Systems, devices, and methods for regulating blood flow in a body lumen

Abstract

Embodiments of the present disclosure relate to blood flow regulation systems and associated methods, and in certain embodiments, include an adjustable blood flow regulation device including an inner tube, an inflatable member coupled to the inner tube, a proximal control handle including a controller operatively coupled to the member and configured to control inflation of the member, and a downstream tip member coupled to a distal portion of the inner tube distal of the member. The tip member is coupled to a first fluid pressure sensor. A second fluid pressure sensor is coupled to a portion of the inner tube proximal of the member.

Description

[0001] Related Applications

[0002] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 777,788, filed December 11, 2018, the entire disclosure of which is incorporated herein by reference. TECHNICAL FIELD

[0003] Embodiments of the present disclosure generally relate to systems, devices, and methods for controlling any and all of venous pressure, renal function changes, and urine output, for example, such as in acute heart failure patients. BACKGROUND

[0004] Congestive heart failure (CHF) is characterized by a gradual loss of the heart's ability to pump blood. Etiologies range from valvular disease to infection. The affected heart struggles to supply blood to the body's organs with each contraction. Congestive heart failure symptoms typically include shortness of breath, fluid retention, and general fatigue. Most CHF patients require additional therapy to help manage their disease, typically oral diuretics, positive inotropes, vasodilators, and beta blockers.

[0005] Diuretics help the kidneys to expel excess fluid from the body, thereby reducing the volume of blood and the workload of the heart. Positive inotropes enhance the pumping action of the heart. Vasodilators, such as ACE (angiotensin-converting enzyme) inhibitors, cause peripheral arteries to dilate, making it easier for blood to flow. Beta-blockers slow the heart rate and lower blood pressure by blocking the effects of adrenaline.

[0006] Many congestive heart failure patients eventually experience a rapid deterioration and worsening of symptoms. This sudden worsening of symptoms is known as acute heart failure (AHF), and refers to a rapid onset or worsening of the signs and symptoms of chronic heart failure. It is a life-threatening medical condition that requires urgent treatment, often leading to emergency hospitalization (one million hospitalizations per year in the United States due to AHF). Fluid congestion relievers are a key treatment for AHF, namely high-dose diuretics: a class of drugs designed to increase urine output and sodium excretion. Acute decompensated heart failure leading to hospitalization marks a fundamental change in the natural history of progression of congestive heart failure. Mortality within one year after acute heart failure patient hospitalization is significantly higher than for patients who are not hospitalized. Moreover, these patients are particularly prone to re-hospitalization, with a recurrent hospitalization rate of 50% within 6 months of discharge.

[0007] A certain percentage of patients (20-30%) admitted to hospital for AHF do not respond to diuretics and are unable to achieve rapid fluid removal or complete reduction of congestion. These figures are supported by published literature and real-life analysis of consecutive admissions. To date, there is no viable treatment for diuretic-resistant AHF patients. These patients are at risk of increased in-hospital mortality, longer hospital stay, and high 30-day readmission rates (23-26%). SUMMARY

[0008] Embodiments of the present disclosure provide systems, devices, and methods for controlling venous pressure, renal function changes, and urine output in, for example, acute heart failure patients, by controlling blood flow in a blood vessel associated with the kidney, which can also be referred to as a body lumen.

[0009] In certain embodiments, a renal function change system is provided, comprising a blood flow regulation device, the blood flow regulation device comprising: an inner tube; an expandable, adjustable member (EAM) coupled to the inner tube; a downstream tip member coupled to a distal portion of the inner tube distal of the EAM, the tip member coupled to a first fluid pressure sensor; and a second fluid pressure sensor coupled to a portion of the inner tube proximal of the EAM. The system can further comprise a proximal control handle comprising a controller operatively coupled to the EAM and configured to control expansion of the EAM, a fluid connector coupled to the control handle, and a supply of a therapeutic agent in fluid communication with the fluid connector. The fluid connector can be coupled to the control handle, and upon delivery of the EAM to a site, for example, near a kidney, the EAM is adjustably expanded so as to achieve a desired reduction in blood flow at the site, and an amount of the therapeutic agent is delivered to the implant site via the fluid connector.

