Stanley Cortell

Membraneless Dialysis – Is It Possible?

Direct contact between uremic blood and a fluid capable of receiving uremic toxins is possible. Such contact by itself is, however, not beneficial because the selection of molecules that are removed is dependent on diffusion coefficients in blood. This selection is inadequate and would result in the exhaustion of a patients albumin pool before useful reduction in the urea pool was achieved. Direct contact that is accomplished by sandwiching blood between two layers of a sheathing fluid, followed by diafiltration of the sheathing fluid through conventional membranes and recirculation of the sheathing fluid, is possible. This adaptation of membraneless transport of molecules from blood eliminates almost all contact of blood with solid artificial surfaces and the subsequent diafiltration and recirculation of the sheathing fluid allows precise control of what is removed from the system. Slightly hyperosmotic protein is carried back by the recirculating sheathing fluid. Only solutes and water that pass the diafilter, which operates on a cell-free fluid, are able to leave the system. The system depends strongly on the ability to keep cells out of the sheathing fluid. Preliminary results and earlier reports indicate that this separation is possible and more precise measurements are underway. A quantitative design of a wearable dialyzer based on a circulating sheathing fluid is presented.

A graph theory model of the glomerular capillary network and its development

Graph theory methods were used to analyze the topology of the renal glomerular capillary network using data both from a serial reconstruction of a rat glomerulus and from the literature. The graphs obtained were tested for planarity, and all but one were found to be nonplanar. This result indicated that the development of the glomerular capillary network must include a nonplanar growth process, and new growth models were proposed. In addition, the statistical properties of capillary branching patterns were analyzed, and a node degree distribution function estimate was obtained.

The Path to Wearable Ultrafiltration and Dialysis Devices

Wearable blood processing devices offer an attractive solution to problems inherent in clinic-based, intermittent end-stage renal disease therapies. What is involved in transitioning even a part of the current clinic-based population to ambulatory therapy has not been clearly enumerated. This paper addresses what a first-generation wearable device might accomplish, how issues of safety will need to be addressed, and what will make the device attractive to, and manageable by, the patient. Medical, technological, and economic issues are identified.

Daily ultrafiltration results in improved blood pressure control and more efficient removal of small molecules during hemodialysis.

Background: Although prior studies have shown that frequent hemodialysis (HD) can lead to improved control of dry weight in end-stage renal disease patients, there are no clinical studies examining whether this can improve blood pressure (BP) control and can also shorten the dialysis time needed to achieve satisfactory removal of small molecules. Several models of wearable dialysis systems are now under various stages of development. These devices present the possibility of hemodialyzing patients to their dry weights. We have built a prototype of a wearable ultrafiltration (UF) device that can provide daily UF. Apart from better fluid control, we hypothesize that separating HD from UF will result in better BP control, and adequate weekly small molecule removal could be achieved with a decreased duration of dialysis. We tested the hypothesis in current HD patients using conventional dialysis equipment. Methods: Thirteen patients were selected from a large urban HD center. The experimental period consisted of 4 weeks of daily UF (4 days/week of UF alone and 2 days/week of HD with UF). The duration of the HD sessions was increased by 15–30 min to maintain weekly standard Kt/V >2.0. The patients were then returned to their conventional 3 days/week of HD with UF and studied for 4 weeks. Predialysis BPs, interdialytic weight gains, and Kt/V results of the experimental and return periods were compared with those of the 3-month control period. No changes were made in antihypertensive or other medication during the study. Results: During the experimental period, mean arterial pressure decreased from 110 to 95 mm Hg (p < 0.001), systolic BP from 158 to 136 mm Hg (p < 0.001), while interdialytic weight gains were reduced from 3.25 to 1.21 liters (p < 0.0001). During the experimental period, weekly standard Kt/V of 2.16 was achieved in 8.24 h/week of HD, as compared to 11.14 h/week. Conclusions: Volume control with daily UF results in improved BP control and, by separating the UF function from HD, adequate weekly standard Kt/V >2 can be achieved with twice weekly HD.

