Altered lung physiology in two cohorts after COVID-19 infection as assessed by computed cardiopulmonography.

The longer-term effects of COVID-19 on lung physiology remain poorly understood. Here, a new technique, computed cardiopulmonography (CCP), was used to study two COVID-19 cohorts (MCOVID and C-MORE-LP) at both ∼6 and ∼12 mo after infection. CCP is comprised of two components. The first is collection of highly precise, highly time-resolved measurements of gas exchange with a purpose-built molecular flow sensor based around laser absorption spectroscopy. The second component is estimation of physiological parameters by fitting a cardiopulmonary model to the data set. The measurement protocol involved 7 min of breathing air followed by 5 min of breathing pure O2. One hundred seventy-eight participants were studied, with 97 returning for a repeat assessment. One hundred twenty-six arterial blood gas samples were drawn from MCOVID participants. For participants who had required intensive care and/or invasive mechanical ventilation, there was a significant increase in anatomical dead space of ∼30 mL and a significant increase in alveolar-to-arterial Po2 gradient of ∼0.9 kPa relative to control participants. Those who had been hospitalized had reductions in functional residual capacity of ∼15%. Irrespectively of COVID-19 severity, participants who had had COVID-19 demonstrated a modest increase in ventilation inhomogeneity, broadly equivalent to that associated with 15 yr of aging. This study illustrates the capability of CCP to study aspects of lung function not so easily addressed through standard clinical lung function tests. However, without measurements before infection, it is not possible to conclude whether the findings relate to the effects of COVID-19 or whether they constitute risk factors for more serious disease.NEW & NOTEWORTHY This study used a novel technique, computed cardiopulmonography, to study the lungs of patients who have had COVID-19. Depending on severity of infection, there were increases in anatomical dead space, reductions in absolute lung volumes, and increases in ventilation inhomogeneity broadly equivalent to those associated with 15 yr of aging. However, without measurements taken before infection, it is unclear whether the changes result from COVID-19 infection or are risk factors for more severe disease.

Patient knowledge and adherence to maintenance hemodialysis: an International comparison study.

BACKGROUND: Non-adherence to hemodialysis (HD) is associated with increased morbidity and mortality. In this cross-sectional study, we compared correlates and rates of non-adherence between the US and Japan to determine if differences in patient knowledge about HD might account for international variation in adherence. METHODS: We evaluated 100 US and 116 Japanese patients on maintenance HD. Patient knowledge was scored based on the identification of their vascular access, dry weight, cause of kidney disease, and ≥ 3 phosphorus- and potassium-rich foods. Patients were considered non-adherent if they missed > 3% of HD sessions in 3 months. RESULTS: 23% of the US and none of the Japanese patients were non-adherent. Using logistic regression, we found that in the US non-adherence was more common in black patients [Odds ratio (OR) 3.98; 95% confidence interval (CI) 1.42-11.22], while high school graduates (OR 0.20; 95% CI 0.05-0.81) and those on the transplant waiting list (OR 0.25; 95% CI 0.083-0.72) were less likely to miss their treatments. There was no significant association between knowledge and non-adherence in the US. However, Japanese patients had significantly higher levels of HD knowledge than US patients after adjusting for age (p < 0.001). CONCLUSION: Age-adjusted HD knowledge was higher and non-adherence rates were lower in Japan vs. the US. However, because of the unexpected finding of 100% adherence in Japan, we were unable to formally test whether knowledge was significantly associated with adherence across both countries. Further research is needed to understand the reasons behind the higher non-adherence rates in the US.

Antineutrophil cytoplasmic antibody-positive pauci-immune glomerulonephritis associated with mantle cell lymphoma.

Renal involvement in non-Hodgkin lymphoma, especially mantle cell lymphoma (MCL) is rare. A 77-year-old man presented with acute kidney injury (AKI), which rapidly progressed to dialysis dependence. Kidney biopsy revealed patchy B-cell lymphocytic aggregates in the interstitium, which were positive for cyclin D1, consistent with atypical CD5-negative MCL as confirmed by the detection of translocation t(11;14) by FISH. Crescents were noted in 3 of 26 glomeruli; while PR-3 antineutrophil cytoplasmic antibody (ANCA) positivity and negative immunofluorescence suggested an additional pauci-immune (rapidly progressive) glomerulonephritis pattern of injury. Patient received chemotherapy (cyclophosphamide, vincristine, and prednisone), which improved his renal function and allowed for discontinuation of hemodialysis. However, he died from pulmonary hemorrhage 8 months after initial presentation. This is the first reported case of a patient with coexistence of renal MCL infiltration and ANCA-positive pauci-immune glomerulonephritis.