[0010] Such embodiments can further include one and / or another of the following features, structures, functionalities or descriptions (and in certain embodiments, at least two of the following, and in certain further embodiments, all of the following), forming further embodiments of the present disclosure:

[0011] - the therapeutic agent is selected from the group consisting of a diuretic, a blood thinning substance, and an anti-platelet substance, wherein the blood thinning substance comprises an anti-coagulant substance;

[0012] - the tip member can be conical, having a rounded distal open tip;

[0013] - the tip member can be concentric with a distal opening of the EAM;

[0014] - the first fluid pressure sensor can be coupled to the tip member via a guidewire fluid connector located on a proximal portion of the inner tube;

[0015] - the first fluid pressure sensor can be disposed in or on the tip member;

[0016] - the first fluid pressure sensor can include a left / first sensor and a right / second sensor;

[0017] - the tip member and the inner tube can be axially movable relative to the EAM;

[0018] - the inner tube can be disposed in an intermediate tube, the intermediate tube can be disposed in a removable outer sheath, and the EAM can be initially disposed in the outer sheath; and

[0019] - a blood flow impermeable cover, the cover can be arranged to cover at least a portion of the EAM.

[0020] In certain embodiments, a renal function altering system is provided, including a blood flow regulation device, the blood flow regulation device including: an inner tube; an expandable, adjustable member (EAM) coupled to the inner tube; a downstream tip member coupled to a distal portion of the inner tube distal of the EAM, the tip member coupled to a first fluid pressure sensor; and a second fluid pressure sensor coupled to a portion of the inner tube proximal of the EAM. Those skilled in the art will appreciate that the blood flow regulation device can be a standalone embodiment (i.e., separate from the system).

[0021] Such embodiments (including standalone blood flow regulation devices) can further include one and / or another of the following features, structures, functionalities or descriptions (and in certain embodiments, at least two of the following, and in certain further embodiments, all of the following), thereby forming further embodiments of the present disclosure:

[0022] - a proximal control handle including a controller operatively coupled to the EAM and configured to control expansion of the EAM;

[0023] - a fluid connector coupled to the control handle;

[0024] - a therapeutic agent supply in fluid communication with the fluid connector;

[0025] - the fluid connector can be coupled to the control handle; and

[0026] - When delivering the EAM to a site near the kidney, the EAM is adjustablely expanded to achieve a desired reduction in blood flow at the site, and optionally a dose of therapeutic agent is delivered to the implantation site via the fluid connector.

[0027] In some embodiments, a method for altering renal function is provided, comprising providing a blood flow regulation system / device according to any of the disclosed embodiments (e.g., see above), and providing a fluid connector coupled to the control handle. The method further comprises delivering the EAM to a site near the kidney, causing the EAM to expand to a desired amount to reduce the reduction in blood flow at the site; and delivering a therapeutic agent to the site via the fluid connector.

[0028] These and other embodiments, advantages, and objects will become even more apparent from the following detailed description and accompanying drawings, to which a brief description of the drawings is given below. Attached Figure Description

[0029] At least some embodiments of the present disclosure will be more fully understood and appreciated through the following detailed description taken in conjunction with the accompanying drawings, which are briefly described below.

[0030] Figure 1 The illustration shows an adjustable blood flow device (BFD) according to certain embodiments, which includes a multi-axis or multi-tube structure, an expansion frame, an impermeable cap, and a distal tip (e.g.).

