Use of synchronous kidney and lung extracorporeal support for severe COVID-19: A single-center retrospective study.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus disease 2019 (COVID-19) has been associated with both kidney and respiratory failure. During the early phase of the coronavirus disease pandemic, patients often required the use of mechanical assistance to provide adequate kidney and lung function. In this paper we describe the clinical outcomes of patients who required synchronous kidney and lung extracorporeal support for COVID-19. MATERIALS AND METHODS: All patients admitted to Baylor University Medical Center, Dallas, between February 1, 2020, to April 23, 2021, with COVID-19 who required both extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) were retrospectively analyzed. Patients who were on hemo- or peritoneal dialysis prior to admission or who required veno-arterial (VA) ECMO were excluded. RESULTS: 35 patients with COVID-19 required ECMO and CRRT support. Four patients (11%) were excluded, 2 due to being on dialysis prior to admission and 2 due to the requirement of VA-ECMO. The median time on CRRT was 33 days (IQR 13 - 51). The median time on ECMO was 28 days (IQR 10.5 - 59.5). At 90 days, 9 patients had died (29%), 4 patients remained hospitalized, and 18 patients had been discharged: 10 to long-term acute care, 2 to inpatient rehabilitation, and 6 to home. CONCLUSION: Patients with severe COVID-19 requiring concurrent ECMO and CRRT in this institution had a 29% mortality at 90 days.

Association of the COVID-19 pandemic with increased adherence among prevalent hemodialysis patients.

BACKGROUND: During the COVID-19 pandemic, there has been a reduction in emergency department visits and hospital admissions. We hypothesized that hemodialysis patients were decreasing their hospital visits and increasing their dialysis adherence during the COVID-19 pandemic. MATERIAL AND METHODS: This is a retrospective analysis of hemodialysis patients treated in the seven American Renal Associates (ARA) dialysis centers in the Dallas-Fort Worth metropolitan area. We conducted a "before-and-after" study using existing clinical data to examine patient adherence with hemodialysis between January 1 and March 14, 2020 (pre-COVID) and March 15 to May 18, 2020 (COVID) time periods. Data points included missed treatments, shortened treatments, post-dialysis weight, and hospital visits. Finally, we conducted an anonymous survey in which patients reported their hemodialysis adherence. RESULTS: Data analysis was performed on 556 patients. Significantly fewer patients missed a single treatment in the COVID vs. pre-COVID time periods (44.1 vs. 58.6%; p < 0.001). Significantly fewer patients finished their treatment with a post-dialysis weight more than 1 kg above their estimated dry weight in the COVID vs. pre-COVID time periods (31.7 vs. 38.9%, p = 0.01). Finally, there was a reduction in total hospital visits during the COVID vs. pre-COVID periods (12.6 vs. 19.4%; p = 0.002). The anonymous survey showed patients reporting increased adherence with hemodialysis and restriction of salt and water intake. CONCLUSION: The COVID time period was associated with increased adherence with hemodialysis and decreased hospital visits, and patients were conscious of these changes.

Euvolemia-A critical target in the management of acute kidney injury.

It has been clearly established that critically ill patients with sepsis require prompt fluid resuscitation. The optimal amount of fluid and when to taper this resuscitation is less clear. There is a growing evidence that fluid overload leads to acute kidney injury, and increased morbidity and mortality. A clinician's best intentions in resuscitating a patient can lead to too much of a good thing. Currently, there are several bedside tools to aid in determining a patient's response to a fluid challenge as well as in the assessment of the current volume status. Guidelines are not available on the exact rate of fluid overload removal and what medicinal or mechanical modality is most favorable. We discuss our experience and an examination of the literature on the problems with fluid overload, and how a patient may benefit from forced fluid removal.

Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II.

