Urine Collecting System Interventions For Improving Kidney Function

Renal and urine collection system interventions are provided that improve kidney function by manipulating pressures and/or infusing therapeutic agents in the renal pelvis of the kidney or kidneys. Setting a vacuum and/or infusing therapeutic agents in the renal pelvis results in increased glomerular filtration rate, general solute clearance, and free water excretion via the kidney through the urinary tract and is useful for treatment of CHF, ADHF, AKI, CKD, and many other conditions characterized by fluid overload by reducing fluid buildup. The fluid drawn from the renal pelvis or pelvises is delivered to an external or implanted reservoir or to the bladder using flow manipulation mechanism such as one-way valves, occlusion balloons, multi-lumen catheters, and other mechanisms. Pumps are provided for use in establishing the vacuum pressures that are either manual or motorized.

BACKGROUND OF THE INVENTION

Congestion in the kidneys can result from low cardiac output, tubuloglomerular feedback, increased intra-abdominal pressure, increased venous pressure, and other conditions. This congestion can lead to Acute Kidney Injury (AKI), which is a sudden episode of kidney failure or kidney damage that occurs rapidly, over the course of a few days or even a few hours. AKI causes a build-up of waste products in the blood and reduces the ability of the kidneys to maintain a proper fluid balance in the body, which may lead to adverse effects on the brain, heart, lungs and other organs.

AKI is very common among hospital patients, especially elderly hospital patients, and represents a massive burden on the health care system, partly due to the complex nature of present treatment therapies. For example, when AKI is a complication of systemic illness, fluid administration is often considered essential to prevent hemodynamic and nephrotoxic insults that might further compromise renal function. A long-standing tenet of AKI management has promoted volume resuscitation in response to hypotension and oliguria to augment cardiac output and urine output, respectively. The benefit of this approach is challenged, however, by increasing evidence suggesting that fluid overload is associated with impaired organ function and generally, iatrogenic morbidity and mortality. Clinicians treating AKI thus have difficulties balancing the need to give fluids to maintain blood pressure while knowing that fluid overload drives mortality and morbidity. Fluid overload in critically ill patients is an iatrogenic consequence of resuscitation. However, resuscitation is critical to treat the hypotension and the systemic inflammatory response.

The attending physician managing AKI is therefore faced with the following scenario: 1) Fluids are required to resuscitate the patient. 2) The patient's kidneys are not functional and cannot offload the administered fluid. 3) The patient is placed on dialysis, a form of renal replacement therapy (RRT). 4) Patients on dialysis have a risk of intradialytic hypotension limiting ultrafiltration and treatment success. In addition to hypotension, RRT has limitations such as waiting for the kidney to gain physiologic function, not promoting renal recovery, expense, time, etc.

There is thus a significant need for a treatment for AKI that promotes renal recovery, ultrafiltration, and/or solute clearance in AKI using the native organ. There have been disclosures that involve applying negative pressures to the urine collecting system to improve volume off-loading and solute clearance. There have also been disclosures of systems and devices for retrograde ureteral access and application of negative pressure to the renal pelvis. One example of such a disclosure is U.S. Pat. 6,500,158, entitled Method of Inducing Negative Pressure in the Urinary Collecting System and Apparatus Therefor, filed on Mar. 26, 1998 by Ikeguchi. However, these disclosures do not discuss, or make allowances for, the application of therapeutic agents in addition to the application of vacuum pressures.

Therapeutic agents could be an advantageous addition to the application of negative renal pelvic pressures. Not only do therapeutic agents provide various direct chemical treatments, infusing chemical agents into the renal pelvis may increase the production of urine and solute clearance by the nephrons due to contact with a fluid that has a different solute concentration, in an attempt to equalize the concentrations. It is also possible that these therapeutic agents limit antidiuretic hormone-mediated reabsorption of water in the urine collection system.

Other conditions that may be treated by increasing renal output include: Acute Decompensated Heart Failure, Chronic Heart Failure, Chronic Kidney Disease, Acute Kidney Disease, Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH—also known as dilutional hyponatremia), Cerebral/Renal Salt Wasting Syndrome, Cirrhosis with refractory ascites requiring regular large volume paracentesis, and other nephrotic syndromes. Additionally, there are some nephrotic syndromes that are associated with poor renal function and therefore require acute initiation of hemodialysis for volume control.

OBJECTS AND SUMMARY OF THE INVENTION

The present invention is directed to meeting the aforementioned needs by providing devices and method for reestablishing renal perfusion, enhancing primary filtrate formation, and augmenting total urine output and solute clearance, allowing the kidneys to return to normal function through the use of vacuum pressures and/or therapeutic agents.

More specifically, various devices and methods are disclosed herein that improve the milieu of the urine collection, glomerular, and medullary anatomy to increase volume off-loading and solute clearance. Several embodiments access the renal pelvis or general urine collection system through a retroperitoneal approach (i.e. a nephrostomy-style access). Other embodiments are delivered to the renal pelvis or general urine collection system via a retrograde ureteral access. Still other embodiments are delivered to the renal pelvis or urine collection system via the cardiovascular system using percutaneous methods.

These access routes are then used to provide therapeutic regimens to the renal pelvis, such as negative pressure and/or intermittent perfusion of diuretic agents (such as furosemide or antidiuretic hormone antagonists), natriuretic agents, or agents that otherwise offload volume and clear solutes from the body.

One aspect of the invention provides improved devices and methods for treating acute kidney injury, acute kidney disease, and chronic kidney disease.

Another aspect of the invention provides devices and methods for treating acutely decompensated heart failure, and/or chronic heart failure.

One embodiment includes a vacuum pump with a pressure check valve that ensures a desired vacuum pressure can be established in the renal pelvis. The valve could be electronically controlled or proportional to modulate pressure depending on therapeutic targets.

