Methods and apparatus for bilateral renal neuromodulation
Methods and apparatus are provided for bilateral renal neuromodulation, e.g., via a pulsed electric field, via a stimulation electric field, via localized drug delivery, via high frequency ultrasound, via thermal techniques, etc. Such neuromodulation may effectuate irreversible electroporation or electrofusion, necrosis and/or inducement of apoptosis, alteration of gene expression, action potential attenuation or blockade, changes in cytokine up-regulation and other conditions in target neural fibers. In some embodiments, neuromodulation is applied to neural fibers that contribute to renal function. In some embodiments, such neuromodulation is performed in a bilateral fashion. Bilateral renal neuromodulation may provide enhanced therapeutic effect in some patients as compared to renal neuromodulation performed unilaterally, i.e., as compared to renal neuromodulation performed on neural tissue innervating a single kidney.
1. A method of treating a disease of a human patient diagnosed with at least one of hypertension, heart failure, chronic kidney disease, and renal failure by bilateral renal neuromodulation, the method comprising:
modulating a first neural fiber that innervates a first kidney of the patient in a manner that inhibits neural activity entering and exiting the first kidney; and
modulating a second neural fiber that innervates a second kidney of the patient in a manner that inhibits neural activity entering and exiting the second kidney,
wherein modulating the first and second neural fibers significantly improves a measureable physiological parameter corresponding to the disease of the patient,
wherein at least one of the first kidney and second kidney continues to secrete renin in the patient after delivering the electric field.
2. The method of claim 1 wherein:
modulating a first neural fiber that innervates a first kidney of the patient further comprises modulating a right neural fiber that contributes to right renal function; and
modulating a second neural fiber that innervates a second kidney of the patient further comprises modulating a left neural fiber that contributes to left renal function.
3. The method of claim 1 wherein:
modulating a first neural fiber that innervates a first kidney of a patient further comprises ablating a left neural fiber that contributes to left renal function; and
modulating a second neural fiber that innervates a second kidney of a patient further comprises ablating a right neural fiber that contributes to right renal function.
4. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises concurrently modulating the first and second neural fibers.
5. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises sequentially modulating the first and second neural fibers.
6. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises modulating the first neural fiber and modulating the second neural fiber via apparatus positioned within renal vasculature of the patient.
7. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises modulating the first neural fiber and modulating the second neural fiber via apparatus positioned external to renal vasculature of the patient.
8. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises modulating the first neural fiber and modulating the second neural fiber via apparatus positioned in proximity to renal vasculature of the patient.
9. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises modulating the first neural fiber and modulating the second neural fiber via apparatus positioned within renal vasculature of the patient and having a neuromodulatory element passed extravascularly.
10. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises modulating the first and second neural fibers via electric fields.
11. The method of claim 10 , wherein modulating the first and second neural fibers via electric fields further comprises exposing the first and second neural fibers to pulsed electric fields.
12. The method of claim 10 , wherein modulating the first and second neural fibers via electric fields further comprises exposing the first and second neural fibers to thermal electric fields.
13. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises delivering a neuromodulatory agent to the first and second neural fibers.
14. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises at least partially denervating the first and second kidneys.
15. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises inducing an effect in the first and second neural fibers chosen from the group consisting of irreversible electroporation, electrofusion, necrosis, apoptosis, gene expression alteration, action potential attenuation, action potential blockade, cytokine up-regulation alteration, and combinations thereof.
16. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises continuously modulating the first and second neural fibers.
17. The method of claim 1 , wherein modulating the first neural fiber and modulating the second neural fiber further comprises intermittently modulating the first and second neural fibers.
18. A method for bilateral renal neuromodulation of a human patient with diagnosed hypertension, diagnosed heart failure, diagnosed chronic kidney disease, or diagnosed renal failure, the method comprising:
inhibiting neural activity along renal nerves that contribute to function of the right kidney of the patient; and
inhibiting neural activity along renal nerves that contribute to function of the left kidney of the patient,
wherein inhibiting neural activity along the renal nerves that contribute to function of the right and left kidneys of the patient results in a therapeutically beneficial reduction in the clinical symptoms of hypertension in the patient,
wherein at least one of the right and left kidney continues to secrete renin in the patient after inhibiting neural activity along the renal nerves.
