A wearable hemofilter for continuous ambulatory ultrafiltration.

Ultrafiltration is effective for treating fluid overload, but there are no suitable machines for ambulatory treatment. This study summarizes the use of a light-weight wearable continuous ambulatory ultrafiltration device consisting of a hollow fiber hemofilter, a battery operated pulsatile pump, and two micropumps to control heparin administration and ultrafiltration. Six volume-overloaded patients underwent ultrafiltration for 6 h with treatment discontinued in one patient due to a clotted catheter. Blood flow averaged 116 ml min(-1), the ultrafiltration rate ranged from 120-288 ml h(-1) with about 150 mmol of sodium removed. Blood pressure, pulse, and biochemical parameters remained stable with no significant hemolysis or complications. Our data show that the wearable hemofilter appears to be safe, effective, and practical for patients. This device could have a major impact on the quality of life of fluid-overloaded patients with heart failure. Additional studies will be needed to confirm these initial promising results.

Simultaneous postinfectious glomerulonephritis and thrombotic microangiopathy: a renal biopsy study.

The simultaneous occurrence of postinfectious glomerulonephritis and thrombotic microangiopathy is described in renal biopsy specimens from three patients. Each presented with diverse manifestations: two patients had hypertension and acute renal failure, and in the third, it was unclear whether an atypical postinfectious glomerulonephritis or an atypical thrombotic microangiopathy was present. All biopsy specimens disclosed a combination of irregular granular complement and immunoglobulin deposits in mesangial regions and capillary walls along with fibrin in a linear pattern in capillary walls by immunofluorescence. Light microscopy showed diffuse hypercellularity in some glomeruli, endothelial cell swelling, luminal thrombi and mesangiolysis in others, and both types of changes in a third group. Ultrastructurally, subepithelial hump-shaped deposits coexisted with widened and lucent subendothelial spaces. Possible pathogenic mechanisms for the synchronous lesions include endothelial injury, perhaps triggered by infection and immunologic tissue damage.

Lupus nephritis. Electron-dense and immunofluorescent deposits and their correlation with proteinuria and renal function.

Thirteen patients who had systemic lupus erythematosus were studied for the purpose of correlating the findings of light and electron microscopy and immunofluorescent studies with renal function and the presence of proteinuria. Subendothelial deposits of electron-dense material were found in all biopsy specimens, whereas mesangial and subepithelial deposits were not always present. IgG and beta 1c were constant findings in the glomerular membrane. The seven patients who were found to have extensive subendothelial deposits had moderate to massive proteinuria, and four of these patients had decreases in renal function. Most of the patients who had smaller subendothelial deposits had slight or insignificant proteinuria. Massive subendothelial deposits were mainly found in specimens showing histologic evidence of active lesions. Correlation was also found between proteinuria and the overall amount of deposits and their distribution. The prognosis was dependent on the severity of subendothelial deposits, the overall amount of deposits, and the morphologic form of lupus nephropathy.

The future of the artificial kidney: moving towards wearable and miniaturized devices.

New directions in dialysis research include cheaper treatments, home based therapies and simpler methods of blood purification. These objectives may be probably obtained with innovations in the field of artificial kidney through the utilization of new disciplines such as miniaturization, microfluidics, nanotechnology. This research may lead to a new era of dialysis in which the new challenges are transportability, wearability and why not the possibility to develop implantable devices. Although we are not there yet, a new series of papers have recently been published disclosing interesting and promising results on the application of wearable ultrafiltration systems (WUF) and wearable artificial kidneys (WAK). Some of them use extracorporeal blood cleansing as a method of blood purification while others use peritoneal dialysis as a treatment modality (ViWAK and AWAK.) A special mention deserves the wearable/portable ultrafiltration system for the therapy of overhydration and congestive heart failure (WAKMAN). This system will allow dehospitalization and treatment of patients with less comorbidity and improved tolerance. On the way to the wearable artificial kidney, new discoveries have been made such as a complete system for hemofiltration in newborns (CARPEDIEM). The neonate in fact is the typical patient who may benefit from miniaturization of the dialysis circuit. This review analyzes the rationale for such endeavour and the challenges to overcome in order to make possible a true ambulatory dialysis treatment. Some initial results with these new devices are presented. We would like to stimulate a collaborative effort to make a quantum leap in technology making the wearable artificial kidney a reality rather than a dream. 