Another embodiment includes a vacuum pump with a pressure sensor and feedback loop that ensures a desired vacuum pressure can be established in the renal pelvis.

Another embodiment provides a nephrostomy and ureter-occluding vacuum catheter for use in treating the above-mentioned conditions.

One embodiment uses a multi lumen balloon catheter to occlude the ureter while pulling a vacuum to draw fluid into the catheter and deliver it to the bladder.

In one variation, the pump used to create the vacuum may be implanted subcutaneously. The pump could have an integrated or connected pressure sensor (measuring mechanical or oncotic pressure) that regulates vacuum to a set level.

One aspect of the invention is a miniaturized pump that is implantable directly in the renal pelvis or ureter. In one embodiment this pump has built in pressure sensors. This pump may be subcutaneously powered or charged. The method of power transfer could be inductive or magnetic, for example.

In one embodiment the pump can be programed to different pressure routines or curve profiles.

In one embodiment a pump is implantable in the bladder, allowing a larger pump size. A bladder implanted pump could be powered or could be manually operated through the abdomen. Conceivably, the pump is also implantable in the peritoneal cavity of the abdominal or retroperitoneal wall and could be manually powered or transcutaneously powered through the derma.

In one embodiment a lower pressure environment could be created within the renal capsule, rather than the renal pelvis. This embodiment could be combined with an injection of an ADH-antagonist/diuretic/dialysate inside the renal capsule.

In one embodiment, a dual nephrostomy system is provided that may alternate between a vacuum and a liquid infusion.

One aspect of the invention provides an infusion/suction catheter with one or more balloons attached thereto for occluding the ureter and controlling flow through the balloon with a pump. Controlling the flow could involve alternating between suction and infusion.

In one embodiment, an infusion/suction catheter is provided with a sample port used to take urine samples during a procedure to perform tonicity or other laboratory tests. The catheter or the sample port could also be used to inject medications or drug instillations.

One aspect of the invention is a method for improving kidney function that includes creating a vacuum within a renal pelvis of a kidney of a patient, thereby drawing urine out of renal tissue surrounding the renal pelvis. Creating the vacuum within the renal pelvis may be accomplished by introducing a suction catheter into the renal pelvis.

In one embodiment, this method further involves occluding the ureter prior to creating the vacuum.

In this or another embodiment, the method further involves directing urine from the renal pelvis to the bladder.

In this or another embodiment, creating the vacuum within the renal pelvis is accomplished by placing a one way valve within a ureter that prevents retrograde flow from a bladder toward the kidney; slowly inflating a balloon within the renal pelvis, thereby reducing a volume within the renal pelvis thus displacing urine contained therein through the valve and toward the bladder; and rapidly deflating the balloon, thereby increasing a volume in the renal pelvis and thus creating a temporary vacuum within the renal pelvis until the urine drawn out of the renal tissue surrounding the renal pelvis refills the renal pelvis.

In another aspect of the invention, creating the vacuum within the renal pelvis includes occluding a ureter associated with the kidney; and using a pump to remove fluid from the renal pelvis. The method may also include directing the fluid removed from the renal pelvis to a bladder through the ureter.

One aspect of the invention is a system for improving kidney function of a patient that includes a catheter having a proximal end and a distal end; a pump connected to one of the ends; and a fluid control mechanism that directs fluid manipulated by the pump out a renal pelvis of the kidney such that a vacuum is established in the renal pelvis resulting in increased fluid production by the kidney.

In some embodiments, the pump is connected to the proximal end. In other embodiments, the pump may be a balloon connected to the distal end. In still other embodiments, the pump may be a propeller pump contained within a distal end of the catheter. The pump may be external to the patient or may be implantable within the patient.

The fluid control mechanism may include holes formed in a sidewall of the catheter.

One aspect of the invention is a system for improving kidney function in a patient that includes a pump; a first nephrostomy tube connected at a proximal end to the pump and having a distal end suited for placement in a renal pelvis of a first kidney of the patient; and a second nephrostomy tube connected at a proximal end to the pump and having a distal end suited for placement in a renal pelvis of a second kidney of the patient; wherein when said first and second nephrostomy tubes are placed in the renal pelvises of the first and second kidneys of the patient, activating the pump creates a negative pressure in the renal pelvises. The pump system may also include a reservoir or a port that can be attached to a reservoir such that the pump may infuse a therapeutic agent.

At least one of the embodiments of this system also includes a catheter connected at a proximal end to the pump and having a distal end suited for placement in a ureter associated with one of the kidneys, and wherein said pump is configured to direct fluid from the first and second nephrostomy tubes into the catheter such that the fluid is delivered to a bladder of the patient.

At least one of the embodiments of this system also includes a container connected to the first and second nephrostomy tubes distal of the pump such that fluid drawn toward the pump through the first and second nephrostomy tubes is deposited in the container. In at least one embodiment, the container is a bag.

At least one of the embodiments of this system also includes a port usable to inject therapeutic fluids into the renal pelvis.

At least one of the embodiments of this system also includes a sample port in at least one of the first and second nephrostomy tubes for use in taking urine samples.

One aspect of the invention is a method of improving kidney function in a patient comprising: reducing pressure in a renal system of a least one kidney of a patient; infusing a therapeutic agent into the renal system of the at least one kidney; said reducing pressure and said infusing a therapeutic agent being conducted in combination during a therapeutic intervention on said patient.

Another aspect of the invention is a method of improving kidney function in a patient comprising: creating an access route to a renal pelvis region of a kidney of said patient through a wall of said kidney; drawing a vacuum through said access route so as to increase kidney function as a result of said vacuum.

Another aspect of the invention is a method of improving kidney function of a patient comprising: creating access to a renal pelvis region of a kidney of said patient through a wall of said kidney; introducing a therapeutic agent into said pelvis region so as to increase kidney function as a result of said introduction of said therapeutic agent.

