by Robin Rose, MD, FNP, RN

Chronic kidney dysfunction has taken epidemic proportions worldwide, and some call it a pandemic. Millions of Americans are affected by kidney-related illness each year. Chronic kidney disease (CKD) is considered reputedly relentless. Early diagnosis and integrative medical intervention offer options for mitigating progression.

End stage renal disease (ESRD), with its great strides and high-tech therapeutic offerings, has captivated the attention of professional and lay communities. A trillion dollars is spent annually on ESRD. Maintenance dialysis, however, presents a financial burden for health systems globally, and this is growing at an unprecedented rate. Unfortunately, in many countries, including the United States, due to shortage, nephrologists do not even examine CKD patients until dialysis is imminent and by then they have few options for delaying the time to dialysis. [1]

The United States Kidney Disease Outcome Quality Initiative (KDOQI) classified CKD with 5 stages, to assist clinicians’ navigation for clinical needs during the various states of progression. The glomerular filtration rate (GFR) is one of the measures devised as a way to assess status over time as well.

The CDC National Chronic Kidney Disease Fact Sheet 2017 notes that 30 million people or 15 percent of US adults are estimated to have CKD. But only 48 percent of those with severely advanced dysfunction (not on dialysis) are aware of having CKD. And an alarming 96 percent people with kidney damage or mildly reduced kidney function are not even aware of having CKD. [2]

To begin to understand CKD, appreciating the nature of early and moderate stages is enlightening. The first and most notable “aha!” is the dramatic drop-off of cases from stage 3 to stage 4.  This critical point of understanding is essential for primary care providers and clinicians of all types and specialties.  [3] This statistical drop-off – in one example,  from 7.6 million cases in stage 3 to 400,000 in stage 4 –  represents the enormous number of patients in the earlier stages of CKD who will die of other disorders – which can be appreciated as conditions clearly exacerbated by the dysfunctional renal syndrome. Half perish from cardiovascular disease, and the majority never progress to end-stage renal failure. [3]

A large number of people are fully unaware of their incipient CKD.  The integrative toolkit and skill set is well-suited to adapt to the unique risk factors and clinical needs of patients with evidence of renal imbalance. Clearly the intent is mitigating progression of a disease believed to be progressive and without specific ameliorating treatments. It is often declared that incipient CKD is asymptomatic, [4] yet a detailed functional history may elucidate subtle symptomatology that can be easily addressed with early intervention and lifestyle guidance.

Unfortunately however, this situation has translated into an inevitable lack of awareness – vital precautions necessary for protecting healthy nephrons are ignored, which results in intensified risk and consequences caused by acute kidney injuries (AKI). Renal hygiene only truly begins when there is awareness of need. The second notable “aha!” offers clinicians more focus for slowing disease progression. AKI, previously known as Acute Tubular Necrosis (ATN) statistically leads to CKD, either immediately or years later. People with CKD sustain more dramatic long-term renal changes following AKIs.  In fact, the two are a continuum. Again, a patient’s awareness of renal hygiene can be awakened, thus eliminating or mitigating the evolution of nephron loss.

The eldering of the baby boomers has offered new challenges. While many over the age of 65 are enjoying vim and vigor, age-related renal tubular changes make them more susceptible to intensified damage caused by AKI. Healthy elders have naturally diminished kidney function, which is to say a lifetime of experiencing the environment has effects on renal function. Even as early as Stage 2 or 3, the occurrence of an AKI may subsequently intensify the ill effects of toxins that might have been previously tolerated. For them, personalizing lifestyle-inspired positive epigenetics can help to balance the accelerated aging known to be a characteristic of CKD.

In the 2014 paper, The Aging Kidney- Increased Susceptibility to Nephrotoxicity, Xin hui Wang writes “Hopefully the deeper understanding of all the mechanisms underlying AKI in elders will lead to progression in development of preventive and protective interventions that decrease the dialysis-requiring AKIs and potentiate resolution of AKIs.” [5]

The third significant clinical CKD “aha!” is that despite the cause or severity of CKD, inflammation and oxidative stress are the unifying factors – readily evaluated and addressed with the integrative skill set. Epigenetics awareness can guide CKD personalized care, and that may instigate renewed interest in healthy lifestyle habits. Many recommendations safely made at the incipient stages are equally beneficial to other aging challenges (comorbidities) caused by inflammation—effects on heart, brain, endocrine, etc. In other words, there is an even stronger impetus to guide patients through a thorough health evaluation, including dental, especially gut issues, with hormonal, cardiac, rheum, and metabolic testing.

Clinical guidance for renal detoxicology as an anti-inflammatory path of healing provides early intervention for the avoidance of possible offending agents in the diet, household, social, occupational, and environmental products. And renal hygiene focuses on balancing the kidney diet, exercise, hydration, stress reduction, sleep, social and occupational needs.