The future of the artificial kidney: moving towards wearable and miniaturized devices

New directions in dialysis research include cheaper treatments, home based therapies and simpler methods of blood purification. These objectives may be probably obtained with innovations in the field of artificial kidney through the utilization of new disciplines such as miniaturization, microfluidics, nanotechnology. This research may lead to a new era of dialysis in which the new challenges are transportability, we arability and why not the possibility to develop implantable devices. Although we are not there yet, a new series of paper shave recently been published disclosing interesting and promising results on the application of wearable ultrafiltration systems (WUF) and wearable artificial kidneys (WAK). Some of them use extracorporeal blood cleansing as a method of blood purification while others use peritoneal dialysis as a treatment modality (ViWAK and AWAK.) A special mention deserves the wearable/portable ultrafiltration system for the therapy of over hydration and congestive heart failure(WAKMAN). This system will allow dehospitalization and treatment of patients with less comorbidity and improved tolerance. On the way to the wearable artificial kidney, new discoveries have been made such as a complete system for hemofiltration in newborns (CARPEDIEM). The neonate in fact is the typical patient who may benefit from miniaturization of the dialysis circuit. This review analyzes the rationale for such endeavour and the challenges to overcome in order to make possible a true ambulatory dialysis treatment. Some initial results with these new devices are presented. We would like to stimulate a collaborative effort to make a quantum leap in technology making the wearable artificial kidney a reality rather than a dream. (AU)

Los nuevos enfoques en la investigación en diálisis incluyen el abaratamiento de los tratamientos, las terapias domiciliarias y métodos más sencillos de purificación sanguínea. Probablemente estos objetivos se consigan gracias a los avances en riñones artificiales mediante el uso de nuevas técnicas, como la miniaturización, los microfluidos o la nanotecnología. Esta línea de investigación podría llevarnos a una nueva era en el campo de la diálisis, en la que los nuevos retos serán la transportabilidad, la portabilidad y, por qué no, la posibilidad de desarrollar dispositivos implantables. A pesar de no haber alcanzado aún ese punto, recientemente se han publicado una serie de trabajos en los que los resultados sobre los sistemas de ultrafiltración portátiles y los riñones artificiales portátiles se revelan prometedores y de gran interés. Algunos de ellos recurren a la modalidad extracorpórea como método de purificación sanguínea, mientras que otros recurren a la diálisis peritoneal como modalidad de tratamiento (ViWAK, Vicenza We arable Artificial Kidney, y AWAK, Automated Wearable Artificial Kidney). Merece mención especial el sistema de ultrafiltración portátil para la terapia de la sobre hidratación y la insuficiencia cardíaca congestiva (WAKMAN). Este sistema permitirá reducir el número de hospitalizaciones, el tratamiento de pacientes con menor comorbilidad y una mayor tolerancia. Durante la investigación en el riñón artificial portátil se han ido sucediendo nuevos avances, como el desarrollo de un sistema completo de hemofiltración para recién nacidos(..) (AU)

Elevated thrombocyte calcium content in uremia and its correction by 1 alpha(OH) vitamin D treatment.

Intracellular calcium plays an important role in the regulation of platelet function. It has also been demonstrated that platelet functions are impaired in uremia. A rise in intracellular calcium has been shown in several tissues and has been held responsible for the impaired function of several organs seen in uremia. This study was undertaken to evaluate whether the calcium (Ca) content of thrombocytes is elevated in uremia and, if so whether treatment with an active vitamin D metabolite might correct this abnormality. In 10 patients on chronic hemodialysis, platelet Ca content was determined by a technique utilizing consecutive freezing and thawing of platelet-rich plasma. The platelet Ca content of uremic patients was found to be markedly higher (20.86 +/- 0.9 ng/200,00 platelets, p less than 0.01) than that of a group of 20 normals (12.8 +/- 1.2 ng/200,000 platelets). 1 months after treatment with 1 alpha (OH) vitamin D at a dosage of 0.5-2.5 microgram/day, the platelet Ca content of the dialysis patients decreased to 14.99 +/- 2.14 ng/200,000 platelets (p less than 0.05). The data show that in dialysis patients the platelet Ca content is markedly elevated in comparison with that of normals, and the treatment with 1 alpha (OH) vitamin D may significantly reverse this abnormality. It is suggested that elevated Ca content may play a role in the pathogenesis of uremic platelet dysfunction, and that 1 alpha (OH) vitamin D administration may be of benefit in correcting this disorder.

Effects of magnesium depletion on myocardial high-energy phosphates and contractility.

The effect of prolonged magnesium depletion on contractility, phosphorylating activity, and organic phosphates of spontaneously beating isolated rat atria was studied. Rats were fed a Mg-deficient diet for 8 weeks, during which serum Mg fell from 1.85 +/- 0.02 to 0.52 +/- 0.10 mg/dl. Atrial contractile activity was measured for 1 hr and at the end of this period tissue samples were taken for the determination of the phosphorylated intermediates. Mg depletion was associated with (a) reduced intracellular inorganic phosphorus and adenine nucleotides; (b) elevated creatine phosphate; (c) reduction in contractile force (CF) with no change in atrial beat rate (BR). There were no significant differences in the activities of creatine phosphokinase and adenylate kinase in control and Mg-depleted rat atrial homogenates determined in the presence of 5 mM MgCl2. Addition of various concentrations of MgCl2 to the medium resulted in an immediate reduction in both CF and BR of normal and Mg-depleted rat atria. Intraperitoneal administration of MgCl2 to Mg-depleted rats resulted in complete recovery of CF of isolated atria. This improvement in CF occurred without changes in the levels of inorganic phosphate and adenine nucleotides. The reduced intracellular level of high-energy phosphate or inorganic phosphate cannot therefore be responsible for the impaired contractility seen in Mg-depleted heart muscle. On the other hand, the fact that the creatine phosphate levels were higher in magnesium depletion suggests that myofibrillar utilization of creatine phosphate is more impaired than production, analogous to phenomena seen in postanoxic recovery.