Yet another aspect of the invention is a system for improving kidney function of a patient comprising: an access device configured for placement through a wall of a kidney to a renal pelvis region of said kidney; a vacuum inducing component associated with said access device configured for drawing a vacuum in said renal pelvis region; an infusion component associated with said access device configured for introducing a therapeutic agent into said renal pelvis region; said access device, said vacuum inducing component and said infusion inducing component in combination, during operation, increasing kidney function.

One aspect of the invention is a system for improving kidney function of a patient comprising: an access device configured for placement through a wall of a kidney to a renal pelvis region of said kidney; a vacuum component associated with said access device configured for drawing a vacuum in said renal pelvis region; said access device and said vacuum inducing component, in operation, increasing kidney function.

Still another aspect of the invention is a system for improving kidney function of a patient comprising: an access device configured for placement through a wall of a kidney to a renal pelvis region of said kidney; an infusion component associated with said access device configured for introducing a therapeutic agent into said renal pelvis region; said access device and said infusion inducing component in combination, in operation, increasing kidney function.

Another aspect of the invention is a method of improving kidney function in a patient comprising: inserting a catheter percutaneously into a renal pelvis region of a kidney; drawing a vacuum through said catheter so as to increase kidney function as a result of said vacuum.

Yet another aspect of the invention is a system for improving kidney function of a patient comprising: a percutaneous access device configured for placement in a renal pelvis region of said kidney; a vacuum component associated with said access device configured for drawing a vacuum in said renal pelvis region; said access device and said vacuum inducing component, in operation, increasing kidney function.

Still another aspect of the invention is a system for improving kidney function of a patient comprising: a percutaneous access device configured for placement in a renal pelvis region of said kidney; an infusion component associated with said access device configured for introducing a therapeutic agent into said renal pelvis region; said access device and said infusion inducing component in combination, in operation, increasing kidney function.

DESCRIPTION OF EMBODIMENTS

In general, the present invention is directed to improving kidney function by controlling the flow into and out of the kidneys, either through the ureters or through a catheter, the general urine collection system, or all. The invention involves several embodiments of devices, systems of devices, and methods for using these systems and devices. From the most general perspective, the invention improves kidney function by inducing a negative pressure in the urine collecting system, provides a means of infusing therapeutic agents that induce polyurea and/or solute clearance, or combines these two methods to induce a multiplicative effect. For purposes of organization, the description of the invention will be broken into catheters, pumps and methods. It is to be understood that every catheter, pump and method can incorporate any of the other components.

Catheter Systems

The catheter systems described herein may be inserted using several percutaneous or non-percutaneous approaches. As used herein, percutaneous approaches involve puncturing the skin of the patient to provide an access point for the catheter. Non-percutaneous approaches do not puncture the skin, and would thus involve routing a catheter through the urethra, bladder, ureters and into the kidney.

One example of a percutaneous approach is a nephrostomy approach in which an artificial opening or stoma is created between the kidney and the skin, which allows for a urinary diversion directly from the upper part of the urinary system, namely the kidneys and/or the ureters. The nephrostomy may be temporary or may include the installation of a semi-permanent or permanent port for use with embodiments of the present invention or with known treatment methods. The catheter systems may also be inserted using a retrograde ureteral approach. Lastly, the renal pelvis may be accessed using a femoral venous approach and trans-ureteral puncture, using a snare, magnet, or other targeting system.

Referring toFIG. 1, there is shown a balloon catheter assembly20that includes a catheter22having a plurality of holes24leading to a central lumen (not shown). At a distal end26of the catheter22is an occlusion balloon28. When inflated, the balloon28blocks the ureter, allowing the catheter22to be used to draw a vacuum in the renal pelvis through the holes24. The holes24can also be used to perfuse the urine collection system with therapeutic agents. In at least one embodiment, this catheter system is used in conjunction with a reversible pump or multiple pumps such that the holes24may be used to alternate between drawing a suction and perfusing a therapeutic agent.

FIG. 2shows a catheter assembly30that includes a catheter32having a plurality of holes34leading to a central lumen. The holes34serve as vacuum holes so that when the catheter is placed across the renal pelvis and into the ureter, as shown, the vacuum collapses the ureter onto the catheter32while simultaneously pulling a vacuum in the renal pelvis. In at least one embodiment the central lumen may be bifurcated into a suction lumen and a perfusion lumen. The suction lumen may lead to the distal most holes that are placed in the ureter such that, when they draw a suction, the ureter collapses around the catheter32. The proximal holes that are placed in the renal pelvis may be in communication with the perfusion lumen such that therapeutic agent may be introduced at the same time suction is being applied to the distal most holes. There may be another lumen that leads directly to a distal end used for directing urine into the ureter.

FIG. 3shows a multi-lumen balloon catheter assembly40that includes a catheter42having at least a first lumen44and a second lumen46that passes through an occlusion balloon48at a distal end50of the catheter42. The second lumen46opens at the distal end50of the balloon48. The catheter42includes a plurality of holes52leading into the first lumen44. The catheter may include a third lumen for infusing therapeutic agents.

The catheter assembly40further includes a pump54connected to a proximal end56of the catheter42and is attached such that the pump may be used to pull a vacuum in the renal pelvis through the first lumen44, which is in communication with the renal pelvis via the holes52. Additionally, the pump may be also connected to the second lumen46so that it may pump the urine from the renal cavity back through the second lumen46into the ureter so the urine may enter the bladder. The pump may have a reservoir (not shown) or be connected to a reservoir to perfuse the renal pelvis with therapeutic agents through the holes52.

