Kidney Health Initiative Roundtable: Roadmap to Advanced RRT

(This post is not finished, but my flight keeps getting delayed in 20 minute increments, so better to publish it unfinished than to not get it up before NRG in case I’m not able to make it. Please forgive typos etc.)

I attended a meeting organized by the Kidney Health Initiative, a collaboration between the American Society of Nephrology (ASN) and the Food and Drug Administration (FDA).

The President of the United States (POTUS), Barak Obama, who was not in attendance, gave us the goal of eliminating the wait list for organ transplants. Jenna Ericson, White House Office of science technology was in attendance and delivered the President’s message to us, well she reiterated what he had pledged.

Lack of donated organs is the reason for the kidney wait list. There are over 90,000 people waiting for kidneys. Both hemodialysis (HD) and peritoneal dialysis (PD) are terribly inadequate replacements for kidney function and the average lifespan is 5 to 10 years, 65% of patients will die in < 5 years. Current dialysis is supposed to be a bridge to transplantation not a life sentence. So, in order to eliminate the wait list, either we need to find more kidneys (xenotransplantation will do this if we can overcome the rejection, David Sachs, MD, Massachusetts General Hospital, has a protocol he says ameliorates if not eliminates this problem, I have not looked into this claim). Another way to  eliminate the wait is to create an artificial kidney, implanted, wearable, or possibly portable. To be considered an artificial kidney there are a number of functions the device needs to perform that current dialysis does not or at least to perform what is does to a greater degree. See PDF. These include, water balance, glucose and salt balance, toxin removal, metabolite removal, retention of hormones. etc.

agenda-and-background-materials-for-khi-advisory-meeting

We talked about technologies and milestones needed for the mechanics of filtration as well as the cellular function needed for reabsorption and. The basic device for mechanical filtration would be an ultrafiltration (UF) device that used a tunneled veno-venous catheter exiting near the waist, a simple filter would remove fluid, shunted to a bag. In the meantime while this is being developed work can proceed on implantation in animals (into the illiac cavity?) with the ultrafiltrate being shunted to the bladder. A basic cellular device would have a membrane growing glomerular cells to produce the filtrate (or just a plain membrane) and a membrane with proximal tubule cells to reabsorb from the filtrate back to the blood.

Random notes:

• $88k per year HD patient
• Engage with CMS (payers) early to see what requirements they have.
• Kidney, 144 L/dy is 30 L/day sufficient for RRT
• Kidney cuts off at 66 kDa, HD dialysers cut off at 12 kDa
• Renal organoids, weird right
• Some patients are platelet deficient and don’t require anti-coagulation.

I’m interested in talking to Dr. Andrew Davenport, MD, Royal Free Hospital (UK) about vascular access. He seemed to have good insights on this. He suggests a CVC using a small lumen tubing, not opening and closing continuously, using modern hemocompatible materials, tunneled to the abdomen may be best for a wearable device.

Discussion:

The benefit of continuously balancing fluid seems to be more widely known/accepted by the nephrologists in this group than in the population of nephrologists we interviewed for ICorps. The thinking is that if you can ultrafilter continuously you can cut dialysis sessions from three a week to two a week (because you will remove some toxins during UF). There are, of course, patients who need only UF and not toxin removal. Slow Continuous Ultrafiltration (SCUF) devices already exist for use in fluid overload, pulmonary edema, and congestive heart failure. A portable, wearable, or implantable SCUF to remove ~3L/day could be the fist point on the roadmap for a mechanical system. This would require the continuous vascular access, a small dialyzer, waste storage/removal, and packaging.

One thing we have never addressed are functions of the kidneys that conventional HD and PD do not perform or do not perform well. These include endocrine function and the  secretion of wastes from the blood to the urine in the tubules.  Most of the functions not accounted for in standard dialysis are taken care of through pharmacological therapy, diet, and lifestyle changes. Some of these can potentially be handled by a cellularized membrane (or 3D matrix) but its not clear there is anyway to do such a sophisticated therapy with passive membranes.