OBJECTIVE: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. DESIGN: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. SETTING: ICUs. PATIENTS: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively). INTERVENTIONS: IV angiotensin II or placebo. MEASUREMENTS AND MAIN RESULTS: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively. CONCLUSIONS: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

Clinical Experience With IV Angiotensin II Administration: A Systematic Review of Safety.

OBJECTIVE: Angiotensin II is an endogenous hormone with vasopressor and endocrine activities. This is a systematic review of the safety of IV angiotensin II. DATA SOURCES: PubMed, Medline, Scopus, and Cochrane. STUDY SELECTION: Studies in which human subjects received IV angiotensin II were selected whether or not safety was discussed. DATA EXTRACTION: In total, 18,468 studies were screened by two reviewers and one arbiter. One thousand one hundred twenty-four studies, in which 31,281 participants received angiotensin II (0.5-3,780 ng/kg/min), were selected. Data recorded included number of subjects, comorbidities, angiotensin II dose and duration, pressor effects, other physiologic and side effects, and adverse events. DATA SYNTHESIS: The most common nonpressor effects included changes in plasma aldosterone, renal function, cardiac variables, and electrolytes. Adverse events were infrequent and included headache, chest pressure, and orthostatic symptoms. The most serious side effects were exacerbation of left ventricular failure in patients with congestive heart failure and bronchoconstriction. One patient with congestive heart failure died from refractory left ventricular failure. Refractory hypotensive shock was fatal in 55 of 115 patients treated with angiotensin II in case studies, cohort studies, and one placebo-controlled study. One healthy subject died after a pressor dose of angiotensin II was infused continuously for 6 days. No other serious adverse events attributable to angiotensin II were reported. Heterogeneity in study design prevented meta-analysis. CONCLUSION: Adverse events associated with angiotensin II were infrequent; however, exacerbation of asthma and congestive heart failure and one fatal cerebral hemorrhage were reported. This systematic review supports the notion that angiotensin II has an acceptable safety profile for use in humans.

Predicting acute kidney injury prognosis.

PURPOSE OF REVIEW: The incidence of acute kidney injury has been steadily increasing. The development of any degree of kidney injury is associated with worse outcomes. Therefore, the ability to risk stratify patients and to predict prognosis is essential to properly educate the patient and family, appropriately utilize healthcare resources, and provide therapeutic interventions that may improve outcomes. RECENT FINDINGS: Numerous biomarkers and clinical prediction models have been developed that improve our ability to predict which patients will progress to higher stages of chronic kidney disease, require dialysis, or survive. The integration of biomarkers in predictive models will likely provide the best information. Further investigation will be required to validate the utility of these tools. SUMMARY: Early risk stratification for acute kidney injury can aid clinical decision making. The use of various biomarkers and predictive clinical models will improve the ability to appropriately utilize resources and provide useful prognostic information.

A case report of defective endogenous vitamin D: a new clinical entity.

OBJECTIVE: To report a case of defective endogenous vitamin D with excellent response to low dose calcitriol replacement therapy. METHODS: We describe the patient's clinical presentation, biochemical workup, and clinical course. RESULTS: The patient initially presented with severe symptomatic hypocalcemia and was diagnosed with pseudohypoparathyroidism type 1b at an outside hospital and started on calcitriol 2.25 mcg twice daily with good response but calcitriol was stopped later for cost concerns which led to recurrence of symptoms, worsening hypocalcemia and increased parathormone levels. On review of her case it was noted that her 1,25 dihydroxy: vitamin D level was within normal limits even before she started taking calcitriol, which is not consistent with pseudohypoparathyroidism type 1b. Restarting low dose calcitriol (0.25 mcg twice daily) improved the patient's calcium level to 10.1 mg/dl and decreased the parathormone level to 17 pg/ml and symptoms resolved. Conditions associated with low serum calcium and high parathormone include pseudohypoparathyroidism, vitamin D deficiency and vitamin D resistance. This patient does not fit into any of the known entities causing hypocalcemia and elevated parathormone. CONCLUSIONS: We hypothesize that this patient had an inadequate number of vitamin D receptors that was corrected by exogenous administration of vitamin D.

