Membrane-based therapeutic plasma exchange: Proposed techniques for preventing filter failure.

BACKGROUND AND OBJECTIVES: Therapeutic plasma exchange (TPE) is commonly performed using membrane-based TPE (mTPE) and is prone to filter failure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We report on 46 patients, with a total of 321 mTPE treatments using the NxStage machine. This was a retrospective study with an aim to evaluate the effect of heparin, pre-filter saline dilution and the impact of total plasma volume exchanged (< 3 L vs. ≥3 L) on the rate of filter failure. Primary outcome was the overall rate of filter failure. Secondary outcomes included factors that may have indirectly influenced the rate of filter failure, including hematocrit, platelet count, replacement fluid (Fresh Frozen Plasma vs. albumin), and access type. RESULTS: We found that treatments that received both pre-filter heparin and saline had a statistically significant decrease in filter failure rate as compared to those that received neither (28.6% vs. 5.3%, P = .001), and compared to the treatments that received pre-filter heparin alone (14.2% vs. 5.3%, P = .015). In treatments that received both pre-filter heparin and saline predilution, we noted a significantly higher filter failure rate when the plasma volume exchanged was ≥3 L as compared to those that had <3 L exchanged (12.2% vs. 0.9%, P = .001). CONCLUSIONS: Rate of filter failure in mTPE can be reduced by implementing several therapeutic interventions including pre-filter heparin and pre-filter saline solution. These interventions were not associated with any clinically significant adverse events. Despite the above-mentioned interventions, large plasma volume exchanges of ≥3 L can negatively impact filter life.

Therapeutic plasma exchange as adjunct therapy for bullous pemphigoid.

Bullous pemphigoid (BP) is a rare autoimmune blistering disease caused by pathogenic antibodies which deposit into the dermo-epidermal junction. We present a case of bullous pemphigoid in a young female refractory to initial therapy with immunosuppressives and steroids who experienced significant improvement in blister burden after a course of adjunct therapeutic plasma exchange (TPE). This case report provides valuable insight into the benefit of utilizing TPE for BP and provides treatment specifics regarding use of TPE in a patient with BP.

Membrane-based therapeutic plasma exchange: Hemodynamics and operational characteristics leading to procedure failure.

BACKGROUND AND OBJECTIVES: Therapeutic plasma exchange (TPE) is a blood purification treatment capable of removing large molecular weight substances from plasma. It is commonly used for the removal of circulating pathogenic immunoglobulins presumed to be the cause of many autoimmune diseases. TPE can be performed with a membrane-based system (mTPE) or a centrifugal-based system (cTPE). When plasma separation is performed with a membrane, filter clotting can lead to longer treatment time, higher cost and can negatively impact patient satisfaction. In this study, we examine the operational characteristics that might influence filter life. DESIGN, SETTING, PARTICIPANTS, & MEASURES: We report on 24 patients, with a total of 135 mTPE treatments in a single tertiary care academic center using the NxStage machine. The study focuses on treatment specific parameters that may lead to procedure failure. The main parameters of interest were transmembrane pressure (TMP) and the filtration fraction as displayed on the machine (FFd) compared to the calculated filtration fraction (FFc). Primary outcome was to measure whether TMP, FFc, and FFd influenced filter survival. Secondary outcomes included factors that might have indirectly resulted in filter failure, including hematocrit (Hct), platelet count, heparin use, and intra-treatment calcium administration. RESULTS: In this study, we demonstrated that machine displayed filtration fractions (FFd) were lower than FFc and this difference was significantly larger in TPE sessions that experienced a clotting event (7.58 vs 6.22, P = .031). TPE sessions that clotted had a higher mean TMP (57.48 mmHg vs 44.43 mmHg, P = .001) and clotting events tended to have a lower mean blood flow rate (175.83 mL/min vs 189.55 mL/min, P = .002). In TPE sessions that received prefilter calcium administration, a higher mean dose of calcium gluconate was found in the sessions that experienced clotting (3.27 g vs 2.70 g, P = .013). Patients who experienced at least one clotting event were noted to be heavier than those patients without any clotting events (91.52 kg vs 72.15 kg, P = .040). Prefilter heparin administration was not associated with a lower incidence of filter clotting. We did not find a statistically significant difference in clotting events based upon type of intravenous access, pretreatment hematocrit, or pretreatment platelet counts. CONCLUSION: Among patients undergoing mTPE, machine FFd on the NxStage system are consistently lower than FFc. Treatments where there was a greater difference between displayed and FFc had a greater likelihood of filter clotting. Treatments with higher TMP were associated with failed treatments. Prefilter calcium administration during treatment was associated with increased filter clotting. Lower blood flow rates and higher patient weight were also associated with increased filter clotting. Prefilter heparin administration did not reduce the incidence of filter clotting.