Saliva Urea Nitrogen Continuously Reflects Blood Urea Nitrogen after Acute Kidney Injury Diagnosis and Management: Longitudinal Observational Data from a Collaborative, International, Prospective, Multicenter Study.

BACKGROUND: Acute kidney injury (AKI) is a growing global concern and often reversible. Saliva urea nitrogen (SUN) measured by a dipstick may allow rapid diagnosis. We studied longitudinal agreement between SUN and blood urea nitrogen (BUN) and the diagnostic performance of both. METHODS: Agreement between SUN and BUN and diagnostic performance to diagnose AKI severity in AKI patients in the United States and Brazil were studied. Bland-Altman analysis and linear mixed effects models were employed to test the agreement between SUN and BUN. Receiver operating characteristics statistics were used to test the diagnostic performance to diagnose AKI severity. RESULTS: We found an underestimation of BUN by SUN, decreasing with increasing BUN levels in 37 studied patients, consistent on all observation days. The diagnostic performance of SUN (AUC 0.81, 95% CI 0.63-0.98) was comparable to BUN (AUC 0.85, 95% CI 0.71-0.98). CONCLUSION: SUN reflects BUN especially in severe AKI. It also allows monitoring treatment responses. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=445041.

Delirium in critically ill military patients following trauma: A cohort analysis.

Critically ill military trauma patients have been found to have a high incidence of psychological morbidity following their Intensive Care Unit (ICU) experience, including recall of significant auditory and visual hallucinations. It follows that this may be attributable to delirium, which has not been previously described in a young, previously fit population following trauma. The case-notes of 85 male patients (mean age 26 years), admitted to a single UK ICU following military trauma, were retrospectively assessed for delirium using DSM-IV criteria. Of the 993 ICU days assessed, 13.4% were delirium-positive, with just over half of patients (51.8%) experiencing at least one day of delirium. On delirium-positive days, 69.2% received a documented intervention, with the majority of interventions (66.4%) being pharmacological, commonly with a sedative or anti-psychotic. Presence of delirium was significantly associated with severity of injury, assessed by Injury Severity Score (OR 1.037, 95% CI 1.003-1.072, p = 0.031). Duration of ICU stay was significantly increased, from 4 to 8 days (p < 0.005), as was the duration of mechanical ventilation (for the 84.7% of patients who were ventilated) from 7 to 13 days (p < 0.005). Delirium is common in military trauma patients, despite their young age and premorbid fitness. A review of longer-term psychological outcomes should be considered.

Disaster Preparedness and Awareness of Patients on Hemodialysis after Hurricane Sandy.

BACKGROUND AND OBJECTIVES: Patients with ESRD on dialysis live in a complex sociomedical situation and are dependent on technology and infrastructure, such as transportation, electricity, and water, to sustain their lives. Interruptions of this infrastructure by natural disasters can result in devastating outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between November of 2013 and April of 2014, a cross-sectional survey was conducted of patients who received maintenance hemodialysis before and after the landfall of Hurricane Sandy on October 29, 2012 in lower Manhattan, New York. The primary outcome was the number of missed dialysis sessions after the storm. Dialysis-specific and general disaster preparedness were assessed using checklists prepared by the National Kidney Foundation and US Homeland Security, respectively. RESULTS: In total, 598 patients were approached, and 357 (59.7%) patients completed the survey. Participants were 60.2% men and 30.0% black, with a median age of 60 years old; 94 (26.3%) participants missed dialysis (median of two sessions [quartile 1 to quartile 3 =1-3]), and 236 (66.1%) participants received dialysis at nonregular dialysis unit(s): 209 (58.5%) at affiliated dialysis unit(s) and 27 (7.6%) at emergency rooms. The percentages of participants who carried their insurance information and detailed medication list were 75.9% and 44.3%, respectively. Enhancement of the dialysis emergency packet after the hurricane was associated with a significantly higher cache of medical records at home at follow-up survey (P<0.001, Fisher's exact test). Multivariate Poisson regression analysis showed that dialysis-specific preparedness (incidence rate ratio, 0.91; 95% confidence interval, 0.87 to 0.98), other racial ethnicity (incidence rate ratio, 0.34; 95% confidence interval, 0.20 to 0.57), dialysis treatment in affiliated units (incidence rate ratio, 0.69; 95% confidence interval, 0.51 to 0.94), and older age (incidence rate ratio, 0.98; 95% confidence interval, 0.97 to 0.99) were associated with a significantly lower incidence rate ratio of missed dialysis. CONCLUSIONS: There is still room to improve the preparedness for natural disasters of patients with ESRD. Provider- or facility-oriented enhancement of awareness of the disease and preparedness should be a priority.

Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement.

OBJECTIVE: Methanol poisoning can induce death and disability. Treatment includes the administration of antidotes (ethanol or fomepizole and folic/folinic acid) and consideration of extracorporeal treatment for correction of acidemia and/or enhanced elimination. The Extracorporeal Treatments in Poisoning workgroup aimed to develop evidence-based consensus recommendations for extracorporeal treatment in methanol poisoning. DESIGN AND METHODS: Utilizing predetermined methods, we conducted a systematic review of the literature. Two hundred seventy-two relevant publications were identified but publication and selection biases were noted. Data on clinical outcomes and dialyzability were collated and a two-round modified Delphi process was used to reach a consensus. RESULTS: Recommended indications for extracorporeal treatment: Severe methanol poisoning including any of the following being attributed to methanol: coma, seizures, new vision deficits, metabolic acidosis with blood pH ≤ 7.15, persistent metabolic acidosis despite adequate supportive measures and antidotes, serum anion gap higher than 24 mmol/L; or, serum methanol concentration 1) greater than 700 mg/L (21.8 mmol/L) in the context of fomepizole therapy, 2) greater than 600 mg/L or 18.7 mmol/L in the context of ethanol treatment, 3) greater than 500 mg/L or 15.6 mmol/L in the absence of an alcohol dehydrogenase blocker; in the absence of a methanol concentration, the osmolal/osmolar gap may be informative; or, in the context of impaired kidney function. Intermittent hemodialysis is the modality of choice and continuous modalities are acceptable alternatives. Extracorporeal treatment can be terminated when the methanol concentration is <200 mg/L or 6.2 mmol/L and a clinical improvement is observed. Extracorporeal Treatments in Poisoning inhibitors and folic/folinic acid should be continued during extracorporeal treatment. General considerations: Antidotes and extracorporeal treatment should be initiated urgently in the context of severe poisoning. The duration of extracorporeal treatment extracorporeal treatment depends on the type of extracorporeal treatment used and the methanol exposure. Indications for extracorporeal treatment are based on risk factors for poor outcomes. The relative importance of individual indications for the triaging of patients for extracorporeal treatment, in the context of an epidemic when need exceeds resources, is unknown. In the absence of severe poisoning but if the methanol concentration is elevated and there is adequate alcohol dehydrogenase blockade, extracorporeal treatment is not immediately required. Systemic anticoagulation should be avoided during extracorporeal treatment because it may increase the development or severity of intracerebral hemorrhage. CONCLUSION: Extracorporeal treatment has a valuable role in the treatment of patients with methanol poisoning. A range of clinical indications for extracorporeal treatment is provided and duration of therapy can be guided through the careful monitoring of biomarkers of exposure and toxicity. In the absence of severe poisoning, the decision to use extracorporeal treatment is determined by balancing the cost and complications of extracorporeal treatment to that of fomepizole or ethanol. Given regional differences in cost and availability of fomepizole and extracorporeal treatment, these decisions must be made at a local level.

Successfully treated calcific uremic arteriolopathy: two cases of a high anion gap metabolic acidosis with intravenous sodium thiosulfate.

Calcific uremic arteriolopathy (CUA) is a rare and potentially fatal disorder of calcification involving subcutaneous small vessels and fat in patients with renal insufficiency. We describe the successful use of intravenous sodium thiosulfate (STS) for the treatment of CUA in two patients. The first case was complicated by the development of a severe anion gap metabolic acidosis, which was accompanied by a seizure. Both patients had complete wound healing within five months. Although STS should be considered in the treatment of CUA, little is known about pharmacokinetics and additional studies are required to determine dosing strategies to minimize severe potential side effects.

