Kidney Disease: Past, Present & Future

For more than two hundred years, scientists have been working to understand how kidneys function and how to treat kidney-related problems. Early strides in understanding organ function led to a rapid period of growth and innovation in kidney care during the 1940s and 50s, and since then, the broader kidney disease space has continued to evolve significantly.

However, medical evolution is not always a smooth, linear development process – it’s often full of stops and starts, periods of rapid growth followed by slow lulls. Take, for example, treatments for hyperkalemia, or elevated potassium levels in the blood, a condition associated with kidney disease. It took more than 50 years for a new hyperkalemia treatment to be approved1 since 1958, when a drug named Kayexalate was approved for use in the treatment of hyperkalemia.2

Check out a recap of the history, present and future of kidney care and see how we’re poised for the biggest leap ever.

1800s:  Basic Science

As far back as the mid-1800s, an understanding of osmosis, diffusion, and semi-permeable membranes emerged. These learnings offered insight into how organs work to maintain balance of chemical elements and proper levels of fluids in the body.3

1940s:  Early Breakthroughs

It wasn’t until 1943 that William Kolff, MD, PhD, developed the first artificial kidney that was successfully used regularly on humans. However, this remarkable advancement wasn’t immediately embraced by all peers in the medical community. Maybe it was because the first prototypes for the rotating drum dialyzer, as it was officially was called, were initially made of sausage casings and orange juice cans.4


“The first artificial kidney was made of sausage casing and orange juice cans.”


Less than a decade later, something that was once thought to be impossible was accomplished, building on knowledge gleaned from Kolff’s invention.

1950s:  Pioneering Transplantation

In 1950, the first-ever successful organ transplant placed the kidney of a recently-deceased person into Ruth Tucker, a 44-year-old woman with polycystic kidney disease. Tucker survived for five years after receiving her new kidney.5

In 1952, the first kidney transplants between living patients were completed successfully by France’s Jean Hamburger. Unfortunately, the transplanted kidney ultimately failed after three weeks of normal function, but Hamburger’s biopsy of the rejected kidney described details of immune system failure.6 This knowledge was a crucial step in evolving transplantation techniques.

In 1958, the first-ever treatment for hyperkalemia was recognized and used: Kayexalate.2 Hyperkalemia, or elevated potassium levels in the blood, is a serious condition that can cause irregular heartbeats and, in severe cases, even death. Patients with chronic kidney disease are especially at risk.7

1960s: A New Hope8

Before the 1960s, kidney disease was often fatal. But the use of the artificial kidney and introduction of outpatient dialysis facilities in the 1960s brought hope to many with chronic kidney disease.

Still, there were serious challenges. Each time a patient received dialysis, an artery and a vein were damaged. After a handful of treatments, doctors wouldn’t be able to find a strong and healthy vein to connect machine to patient. This meant that dialysis treatment was only a short-term option and not a viable long-term solution for those with chronic renal failure.  

Then came an innovation known as the Scribner Shunt, a U-shaped tube installed in a patient’s arm between an artery and a vein. Instead of poking the patient each time they came in for dialysis treatment, the device could semi-permanently stay in the arm and easily be attached or disconnected from the kidney machine as often as necessary. This, plus the development of smaller and relatively portable kidney machines, made long-term dialysis a real possibility.

1970s-80s:  Broadening Access & Emphasizing Organ Transplants

By the early ‘70s, it had become clear that dialysis therapy worked. As a result, nephrologists, nurses, and patient advocacy groups began lobbying to broaden Medicare in the United States to cover dialysis patients. In 1972, legislation was passed authorizing the End Stage Renal Disease (ESRD) Program.9 And by 1978, thanks partly to the efforts of the National Kidney Foundation, kidney transplants were also included under Medicare coverage.10 

As this decade came to a close, two innovations introduced the potential for routine, safe, and successful kidney transplantation: the clinical application of HLA-DR matching which tests if the potential donor and transplant recipient have tissues that are compatible with each other, and adoption of cyclosporine—a powerful immunosuppressive agent used in organ transplantation to prevent rejection.11

Into the ‘80s, both tissue typing and immune suppressant drugs would continue to get better and better. And by the late ‘80s, University of Washington researchers synthesized a drug to treat anemia in dialysis patients.12

1990s:  Refining Treatments

In the 1990s, researchers were able to pinpoint a second gene for autosomal dominant polycystic kidney disease,13 and The Modification of Diet in Renal Disease Study found that a low-protein diet could retard the decline of kidney function in people with moderate kidney disease.14 Researchers also continued to search for ways to encourage immune system tolerance of a transplanted organ.

2000s & into Today: Innovation Continues

Recent advances in kidney research are leading to a deeper understanding of risk factors leading to kidney disease and new renal replacement therapies are inching closer to the ideal state of mimicking the kidneys completely.

The Study of Drugs and Therapies
In the early 2000s a landmark study showed that commonly-used blood pressure medicines, known as renin angiotensin aldosterone system (RAAS) inhibitors, used in patients with type 2 diabetes—the most common form—significantly reduced their risk of reaching end-stage renal disease by 28 percent. Researchers estimated that this corresponded to an average of a two-year delay in the need for dialysis or transplantation. This was an important finding that suggested, if diagnosed early enough, readily available medicines might delay the progression of kidney disease.15

Other studies conducted during this time have also revealed that therapies such as hemodialysis cause rapid alterations of potassium, calcium and fluid levels in the blood, and can trigger sudden cardiac death. As researchers are learning more about these connections, treatment approaches are becoming more refined.16

Finding Relationships Between Different Diseases
Work being done to explore the human genome along with a variety of association studies17 are uncovering more and more factors that influence chronic kidney disease’s relationship to other conditions. Over the last decade or so, a stronger link between diabetes18, hypertension and kidney disease19 has been documented.