Targeting Glomerular Hemodynamics for Kidney Protection.

The kidney microcirculation is a unique structure as it is composed to 2 capillary beds in series: the glomerular and peritubular capillaries. The glomerular capillary bed is a high-pressure capillary bed, having a 60 mm Hg to 40 mm Hg pressure gradient, capable of producing an ultrafiltrate of plasma quantified as the glomerular filtration rate (GFR), thereby allowing for waste products to be removed and establishing sodium/volume homeostasis. Entering the glomerulus is the afferent arteriole, and the exiting one is the efferent arteriole. The concerted resistance of each of these arterioles is what is known as glomerular hemodynamics and is responsible for increasing or decreasing GFR and renal blood flow. Glomerular hemodynamics play an important role in how homeostasis is achieved. Minute-to-minute fluctuations in the GFR are achieved by constant sensing of distal delivery of sodium and chloride in the specialized cells called macula densa leading to upstream alternation in afferent arteriole resistance altering the pressure gradient for filtration. Specifically, 2 classes of medications (sodium glucose cotransporter-2 inhibitors and renin-angiotensin system blockers) have shown to be effective in long-term kidney health by altering glomerular hemodynamics. This review will discuss how tubuloglomerular feedback is achieved, and how different disease states and pharmacologic agents alter glomerular hemodynamics.

Hypocomplementemic Urticarial Vasculitis Syndrome or Systemic Lupus Erythematosus in Evolution?

Hypocomplementemia urticarial vasculitis syndrome (HUVS) is a rare form of systemic vasculitis which is characterized by the presence of urticaria and hypocomplementemia. The presence of recurrent and chronic urticarial rash is the dominant clinical finding in HUVS. Other manifestations including angioedema, arthritis, gastrointestinal symptoms, ocular inflammation, pulmonary involvement, renal involvement, and central nervous system involvement are also seen. Although the pathophysiology of HUVS is yet to be fully understood, it has been demonstrated that immune complex-mediated injury is the predominant mechanism responsible for severe systemic manifestations; a mechanism of injury similar to systemic lupus erythematosus (SLE). HUVS shared many clinicopathological features with SLE and it is prudent to question whether HUVS is a separate disease entity or SLE in evolution. Herein we present a case of a male patient who was diagnosed with SLE a year after being diagnosed with HUVS.

Glomerular Endotheliosis in COVID-19-Associated Acute Kidney Injury.

Acute kidney injury (AKI) has been seen in patients hospitalized with a SARS-CoV-2 (COVID-19) infection,but the pathophysiology of glomerular injury is not yet fully understood. We present a case of COVID-19-related "glomerular endotheliosis" in which a 51-year-old female with a 13-year history of class IV lupus nephritis was admitted for COVID-19 pneumonia. Her lupus nephritis had been in complete renal remission for the past 10 years with a baseline serum creatinine level of 1.3 mg/dL and no proteinuria. Her serological workup, including complement levels, was unremarkable. Due to the worsening renal function and persistent proteinuria, she underwent a kidney biopsy that revealed diffuse glomerular endothelial cell swelling, also known as glomerular endotheliosis. Her clinical course unfortunately deteriorated and she succumbed to acute respiratory distress syndrome. As circulating anti-angiogenic factors may contribute to the pathogenesis of endothelial dysfunction leading to glomerular endotheliosis, we propose that a similar circulating antiangiogenic factor may have been triggered by COVID-19 and played a role in our patient's progressive renal failure.

