Predictable removal of anticardiolipin antibody by therapeutic plasma exchange (TPE) in catastrophic antiphospholipid antibody syndrome (CAPS).

Catastrophic antiphospholipid antibody syndrome (CAPS) is a rare life-threatening variant of antiphospholipid antibody syndrome (APS), with an associated mortality rate of > 50%. Treatment recommendations are aggressive and consist of intravenous heparin, steroids, immunoglobulins and/or therapeutic plasma exchange (TPE). At present, insufficient data exist to make precise recommendations regarding the most effective therapy for CAPS. Accumulating evidence over recent years is encouraging and may lead to future guidelines. We report predictive and effective removal of pathological anticardiolipin antibody (aCL AB) in a patient with CAPS. The case report and discussion provide valuable insight into aCL AB production and its removal by first- order kinetics using TPE.

Carboplatin-related hematuria and acute renal failure.

Cisplatin is a potent tubular toxin with a high incidence of nephrotoxicity. Carboplatin is considered less nephrotoxic but can still cause tubular injury and interstitial nephritis in patients who have been previously treated with cisplatin. The affected individuals usually have nonoliguric renal failure with a urine output of more than a liter per day. We present a 57-year-old white woman with no history of renal disease who underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for stage IC ovarian carcinoma. One month later, she received chemotherapy with paclitaxel (Taxol) and carboplatin. On the following day, she developed frank hematuria and flank pain associated with a diminished urine output. Intravenous pyelogram (IVP) showed bilateral hydronephrosis with a total blockage of dye flow at the level of intraureteral lucencies consistent with bilateral blood clots. Her coagulation profile and uric acid was normal. Her acute renal failure (ARF) spontaneously resolved in the following 24 hours, with a brisk diuresis presumably due to clot lysis. The follow-up IVP showed a resolution of obstructive changes. A review of the literature shows a previous case in which high doses of carboplatin were implicated as the cause of hemorrhagic cystitis, presumably by toxicity to transitional epithelium of the bladder. We believe that the current case represents carboplatin-induced damage to the transitional epithelium in the renal pelvi and ureters causing gross hematuria and blood clots, resulting in bilateral ureteral obstruction and hydronephrosis.

Impact of therapeutic plasma exchange on cyclosporine kinetics during membrane-based lipid apheresis.

Cyclosporine is used widely as an immunosuppressant in transplant recipients and for various autoimmune diseases. In some cases, these patients require therapeutic plasma exchange (TPE). Cyclosporine is known to be highly bound to lipoproteins, and their removal by TPE would be expected to have an impact on drug dosing. We studied cyclosporine kinetics in a 54-year-old woman who is status post-cardiac transplant and has been receiving weekly TPE for familial hypercholesterolemia. We obtained serial measurements of cyclosporine, low-density lipoproteins, and high-density lipoproteins at scheduled times related to the dosing of the medication on days that she received TPE versus a day she did not. We also measured cyclosporine, low-density lipoprotein, and high-density lipoprotein levels in the fixed volume (3.5 L) of the discarded plasma. Our results show a similar rate of decline of serum cyclosporine levels on TPE days as compared with a day without TPE. Net cyclosporine in the discarded plasma was found to be approximately 1 mg per treatment or less, a relatively insignificant amount when compared with the ingested daily dose of 150 to 250 mg twice a day. Despite substantial removal of lipoproteins, there is minimal impact of TPE on serum levels of cyclosporine, and dosage adjustment is not needed for patients undergoing this procedure.

Role of the nephrologist in the intensive care unit.

Intensive care units (ICUs) are increasingly becoming a focal point for tension between medical specialists. In an extreme approach to this issue, some ICUs have become closed units managed by intensivists, with other specialists, such as nephrologists, having a restricted supportive role. The nephrologist, a subspecialist with broad skills in general internal medicine, has trained and appropriately can serve as the primary physician for patients with significant renal failure and end-stage renal disease in multiple hospital settings, including the ICU. Sick and complex hospitalized patients offer ample opportunity for a collaborative interaction between the nephrologist and intensivist in the ICU.

Shunt nephritis from Propionibacterium acnes in a solitary kidney.