In this embodiment, a reciprocating pump may be used to draw urine proximally from the renal pelvis during one half cycle of the reciprocating pump and push the urine through a second lumen during the other half of the reciprocating pump cycle. One or more check valves may be employed to prevent retrograde flow through the lumens. Alternatively, two pumps may be employed, a vacuum pump associated with a first lumen44, and a positive pressure pump associated with the second lumen46. A controller, switching system, clock, or other mechanism may be used to synchronize the two pumps. Alternatively, both pumps could be non-positive displacement pumps that run continuously. Other pump embodiments include peristaltic or impeller pumps. These could also be reversible.

The embodiments ofFIGS. 2 and 3have a chronic application, where the pump can be implanted subcutaneously. The pump could have an integrated or connected pressure sensor that regulates a vacuum to a set level.

It is also envisioned that the first lumen44could be used for both suction and perfusion of a therapeutic agent, while the second lumen46could be used simultaneously, sequentially, or alternatingly for discharge of urine into the bladder. This embodiment may be accomplished with a reciprocating pump aligned with the first lumen, and a non-positive displacement pump aligned with the second lumen. Alternatively, a single, reciprocating pump could be used that draws suction through the first lumen during one half cycle, and during the other half cycle pumps therapeutic agent through the first lumen while simultaneously pumping urine through the second lumen.

FIG. 4depicts a catheter system500of the invention that allows a therapeutic regimen that intermittently perfuses a therapeutic agent or agents and applies a vacuum to the urine collecting system. The system500includes a fluid management assembly502that includes a housing that may serve as a handle504, an infusion pump506, a vacuum pump508, a urine collection system510as well as pressure sensors512and514that take reading from a therapy catheter520and a central venous catheter530. The therapy catheter520include port holes522at a distal end thereof, just proximal of an isolation or sealing element524, shown as a balloon by way of example. The catheter520may include both infusion and vacuum lumens526and528, respectively. The urine collection system510may include a foley catheter530routed to the bladder through the urethra, and a urine collection reservoir532connected to the foley catheter530via a urine routing chamber533. The urine routing chamber533is connected to the vacuum pump508such that urine may be drawn from the bladder and into the urine collection reservoir532as shown. The vacuum pump draws a vacuum at an elevated location on the urine routing chamber533such that when urine enters the chamber533, gravity draws it downward, preventing it from entering the vacuum pump. The urine collection reservoir is connected at a low point on the routing chamber533such that the urine drains into the reservoir532.

The fluid management assembly502further includes connectors or ports for connecting the catheters and other fluid lines to the components of the fluid management assembly502. For example, a first connector540attaches the central venous catheter to the pressure sensor514. A second connector542acts as an input for connecting a fluid agent supply544to the infusion pump506. A third connector546is an output port that connects the infusion pump to an infusion line548that is connectable to the therapy catheter520. A fourth connector550connects the vacuum pump508to the therapy catheter520. A fifth connector552connects the therapy catheter to the pressure sensor512. A sixth connector554connects the foley catheter530to the vacuum pump508. Alternatively, gravity could be used. A seventh connector556connects the urine routing chamber533to the urine collection reservoir532.

The fluid management assembly502may further include a display560, depicted inFIG. 5, that provides data fields562and564provided by the sensors512and514as well as data fields566and568for measured urine output and infusion rate. Graphical displays567and569of pressure over time, urine output over time, pelvis pressure over time, and infusion rate over time. A control570is also provided that sets a target urine output. A target central venous pressure may also be set (not shown). The assembly502may be programmed such that increasing the target output may automatically increasing the speeds, duty cycle, or duration, for example, of one or both of the suction pump and the infusion pump. It is envisioned that the fluid management assembly502would have further sensors and capabilities, such as a urine off total, various flow rates, integration with an electronic medical record, MRI compatibility, and the like.

FIG. 6depicts a diagram of a port feature60, which can be incorporated into any of the catheter assemblies described herein, that provides a first port62to which a syringe64may be attached for introducing medications or other fluids into the kidney. This first port62may also be attached to a pump embodiment, as previously described. Additionally, a sample port66may be provided that is used to take urine samples to test the tonicity of the urine, assessing the efficacy of the treatment, sampling the sodium content of the urine, Sample the sodium content of the urine, assessing creatinine, inulin, and/or general solute clearance, assessing glomerular filtration rate, and the like.

This embodiment may be used with one or multiple lumens. The use of multiple lumens may be desirable if samples are being taken after the introduction of medication or other fluids to prevent contamination of the urine samples.

FIG. 7shows an embodiment of a catheter system70that can be used to manually induce a negative pressure in the renal pelvis. The system70includes a catheter72with multiple fenestrations or ports74at a distal end76thereof, useable to suck renal fluid into the catheter when a negative pressure is created at a proximal end78of the catheter72. The negative pressure may be created with a syringe80, as shown, or another form of a powered or manual pump. The catheter72includes a branch82that is connected to a urine collection bag or container84. The branch82and container84are oriented such that, when the syringe is used to create a vacuum in the catheter72, urine flows out of the renal cavity and drops into the container or bag84, due to gravity, instead of entering the syringe72. It is conceivable that this embodiment could also be used to pump infusate into the renal cavity. A valve, manually operated or otherwise, could be placed at the neck of the bag84to close the bag while the syringe80is used to introduce a therapeutic agent into the renal cavity.

FIG. 8shows an embodiment of a balloon catheter system90that includes a catheter92with a balloon94attached to a distal end96of the catheter92. A fluid pump98is attached to a proximal end100of the catheter92that is able to slowly inflate and rapidly deflate the balloon94such that the flow of fluid through the ureter is assisted or enhanced via the creation of a temporary vacuum. The catheter92is positioned such that the balloon94is located within the ureter. The balloon, in another embodiment, could perceivably be placed in the renal pelvis. When the balloon94is inflated, pressure fails to build on the kidney or upstream side of the balloon94due to the relatively slow nature of the inflation. When the balloon is rapidly deflated, the occupied volume is quickly released and the flow through the ureter is greater than a steady state flow that would occur if the balloon were not inflated. As it is shown inFIG. 8, the catheter is routed through the renal capsule, past the renal pelvis, and into the ureter. It is conceivable that the catheter of this embodiment could be routed through the urethra, bladder, and into the ureter or renal pelvis.