Impact of prefilter dilution on IgG removal in membrane-based therapeutic plasma exchange.

INTRODUCTION: Previous studies have demonstrated that a "one plasma volume exchange" would result in an estimated 63% decline in pretreatment IgG levels. We evaluated the use of prefilter dilution with normal saline as a method to prevent filter failure without decreasing the efficiency of IgG removal. METHODS: Twenty-one treatment sessions were analyzed and all received prefilter dilution with normal saline. Primary outcome was to determine whether prefilter dilution resulted in decreased treatment efficiency in removing the targeted IgG. Secondary outcome was filter failure in conjunction with the combined use of prefilter heparin and saline infusions. RESULTS: All 21 treatments (100%) received prefilter dilution with saline solution and 19/21 (90.47%) also received prefilter heparin (bolus and/or hourly infusion). We demonstrated a 60%-70% decline in pretreatment IgG levels. CONCLUSION: Prefilter dilution during membrane-based therapeutic plasma exchange based treatment did not result in a demonstrable decrease in efficiency of IgG removal while maintaining filter patency.

Primary central nervous system diffuse large B-cell lymphoma masqueraded as Bing-Neel syndrome: Steps in management and review of future directions.

Bing-Neel syndrome (BNS) remains a rare complication of Waldenstrom Macroglobulinemia. Given the paucity of this disease, treatment guidelines are based on small clinical trials with limited participants. Here, we present a case of primary CNS diffuse large B-cell lymphoma masqueraded as BNS that developed while on ibrutinib therapy.

Diabetic nephropathy in pregnancy: Report of two cases progressing to end-stage renal disease within one year postpartum.

BACKGROUND: Diabetes mellitus is a leading cause of nephropathy and end-stage renal disease. However, diabetic nephropathy during pregnancy in patients with normal glomerular filtration rate and subsequent progression to end-stage renal disease has not been well studied. CASES: This report presents two patients with poorly controlled type 1 diabetes mellitus who had diabetic nephropathy with preserved estimated glomerular filtration rate (Case 1: 117 mL/min/1.73m2; Case 2: 79 mL/min/1.73m2) and shared a similar clinical course, with glomerular filtration rates decreasing by approximately one-half during pregnancy and progression to end-stage renal disease within the first year postpartum. Both women had a long history of type 1 diabetes: 18 years and 24 years for case 1 and case 2 respectively. The first patient's course of pregnancy was complicated by difficult-to-control blood glucose and hypertension with subsequent preeclampsia. The second patient's course of pregnancy was complicated by difficult-to-control blood sugars and preterm labor resulting in classical cesarean delivery at 24 weeks. Both patients had renal biopsies shortly after delivery as their renal function continued to worsen postpartum. Both kidney biopsies demonstrated advanced diabetic nephropathy changes and ultimately required chronic renal replacement therapy within 7-9 months postpartum. CONCLUSION: Comprehensive family planning discussions with women who have diabetic nephropathy should include the risks of renal disease progression, even in those patients with preserved renal function at the time of conception.

Inhalation of 1-1-difluoroethane: A Rare Cause of Pneumopericardium.

We report a case of a 32-year-old man with a past medical history of ethanol use disorder who was brought in unresponsive after inhaling six to 10 cans of the computer cleaning product, Dust-Off. After regaining consciousness, he endorsed severe, pleuritic chest and anterior neck pain. Labs were notable for elevated cardiac enzymes, acute kidney injury, and his initial electrocardiogram (ECG) revealed a partial right bundle branch block with a prolonged corrected QT interval (QTc). On chest X-ray as well as chest computed tomography, the patient was found to have pneumomediastinum, pneumopericardium, and subcutaneous emphysema. The patient's course was uneventful and he was discharged home two days later after extensive substance abuse cessation counseling. Intentionally inhaling toxic substances, also known as "huffing," is a dangerous new trend with significant consequences that clinicians need to be aware of and suspect in young patients presenting with chest pain. We present a rare case of pneumopericardium induced by inhalation of Dust-Off (1-1-difluoroethane).