Since its initial description in 1965, immune complex glomerulonephritis associated with ventriculoatrial shunts (VAS) has been reported widely in the literature. The most common incriminating organism is Staphylococcus epidermidis, but less often, an organism generally regarded as nonpathogenic, such as Propionibacterium acnes, has been noted as the cause. Shunt infection usually occurs within a few months after placement or manipulation of the shunt, and shunt nephritis (SN) develops gradually over months to years after. Treatment involves mandatory removal of the shunt and antibiotics; prognosis is variable. We report a case of SN with P acnes that is unusual because of its occurrence in a solitary kidney 6 years after shunt placement, persistently negative blood cultures, and normal complement levels. Percutaneous biopsy of a solitary kidney should be considered if it is expected that the result may guide therapy of progressive renal failure.

Extracorporeal blood purification in the management of patients with hepatic failure.

With the increasing success of orthotopic liver transplantation, the time has come for a reassessment of the role of extracorporeal blood purification in the management of patients with liver failure. In those patients with combined liver and kidney failure, both standard hemodialysis and the newer continuous renal replacement therapies have been found to be helpful in maintaining fluid, electrolyte, and acid base balance. In those patients with liver failure but without kidney dysfunction, extracorporeal purification techniques have been found useful for the removal of hepatic toxins and in facilitating the replacement of clotting factors. This review will outline the rationale and documented utility of a wide variety of blood purification modalities used in the management of patients with liver failure.

High flux plasma exchange using a modified rotating membrane system.

The results of increasing blood flow capability in a modified system for plasma exchange with a rotating filter are reported. There were 742 treatments performed with the authors' original system (OS), limited to blood flows of 100 ml/ min, and 327 treatments performed with the updated system (US), allowing for blood flows of 150 ml/min. Blood flows for OS were 98 +/- 5 ml/min (mean +/- SD) vs 145 +/- 12 ml/min for US (p < 0.001). Plasma flows were 65 +/- 7 ml/min for OS vs 98 +/- 12 ml/min for US (p < 0.001). Plasma removal rate was 42 +/- 8 ml/min for OS vs 61 +/- 14 ml/min for US (p < 0.001). Mean treatment time was reduced from 76 +/- 23 min for OS to 52 +/- 17 min for US (p < 0.001) in spite of providing a similar amount of plasma removed per treatment (3,113 +/- 577 ml/Rx for OS vs 3078 +/- 797 ml/Rx for US; p = 0.48). Despite statistical significance, there were only small differences in filtration fractions (65 +/- 12% for OS vs 62 +/- 11% for US; p < 0.001) and patient hematocrits (34 +/- 6% for OS vs 33 +/- 6% for US; p < 0.001). In conclusion, modification of the OS to allow for increased blood flow has resulted in a substantial improvement in procedure efficiency and a clinically useful decrease in treatment time.

Sieving characteristics of a new polysulfone hemofilter for use with continuous arterio-venous hemofiltration.

Sieving coefficients (SC) for middle molecular weight (MMW) substances have been found to decrease markedly as filtration rates (Qf) are increased. To best evaluate the newly available Renaflo hemofilter, we studied the effect of increasing filtration rates on the SC of a sample MMW substance (inulin). An in-vitro filtration system was designed to deliver varying Qf from 4.1 to 17.7 ml/min. Serum and filtrate chemistries (urea, creatinine, total protein) were determined. The results revealed no change in sieving for urea or creatinine and a universally low sieving for protein. The sieving coefficient for inulin, however, decreased significantly; from 0.93 at a Qf of 4.1 ml/min to 0.79 at a Qf of 17.7 ml/min (p less than 0.03). These results confirm that the SC of MMW substances do decrease as Qf increase. Despite the decrease found, when compared to previously published data, the Renaflo hemofilter seems to offer a greater degree of middle molecular weight sieving under conditions encountered during CAVH.

Transmembrane pressures generated by filtrate line suction maneuvers and predilution fluid replacement during in vitro continuous arteriovenous hemofiltration.

A recirculating in vitro CAVH system was designed which generated pulsatile blood and filtrate flows. Monitors recorded hydrostatic pressures simultaneously in the arterial, venous and filtrate lines during varying plasma or blood flow rates and predilution (vs postdilution) replacement fluid flow rates. Similar hydrostatic pressure monitoring was carried out during multiple maneuvers to generate suction on the filtrate side of the hemofilter (Amicon D-20's and Renaflo's). With a plasma flow (Qp) of 100 cc/min and predilution replacement fluid infusion rate of 500 cc/hr, the arterial pressure was 5% greater than during postdilution (p less than 0.05). With a blood flow (Qb) of 50 cc/min, predilution fluid replacement rates of 500 and 1000 cc/hr, and vacuum suction applied to the filtrate compartment, the arterial pressure was 33% lower than during postdilution fluid replacement (p less than 0.03). Nonetheless, the ultrafiltration rate (UFR) was 10 to 30% higher (p less than 0.03). At many other combinations of Qp, Qb and replacement rates and modes, there were no significant changes in arterial pressure. Despite these arterial pressure changes, greater than 70% of the transmembrane hydrostatic pressure (TMP) was due to the negative pressure induced by filtrate suction (gravity, Gomco, wall suction, IMED). The actual pressure in the filtrate compartment measured during Gomco or wall suction was 3/4 of that stated by their gauges, presumably due to leakage. Maximum wall suction never generated TMP's greater than 150 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug removal during continuous arteriovenous hemofiltration: theory and clinical observations.