[0031] Figure 2 for Figure 1 A diagram of the distal expansion element of the device;

[0032] Figure 3 For use Figure 1 The illustration shows an external control handle of a device according to certain embodiments, the external control handle including a control knob, a pressure measurement fluid connector (e.g., a Luer connector for upstream and / or downstream), and a therapeutic agent introduction fluid connector (e.g., a Luer connector);

[0033] Figure 4 for Figure 1 The illustration shows a device that includes an expanded distal element and an external control handle.

[0034] Figure 5 for Figure 1 The illustration shows the device after it has been introduced into the patient's body and connected to one or more therapeutic agents and pressure sensors;

[0035] Figure 6 for Figure 1An illustration of a device introduced through a body cavity (e.g., shown in this example, a catheter system is introduced into the common groin vein);

[0036] Figure 7 for Figure 1 An illustration of the distal end of the device at the treatment site / location (e.g., shown in this example, in the inferior vena cava (IVC), near the junction with the left and right renal veins);

[0037] Figure 8 for Figure 1 The diagram shows the outer shaft of the device beginning to have its sheath removed;

[0038] Figure 9 for Figure 1 The illustration shows the device in its fully radially expanded orientation, where the distal element has not yet achieved regulation of blood flow in the body cavity;

[0039] Figure 10 To enable the control knob to operate in accordance with certain embodiments, and Figure 1 The diagram illustrates the rotation of a control handle associated with the device, which causes a foldable leaflet (not shown here) in the distal end of the device to be pulled radially inward, thereby regulating the flow in the body cavity by partially blocking a portion of the flow; and

[0040] Figure 11A and 11B for Figure 1 The illustration shows the distal elements of the device in partially closed and fully closed positions, respectively, wherein the foldable leaflets are pulled radially inward to regulate blood flow therein until and include substantially blocking the flow in the body cavity (i.e., in some embodiments, blocking a significant portion of the flow). Detailed Implementation

[0041] Now for reference Figure 1 and 2 , Figure 1 and 2 An adjustable blood flow device 10 according to certain embodiments of the present disclosure is shown. Thus, device 10 may include an inner tube 12, such as a hollow flexible catheter. The inner tube 12 may be disposed in an intermediate tube 13, which in turn may be disposed in an outer sheath 16. An expandable member 14 (which is adjustable in some embodiments) is coupled to the inner tube 12 and may initially be disposed in the outer sheath 16. The member 14 can be deployed by retracting the outer sheath 16, which removes the covering of the member 14 and allows it to expand radially outward.

[0042] In certain embodiments, member 14 is self-expandable (e.g., constructed of shape memory material, such as but not limited to Nitinol), or can be expanded mechanically (e.g., by pushing / pulling a wire that expands the expandable element), or can be expanded fluidically (e.g., hydraulic or pneumatic inflation / deflation of a flexible member such as but not limited to a balloon).

[0043] In certain embodiments, member 14 expands radially (and / or axially) and conforms to the shape of the body lumen / vessel in which it is deployed. Thus, member 14 can be generally cylindrical in shape (although other shapes are within the scope of the present disclosure).

[0044] In certain embodiments, member 14 is constructed of foldable leaflets or struts 18, such as wires or other elongate elements, which can be coupled to a flexible frame 19, which includes loops interconnected at different junctions, for example. Such a structure of interconnected struts 18 and flexible frame 19 can be easily compressed and subsequently expanded to a predetermined shape.

[0045] In certain embodiments, member 14 can be formed with a distal opening 15( Figure 2 ), which can be referred to as an orifice, through which inner tube 12 protrudes. Foldable leaflets or struts 18 can be coupled to a guidewire 34 (connected to a control knob shown below in Figure 3 ), while a proximal outer portion of flexible frame 19 of member 14 can be coupled to intermediate tube 13. Similar functionality can be found in the associated published PCT WO2017081561A1, the entire disclosure of which is incorporated herein by reference.

