Dialysis and End Stage Renal Disease Overview
Based on diabetes, hypertension, obesity and associated comorbidities; the dialysis and end stage renal disease healthcare sector is a costly and clinically challenging healthcare segment.
There are 3 types of dialysis:
- Hemodialysis is the most common
- Peritoneal dialysis ( PD ) requires surgery to implant a peritoneal dialysis catheter into the patient's abdomen
- Continuous renal replacement therapy ( CRRT )
Advances in technology, patient monitoring, medication management and clinical knowledge have increased home hemodialysis dialysis options but most end stage renal disease ( ESRD ) patients must still be treated within a dialysis center or clinic.
Due to the array of oral and injectable pharmaceutical therapies, devices ( IV tubing sets, IV containers, syringes, cannulas, catheters, other assorted disposables ), pharmacy fixtures, cleaning supplies and equipment ( dopplers, diagnostic units, dialysis machines, infusion pumps, refrigerators, water filtration systems, etc.) the dialysis sector relies on numerous drug, medical device, instrumentation and equipment manufacturers as well as distributors, wholesalers and GPOs to source products from. The growing global population of ESRD patients and the high consumption rate of products it entails drives a vibrant and competitive commercial dialysis worldwide marketplace.
The global dialysis market is valued at over $115 billion; the United States is the largest segment of the present market. Rapidly growing dialysis markets are emerging in Australia, Central America, China, India, Mexico, South America, Japan and Singapore due to increases in disposable income which result in diet and lifestyle changes predisposed to creating diabetes, hypertension and obesity issues as well as having growing geriatric populations.
- End Stage Renal Disease impacts roughly 650,000 persons in the United States; chronic kidney disease ( CKD ) and ESRD is typically managed by nephrologists although endocrinologists are usually part of the sphere of care for dialysis patients due to diabetes as well as internists, cardiologists, family / general practitioners for hypertension, diabetes and other healthcare needs associated with ESRD patients
- There are about 100,000 patients on the kidney transplant list in the U.S. but only about 20,000 kidneys are available annually due to lack of participation in organ transplant programs; this is a serious, ongoing issue for ESRD and other areas of patient care
- Hispanics and Native Americans are 1.5 times more likely to have ESRD, African Americans are 3.5 times more likely to have ESRD
- Annual dialysis treatment cost (through an outpatient dialysis clinic or dialysis center) for one patient is $90,000
- Cost of dialysis annually in the U.S. is $42 billion; $34 billion covered by Medicaid, the remainder by commercial insurance or other means
Due to the multiple healthcare issues dialysis patients possess they are on a host of medications to control blood pressure ( hypertension ), blood sugar and insulin levels ( diabetes ) and other care needs that require pharmaceutical therapy. There is a standard grouping of medications that specifically align with the dialysis process and corresponding care. Any challenges with product availability can create a spike in costs and require changes to a dialysis patient's medication therapy to accommodate the variance between products they are normally on and the ones they have been changed over to. Based on the typical fragile characteristics of dialysis patients, there is a high degree of caution involved when their medications have to substituted as interchangeability of therapies is not transparent and significant side effects can emerge.
Standard pharmaceutical therapies administered within the dialysis care space are:
Most patients with ESRD who are on dialysis have anemia which means they have a low red blood cell count. Kidneys make and secrete the hormone erythropoietin; erythropoietin is the hormone responsible for keeping a normal red blood cell count and the kidneys are responsible for making and secreting this hormone. Patients with renal failure on hemodialysis will get erythropoietin during each treatment by intravenous injection into the return dialysis tubing. Most peritoneal dialysis ( PD ) patients will get erythropoietin by injection directly under the skin. In healthy individuals, red blood cells make up about 36-44 percent of the blood. Before erythropoietin was available, most dialysis patients had a red blood cell count of only 20-26 percent.
For years Amgen's Epogen product dominated the erythropoietin dialysis market sector. Biosimilars and newer erythropoieten therapies from other manufacturers have emerged including those from Biocon, Hoffman-LaRoche, Johnson & Johnson, Novartis, Pfizer ( Hospira ), Ranbaxy and Teva.
In order for erythropoietin to work well, iron needs to be present to make red blood cells. Without iron fewer red blood cells are made, and are smaller in size, From smaller red blood cells another issue presents itself as they are not able to carry as much oxygen. Small amounts of red blood cells and iron with iron are depleted during the hemodialysis. Due to a reduction of iron, red blood cells and erythropoietin, these vital elements must be replaced.
Dialysis centers usually administer iron intravenously ( iron sucrose or ferric gluconate) during hemodialysis; quantities are determined by routine blood tests. Iron can also be administered orally but frequently this triggers gastrointestinal issues including pain, cramping and constipation especially if high doses are required. For these reasons, iron supplementation must take place via intravenous routes of administration.