Border-crossers' nephropathy: the risk of coming to America.

Immigrants attempting to cross the border often wander for days without food or water, subsequently developing acute kidney injury (AKI) secondary to rhabdomyolysis. In this article, we describe our experience with myoglobinuric AKI in these border crossers. Records from all patients in the custody of the border patrol from 1 June 2010 to 30 June 2011, who had AKI defined by the Acute Kidney Injury Network (AKIN) criteria and a CK > 1000 IU/L, were reviewed. The age, gender, temperature, days in the desert, initial serum creatinine, CK on presentation, need for dialysis, length of hospital stay, and serum creatinine at discharge were recorded and analyzed. Forty-two patients developed myoglobinuric AKI with a mean age of 32.5 years. Among them, 38 were males and four females. There was a mean of 4.2 days in the desert. Seven had stage 1 AKI, 10 stage 2, and 25 stage 3. 5 patients required hemodialysis. Only one patient had a temperature >100.6ºF on arrival. CKs ranged between 1101 and 447,966 IU/L. Mean length of stay was 4 days. Two patients were discharged on hemodialysis and eight were discharged with serum creatinine levels of  >1.3 mg/dL. This is the largest series of myoglobinuric AKI reported in border crossers. The kidney injury is presumably due to the excessive heat combined with volume depletion. We have coined the term "border crossers' nephropathy" for this disorder. This is a serious problem that has both political and economic consequences on both sides of the border.

Acid-Base Disorders in the Critically Ill Patient.

Acid-base disorders are common in the intensive care unit. By utilizing a systematic approach to their diagnosis, it is easy to identify both simple and mixed disturbances. These disorders are divided into four major categories: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. Metabolic acidosis is subdivided into anion gap and non-gap acidosis. Distinguishing between these is helpful in establishing the cause of the acidosis. Anion gap acidosis, caused by the accumulation of organic anions from sepsis, diabetes, alcohol use, and numerous drugs and toxins, is usually present on admission to the intensive care unit. Lactic acidosis from decreased delivery or utilization of oxygen is associated with increased mortality. This is likely secondary to the disease process, as opposed to the degree of acidemia. Treatment of an anion gap acidosis is aimed at the underlying disease or removal of the toxin. The use of therapy to normalize the pH is controversial. Non-gap acidoses result from disorders of renal tubular H + transport, decreased renal ammonia secretion, gastrointestinal and kidney losses of bicarbonate, dilution of serum bicarbonate from excessive intravenous fluid administration, or addition of hydrochloric acid. Metabolic alkalosis is the most common acid-base disorder found in patients who are critically ill, and most often occurs after admission to the intensive care unit. Its etiology is most often secondary to the aggressive therapeutic interventions used to treat shock, acidemia, volume overload, severe coagulopathy, respiratory failure, and AKI. Treatment consists of volume resuscitation and repletion of potassium deficits. Aggressive lowering of the pH is usually not necessary. Respiratory disorders are caused by either decreased or increased minute ventilation. The use of permissive hypercapnia to prevent barotrauma has become the standard of care. The use of bicarbonate to correct the acidemia is not recommended. In patients at the extreme, the use of extracorporeal therapies to remove CO 2 can be considered.

A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19.