Hepatorenal syndrome treated for eight months with continuous-flow peritoneal dialysis.

The case documented here represents the longest course of continuous-flow peritoneal dialysis (PD) reported in the literature. A 61-year-old man with hepatorenal syndrome type 1 and ascites presented with hypotension and bright red blood per rectum and was found to be in acute renal failure with severe anemia. Continuous-flow PD was initiated, and the patient improved clinically. The patient died of a jejunal bleed 8 months later, before discharge. Acute PD or continuous-flow PD is a viable alternative in the setting of hemodynamic instability and ascites, can be used as a chronic modality, and addresses many of the weaknesses of continuous ambulatory and automated PD.

Hemodialysis for the treatment of pulmonary hemorrhage from dabigatran overdose.

Dabigatran is an oral direct thrombin inhibitor indicated for thromboembolism prophylaxis in patients with nonvalvular atrial fibrillation. Since its approval in the United States in 2010, dabigatran-associated hemorrhages have garnered much attention because bleeding rates were higher than initially expected. Additionally, reversing anticoagulation remains challenging. Traditional modes of reversing warfarin-associated coagulopathies are ineffective in reversing anticoagulation from dabigatran. Although hemodialysis is proposed as a method to accelerate dabigatran elimination, evidence supporting its clinical utility remains unproved. We report the case of an 80-year-old man who presented with worsening hemoptysis in the setting of unintentional ingestion of excess dabigatran. Despite transfusion of 2 units of fresh frozen plasma, he continued to bleed, although his international normalized ratio improved from 8.8 to 7.2. He underwent hemodialysis, and serum dabigatran concentration decreased from 1,100 to 18 ng/mL over 4 hours, with an initial extraction ratio of 0.97 and blood clearance of 291 mL/min. Although his serum dabigatran concentration rebounded to 100 ng/mL 20 minutes after the cessation of dialysis, his bleeding stopped and he improved clinically. Hemorrhage in the setting of dabigatran anticoagulation remains a therapeutic predicament. Hemodialysis may play an adjunct role in accelerating the elimination of dabigatran in bleeding patients.

Extracorporeal treatment for thallium poisoning: recommendations from the EXTRIP Workgroup.

BACKGROUND: The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl). METHODS: After an extensive search, the co-chairs reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed during a conference call. A second vote determined the final recommendations. RESULTS: Forty-five articles met inclusion criteria. Only case reports and case series were identified, yielding a very low quality of evidence for all recommendations. Data on 74 patients, including 11 who died, were abstracted. The workgroup concluded that Tl is slightly dialyzable and made the following recommendations: ECTR is recommended in severe Tl poisoning (1D). ECTR is indicated if Tl exposure is highly suspected on the basis of history or clinical features (2D) or if the serum Tl concentration is >1.0 mg/L (2D). ECTR should be initiated as soon as possible, ideally within 24-48 hours of Tl exposure (1D), and be continued until the serum Tl concentration is <0.1 mg/L for a minimal duration of 72 hours (2D). CONCLUSION: Despite Tl's low dialyzability and the limited evidence, the workgroup strongly recommended extracorporeal removal in the case of severe Tl poisoning.

Continuous flow peritoneal dialysis: update 2012.

Continuous flow peritoneal dialysis (CFPD) is a technique of renal replacement therapy (RRT) dating back to the 1950s. Its essential features are a fixed intraperitoneal volume and rapid, continuous movement of dialysis solution into and out of the peritoneal cavity. Inlet and outlet catheters and a means of generating a large volume of sterile dialysate are required. External regeneration of dialysate via conventional hemodialysis equipment or sorbent technology mitigates the need for large volumes of sterile fluid and makes the technique feasible. Clearance depends on peritoneal mass transfer coefficient, rate of dialysate flow and efficiency of external regeneration. Studies to date all demonstrate small solute clearances 3-8 times greater than conventional automated peritoneal dialysis (APD). Catheter design is crucial to the clinical success of the technique and will be discussed. Potential applications include daily home dialysis, treatment of acute renal failure in the ICU, ultrafiltration of ascites, and the wearable artificial kidney.

The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: guideline methodology.

Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.

Uric acid levels and all-cause and cardiovascular mortality in the hemodialysis population.