FIG. 9shows an embodiment of a catheter system110including a catheter112that operates in conjunction with a check valve114placed in the ureter. The proximal end116of the catheter112is attached to a pump118. The embodiment of the pump118shown is a manual, fluid-filled, spring-open pump that may be implanted subcutaneously and operated by the user. The one-way or check valve114is placed in the ureteropelvic junction. When the pump118is compressed, fluid contained in the pump118is driven through the catheter112and into the renal pelvis where it forces the fluid already contained within the renal pelvis through the check valve114. Spring force within the pump118then begins bringing the pump118to a pre-compressed state, which creates negative pressure within the renal pelvis. This draws urine from the outer components of the kidney into the renal pelvis, thus improving kidney function. As urine flows into the pelvis, some of the urine will travel into the pump118until the pump is full and the pressure in the renal pelvis is equalized. The user may then recompress the pump118. It is also perceivable that the actuation of the pump is automatically cycled to match a physiologic signal, such as pressure in the renal pelvis, central venous pressure, urine output, etc.

FIG. 10shows an embodiment of a catheter system120that is similar to catheter system110except that it includes a catheter122with a balloon124at a distal end126of the catheter122. The proximal end128of the catheter is attached to a pump130similar to pump118of the embodiment110ofFIG. 9. A check valve132is placed in the ureteropelvic junction. When the pump130is compressed, fluid contained in the pump130is driven through the catheter122and into the balloon124, causing the balloon to inflate and displace urine in the renal pelvis. The urine is forced through the check valve132and into the ureter where it continues to the bladder. Spring force within the pump130then begins bringing the pump130to a pre-compressed state, sucking the fluid out of the balloon124. The decrease in balloon size creates negative pressure within the renal pelvis. This draws urine from the outer components of the kidney into the renal pelvis, thus improving kidney function. As urine flows into the pelvis, all of the fluid will travel into the pump130from the balloon124until the pump is full and the pressure in the renal pelvis is equalized. The user may then recompress the pump130. It is also perceivable that the actuation of the pump is automatically cycled to match a physiologic signal, such as pressure in the renal pelvis, central venous pressure, urine output, etc.

FIG. 11depicts a catheter system140that includes a small-diameter catheter142that has a distal end144that includes a balloon146that is placed in the ureter. The distal end of the catheter140extends through the balloon146and includes a valve148, such as a bi-leaflet or duckbill valve, that prevents retrograde flow through the catheter. The proximal end150of the catheter142is connected to a compressible pump152. Using the pump to inflate the balloon146creates a pumping action similar in operation to the system ofFIG. 10. The pump152shown is an implantable, nitinol-reinforced compressible vacuum generator with a saline/drug infusion capability.

Pumps

Referring now toFIG. 12, there is shown an embodiment200of a pump assembly that includes a rigid container202, preferably graduated, with a rigid, removable lid204. The lid204includes a vacuum pump206, a check valve208and a drainage catheter210or a port212to which a drainage catheter210may be attached. The check valve208is optional but acts as a safety feature that allows a set pressure to be maintained inside the container. The check valve208opens when the pressure inside the container202exceeds the set pressure and allows air or another selected gas to enter the container202until the set pressure is reestablished.

Alternatively, the vacuum pump206could have an integrated pressure sensor and feedback loop that allows the vacuum pressure to be automatically regulated. In one embodiment, the feedback loop is programmable such that various pressure profile curves may be entered and followed. In another embodiment, the check valve208may be controlled with a programmable motor such that various pressure profile curves or variances may be entered and followed.

FIGS. 13A and 13Bshow an embodiment of an implantable pump220. The pump220may be a miniaturized version of any of the non-manual embodiments of the pumps described herein. The pump220may be implanted in the renal pelvis, at the ostium to the ureter. In one embodiment, the pump may be implanted in the ureter. In one embodiment, the pump includes an inflatable balloon or resilient balloon that anchors the balloon at the ostium to the ureter and creates a seal.

The pump220may configured with built in pressure sensors. For example, the pump may have an inlet side222oriented in the renal pelvis and an outlet or discharge side224oriented facing, or located within, the ureter. A first pressure sensor226may be located on the inlet side222and a second pressure sensor228may be located on the outlet side224. Having pressure sensor on either side of the pump220allows a differential pressure across the pump to be determined, thereby allowing a determination of flow rate.

The pump220may be subcutaneously powered or charged. In one embodiment, the pump220may be charged using wireless charging technology. Further, the pump220may be programmed to different pressure routines. Alternatively, the pump220could be designed for placement in the bladder, and have tubing extending into the renal pelvis. A bladder version of the pump220could be much larger as the bladder has more room than the renal pelvis.

FIG. 13Bshows one embodiment of the internal mechanisms of the pump220. In this embodiment, the pump220is powered by a motor221that drives a travel nut223with a lead screw225in, for example, reciprocating fashion. The travel nut223is attached to a bellows227that is expanded and contracted by the axial movement of the travel nut223, thus pumping fluid through the inflow222and outflow224via check valves229.

FIG. 14shows an embodiment of a manual pump230that includes a compressible chamber232that returns to a restored state with spring force. The spring force may be provided by a spring located within or around the chamber232, or as shown inFIG. 14, the chamber232may include pleated bellows234that resist being compressed and return to an expanded state when released.