This is not something that fits in a seven-minute office visit. Delegation to other providers (nutritionist or exercise coach) is possible once the education and urgency is communicated repeatedly by the primary care physician or clinician. Integrative and functionally-focused awareness plants the seeds that take time to germinate. When we lift this rock, there are many issues that can be offered to integrative care-seeking patients.

When a patient has angina, for example, there is focused attention on prevention of infarction. Similarly, once AKI occurs, and a GFR decrease is noted or albuminuria recognized, there are nephro-health-supportive methods to prevent and possibly reverse early damage after toxic exposures occur. [6]

Next Steps

So, where do we go from here? Since the advent of modern medical procedures for Renal Replacement Therapy (RRT), CKD seems to have lost much of the perceived immediacy of its life-threatening quality. These technical accomplishments in the field of renal failure are contrasted by an obvious lack of preventative or curative approaches earlier in the course of pathology.

There are some remaining remnants of the prior-to-dialysis era of kidney care that reflect the current lifestyle medicine focus. In the 1800s Richard Bright, MD prescribed diet therapy, warm clothing, avoidance of “spirits,” atmospheric exposures, and moving to a warm climate [4]. What is referred to as “conservative” treatment has taken a back seat.

The KDOQI created a staging system for clinicians’ ease of navigating the unique needs of renal dysfunction at varying CKD stages, independent of cause. Each stage presents unique characteristics, personality, presentation, prognosis, and needs. Like the GFR, staging is a useful, however conceptualized, way of categorizing needs. [4]

Incipient (early) kidney disease, and, to some extent, moderate CKD, have taken a back seat, with considerably less research and documentation available. In fact, the Kidney Disease Outcomes Quality Initiative of 2002 (KDOQI) suggests that primary care assume management of the less advanced CKD cases.

Primary care however is not yet taking the reins. Most allopathic-trained physicians lack the passion or skill set to focus on individualizing a lifestyle prescription for optimal kidney health and function. Nephrologist Kamyar Kalantar-Zadeh, MD, at the University of California Irvine, expresses the concern that many doctors lack the needed education, insight, or prior training for clinical nutritional intervention, but with the rise of the industry of dialysis, they are well-trained to prepare CKD patients for transition to conventional dialysis. He too says CKD needs to be re-conceptualized as part of primary care. [7]

It seems as though the kidneys are too often hidden, remaining invisible in the clinical shadows until late in the game. Despite the fact that chemistry panels flow liberally through most clinical settings, the awareness of incipient kidney health remains obscure, or is often missed.

The ubiquitous chemistry panel and urinalysis provide enough information to recognize someone who is at risk. Unfortunately, many laboratory studies still say “> 60” for the estimated glomerular filtration rate (eGFR).  Whether it is 62 or 90—stage 1 and 2, respectively—remains unknown. Recognition of Stage 1 and 2 is rare, unless there is albuminuria found on a urinalysis, or if structural abnormalities are found. And many pathological changes of CKD are already taking place in these early stages.

There is a lack of agreement in the nephrology community about how to proceed. There is mention in Brenner and Rector’s The Kidney that it isn’t cost effective to screen whole populations for CKD. In another section, nephrologist MaartenTaal writes that screening older adults for CKD is in fact a cost-effective strategy, with the intention of attenuating CKD-associated risks by intervention [8]. The American Society of Nephrology states that universal screening is appropriate, even without RCT support, earlier intervention and awareness of CKD slows nephron loss, which is especially relevant in the hospital. [7] Even a mild decrease in GFR effects long-term health outcomes. Sustainable improvement is possible, with decreased metabolic complications.

Early Diagnosis

Anne Williams, ND, LAc, a naturopathic physician at Rochat Holistic Health in New York City, writes in a September 2015 Holistic Primary Care article that diagnosis at stage 1 could mitigate risk factors and prevent development of comorbidities and progression of CKD. She writes that the kidneys need support at “any stage of hypertension.” Early CKD indicators that raise index of suspicion include persistent nocturia, high normal creatinine, and cystatin C as an early marker for renal ischemic injury and dysfunction before creatinine rises. [11]

Patients in the early stages of compromised kidney function may not be aware of their less-than-optimal ability to deal with damaging nephrotoxins in the diet and environment, including for example phosphates – so they are not consciously avoiding abundant dietary phosphate additives.[24]

Because there is a worldwide, shortage of nephrologists, CKD patients’ clinical needs are unmet.[6] Surprisingly, there is little mention of a worldwide collaboration with primary care to assume the reins of medical attention for incipient CKD.  The rate of disease progression varies from patient to patient, and it is thought that 15 percent may actually improve. [6] The mention of epigenetics has not resulted in specific therapeutic interventions in nephrology practice.