The Seraph100 Microbind Affinity Blood Filter (Seraph 100) (ExThera Medical, Martinez, CA) is an extracorporeal therapy that can remove pathogens from blood, including severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for COVID-19. DESIGN: Retrospective cohort study. SETTING: Nine participating ICUs. PATIENTS: COVID-19 patients treated with Seraph 100 (n = 53) and control patients matched by study site (n = 53). INTERVENTION: Treatment with Seraph 100. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no differences between the groups in terms of sex, race/ethnicity, body mass index, and need for mechanical ventilation. However, patients in the Seraph 100 group were younger (median age, 54 yr; interquartile range [IQR], 41-65) compared with controls (median age, 64 yr; IQR, 56-69; p = 0.009). Charlson comorbidity index scores were lower in the Seraph 100 group (2; IQR, 0-3) compared with the control group (3; IQR, 2-4; p = 0.006). Acute Physiology and Chronic Health Evaluation II scores were also lower in Seraph 100 subjects (12; IQR, 9-17) compared with controls (16; IQR, 12-21; p = 0.011). The Seraph 100 group had higher vasopressor-free days with an incidence rate ratio of 1.30 on univariate analysis. This difference was not significant after adjustment. Seraph 100-treated subjects were less likely to die compared with controls (32.1% vs 64.2%; p = 0.001), a difference that remained significant after adjustment. However, no difference in mortality was observed in a post hoc analysis utilizing an external control group. In the full cohort of 86 treated patients, there were 177 total treatments, in which only three serious adverse events were recorded. CONCLUSIONS: Although this study did not demonstrate consistently significant clinical benefit across all endpoints and comparisons, the findings suggest that broad spectrum, pathogen agnostic, blood purification can be safely deployed to meet new pathogen threats while awaiting targeted therapies and vaccines.

Half the V by 120: A practical approach to the prevention of the dialysis disequilibrium syndrome.

The dialysis disequilibrium syndrome (DDS) results from osmotic shifts between the blood and the brain compartments. Patients at risk for DDS include those with very elevated blood urea nitrogen, concomitant hypernatremia, metabolic acidosis, and low total body water volumes. By understanding the underlying pathophysiology and applying urea kinetic modeling, it is possible to avoid the occurrence of this disorder. A urea reduction ratio (URR) of no more than 40%-45% over 2 h is recommended for the initial hemodialysis treatment. The relationship between the URR and Kt/V is useful when trying to model the dialysis treatment to a specific URR target. A simplified relationship between Kt/V and URR is provided by the equation: Kt/V = -ln (1 - URR). A URR of 40% is roughly equivalent to a Kt/V of 0.5. The required dialyzer urea clearance to achieve this goal URR in a 120-min treatment can simply be calculated by dividing half the patient's volume of distribution of urea by 120. The blood flow rate and dialyzer mass transfer coefficient (K0 A) required to achieve this clearance can then be plotted on a nomogram. Other methods to reduce the risk of DDS are reviewed, including the use of continuous renal replacement therapy.

Continuous renal replacement therapy: cause and treatment of electrolyte complications.

Continuous renal replacement therapy (CRRT) has become the modality of choice for critically ill patients. Although often hemodynamically better tolerated than intermittent dialysis, the continuous nature of this therapy may cause significant electrolyte complications. These complications commonly result from removal of electrolytes from the body without adequate replacement or because of the use of trisodium citrate as the anticoagulant. Both hypophosphatemia and hypokalemia frequently complicate prolonged treatment. These complications can be avoided by adding these electrolytes to the dialysate or replacement fluid. The use of citrate, especially if this anticoagulant is not used routinely following established protocols, can also result in several electrolyte abnormalities. Because citrate works by chelating calcium, hypo- and hypercalcemia occur because of under- or overreplacement of calcium. Because citrate is a base equivalent, if the bicarbonate concentration of the dialysate or replacement fluid is not decreased, a metabolic alkalosis may develop. Less commonly, in patients with severe liver dysfunction who cannot metabolize citrate back to bicarbonate, a metabolic acidosis may develop. Although CRRT may cause electrolyte complication it also can be the treatment of choice for the correction of certain electrolyte complications. In patients with acute or chronic renal failure who present with significant dysnatremias, intermittent hemodialysis may cause overly rapid correction of the serum sodium with serious neurologic sequelae. The ability to manipulate the sodium concentration of the dialysate or replacement fluid and the more sustained nature of the treatment allows for a slower correction thus avoiding complications.