FIG. 15shows a magnetically-driven, implantable pump240that includes a rotatable implantable impeller242that drives fluid from the renal pelvis towards the urinary outflow tract through a catheter243that has at least one terminus in a kidney. The impeller242has magnetic north244and south246poles that are respectively attracted to south248and north250poles of an electrically-powered drive impeller252. The drive impeller is, in one embodiment, worn on the body, such as on a belt, near the skin and proximal the implantation site of the implanted impeller242. The drive impeller252may be battery-powered.

In one embodiment the pump impeller242is implanted next to the kidney or subcutaneously and attached to a renal catheter such as that shown inFIG. 3, for example. The internal component242of the pump240does not require electronics.

FIGS. 16A through 16Ddepict an axial flow impeller260that resides within an impeller catheter262. The axial flow impeller260includes an impeller264, shown inFIG. 16B, that is driven by a motor266. A gap in the catheter262is located between the motor266and the blades268of the impeller264, forming a urine inlet where urine is drawn into the catheter by the negative pressure created on the inlet side of the impeller. The axial flow impeller260may further include an optical sensor270which allows feedback control of the pump speed and associated vacuum or infusion level.

FIGS. 16E and 16Fshow two examples of impellers264A and264B, respectively.FIG. 16Eshows a three-bladed propeller. By way of convention, as used herein, a propeller has an open design whereas an impeller is in a casing or catheter and is used to move water through the catheter. As such, when the propeller shown inFIG. 16Eis placed within the pump catheter262, it becomes an impeller.

FIG. 16Fshows an example of a four-bladed 45-degree pitched blade turbine. The devices of16E and16F are just examples of impeller/propeller designs useable with the pumps of the invention and are not to be interpreted as limiting examples.

The axial flow impeller260may be fully implantable, subcutaneous or intra-renal. For example, this axial flow impeller260, including its power source and drive train, could be implanted subcutaneously and charged via induction. The impeller260could also be placed in the retrograde ureteral fashion with no percutaneous access.

Another pump system270of the invention is shown inFIG. 17. This pump system270includes a rigid container271defining a chamber272that may include a slider assembly273that separates the chamber272into a liquid portion272A and an air portion272B and to which springs may be attached to strengthen the rebound force of the deflectable diaphragm275covering the container271. The container271includes a plurality of inlets and outlets leading into and out of the chamber of the container272. There is a renal pelvis inlet276that is connectable to a catheter277leading to the renal pelvis. This inlet276includes a check valve278directed such that urine from the renal pelvis may flow into the container271but may not flow out of the container271through the renal pelvis inlet276.

A second inlet is the therapeutic agent inlet278that is attachable to a source279of therapeutic agent. This inlet278also includes a check valve280directed such that therapeutic agent may flow into the container271from the source279but may not flow out of the container271through the therapeutic agent inlet278.

One of the outlets from the container271is a renal pelvis outlet281that leads from the container271to the renal pelvis via a catheter. The outlet281includes a check valve282that prevents retrograde flow through the outlet back into the container2271. Another outlet is an exhaust outlet283. The exhaust outlet283allows air to escape from the air portion272B of the chamber272when the deflectable diaphragm275is depressed.

Additionally, known pump designs could also be used such as piezo-electric disc pumps, mini diaphragm pumps, and the like.

Methods

Having described the various mechanical components of the invention and how they interact with each other, attention can be drawn now to how to use these components to improve kidney function.

In general, the excretion of fluid from the body is driven by filtration at the glomerulus as well as reabsorption and secretion in the peritubular capillaries. The dynamics by which this happens can be modeled using equations derived from Starling's Law. The Starling equation governs the formation of primary filtrate. The Starling equation can be broken into mechanical components and chemical components. The mechanical components deal with the hydrostatic pressure inside the of the Bowman's capsule and can be modified by a vacuum in the renal pelvis. A vacuum in the renal pelvis will reduce the pressure in Bowman's capsule, increasing the flux of primary filtrate and increasing glomerular filtration rate (GFR).

The chemical component of Starling's equation is also modified by the invention. By increasing the oncotic pressure in Bowman's capsule, the amount of primary filtrate is increased, augmenting GFR using known physics of filtration, as explained below. Further, the perfusion of agents may modify the increase in the chemical reflection coefficient in the Starling equation, thus limiting the amount of reabsorption and increasing the amount of filtrate and GFR.

Additionally, the perfusion of agents could impact the distal urine collecting areas of the nephron. ADH-antagonist perfusion is a targeted drug delivery method to reduce the amount of mediated water reabsorption that is typically upregulated in ADHF, CHF, CKD, and AKI. Other infusion could regulate the medullary gradient that is thrown out of sync in ADJF, CHF, CKD, and AKI. This allows the paradigm of “water follows sodium” to work to the patient's advantage, as sodium is being placed in the urine collecting area as opposed to the interstitium.

For example, as blood flows through the kidneys, various filtrate exchanges take place between the renal capillary structure and the Bowman's capsules of the nephrons. Using the following variables from Starling's law, various filtrate flow rates can be calculated:

First, blood flows through the afferent arteriole and enters glomerular capillaries, which are contained in a Bowman's capsule of the kidney. Filtration of the blood occurs as the blood is flowing through the glomerular capillaries. The flow of filtrate from the glomerular capillaries into the Bowman's capsule can be modeled by a reduced, modified Starling Law as follows:

Next, as the filtrate travels from the Bowman's capsule to the renal tubule, reabsorption of some of the filtrate occurs between the renal tubule and the peritubular capillaries. The rate at which this occurs is modeled with a modified Starling law as follows:

Finally, excretion happens from the peritubular capillaries back into the renal tubule according to the above modified Starling law. Thus, the total urinary excretion rate from the blood is equal to the filtration rate minus the reabsorption rate plus the secretion rate.

