New Innovation for Chronic Kidney Disease
Submitted by John Cope, RN
It is vital for nurse practitioners to explore and have a deeper understanding of treatment options, both current and emerging, for chronic kidney disease. As Weiland (2015) illustrates, the role of nurse practitioners is both vital, and well-documented as effective in terms of providing primary care services to an expanding patient population within the United States. In addition to an expanding patient population, nurse practitioners must seek out the newest and latest information regarding diseases and disease processes in order to most effectively manage precious and limited healthcare dollars.
Nurse practitioners can expect to encounter chronic kidney disease quite frequently during their routine practice. Chronic kidney disease affects approximately 10% of society. Further, CKD affects elders, non-whites, and lower socioeconomic groups at disproportionally higher rates (Mendu et al., 2016). Nurse practitioners clearly need to assess for the problem, and be proactive in prevention; especially in the aforementioned target groups. Current treatment options generally involve the passive action of preventing further damage and assault to renal structures. This is achieved by tight control of diabetes and control of blood pressures, along with careful review and management of nephrotoxic medications (Campbell & Weir, 2015). Though there are a several causative factors for chronic kidney disease, it is hypertension and diabetes which are the leading causes. When hypertension is suspected as a causative factor in CKD, treatment involves: inhibition of the renin/angiotensin/aldosterone system, diuretics, and antihypertensive medications. When diabetes mellitus is suspected, treatment involves the use of oral hypoglycemics and insulin to maintain an acceptable blood sugar level, thus preventing further damage to renal structures in both cases (Campbell & Weir, 2015).
Chronic kidney disease presents another unique problem, it progresses slowly and without a great number of symptoms, therefore patients don't normally present with any complaints until the kidneys have nearly stopped working (Bell & Spigler, 2015). When in fact the kidneys have stopped working, patients have likely arrived at end-stage renal disease (ESRD). The standard treatment for ESRD is hemodialysis, which can cost up to $180,000 annually for an individual patient, and cost Medicare over $8.6 billion in 2007 (Caple, 2016). Kidney transplant comes at a great cost as well. In 2014, the average estimated cost for kidney transplant, and for the first year of follow-up and medications, is approximately $334,300 for a single kidney (Bentley, 2014).
With these noted extreme costs and nuisance treatment options, which include many hours per week at a dialysis center or a lifetime of expensive medications and immunosuppression, it is appropriate to ask: What new and innovative treatments are being developed for patients suffering chronic kidney disease?
Methodology in Research
To aid in answering this research question, this researcher sought to pool together information from a wide variety of resources including: scholarly databases, government agencies, and obtainment of information directly from those doing research. While searching scholarly databases, search terms such as: 'chronic kidney disease research' and 'innovation in the treatment of chronic kidney disease' are just an example of the many that were used in this endeavor. Further, information was obtained directly from those entities who are currently engaged in research and development for the treatment of chronic kidney disease. It must be stated very clearly that, while specific companies and proprietary formulations are mentioned in this literature review, this researcher does not endorse, promote, or represent any individual company or body of research. It must also be stated that the intent of this literature review is to expose new innovation for chronic kidney disease, and is not a comprehensive and exhaustive review of the totality of research that is being performed for the treatment of chronic kidney disease.
For direct treatment of damaged kidneys, and as with any chronic disease, early detection will lead to improved outcomes. Work is being done on early diagnosis and prognostic indicators for CKD. One of these areas being researched surrounds identification of biomarkers which could be prognostic of CKD. Lin et al., (2015) propose that urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker for renal tubular damage, may be predictive of future CKD at a greater sensitivity and specificity than traditional creatinine levels alone. Lin et al. (2015) conducted a prospective observational study on patients spanning two different hospitals, and over a period of six months. The researchers noted that an elevated uNGAL level was strongly predictive of ESRD in CKD patients (Lin et al., 2015) Further, this team of researchers acknowledged limitations in their study which included: small cohort, lack of ethnic diversity (mostly asian), and lack of confirmatory renal biopsies; determination of end-stage renal disease was established by the traditional clinical indicators. Clearly, larger scale studies need to be performed in this area, however, deeper understanding and discovery of biomarkers for CKD, as well as many other chronic illnesses, is being heavily researched. Further research into methods of early diagnosis will be a key component to the success of nephrogenesis both in the bioengineering and pharmaceutical arenas.
Winyard and Price (2014) note that we are currently in an exciting time for kidney repair and regeneration. The aforementioned authors discuss the emerging biotechnology of actually repairing and re-creating kidneys. Winyard and Price (2014) outline significant work that is being done in the biotechnology arena for the exploitation of cells with in a person's own body. Totipotent cells have been identified that parallel true embryonic stem cells in the fact that they are undifferentiated, able to self renew repeatedly, and can give rise to cell lineages from all three germ layers. These kidney stem/progenitor cells can, and have in laboratory conditions, regenerated renal tissues by the careful manipulation of cell surface markers causing expression of the cell into highly differentiated renal tissues. The goal of this research is to generate nephrons de novo, and refinement of these techniques can open up the opportunity to increase renal function in humans. The process of stimulating undifferentiated cells into highly differentiated renal tissues is significantly more complex than activation of cell surface receptors. In one experiment, cells were harvested from mouse kidneys, cultured, then a final important step was the blockade of apoptosis. The cells were further cultured and renal structures formed including nephrons and collecting ducts (Winyard and Price, 2014). The final undeveloped portion of this strategy would be the transplantation, or even possibly xenotransplantation, of cultured cells directly into the kidneys with the aim of developing a neo-organ in vivo. Finally, Winyard and Price (2014) argue that starting with a partially built kidney (the damaged kidney), and seeding it with newly cultured cells, will be easier than attempting to develop an entire kidney from scratch. The researchers feel that this technology will be developed for clinical practice within the next decade.