[0046] In certain embodiments, the foldable leaflets, which in certain embodiments include struts 18 or can be separate, can be retracted proximally (by appropriate movement of the guidewire) to expand member 14 from a radially closed position for transport through the body lumen to a radially open position at the target site. The radially open position has a larger diameter than the radially closed state. Alternatively, in certain embodiments, the device can be designed such that distal advancement of the foldable leaflets or struts 18 expands member 14 from the radially closed position to the radially open position.

[0047] In certain embodiments, covering 20 can cover a portion of member 14, and can include a membrane that is impermeable to blood flow.

[0048] In certain embodiments, a downstream tip member 22 can be coupled to the distal portion of inner tube 12. Tip member 22 can be conical, with a circular distal open tip 24 that provides little fluid resistance so as not to impede fluid flow in the body lumen and not to cause local turbulence. Downstream tip member 22 can be concentric with distal opening 15 of member 14, which further ensures that no local turbulence or vortex is created and that there is very little pressure drop at the region of tip member 22.

[0049] Reference is now made to Figure 3 , Figure 3 An external control handle for the device according to certain embodiments is shown. To this end, all the members at the distal end of device 10 (according to certain embodiments) are operatively coupled to a proximal control handle 30, which is located outside the patient's body during treatment. The distal end of control handle 30 can be coupled to outer sheath 16, so as to move outer sheath 16 proximally to allow member 14 to radially expand (dilate) or so as to move outer sheath 16 distally to cause member 14 to contract from its radially open state to its radially closed state.

[0050] In certain embodiments, device 10 can be introduced using an over-the-wire percutaneous method, as is known in the art. As mentioned above, a guidewire 34 can pass through inner tube 12, with the distal end of guidewire 34 reaching distal tip 22 Figure 1 and the proximal end of guidewire 34 exiting through a guidewire fluid connector 36 (e.g., a luer fitting) at the proximal end of control handle 30.

[0051] Controller 32 (which in certain embodiments is also referred to as a control knob, but can also be an automated electric controller) can be located on control handle 30 (e.g., the proximal end) and can control the degree of flow of member 14 (i.e., the size of the openings through which blood flows out of member 14) by controlling the degree of radial dilation of member 14. In certain embodiments, control knob 32 is coupled to guidewire 34, which is coupled to leaflets or struts 18 Figure 1 Thus, by turning control knob 32, the user can move the foldable leaflets 18 to dilate member 14 at the site of the body lumen, thereby regulating the blood flow in the blood vessel and causing a local pressure drop in the vicinity of the location where member 14 is positioned. The user can control the degree of size of the openings through which blood exits member 14 by appropriately turning control knob 32 (note that in other embodiments, other kinds of mechanical or electrical controllers can be employed instead of a control knob).

[0052] In certain embodiments, once the distal end of the device is in place in the body lumen, the guidewire 34 can be removed and the first fluid pressure sensor 26 can be connected to the guidewire fluid connector 36 in the control handle 30. The pressure sensor 26(s) senses the fluid (blood) pressure in the vicinity of the open tip 24( Figure 2 ) which is the pressure in the blood vessel downstream of the location of the device. The fluid pressure sensor 26 can transmit the blood pressure information to the external controller 28 for data processing and display.

[0053] In certain embodiments:

[0054] - the intermediate tube 13 can couple the flexible frame 19 of the member 14 to inflate or deflate the member 14 (and as described above);

[0055] - the flexible frame 19 can be configured to ensure contact between the member 14 and the inner wall of the blood vessel;

[0056] - the gap between the intermediate tube 13 and the inner (guidewire) tube 12 can be used to measure the pressure upstream of the location of the member 14;

[0057] - a fluid connector 38 (e.g., a luer fitting) can be coupled to the control handle 30 and in fluid communication with the intermediate tube 13 via a passageway in the control handle 30;

[0058] - a second fluid pressure sensor 40 can be connected to the fluid connector 38 to continuously monitor the upstream pressure in the blood vessel in the vicinity of the location of the member 14. The pressure difference between the upstream and downstream sites can be used to control the degree of flow as needed by the patient (as described above, alternatively, the second fluid pressure sensor 40 can be provided in or on other parts of the device);

[0059] - in certain embodiments, depth or distance markers 39 can be provided on the device 10 to help the user during the procedure (see Figure 4 ); and / or

[0060] - as described above, the outer sheath 16 is coupled to the distal end of the control handle 30.