The total urinary excretion rate can be improved according to the invention by creating a vacuum in the renal pelvis and by infusing therapeutic agents. Creating a vacuum in the renal pelvis or ureter could result in a decrease in the Bowman's space hydraulic pressure, which is subtracted from the capillary hydrostatic pressure in the above equations. Thus, a decrease in the Bowman's space hydraulic pressure increases the overall urinary excretion rate.

Creating a vacuum in the ureter and/or renal pelvis may have a further effect that is understood by examining the formula for the filtration coefficient:

In which:

A vacuum in the renal pelvis could increase the radius r of the filtering pores, or the width of the podocyte filtration slits. An increase in this variable is raised to the fourth power in the formula for the filtration coefficient.

The benefits of using therapeutic infusates also may also be demonstrated by further examination of the above equations. For example, a deeper understanding of the reflection coefficient component of the Starling Force Law can be used to further reduce absorption, resulting in greater total urinary excretion rate. The reflection coefficient is calculated using the following formula:

In which:

It is likely possible to decrease the reflection coefficient through infusion of polycations such as protamine, thereby decreasing absorptive flux. This has been demonstrated in isolated glomeruli. By infusing solutes (e.g. polycations or other highly oncotic pressure solutes), the concentration of solute in the filtrate space is increased, resulting in a decrease of the reflection coefficient and thereby increasing the total amount of filtrate.

Infusion of therapeutic agents, such as polycations and/or protamine, could also impact the filtration coefficient of the glycocalyx, increasing the total urinary excretion rate. The modified Starling law accounts for the presence of glycocalyx, as detailed in the below charts comparing showing the Starling principle with and without the presence of glycocalyx:

Furthermore, it is possible that modifying the temperature, pH, and tonicity of the infusate could have an impact that improves renal function. It can also be perceived that in situ modifications such as electrical pulses in the renal pelvis or pulsed magnetic polarizations in the renal pelvis could improve renal function. For example, a pulsed magnetic field was shown to improve cerebral blood flow and tissue oxygenation in the cerebral space in rats. Bragin, Denis, et al. Pulsed Electromagnetic Field (PEMF) Mitigates High Intracranial Pressure (ICP) Induced Microvascular Shunting (MVS) in Rats. Acta Neurochir Suppl. 126, 93-95 (2019). It is plausible, for example, that a pulsed electromagnetic field in situ in the renal pelvis, urine collecting system, or general kidney increases renal blood flow and improves kidney oxygenation, resulting in improved kidney performance. Another embodiment could employ an electrode placed within the venous system and another electrode placed within the urinary system (renal pelvis, ureter, or bladder) to create an electrical potential. This potential could drive ion flow into the renal pelvis.

Turning toFIG. 18for reference, one method of the present invention involves placing an introducer sheath301into the bladder through the urethra of a patient. The introducer sheath301may be used then to route guidewires302and304through the ureters into the renal pelvis cavities of each kidney. Next, catheters306and308are advanced over the guidewires until the distal ends310and312of the catheters306and308are located in the renal pelvises.

Next, balloons314and316are inflated to occlude the ureters such that a vacuum may be drawn in the renal pelvises without drawing urine back into the kidneys via the ureters. Once inflated, the catheters306may be proximally attached to a suction source, such as a pump, to remove fluid from the kidneys and to establish a negative pressure in the renal pelvises. Creating a vacuum in the ureteral pelvises increases renal blood flow. This method may be performed contralaterally or ipsilaterally.

FIG. 19illustrates another embodiment of a method of the invention. This method involves placing an introducer sheath320into the bladder through the urethra of a patient. The introducer sheath320may be used then to route guidewires322and324through the ureters into the renal pelvis cavities of each kidney. Next, catheters326and328are advanced over the guidewires until the distal ends330and332of the catheters326and328are located in the renal pelvises.

Next, balloons334and336are inflated to occlude the ureters such that the renal pelvises are isolated from the ureters. Once inflated, a therapeutic solution is injected into the renal pelvises at various rates for a various time. The rates and times could be adjusted to one or more physiologic parameters. Once injected, a settling time is provided to allow the hypertonic to infiltrate the collecting ducts that lead to the renal pelvises. Finally, a vacuum is drawn through the catheters to aspirate and offload urine to the bladder.

This method incorporates benefits determined in various studies. For example, renal blood flow has been shown to increase by 25 percent immediately after transient bilateral ureteral obstruction (for up to 1-2 hours) due to hypothesized efferent vasodilation. Loo, M. H., Felsen, D., Weisman, S., Marion, D. N. & Vaughan, E. D. Pathophysiology of obstructive nephropathy. Kidney Int. 18, 281-292 (1980). GFR is only 80% of normal after transient bilateral ureteral obstruction (for up to 1-2 hours), suggesting limited filtration impact. (Id.) Additionally, fluid resorption decreased in obstructed kidneys. Hanley, M. J. Studies on acute disease models. Kidney Int. 22, 536-545 (1982). Relief of bilateral ureteral obstruction caused marked increase in sodium and water excretion. (Loo, et al.) The main inference is that obstruction increases ureteral pressure, which may reduce GFR and force solutes into the interstitial space of the kidney, causing a vicious cycle of reduced filtration and increased reabsorption. This invention infers that causing the opposite condition, namely inducing a negative pressure and perfusing the urine collecting system with polyurea-inducing and other general agents that promote solute clearance could substantially improve kidney function.

One aspect of the use of the non-manual pump systems described herein is maintaining a desired pressure in the kidneys. A method for doing so is shown inFIG. 20. Control is established by first applying therapy to the renal pelvis via negative pressure or via a therapeutic agent such as a diuretic, an ADH antagonist, dialysate, or salt injection. Next, various physiologic signals are monitored, such as central venous pressure, urine output, serum creatinine, creatinine clearance, urea, pressure in the renal pelvis, etc. Finally, the therapy level is adjusted to reach the target physiologic output.