Blue toe syndrome as a clue to the underlying cause of acute renal failure

To the Editor, We present here a scenario of acute renal failure in the setting of blue toe syndrome. A 62-year-old male with a past medical history of hyperlipidaemia, hypertension and stroke presented with a 2-week history of severe diarrhoea, generalized weakness and myalgias. His home medications included Lipitor, Coumadin, Lopressor, Aspirin and lisinopril. During his prior hospitalization, one and a half months ago, he had undergone coronary artery bypass graft which was complicated by an ascending and descending aortic dissection post-operatively. The ascending dissection was surgically repaired. The origin of the celiac axis, superior mesenteric artery and renal arteries was from the true lumen, and thus, the blood flow was not compromised from the descending aortic dissection (Figure 1a). On examination, the patient’s blood pressure was 157/91 mmHg and pulse 85 beats/minute of equal strength in both upper and lower extremities. His systemic examination was significant for painful bluish discoloration of the toes bilaterally (Figure 1b). Initial laboratory results revealed blood urea nitrogen 111 mg/dL, serum creatinine 10.8 mg/dL, potassium 5.8 mEq/L, bicarbonate 15 mEq/L and creatinine phosphokinase 12 893 IU/L. Complement C3 level was decreased. Urine analysis did not reveal muddy brown casts. The remainder of the laboratory panel was also unremarkable. Lipitor was discontinued. Despite adequate hydration, the patient remained oliguric with no improvement in his renal function (Figure 1c). In the setting of surgical history and blue toe syndrome, an atheroembolic phenomenon as the cause of renal failure was considered. Direct ophthalmoscopy and slit lamp examination of the eye revealed cholesterol crystal emboli in the retinal arterioles (Hollenhorst plaques, Figure 1) and thus confirmed the diagnosis of atheroembolic disease. The patient was started on haemodialysis. Fig. 1 (a)The aortic dissection/aneurysm at the level of the left renal artery measured 3.5 cm, and the renal arteries originated from the true lumen. In addition, there was no evidence of aortic leak, and at the level of the origin of the celiac artery and ... Atheroembolic disease may present with general symptoms of fever, myalgias, headache, weight loss and diarrhea [1]. Though sometimes subtle, the pathological process of dislodging multitude of cholesterol crystals from atherosclerotic plaques in the arteries (often post-operatively) can manifest symptomatically diversely. The emboli may travel to the capillary beds of the renal, mesenteric, retinal, tibial and peroneal arteries capable of producing digital or skin ischaemia, and even overt organ failure. Therefore, a high degree of clinical suspicion is warranted since, in the setting of gastrointestinal symptoms, abnormal renal parameters may be confused for acute renal failure secondary to severe dehydration. While the cholesterol showers to the lower extremities are often labeled as ‘blue toe syndrome’, the actual cutaneous manifestations of the bluish discoloration are uncommonly seen in only 5% of patients with atheroembolic disease [1]. In our patient, the blue toes were the sole dermatological manifestation. Other more classical manifestations include cord-like purplish cutaneous discoloration in the lower extremities (livedo reticularis). Acute renal failure is present in 25–50% of atheroembolic cases [2]. Although the disease commonly occurs after invasive vascular procedures (i.e. coronary angiography via femoral artery), instances of spontaneous embolization have also been reported. In the latter cases, the diagnosis may be difficult to establish without a renal biopsy confirmation. However, other embolic signs may be used to reach a presumptive diagnosis. In our patient, the presence of Hollenhorst plaques in the retina with the recent history of aortic surgery was thus diagnostic of atheroembolic renal disease. Blue toe syndrome may be the sole dermatological manifestation of atheroembolic renal disease. Hollenhorst plaques in the retina may aid in the diagnosis. Conflict of interest statement. None declared.