[0061] In certain embodiments, a third fluid connector 42 (e.g., a luer fitting) can be coupled to the outer sheath on the control handle 30. The third fluid connector 42 can be used to introduce therapeutic agents through the outer sheath 16, which can be, but are not limited to, diuretics and / or blood thinning substances to reduce the risk of thrombus formation on the distal inflated end during blood flow regulation.

[0062] Reference is now made to Figure 5 , Figure 5A device 10 according to certain embodiments is shown after being delivered to a site near the renal vasculature Figure 5 The option of bedside delivery is shown. Thus, the control handle 30 is shown outside of the device 10 and coupled to the fluid pressure sensor 26 (and / or circuitry) to continuously monitor the pressure in the blood vessel downstream of the site and to the second fluid pressure sensor 40 (and / or circuitry) to continuously monitor the upstream pressure near the site. The control handle 30 is in fluid communication with one or more therapeutic agents, such as a blood thinning substance 43 and / or a diuretic 45.

[0063] In certain embodiments, the therapeutic agent 43 (e.g., blood thinning substance) can be an anti-platelet substance. Anti-platelet therapy has been shown to reduce clinical ischemic events and improve prognosis in patients with acute coronary syndromes. Non-limiting examples of anti-platelet substances include GPIIb / IIIa inhibitors, dipyridamole, (low dose) aspirin (acetylsalicylic acid), selective COX-2 or non-selective COX-1 / COX-2 inhibitors, or ADP receptor inhibitors such as thienopyridines (e.g., clopidogrel, ticlopidine or prasugrel), eliquide or ticagrelor, or thrombin receptor antagonists such as vorapaxar, or analogs or derivatives thereof or combinations thereof. Thienopyridines such as clopidogrel irreversibly inhibit the P2Y 12 receptor, which plays an active role in platelet activation. In a normal state, platelet activation mediated by the P2Y 12 receptor plays an important role in stopping bleeding at the site of injury. In a diseased state, platelet activation leads to vascular occlusion and ischemic damage. Thus, P2Y 12 receptor antagonists play a key role in anti-platelet therapy, helping to prevent coronary artery disease as well as immediate treatment of acute coronary syndromes and percutaneous coronary intervention.

[0064] In certain embodiments:

[0065] - the therapeutic agent 43 (blood thinning substance) can be an anti-coagulation substance such as, but not limited to, heparin, warfarin, rivaroxaban, dabigatran, apixaban, edoxaban, enoxaparin or fondaparinux; and

[0066] - the diuretic 45 can include, but is not limited to, thiazide diuretics (e.g., chlorothiazide, hydrochlorothiazide, metolazone, indapamide), loop diuretics (e.g., torsemide, furosemide, bumetanide), and / or potassium-sparing diuretics (e.g., amiloride, aminophylline, spironolactone eplerenone).

[0067] In certain embodiments, the device can also include a controllable device having a continuous pressure measurement across the device. For example, as shown inFigure 2 Alternatively, as shown by the dashed lines in FIG. 27, fluid pressure sensors 26 can be disposed in or on tip member 22. Fluid pressure sensors 26 can be wireless blood pressure sensors available from many manufacturers that wirelessly transmit blood pressure information to circuitry 27 and / or external controller 28. Figure 3 Two fluid pressure sensors 26 can be used: left and right sensors (and even in some embodiments, a center sensor) for measuring blood pressure near the left and right renal veins, respectively (see FIG. 27). The pressure sensors can be left, center, and / or right portions of tip member 22; alternatively, a bifurcated tip member can be employed (shown in dashed lines). In another alternative, tip member 22 and inner tube 12 can be axially movable relative to member 14. In this manner, a user can adjust the distance that tip member 22 extends from member 14 to accommodate different anatomical geometries. Figure 2

[0068] Referring now to FIG. 28, Figure 6 , Figure 6 shows delivery of device 10 via the common iliac vein toward the inferior vena cava (IVC) in accordance with certain embodiments. In Figure 7 , the distal end of device 10 is at a site; in this example, in the IVC, near the junction with the left and right renal veins.