FIG. 20shows an example of a feedback loop340that can be used to practice this method. In this example, pressure is being used as an input for the feedback loop340. Pressure readings are taken using a pressure sensor342. Inputs into the sensor342include central venous pressure CVP344provided via a central venous catheter346, and ureter pressure UP348, which is sampled from the therapy catheter350. The pump352receives an output354from the sensor342such that it can adjust speed to achieve a desired pressure.

FIG. 21illustrates a method in which intervention is achieved inside the renal tissue, rather than in the renal pelvis. This method involves using a suction catheter360to create a low-pressure zone inside the renal tissue. Additionally, an ADH-antagonist, a diuretic, or a dialysate could be injected through the catheter360inside the tissue.

FIG. 22illustrates a method in which the system ofFIG. 8is used with an implantable pump220, such as that shown inFIG. 13or an external unit372such as that shown inFIG. 22. The pump is used to slowly inflate and rapidly deflate the balloon374such that the flow of fluid through the ureter is assisted or enhanced. The catheter376is positioned such that the balloon374is located within the ureter. When the balloon374is inflated, pressure does not build on the kidney or upstream side of the balloon374due to the slow inflation of the kidney. When the balloon is rapidly deflated, the pressure is quickly released and the flow through the ureter is greater than a steady state flow that would occur if the balloon were not inflated. It is also possible that the balloon374is rapidly inflated and rapidly deflated. The rapid inflation would cause an increase in ureteral pressure; rapid reversal of this increase through a rapid deflation of the balloon could cause a sharp relief of the ureteral obstruction, causing significant post-obstructive diuresis. As it is shown inFIG. 22, the catheter is routed through the renal capsule, past the renal pelvis, and into the ureter. The catheter could also be perceivably be routed through the urethra into one or both ureters or renal pelvises.

FIG. 23depicts a method380that uses two suction flow paths382and384, as indicated by the arrows, and one drainage path386for urine to flow to the bladder. In cases where both kidneys need to be intervened, a double nephrostomy can be performed. In one kidney, a standard nephrostomy tube can be placed. In the other kidney (the left kidney inFIG. 23), a ureter is catheterized and there is a lumen to suck out urine from the renal pelvis and another lumen distally that pushes the urine towards the bladder. The pump388would therefore vacuum out urine from both renal pelvises but then only reintroduce the urine back into one of the catheters and direct the urine towards the bladder.

FIG. 24depicts a dual nephrostomy method400. This method uses two catheters402extending between the kidneys and a nephrostomy bag404. The catheters402could be connected to a pump that alternates between vacuum and infusion pressures. One option for the dual nephrostomy approach is that it could double the effectiveness of the therapy by alternating which kidney is exposed to vacuum and which is exposed to infusion, effectively ensuring that one kidney is always being exposed to vacuum. Another option for this approach is to help to mitigate a theoretical reno-reno reflex. In some conditions, this reflex seeks to maintain an average kidney function between the two kidneys (i.e. if one is underperforming the other will increase function to maintain the same total average function).

FIG. 25depicts a method for determining adequate vacuum pressure. The method410uses a flow meter412tapped into a catheter414between the kidney and a suction device416. The catheter414includes a distal occlusion balloon418, a proximal pressure sensor420on one side of the balloon, and a distal pressure sensor422on the other side of the balloon. The method involves first reading the pressure measurements from the pressure sensors420and422. Next, the balloon418is inflated and the pressure is again measured on the proximal side of the balloon418using the proximal pressure sensor420and on the distal side of the balloon422. The urine output can be calculate using the measured pressure differential and by utilizing the known resistance of the tube to flow. Next, a determination is made whether the calculated urine output is adequate. The suction device is then adjusted accordingly depending on the urine flow. The balloon418is then deflated and the suction is again adjusted based on the flow. Flow may be enhanced by reducing the duration of the balloon inflation.

In some situations, it may be preferable for the referral physician to access the renal pelvis transvenously. The advantages of doing so include the leverage of existing access in ICU patients, and the ability to use a multi-lumen catheter to concurrently perform veno-venous dialysis, if needed. This leverages existing provider care pathways for AKI and integrates into standard practice.

FIGS. 26-28depicts a method430utilizing a transvenous approach to access the kidney.FIG. 26shows the steps of accessing the renal pelvis. First, a needle432is navigated through the renal vein RV via the vena cava VC and into the renal pelvis RP. Next, as shown inFIG. 27, a therapy catheter434is advanced over the needle432and the needle432is retracted. The therapy catheter434may be one of the catheters described herein and may include perfusion/vacuum holes436. A proximal end of the therapy catheter434is connected to a hemodialysis machine438and a renal pelvis decompression device440. A cross section of an embodiment of a catheter434is shown inFIG. 28. The catheter434in this embodiment may include a venous blood in lumen437, a venous blood out lumen438and a renal pelvis vacuum and/or perfusion lumen440. This central lumen440could serve as both a vacuum and a perfusion lumen or could be bifurcated such that one side becomes a vacuum lumen and the other side becomes a perfusion lumen.

After the needle432is retracted, a sealing element, such as a balloon442for example, is inflated, isolating the renal pelvis from the ureter. A combination therapy is then administered involving infusion of a therapeutic agent444and vacuum suction446, both delivered via the catheter434.

In addition to superior vena cava (central line-style) access, it is possible to access the renal pelvis via the femoral vein and create a puncture into the ureter to access the urine collecting system. In some cases this route may be preferred for navigating a chronic-indwelling renal pelvis decompression device.FIG. 29is an anatomical diagram showing an optimal access point460where the femoral vein and the ureter are in close natural proximity.