Nephrogenous cyclic AMP during extracellular volume expansion: relationship to early and late aortic constriction.

Prior data showed that both volume expansion (ECVE) and renal vasodilatation are associated with natriuresis and increased nephrogenous cAMP (NcAMP). Studies were done to examine the effect of ECVE on sodium excretion and NcAMP during early or late reduction in renal perfusion pressure (RPP) in an effort to define the role of renal vasodilatation on NcAMP during ECVE. In 8 thyroparathyroidectomized (TPTX) dogs, RPP to the left kidney was reduced (130 +/- 1.7 to 69 +/- 4 mm Hg), ECVE was then produced and finally RPP was allowed to rise to 126 +/- 2.2 mm Hg (group I). In 8 TPTX, ECVE was produced and then followed by a reduction in RPP (121 +/- 5 to 69 +/- 5 mm Hg; group II). cAMP was measured in aorta, renal veins and urine. In group I, renal plasma flow (RPF), fractional excretion of Na filtered (FeNa), urinary NcAMP (UNcAMP) and renal vein NcAMP (RVNcAMP) did not change in the constricted kidney while these parameters increased in the other kidney. After release of the constriction RPF (122 +/- 24 to 157 +/- 26 ml/min), FeNa (0.5 +/- 0.1 to 5 +/- 1.2%), UNcAMP (204 +/- 121 to 785 +/- 198 pmol/min, p less than 0.05) and RVNcAMP (277 +/- 213 to 1,565 +/- 403 pmol/min, p less than 0.02) rose significantly. In group II, FeNa, UNcAMP and RVNcAMP increased during ECVE and remained significantly elevated during the reduction in RPP.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic lupus erythematosus associated with mixed cryoglobulinaemia and circulating anticoagulant.

We describe a 30-year-old woman with systemic lupus erythematosus (SLE), in whom the only evidence of the disease, during the 10 years before diagnosis was established, was an accelerated erythrocyte sedimentation rate and a positive Wassermann test. Her disease was characterized by the presence of an anticoagulant without indication of bleeding, mixed cryoglobulinaemia, steroid-resistant renal damage, and persistent false-positive tests for syphilis. The relationship between these results and the presence of anticoagulant, mixed cryoglobulinaemia and renal damage in patients with SLE are discussed.

Pulmonary function abnormalities in Sjögren's syndrome and the sicca complex.

The frequency of pulmonary involvement in a group of 20 patients with Sjögren's syndrome or the sicca complex was evaluated with pulmonary function studies. In 12 patients pulmonary functional abnormalities were demonstrated. The most common abnormality was airway obstruction. Nine out of 13 patients with the limited variant of the disease (sicca complex) and three out of seven patients with the complete syndrome had abnormal pulmonary function.

Hyperprolactinemia: a possible cause of sexual impotence in male patients undergoing chronic hemodialysis.

Hyperprolactinemia is known to cause impotence in patients with normal renal function and elevated serum prolactin levels (SPLs) have also been reported in uremia. This study was undertaken to examine a possible role of elevated SPLs in the impotence of male patients undergoing chronic hemodialysis (CHD). SPLs in 16 male patients undergoing CHD were evaluated using a homologous double-antibody radioimmunoassay with prolactin isohormones isolated from human amniotic fluid. Patients were divided in 2 groups: 6 patients were sexually impotent and 10 sexually potent. Patients with emotional disturbances or marital conflicts known to cause impotence were excluded from the study. The SPLs of the impotent patients were found to be significantly elevated in comparison to the levels of the potent patients (136.7 +/- 28.2 vs. 37.3 +/- 2.7 ng/ml, p less than 0.001). Furthermore, in 2 patients who were successfully treated with bromocriptine to suppress hyperprolactinemia, recovery of sexual potency was noted. Thus, sexual impotence in male CHD patients seems to be associated with marked hyperprolactinemia. It is suggested that elevated SPLs may be an important cause of impotence among CHD patients.

Sexual dysfunction associated with hyperprolactinemia in males and females undergoing hemodialysis.

Fifty-nine uremic patients (38 males and 21 females) maintained on chronic hemodialysis (CHD) served as the subjects in a study of the relationship between sexual dysfunction and serum prolactin levels (SPL). Sexual desire and activity were evaluated by a self-report sexual function rating scale (SFRS). About half the population of this study reported sexual dysfunction. Males and females reporting disturbance of sexual function had significantly higher SPL than those with normal sexual function. Bromocriptine treatment in five hyperprolactinemic patients reduced SPL to normal range and improved the sexual function. Association between sexual dysfunction and hyperprolactinemia in uremic patients is suggested.