[0069] Referring now to FIG. 29, Figure 8 , Figure 8 shows the beginning of removal of the sheath of outer sheath 16 of device 10 in accordance with certain embodiments.

[0070] Referring now to FIG. 30, Figure 9 , Figure 9 shows device 10 in its fully radially expanded orientation in accordance with certain embodiments. Distal member 14 has not yet affected flow in the body lumen.

[0071] Referring now to FIG. 31, Figure 10 , Figure 10 shows rotating control knob 32 on the control handle in accordance with certain embodiments, which causes the member to expand radially outward to ultimately cause a change in flow in the body lumen.

[0072] Referring now to FIG. 32, Figure 11A and Figure 11B , Figure 11A shows member 14 in a partially expanded position and Figure 11B shows member 14 in a fully expanded position, substantially occluding flow in the body lumen (and in some embodiments, occluding flow) in accordance with certain embodiments.

[0073] ​In certain embodiments, the device 10 is placed in the inferior vena cava, caudal to the entrance of the renal veins, to effect a change in flow and create a lower pressure zone in its region, thereby increasing the pressure gradient on the kidneys and increasing urine output. The controllable device catheter can be designed for bedside delivery, which minimizes treatment time and recovery. Once the desired change in flow is achieved, a diuretic can be provided to the patient. The combination of the change in flow and the diuretic can improve kidney function, increase urine output in the patient, and help extract excess fluid from interstitial tissue.

[0074] While various inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations will depend upon the specific application or applications for which the teachings of the present application are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, inventive embodiments can be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are directed to each individual feature, system, article, material, kit, step and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, steps and / or methods, if such features, systems, articles, materials, kits, steps and / or methods are not mutually inconsistent, is included within the inventive scope of the present disclosure.

[0075] Embodiments disclosed herein can also be combined with one or more features and complete systems, devices, and / or methods to produce other embodiments and applications. Also, certain embodiments can differ from the prior art by specifically excluding one or more features that are present in the prior art; i.e., the claims can specifically exclude one or more features that are present in the prior art.

[0076] Furthermore, various inventive concepts can be implemented as one or more methods, of which an example has been provided. The acts performed as part of the method(s) can be ordered in any suitable way. Accordingly, embodiments can be constructed in which acts are performed in an order different than illustrated, and / or acts are performed concurrently, even though shown as being performed sequentially, and / or even though some acts are not shown. A variety of inventive concepts can be embodied in the methods.

[0077] Any and all references to publications or other documents, including but not limited to patents, patent applications, articles, webpages, books, and / or treatises, primarily located in the background art section of the specification, in whole or in part, are hereby incorporated by reference. Moreover, all definitions, as defined and used in connection with the description herein, should be understood to control over dictionaries, of which definitions in documents cited in the specification, and / or the meanings of the terms in the art, and / or the plain meaning of the term.

[0078] As used in the specification and claims, the indefinite article "a" should be understood to mean "at least one," unless explicitly stated otherwise.

[0079] As used in the specification and claims, the phrase "and / or" should be understood to mean "either or both" of the elements so conjoined, i.e., elements conjoined with "and / or" are to be construed in the nature of alternatives rather than in the nature of exclusivities. As used in the specification and claims, the phrase "at least one of means "one or more" of the elements conjoined, i.e., one or any combination of the elements conjoined with "at least one of." Other elements can optionally be present in addition to those specifically identified by the "and / or" clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to "A and / or B" when used in conjunction with open-ended language such as "comprising" can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including additional elements); etc.