Due to their weakened condition ESRD patients are more vulnerable to infection and this is compounded by the ongoing use of catheters, IV drug administration and other contributing issues. Antibiotic selection and administration is quite complicated as ESRD patients have altered pharmacokinetics (absorption, distribution, metabolism and elimination) and at increased risk of side effects. While vancomycin is a primary go-to antibiotic for infections associated with hemodialysis patients, others including aminoglycosides, b-lactam antibiotics, carbapenems, cephalosporins, fluoroquinolones, lipoglycopeptides, lipopeptides, oxazolidinones, penicillins and others are potential candidates. Therapeutic selection of antibiotic therapy for dialysis patients is carefully conducted and their administration closely monitored to achieve the desired outcome of treating the infection successfully without triggering patient side effects and disruption to the hemodialysis process which impacts time, resources and costs.
Various solutions are administered in the dialysis process combining these and other elements including calcium, chloride, magnesium, potassium and sodium. The top three manufacturers of IV solutions on a global basis are B. Braun, Baxter and ICU Medical. Dialysis consumes substantial quantities of IV solutions and despite having three large manufacturers producing IV solutions, significant shortages have occurred. Low inventories and lengthy backorder periods for dialysis centers are common. Fresenius, a global leader in dialysis clinic ownership / management as well as a leading manufacturer of dialysis machines ( it is estimated 50% of the dialysis machines used are produced by Fresenius ) has been developing its own capabilities to produce IV solutions to resolve their access and supply issues regarding IV solutions.
Additional products associated with dialysis patients
As the hemodialysis process may require other medications during its administration ( such as heparin, an injectable anticoagulant that reduces blood clots ) it impacts other elements as well within the dialysis patient's biosystem. Oral phosphate binders ( to prevent excess phosphate serum ) and supplements such as B-complex, Vitamin D, Vitamin E and folic acid are frequently taken by dialysis patients as directed by their nephrologists to either reduce the incidence of dialysis-caused side effects or to enhance the actual hemodialysis process. This is in addition to any other maintenance therapies ( diabetes, hypertension, etc.) they may also be prescribed by their primary care physician. When combined with the products necessary to be administered with the dialysis process, it is clear how costs are high and clinical care challenges are multiplied with ESRD patients.
Leaders in Dialysis Center Ownership and Management: DaVita and Fresenius
DaVita, headquartered in Denver, Colorado, is a top contender in dialysis clinics and has attempted to reach into the broader patient care market beyond dialysis after its acquisition of Renal Ventures Management. They purchased the Everett Clinic, a 500-physician independent practice located north of Seattle in 2016. It operates 20 care sites serving over 315,000 patients. Everett clinic facilities feature physician offices, urgent-care centers, hearing & vision centers, lab services, imaging, behavioral healthcare and cancer treatment. They sold it to United Healthcare / Optum for $5.4 billion in 2018. DaVita continues to operate and expand HealthCare Partners, a business unit which operates multi-specialty medical groups and affiliated physician networks, it serves over 800,000 patients in Arizona, California, Nevada, New Mexico, Florida and Colorado.
Fresenius, based in Bad Homburg, Germany, is the other dialysis sector leader. Like DaVita, Fresenius owns thousands of dialysis clinics but also operates dialysis centers within hospitals. Fresenius is also an established leader in the manufacturing of hemodialysis machines and other equipment plus has entered the IV solution business.
Recently introduced biosimilars centered on the erythropoeitin and related therapies will not deliver immediate cost relief to the dialysis sector; they are not inexpensive to produce. Clinicians will not immediately seek to convert patients from their existing therapeutic regimens until biosimilars can demonstrate parallel clinical performance and safety in the widespread market -and deliver meaningful price advantages. They will be much more likely to maintain patients on their present regimens for as long as possible to avoid the issues associated with interchanging medications used with dialysis patients. New patient starts for biosimilar products are a more amenable way for nephrologists to utilize the available biosimilar alternatives.
The global dialysis market, while expanding, remains highly competitive with all competing stakeholders driving to gain market share and sales. Rapid advancements in technology, government policy and regulation changes plus competitive pricing / market access strategies are integral to the dialysis commercial landscape. Other primary considerations include:
- High initial investment, implementation, maintenance costs of entering new and existing dialysis markets
- Competitive pricing pressures across specific individual nations, regions, large and small accounts
- Protection of proprietary clinical and technology innovation; fortification of competitive immunity
- Well-entrenched pharmaceutical, medical device and equipment manufacturer competitors with solid formulary positioning, binding supplier GPO contracts and tight market access channels