19. The method of claim 18 , wherein inhibiting neural activity along renal nerves that contribute to renal function of the right and left kidneys further comprises at least partially denervating the right and left kidneys of the patient.
20. The method of claim 18 , wherein inhibiting neural activity along renal nerves that contribute to renal function of the right and left kidneys further comprises inducing an effect in the neural fibers chosen from the group consisting of irreversible electroporation, electrofusion, necrosis, apoptosis, gene expression alteration, action potential attenuation, action potential blockade, cytokine up-regulation alteration, and combinations thereof.
21. The method of claim 18 , wherein inhibiting neural activity along renal nerves that contribute to renal function further comprises:
positioning a modulating apparatus within right and left renal vasculature of the patient, and
modulating the renal nerves with the modulating apparatus.
22. The method of claim 18 , wherein inhibiting neural activity along renal nerves that contribute to renal function further comprises:
positioning a modulating apparatus in a vicinity of right and left renal vasculature of the patient, and
modulating the renal nerves with the modulating apparatus.
23. The method of claim 22 , wherein positioning modulating apparatus in the vicinity of the right and left renal vasculature of the patient further comprises positioning the modulating apparatus within the patient external to the renal vasculature.
24. The method of claim 23 , wherein positioning the modulating apparatus within the patient external to the renal vasculature further comprises positioning the modulating apparatus within the patient external to the renal vasculature via an intra-to-extravascular approach.
25. The method of claim 18 , wherein inhibiting neural activity along renal nerves that contribute to renal function further comprises applying an electric field to the renal nerves.
26. The method of claim 25 , wherein applying an electric field to the renal nerves further comprises applying a pulsed electric field to the renal nerves.
27. The method of claim 25 , wherein applying an electric field to the renal nerves further comprises applying a thermal electric field to the renal nerves.
28. The method of claim 18 , wherein inhibiting neural activity along renal nerves that contribute to renal function further comprises delivering a neuromodulatory agent to the renal nerves.
29. The method of claim 18 , wherein inhibiting neural activity along renal nerves that contribute to renal function of the right and left kidneys further comprises concurrently inhibiting neural activity along renal nerves that contribute to renal function of the right and left kidneys.
30. The method of claim 18 , wherein inhibiting neural activity along renal nerves that contribute to renal function of the right and left kidneys further comprises sequentially inhibiting neural activity along renal nerves that contribute to renal function of the right and left kidneys.
31. The method of claim 18 , wherein inhibiting neural activity along renal nerves that contribute to renal function of the right and left kidneys further comprises continuously inhibiting neural activity along renal nerves that contribute to renal function of the right and left kidneys.
32. The method of claim 18 , wherein inhibiting neural activity along renal nerves that contribute to renal function of the right and left kidneys further comprises ablating the renal nerves.
33. A method for bilateral renal denervation of a human patient diagnosed with hypertension, heart failure, chronic kidney disease, or renal failure, the method comprising:
reducing neural activity along nerves that innervate a first kidney of the patient; and
reducing neural activity along nerves that innervate a second kidney of the patient,
wherein reducing neural activity along the nerves that innervate the first and second kidneys of the patient results in a therapeutically beneficial reduction in central sympathetic overactivity in the patient,
wherein at least one of the first kidney and second kidney continues to secrete renin in the patient after reducing neural activity along the renal nerves.
34. The method of claim 33 , wherein the therapeutically beneficial reduction in central sympathetic overactivity comprises a reduction in clinical symptoms of hypertension in the patient.
35. The method of claim 33 , wherein the therapeutically beneficial reduction in central sympathetic overactivity comprises a reduction in clinical symptoms of heart failure in the patient.
36. The method of claim 33 , wherein the therapeutically beneficial reduction in central sympathetic overactivity comprises a reduction in clinical symptoms of chronic renal failure in the patient.
37. The method of claim 33 , wherein the therapeutically beneficial reduction in central sympathetic overactivity comprises a reduction in clinical symptoms of impaired renal function in the patient.
38. The method of claim 33 , wherein the therapeutically beneficial reduction in central sympathetic overactivity comprises a reduction in clinical symptoms of acute myocardial infarction in the patient.