[0080] "and / or" as defined above. For example, "or" or "and / or" shall be interpreted as inclusive, i.e., comprising one or more elements, but not excluding additional, unlisted items, in addition to at least one of the items listed. Only the terms "only one of' or "exactly one of' or, when used in the claims, "consisting of shall be interpreted as excluding any of the additional, unlisted items. In general, the term "or" as used herein, when used in a list of items, shall be interpreted as indicating exclusive alternatives (i.e., "one or the other but not both") only when preceded by terms that state such a meaning is to be inferred, e.g., "only one of' or "either... or." The terms "consisting of and "consisting essentially of when used in the claims shall have their ordinary meanings as understood by those of ordinary skill in the art.

[0081] The phrase "at least one", in reference to a list of one or more elements, should be understood as meaning at least one of the elements in the list, but not necessarily including at least one of each and every element specifically listed within the list. In other words, this phrase, "at least one", should be interpreted to include "one or more" of the elements listed, but not necessarily including each and every one of the elements in the list. Accordingly, this phrase, "at least one", should be interpreted to include one or more of the elements listed, but not necessarily including each and every one of the elements in the list. This definition also allows for the inclusion of additional elements not listed within the list, whether related to the elements specifically listed or unrelated to the elements specifically listed. For example, if a method is described as comprising "at least one of A and B", this means that the method can comprise A alone, B alone, or A and B together, and can also include additional elements not listed, whether related to A, B, or unrelated to A and B. In other words, the phrase "at least one of A and B" should be interpreted to include A alone, B alone, A and B together, and additional elements not listed.

[0082] In the claims, as well as in the specification above, all conjunctions, such as "comprising," "including," "carrying," "having," "containing," "involving," "holding," "composed of," and the like, are to be construed in an open, as opposed to a limiting sense, i.e., in a sense of "including, but not limited to," unless expressly limited otherwise. As used herein, the term "consisting essentially of shall have its ordinary meaning as understood by those of ordinary skill in the art.

Claims

1. A renal function altering system, comprising: a blood flow regulation device, comprising: an inner tube; an expandable, adjustable member (EAM) coupled to the inner tube, the EAM comprising: a proximal end and a distal end; a cylindrical section between the proximal and distal ends of the EAM; a plurality of radially inwardly foldable leaflets connected between a distal end of the cylindrical section and an adjustable opening at the distal end of the EAM; and a blood impermeable cover configured to cover at least a portion of the EAM; wherein the inner tube passes through the cylindrical section and the adjustable opening; a downstream tip member coupled to a distal portion of the inner tube distal of the EAM, the downstream tip member coupled to a first fluid pressure sensor, and a second fluid pressure sensor disposed proximal of the EAM; a proximal control handle containing a controller operatively coupled to the foldable leaflets and configured to control a size of the adjustable opening; a fluid connector coupled to the proximal control handle; and a therapeutic agent supply in fluid communication with the fluid connector; wherein: upon delivery of the EAM to a site proximate a kidney, the adjustable opening of the EAM adjustably expands so as to effect a desired reduction in blood flow at the site, and an amount of therapeutic agent is delivered to the site via the fluid connector. the therapeutic agent is selected from the group consisting of a diuretic, a blood thinning substance, and an anti-platelet substance.

2. The renal function alteration system according to claim 1, characterized by, the blood thinning substance comprises an anti-coagulant substance.

3. The renal function alteration system according to claim 2, characterized in that, the downstream tip member:

4. The renal function alteration system according to any one of claims 1 to 3, characterized in that, is tapered with a rounded distal open tip; and / or is concentric with a distal opening of the EAM. the first fluid pressure sensor:

5. The renal function alteration system according to claim 1, characterized by, is coupled to the downstream tip member via a guidewire fluid connector on a proximal portion of the inner tube, is disposed in or on the downstream tip member, and / or comprises a first sensor and a second sensor. the downstream tip member and the inner tube are axially movable relative to the EAM.