We have discussed the basic principles of pharmacokinetics and convective solute removal in the context of each other. Clinical observations appear to follow the theoretical expectations. For practical purposes plasma and plasma water are not different. In the calculation of drug sieving, venous samples do not contribute enough to warrant their extra costs. We recommend that drug removal in hemofiltration be expressed by the sieving coefficient, UF/A. Drug sieving data in humans undergoing CAVH are tabulated. Recommendations for supplemental dosing are discussed which are applicable to any clinical setting.

[Mental disorders as late sequelae of closed cranio-cerebral trauma]. / Psikhicheskie narusheniia v klinike otdalennykh posledstvii zakrytoi cherepno-mozgovoi travmy.

In a total of 308 patients with late sequelae of closed craniocerebral trauma inflicted during war or peace time studied in hospital conditions were the peculiarities of the course of trauma-related disease as related to various additional factors. The course of several syndromes was followed with special reference to the nature, severity and repetitiveness of the trauma, the age of affliction, and such additional determinants as alcoholism and vascular pathology. The risk factors of vascular disorders and alcoholism were determined and measures designed for their prevention and treatment.

[Clinico-morphologic correlations in the late period of closed craniocerebral injuries]. / Kliniko-morfologicheskie korreliatsii v otdalennom periode zakrytoi cherepno-mozgovoi travmy.

Clinical and morphological correlations were studied in 69 cases of old closed head trauma. It was found that the degree of the existing morphological changes correlated with the trauma severity, which was reflected in the clinical picture of the disease. Convulsive syndromes developing immediately and in the first years after the trauma correlated with its severity and localization. In the long terms the principal contributors to the condition were chronic alcoholism and other factors. The patients with brain injury (particularly with the convulsive syndrome) earlier developed vascular pathology and their life span was shorter, vs. the general population.

Therapeutic apheresis for cancer related hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) can be seen as a result of disseminated cancer, as a consequence of chemotherapy, or in association with bone marrow transplantation (BMT). Further distinction can be made when the clinical presentation is that of an acute, fulminant course with rapidly progressive renal failure or that of a sub-acute form with a slow progression of renal involvement. Each of the different etiologies (cancer, chemotherapy, or BMT) and each of the two basic clinical presentations has its own prognosis. There are no randomized, controlled studies to elucidate the role of therapeutic apheresis for cancer-related HUS. Hemolytic uremic syndrome related to disseminated cancer is most often a terminal event and is not commonly treated with apheresis procedures, although there are anecdotal reports that plasma exchange may be beneficial. Chemotherapy and drug-related HUS have a prognosis that is strongly dependent on the severity of the presentation, but even in the most severe cases may respond to either immunoadsorption or plasma exchange with fresh frozen plasma (FFP). Finally, BMT-related HUS has a poor prognosis but may respond to immunoadsorption, plasma exchange, or a combination of the two.

Dialyzer reuse: what we know and what we don't know.

Despite extensive clinical experience, the effects of different reuse procedures have not been fully evaluated. The available data suggest that the effect of reuse on dialyzer performance depends upon the type of chemicals employed, the membrane type, and the size of the solute whose removal is being assessed. The effect of reuse on urea clearance is essentially defined by the residual cell volume with a total cell volume of > 80% associated with a dialyzer clearance that is within 10% of its original value. The effect of reuse on large solute clearance can be dramatic, with the procedure resulting in substantial changes in the beta2-microglobulin clearance of different dialyzers. Of note is the limited data available regarding the effect of reuse procedures on dialyzers processed more than 20 times.

Therapeutic apheresis for renal disorders.