Efficacy and safety of renal tubule cell therapy for acute renal failure.

The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration + RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF.

Hydralazine-induced pericardial effusion.

Drug-induced lupus (DIL) is due to an autoimmune reaction to a drug with an estimated incidence of 15,000 to 30,000 cases every year in the US. Hydralazine is a well-known offender. Antinuclear antibody (ANA) is present in most cases, though four cases of ANA-negative DIL have been reported. In this report, we present another case of ANA-negative DIL secondary to hydralazine.

Partial Fanconi syndrome induced by ifosfamide.

Ifosfamide-induced proximal tubular nephropathy can present as a spectrum of disease, from isolated hyperaminoaciduria to a partial or complete Fanconi syndrome. We report a case of ifosfamide-induced partial Fanconi syndrome in a man with metastatic progressive Ewing sarcoma and put forth a hypothesis on the mechanism.

Icosapent ethyl reduces atherogenic markers in high-risk statin-treated patients with stage 3 chronic kidney disease and high triglycerides.

Objective: Patients with chronic kidney disease (CKD) have increased cardiovascular disease (CVD) risk, likely driven by atherogenic and inflammatory markers beyond low-density lipoprotein cholesterol (LDL-C). The objective of this hypothesis-generating post hoc subgroup analysis was to explore the effects of icosapent ethyl at 2 or 4 g/day (prescription pure ethyl ester of the omega-3 fatty acid eicosapentaenoic acid [EPA]) on atherogenic lipid, apolipoprotein, inflammatory parameters (high-sensitivity C-reactive protein [hsCRP], lipoprotein-associated phospholipase A2 [Lp-PLA2]), and oxidative parameters (oxidized-LDL [ox-LDL]) in statin-treated patients from ANCHOR with stage 3 CKD.Methods: The 12-week ANCHOR study evaluated icosapent ethyl in 702 statin-treated patients at increased CVD risk with triglycerides (TG) 200-499 mg/dL despite controlled LDL-C (40-99 mg/dL). This post-hoc analysis included patients from ANCHOR with stage 3 CKD (estimated glomerular filtration rate [eGFR] ≤60 mL/min/1.73 m2 for ≥3 months) randomized to icosapent ethyl 4 g/day (n = 19), 2 g/day (n = 30), or placebo (n = 36).Results: At the prescription dose of 4 g/day, icosapent ethyl significantly reduced TG (-16.9%; P = 0.0074) and other potentially atherogenic lipids/lipoproteins, ox-LDL, hsCRP, and Lp-PLA2, and increased plasma and red blood cell EPA levels (+879% and +579%, respectively; both P < 0.0001) versus placebo. Icosapent ethyl did not significantly alter eGFR or serum creatinine. Safety and tolerability were similar to placebo.Conclusions: In patients with stage 3 CKD at high CVD risk with persistent high TG despite statins, icosapent ethyl 4 g/day reduced potentially atherogenic and other cardiovascular risk factors without raising LDL-C, with safety similar to placebo. These findings suggest prospective investigation may be warranted.

Fibromuscular dysplasia: an uncommon cause of secondary hypertension.

Fibromuscular dysplasia is a noninflammatory vascular disease that commonly affects the distal two thirds of the renal artery and branch vessels, but occasionally involves other arteries. Progression of stenosis occurs in 16%-38% of renal arteries. Although the etiology is unknown, genetic studies suggest a relationship to the angiotensin-converting enzyme I allele. Thin, young Caucasian women without a family history of hypertension are most commonly affected. An abdominal or flank systolic-diastolic bruit is an important clue for the diagnosis. Most noninvasive screening tests are not sensitive or reproducible to be used to rule out renal artery stenosis, but digital subtraction renal angiography usually confirms the diagnosis. Percutaneous renal artery angioplasty is the treatment of choice, but may not result in normalization of blood pressure if diagnosis is delayed. Since restenosis occurs, continued follow-up is necessary.