6. The renal function alteration system according to claim 1, characterized by, 7. The renal function altering system of claim 1, wherein: the inner tube is disposed in an intermediate tube, the intermediate tube disposed in a removable outer sheath, the EAM is initially disposed in the outer sheath.

8. A renal function altering system, the renal function altering system comprising a blood flow regulation device, the blood flow regulation device comprising: an inner tube, an expandable, adjustable member (EAM) coupled to the inner tube, the EAM comprising: a proximal end and a distal end; a cylindrical section between the proximal and distal ends of the EAM; a plurality of radially inwardly foldable leaflets connected between a distal end of the cylindrical section and an adjustable opening at the distal end of the EAM; and a blood impermeable cover configured to cover at least a portion of the EAM and an outer surface of the foldable leaflets; and a therapeutic agent supply in fluid communication with the fluid connector. ​ a downstream tip member coupled to a distal portion of the inner tube distal of the EAM, the downstream tip member coupled to a first fluid pressure sensor, and a second fluid pressure sensor disposed proximal of the EAM.

9. The renal function altering system of claim 8, further comprising a proximal control handle, the proximal control handle containing a controller operatively coupled to the foldable leaflets and configured to control a size of the adjustable opening of the EAM.

10. The renal function altering system of claim 9, further comprising a fluid connector coupled to the proximal control handle.

11. The renal function altering system of claim 10, further comprising a therapeutic agent supply in fluid communication with the fluid connector.

12. The renal function alteration system according to claim 10, characterized by, the fluid connector coupled to the proximal control handle, and upon delivery of the EAM to a site proximate a kidney, the EAM adjustably inflates so as to achieve a desired reduction in blood flow at the site, and an amount of therapeutic agent is delivered to the site via the fluid connector.

13. A blood flow regulation device, comprising: an inner tube, an inflatable, adjustable member EAM coupled to the inner tube, the EAM member comprising: a proximal end and a distal end; a cylindrical section between the proximal and distal ends of the EAM; a plurality of adjustable, radially inwardly foldable leaflets connected between a distal end of the cylindrical section and an adjustable opening at the distal end of the EAM; and a blood impermeable cover configured to cover at least a portion of the EAM and an outer surface of the foldable leaflets; and a downstream tip member coupled to a distal portion of the inner tube distal of the EAM, the downstream tip member coupled to a first fluid pressure sensor, and a second fluid pressure sensor disposed proximal of the EAM. the blood flow regulation device configured to inflate via a proximal control handle located outside a patient's body.

14. The flow regulation device of claim 13, wherein, the proximal control handle containing a controller operatively coupled to the foldable leaflets to control inflation of the adjustable opening.

15. The flow regulation device of claim 14, wherein, the downstream tip member is tapered with a rounded distal open tip.

16. The blood flow regulating device of any one of claims 13-15, wherein, the downstream tip member is concentric with a distal opening of the EAM.

17. The flow regulation device of claim 13, wherein, the first fluid pressure sensor coupled to the downstream tip member via a guidewire fluid connector located on a proximal portion of the inner tube.

18. The flow regulation device of claim 13, wherein, the first fluid pressure sensor disposed in or on the downstream tip member.

19. The flow regulation device of claim 13, wherein, the first fluid pressure sensor comprises a first sensor and a second sensor.

20. The flow regulation device of claim 13, wherein, the downstream tip member and the inner tube are axially movable relative to the EAM.

21. The flow regulation device of claim 13, wherein, the inner tube is disposed in an intermediate tube, the intermediate tube is disposed in a removable outer sheath, and the EAM is initially disposed in the outer sheath.

22. The flow regulation device of claim 13, wherein, ​

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