acute injury of the kidney relies on serum creatinine (SCr), a functional marker with poor temporal resolution as well as limited sensitivity and specificity for cellular injury. In contrast, urinary biomarkers of kidney injury have the potential to detect cellular stress and damage in real time. METHODS: To detect the response of the kidney to injury, we have tested a lateral flow dipstick that measures a urinary protein called neutrophil gelatinase-associated lipocalin (NGAL). Analysis of urine was performed in a prospective cohort of 479 patients (final cohort N = 426) entering an emergency department in New York City and subsequently admitted for inpatient care. RESULTS: Colorimetric development had high interrater reliability (88% concordance rate) and correlated with traditional enzyme-linked immunosorbent assay (ELISA) measurements (ρ = 0.732, P < .0001). Of the 14% of the cohort who met Acute Kidney Injury Network (AKIN) SCr criteria for acute kidney injury (AKI), 67% demonstrated transient (<2 days) and 33% demonstrated sustained (>2 days) elevation of SCr. Comparing the outcomes of patients with sustained versus transient or undetectable changes in SCr revealed that the urinary NGAL (uNGAL) dipstick had high specificity and negative predictive value (NPV) (high- vs. low-intermediate readings, sensitivity = 0.55, specificity = 0.91, positive predictive value = 0.24, NPV = 0.97, χ2 = 20.39, P < 0.001). CONCLUSION: We show that the introduction of a bedside uNGAL dipstick permits accurate triage by identifying individuals who do not have tubular injury. In an era of shortening length of stay and rapid decisions based on isolated SCr measurements, real-time exclusion of kidney injury by a dipstick will be particularly useful to overcome the retrospective, insensitive, and nonspecific attributes of SCr.

Outcomes for Patients With COVID-19 and Acute Kidney Injury: A Systematic Review and Meta-Analysis.

INTRODUCTION: There are limited data on the association of kidney dysfunction with prognosis in coronavirus disease 2019 (COVID-19), and the extent to which acute kidney injury (AKI) predisposes patients to severe illness and inferior outcomes is unclear. We aim to assess the incidence of AKI among patients with COVID-19 and examine their associations with patient outcomes as reported in the available literature thus far. METHODS: We systematically searched MEDLINE, EMBASE, SCOPUS, and MedRxiv databases for full-text articles available in English published from December 1, 2019 to May 24, 2020. Clinical information was extracted and examined from 20 cohorts that met inclusion criteria, covering 13,137 mostly hospitalized patients confirmed to have COVID-19. Two authors independently extracted study characteristics, results, outcomes, study-level risk of bias, and strength of evidence across studies. Neither reviewer was blind to journal titles, study authors, or institutions. RESULTS: Median age was 56 years, with 55% male patients. Approximately 43% of patients had severe COVID-19 infection, and approximately 11% died. Prevalence of AKI was 17%; 77% of patients with AKI experienced severe COVID-19 infection, and 52% died. AKI was associated with increased odds of death among COVID-19 patients (pooled odds ratio, 15.27; 95% CI 4.82-48.36), although there was considerable heterogeneity across studies and among different regions in the world. Approximately 5% of all patients required use of renal replacement therapy (RRT). CONCLUSIONS: Kidney dysfunction is common among patients with COVID-19, and patients who develop AKI have inferior outcomes. Additional research into management and potential mechanisms of this association is needed.