Many primary renal diseases are associated with either antibody deposition within the glomerulus or an antibody associated autoimmunity, as may be seen with certain vasculitidies. Other immunoglobulins may be nephrotoxic or glomerulopathic; such may be the case with myeloma related light chains or cryoglobulins. Given the rapid removal of immunoglobulins by therapeutic plasma exchange, this modality has been considered an appealing management option in the treatment of these autoimmune related renal diseases. Although not classically considered as autoimmune diseases, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are related syndromes which often involve the kidneys. In many cases therapeutic plasma exchange has been found to be a useful treatment modality for these microangiopathic hemolytic anemias. This paper will provide a concise review of the renal indications for therapeutic plasma exchange.

Extracorporeal blood purification in the treatment of acute renal failure with multiorgan involvement.

It has been more than 35 years since the early use of dialytic techniques for the treatment of acute renal failure. Considering the survival of patients who would have clearly succumbed to renal failure, attempts were made to determine at what level of uremic toxicity it would be beneficial to offer dialysis on a prophylactic basis. Those early attempts at defining a preventive strategy seemed to provide an improved survival by limiting incidence and severity of hemorrhage and sepsis. Subsequently, measurable advances have been difficult to attain, and the prognosis of complicated acute renal failure remained dismally poor. More recently, continuous renal replacement techniques were developed to offer a more physiologic treatment to those patients who were the most critically ill and unstable. These treatments offered the potential for a better tolerated fluid removal and a more constant control of electrolyte and acid-base balance. Other potential advantages included the use of more biocompatible membranes and the convective mode of solute transfer with its inherently greater removal of larger molecular weight substances such as the vasodilatory and inflammatory cytokines. Another approach has been to use extracorporeal purification to lower the levels of endotoxin, a goal which can be accomplished by either standard plasma exchange or, more elegantly, the use of selective adsorption columns. Despite the promise of these methodologies, the lack of an acceptable grading system for the severity of critical illness has hampered investigators who have tried to prove the eventual advantage of one blood purification technique over another.

Therapeutic apheresis for the renal complications of multiple myeloma and the dysglobulinemias.

Disordered immunoglobulin synthesis can result in a variety of different types of renal pathology. Multiple myeloma is often associated with the overproduction of light chains which may result in toxicity to the renal tubules and acute renal failure. Patients with mixed cryoglobulinemia will have renal involvement which is most often in the form of a membranoproliferative glomerulonephritis. Renal involvement in macroglobulinemia is relatively uncommon, but IgM thrombi can be so voluminous as to occlude the glomerular capillary lumen. In each of these examples, therapeutic plasma exchange has been found to be a useful adjunct to the eventual chemotherapy required for the definitive treatment of these disorders.

Apheresis for renal disease.

Many primary renal diseases are associated with either antibody deposition within the glomerulus or an antibody associated autoimmunity, as may be seen with certain vasculitidies. Examples of these diseases include Goodpasture's syndrome, cryoglobulinemia, antineutrophil cytoplasmic antibody positive syndromes, and other forms of rapidly progressive glomerulonephritis. Immunoglobulins also may be nephrotoxic to the tubules such as is the case with myeloma related light chains. Given the rapid removal of immunoglobulins by therapeutic plasma exchange, this modality has been considered an appealing management option in the treatment of these renal diseases. Although not classically considered as autoimmune diseases, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are related syndromes which often involve the kidneys. Although previously unexplained, it has been long appreciated that therapeutic plasma exchange (PE) can be a useful treatment for these microangiopathic hemolytic anemias, but the most recent insights into their pathogenesis suggest that PE may be beneficial by replacing a missing enzyme or removing pathogenic autoantibodies.

A simple and accurate method for prescribing plasma exchange.

During plasma exchange, prediction of treatment results requires an estimate of plasma volume (EPV). Using a simplified formula for EPV, EPV = [0.065 X wt(kg)] X [1-Hct], the predicted and actual decline in serum levels of several large molecular weight substances was evaluated during 102 treatments in 18 patients. Predicted as opposed to actual percent of decline in serum levels for IgG was 67 +/- 7% vs. 64 +/- 10% (+/- SD, R = 0.66, n = 40, p = 0.0001); for IgA was 66 +/- 8% vs. 66 +/- 9% (R = 0.59, n = 36, p = 0.0001); and for IgM was 66 +/- 7% vs. 69 +/- 8% (R = 0.63, n = 39, p = 0.0001). For the third component of complement the values were 58 +/- 7% vs. 61 +/- 5% (R = 0.73, n = 17, p = 0.009), and for total cholesterol 66 +/- 3% vs. 70 +/- 4% (R = 0.62, n = 28, p = 0.005). It can be concluded that a simplified method for estimating plasma exchange allows for a reasonably reliable prediction of treatment results.