Improving Kidney Transplantation
On the kidney-transplantation front, new regimens are in development to help reduce the risk of the body rejecting the implanted organ, allowing patients to thrive without the need to take immune-suppressing medications every day for the rest of their lives. For example, stem cells from the kidney donor’s blood are carefully introduced to a recipient’s immune system to create a ‘friendlier’ environment that won’t reject the new organ.20 This is a remarkable advancement in transplantation.

The Near Future

We’re about to embark on a new era in kidney care. Researchers and institutions around the world are uncovering new breakthroughs that could translate into meaningful progress in the treatment of kidney patients—like a wearable artificial kidney or one that may be implanted—to more effective and targeted drugs, and approaches to predict kidney health.

Our focus is firmly planted in this vision, dedicated to addressing the unmet needs of patients, such as those with chronic kidney disease and hyperkalemia. That’s why it’s our goal at Relypsa to improve lives through the discovery, development and delivery of therapeutics that leverage polymer science and other equally novel approaches.

References:

1. FDA Approves New Drug to Treat Hyperkalemia. US Food & Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468546.htm Accessed September 30, 2016.

2. Sterns, R; Rojas, M; Bernstein, P; Chennupati, S. Ion-Exchange Resins for the Treatment of Hyperkalemia: Are They Safe and Effective?  2010. J Am Soc Nephrol 21; p. 733-755.

3. Hakim, N (ed). Artificial Organs. London: Springer-Verlag; 2009. Chapter 3, The Artificial Kidney; p. 40.

4. Blakeslee, S. Willem Kolff, Doctor Who Invented Kidney and Heart Machines, Dies at 97. NY Times. Accessed September 30, 2016.

5. Bakalar, N. Kidney Transplant. NY Times. Accessed September 30, 2016.

6. Legendre, Ch; Kreis, H. A Tribute to Jean Hamburger’s Contribution to Organ Transplantation. October 2010. American Journal of Transplantation 10(11): p. 2392-2395.

7. Clinical Update on Hyperkalemia. National Kidney Foundation. https://www.kidney.org/sites/default/files/02-10-6785_HBE_Hyperkalemia_Bulletin.pdf Accessed September 30, 2016.

8. Pioneers in Kidney Dialysis: From the Scribner Shunt and the Mini-II to the “One-Button Machine.” University of Washington. https://www.washington.edu/research/pathbreakers/1960c.html Accessed September 30, 2016.

9. Overview: Brief History of Medicare End-stage Renal Disease (ESRD) Reimbursement. American Nephrology Nurses’ Association. https://www.annanurse.org/download/reference/health/esrdReimbursementFactSheet.pdf Accessed September 30, 2016.

10. Eggers, P. Medicare’s End Stage Renal Disease Program. Fall 2000. Health Care Financing Review. 22(1): p. 55-60. 

11. Morris, P; Knechtle, S. Kidney Transplantation: Principles and Practice. Seventh ed. London: Elsevier Saunders; 2014. Chapter 1, Kidney Transplantation: A History; p. 7.

12. Schmeck Jr, H. Synthesized Drug Eases Kidney Ills. NY Times. Accessed September 30, 2016. 

13. Peters, DJ; Spruit, L; Saris, JJ; Ravine, D; Sandkuijl, LA; Fossdal, R; Boersma, J; van Eijk, R; norby, S; Constantinou-Deltas, CD; et al. Chromosome 4 Localization of a Second Gene for Autosomal Dominant Polycystic Kidney Disease. December 1993. Nat Genet. 5(4): p. 359-62.

14. Effects of Dietary Protein Restriction on the Progression of Moderate Renal Disease in the Modification of Diet in Renal Disease Study. December 1996. J Am Soc Nephrol. 7(12): p. 2616-26.

15. Brenner, B; Cooper, M; Zeeuw, D; Keane, W; Mitch, W; Parving H; Remuzzi, G; Snapinn, S; Zhang, A; Shahinfar, S. Effects of Losartan on renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy. September 2001. N Engl J Med, Vol. 345, No. 12

16. Kidney Damage and High Blood Pressure. American Heart Association. http://www.heart.org/HEARTORG/Conditions/HighBloodPressure/WhyBloodPressureMatters/Kidney-Damage-and-High-Blood-Pressure_UCM_301825_Article.jsp#.V-7E_5MrLUI Accessed September 30, 2016. 

17. Mining the Genome for Insights into Kidney Function and Development. National Institute of Diabetes and Digestive and Kidney Disease. https://www.niddk.nih.gov/news/research-updates/Pages/mining-genome-insights-kidney-function-development.aspx Accessed September 30, 2016. 

18. Diabetes: A Major Risk Factor for Kidney Disease. National Kidney Foundation. https://www.kidney.org/atoz/content/diabetes Accessed September 30, 2016. 

19. Epstein, M; Roy-Chaudhury, P. Arrhythmias and Sudden Cardiac Death in Hemodialysis Patients. Nephrology News & Issues. Accessed September 30, 2016. 

20. New Regimen Frees Kidney-Transplant Patients from Dependency. Stanford Medicine. http://med.stanford.edu/news/all-news/2011/10/new-regimen-frees-kidney-transplant-patients-from-dependency.html Accessed September 30, 2016.