This exciting new tissue-based therapy is currently undergoing phase II clinical trials by RegenmedTX, a company whose sole mission is development of tissue-based therapies, and is currently focused on CKD (Clinical Trial, n.d.). RegenmedTX's premier product, Neo-Kidney Augment™ (NKA™), is intended to prevent or delay dialysis and transplantation by increasing renal function in patients with advanced CKD. Their injectable product is intended to catalyze the regeneration of functional kidney tissue. Additionally, their phase II clinical study is built on the success of their phase I study, in which seven human patients were implanted with NKA™. The phase I clinical trial is regarded as successful as these seven patients have now been followed for two years and remain dialysis free with stable renal function. The manufacturer states that the product is safe and well tolerated. RegenmedTX researchers describe NKA™ as: “a percutaneous minimally invasive injectable product composed of the patient’s own selected renal cells (SRC). The renal cells are obtained via a standard kidney biopsy procedure following standard medical biopsy practice. The SRC’s are isolated and expanded from the biopsy and formulated with a gelatin hydrogel making NKA™. NKA™ is then implanted into the patient’s diseased kidneys. Access to the kidney may be obtained using standard minimally invasive percutaneous methods commonly used in hospitals and outpatient surgeries” (Clinical Trial, n.d.). In terms of criticism for this emerging technology, RegenmedTX has not published quantitative results from the phase I study, and has not suggested a quantifiable speculated increase in renal function.
Information surrounding new research pharmaceuticals is difficult to source due to high levels of secrecy surrounding lucrative and proprietary formulations that the pharmaceutical companies are developing. Further, the Food and Drug Administration (FDA) only releases information regarding approved medications; all other information is considered confidential.
A promising and beneficial medication that has come to clinical use within the past decade is paricalcitol. Paricalcitol is a selective vitamin D receptor activator prescribed for the treatment of secondary hyperparathyroidism. It has been noted and observed that paricalcitol may have expanded indications, and has been associated with a survival advantage in long-term hemodialysis patients. It is suggested that paricalcitol influences inflammatory cytokines, which is leading to further research into the importance of the vitamin D receptor (Donate-Correa et al., 2014). It is worth noting that this particular body of research contained a small sample size, was not randomized, and was intended as a proof of concept study.
Many pharmaceutical companies are working towards medications that will prevent, reduce progress, or reverse CKD progression. One such pharmaceutical company is VidaSym Inc. VidaSym Inc. is researching their proprietary vitamin D receptor modulator, Vita–5. According to their website: “Vidasym has taken a unique drug discovery/development approach to discover novel Vitamin D receptor modulators (VDRMs) that are highly differentiated from existing VDRMs. With Vida-5's superior safety and efficacy profiles established, the next step is to determine the feasibility of using Vida-5 to treat kidney disease progression and also its long-term side effect potential in animal studies” (New drug Vida-5 for treating chronic kidney disease progression, 2011) VidaSym feels that, once developed, such a drug will not only reduce the mortality rate of CKD, but also reduce the need for dialysis (New drug Vida-5 for treating chronic kidney disease progression, 2011). Further research regarding the VDRMs may prove to be a true pharmaceutical solution to delay or prevent further progression of CKD in addition to reduced need for hemodialysis.
Nurse Practitioner Role
The role of the nurse practitioner in modern healthcare cannot be emphasized strongly enough. In one large randomized controlled trial, it is demonstrated that patients valued the care provided by nurse practitioners equally to that of care provided by physicians. Further, in this study it was demonstrated that nurse practitioners had a statistically significant number of follow-up adherence by their patients, and that nurse practitioner consultations were longer in duration with each individual patient (Dierick-van Daele, Metsemakers, Derckx, Spreeuwenberg, & Vrijhoef, 2009). The increasing role of nurse practitioners in primary care demands high levels of education and knowledge of emerging therapies; CKD is just but one chronic illness that nurse practitioners encounter.
This author has established, by a preponderance of evidence, that new and emerging treatments are in the pipeline for chronic kidney disease. It is conceivable that many of these therapies will be available to patients within a few short years and that nurse practitioners will be at the forefront of prescribing or referring many of these treatments.
American Academy of Nurse Practitioners. (2002). Nurse practitioners as an advanced practice nurse: Role position statement. Austin, TX: Author.
Bentley, T. (2014, December). 2014 U.S. organ and tissue transplant cost estimates and discussion. In Millman.com. Retrieved from http://www.milliman.com/uploadedFiles/insight/Research/health-rr/1938HDP_20141230.pdf
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