BACKGROUND AND OBJECTIVES: Hyperuricemia is associated with hypertension, coronary artery disease, and chronic kidney disease. However, there are no specific data on the relationship of uric acid to cardiovascular disease in the chronic hemodialysis setting. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from 5827 patients on chronic hemodialysis from six countries affiliated with the Dialysis Outcomes and Practice Patterns Study (DOPPS) were analyzed. All laboratory data were based upon the initial cross-section of patients in DOPPS I and II. Cox regression was used to calculate the hazard ratio (HR) of all-cause and cardiovascular (CV) mortality with adjustments for case-mix including 14 classes of comorbidity. RESULTS: There were no clinically significant differences in baseline characteristics between those who had measured uric acid (n = 4637) and those who did not (n = 1190). Uric acid level was associated with lower all-cause mortality (HR: 0.95, 95% confidence interval [CI]: 0.90 to 1.00 per 1 mg/dl higher uric acid level) and CV mortality (HR: 0.92, 95% CI: 0.86 to 0.99). When analyzed as a dichotomous variable, the adjusted HR at uric acid ≤8.2 mg/dl compared with >8.2 mg/dl was 1.24 (95% CI: 1.03 to 1.49) for all-cause mortality and 1.54 (95% CI: 1.15 to 2.07) for CV mortality. CONCLUSIONS: Higher uric acid levels were associated with lower risk of all-cause and CV mortality in the hemodialysis population. These results are in contrast to the association of hyperuricemia with higher cardiovascular risk in the general population and should be the subject of further research.

Intoxications amenable to extracorporeal removal.

Extracorporeal removal of drugs was first attempted in 1913, by John Jacob Abel. Previously known to be a rarity, dialysis and to a lesser extent hemoperfusion have now become obvious tools for nephrologists in treating life-threatening cases of poisoning. Moreover, for dialysis patients, dialysis along with chelation therapy for removal of aluminum, once known to be common in the United States, is resurging in some countries. This article will discuss the principles of drug removal, the indications for dialysis, and give a brief outline of poisons amenable to dialysis.

Nephrolithiasis: evaluation and management.

Nephrolithiasis is a major cause of morbidity involving the urinary tract. The prevalence of this disease in the United States has increased from 3.8% in the 1970s to 5.2% in the 1990s. There were nearly two million physician-office visits for nephrolithiasis in the year 2000, with estimated annual costs totaling $2 billion. New information has become available on the clinical presentation, epidemiologic risk factors, evaluative approach, and outcome of various therapeutic strategies. In this report, we will review the epidemiology and mechanisms of kidney-stone formation and outline management aimed at preventing recurrences. Improved awareness and education in both the general population and among health-care providers about these modifiable risk factors has the potential to improve general health and decrease morbidity and mortality secondary to renal-stone disease.

Arteriovenous fistula toxicity.

The arteriovenous fistula (AVF) has been a mainstay of hemodialysis treatments and the preferred access route since its inception in the 1960s, due to its longevity and resistance to infection. However, the AVF is not benign. There is significant primary failure, as well as cardiac, vascular, and other, less well recognized, complications. Together, they represent toxicity, to which considerable morbidity and mortality can be attached. Official policy, based on guidelines where AVF toxicity is given short shrift, drives an increase in use of these devices, and may have undesired consequences.

The impact of residual renal function on hospitalization and mortality in incident hemodialysis patients.

BACKGROUND/AIMS: Few data are available on the impact of residual renal function (RRF) on mortality and hospitalization in hemodialysis (HD) patients. The objective of our study was to compare clinical outcomes for HD patients with and without RRF. METHODS: In a cohort of 118 incident HD patients with RRF (n = 51) and without RRF (n = 67) who started dialysis in a single center, we recorded demographics, laboratory data, medication, hospitalizations and mortality. RESULTS: Patients without RRF were older (p = 0.007), had lower baseline serum albumin levels (p = 0.002) and spent 18.6 more days in hospital per year than those with RRF (p = 0.055). Mean survival time was significantly lower in patients without RRF (p = 0.027). In a Cox proportional hazards model, only RRF remained as a significant independent predictor. CONCLUSIONS: RRF is associated with significantly reduced mortality and hospital days, but does not decrease the hospitalization rate and time to first hospitalization.