We know that patients with CKD have substantially increased risk of cardiovascular events, exceeding their risk of progression to end-stage. According to KDOQI Guideline 15, “Patients with chronic kidney disease, irrespective of diagnosis, are at increased risk of cardiovascular disease (CVD), including coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. Both “traditional” and “chronic kidney disease related (nontraditional)” CVD risk factors may contribute to this increased risk.” [4]

Appreciate that traditional cardiac risk factors underestimate cardiovascular risk for CKD patients. [1] KDOQI says, “All patients with chronic kidney disease should be considered in the “highest risk” group for cardiovascular disease, irrespective of levels of traditional CVD risk factors.” This represents one of many vicious cycles of CKD.

Nontraditional risk factors have evolved and offer needed clues to identify and to understand factors associated with this increased risk in CKD. Nontraditional risk factors for CKD brings an expanded spectrum of Actionable Therapies that are familiar territory in the field of naturopathic and integrative medicine:

  1. Oxidative damage, mitochondrial issues
  2. Inflammation
  3. Hypoxia
  4. Toxins
  5. Metabolic
  6. Microbiome and dysbiosis
  7. Homocysteine
  8. Nutrient Deficiencies
  9. Endocrine abnormalities

Jeffrey Bland, PhD, president of the Personalized Lifestyle Medicine Institute and functional medicine leader, writes: “Among strategies for both the prevention and treatment of renal disease, reduction of uremic toxins and bacterial lipopolysaccharides that activate toll-like receptors and improvement in the composition of the microbiome represent valuable and clinically proven approaches. Dietary components, specifically soluble and insoluble prebiotic fibers, phytochemicals such as curcumin, berberine, epigallocatechin gallate, withanolides that modulate gut immune function and improve detoxification of uremic toxins; and supplemental, clinically tested probiotics constitute a family of therapeutics that can positively affect patients. In addition, the bidirectional relationship of the microbiome to kidney disease is an important concept in designing a personalized approach to the management of kidney disease, especially with regard to its relationship to cardiovascular disease.” [9]

We cannot take a mechanistic view of CKD, we cannot separate the CKD patient from their environment, and we cannot use reductionist thinking or univariate approaches to the kaliedoscopic complexity of living with CKD. [9,10]

Early Intervention
A pertinent question is when does the dysfunction start? Obviously something initiates the process. Abnormal chemistry becomes apparent in Stage 3, and very often changes can be found during stages 1 and 2. [8,12]  It is perhaps the rare allopath, but more often holistic integrative natural doctors, who have interest in the strategies for diagnosing and mitigating subtle presenting symptoms. The current technology leading to dialysis and transplant offers powerful diagnostic tools, but it is the human-to-human clinical factor that effectively invites needed lifestyle changes.

Without lifestyle interventions, the patients are left confused about sleep, hydration, stress management, eating properly, and exercise. This is where naturopathic/integrative/functional medicine has an already honed skill set, at home with terms like nutrition and nutrients, mitochondria, inflammation, oxidative stress, microbiome, meditation, genomics, and comfortable with lifestyle prescriptions.

Instead of ignoring the early stages, we can recognize that a portion of people in stage 1 and 2 will possibly reverse or remain stable. Despite what is considered a paucity of information, there is an invitation to explore a personalized lifestyle approach with each patient. They are at significantly greater risk of exacerbated damage from AKI.

So, why not educate patients about their need to avoid the devastating risk of AKI?  It is a slow process, learning to adapt and manage the situation, to change identified eating habits, exercise habits, drinking habits, and work habits.

Some patients report that they did not even find out they had CKD until stage 4 or 5.  There is a window of opportunity in more incipient and moderate CKD stages when lifestyle interventions are actually the only specific kidney-related therapies available. Comorbidities, which may or may not be the cause of the kidney disease, are likely to benefit from lifestyle changes for the kidney. Such empowerment for the patient is matched by economic sensibility.

It is true that not all patients can or will step up to these challenges. The allopathic guidelines that exist provide a template considered standard of care. These are appropriate for those patients who prefer to go that route. There is a significant population of patients who are clamoring for nature-based anticipatory guidance.

According to 20th century inventor, architect, systems theorist, author, designer, and visionary Buckminster Fuller, you never change things by fighting the existing reality. To change something, build a new model that makes the existing model obsolete. The secret of change is to focus all of your attention not on fighting the old, but on building the new.

Treating people, not diagnoses, practicing physiology before pharmacology, and manifesting long-term sustainable solutions is the maxim for CKD. Integrative and functional naturopathic medical care has evolved a skill set that includes and understands epigenetics.

Looking ahead, we see the need for a new model for reining in this epidemic.  We cannot wait for the faceless and unknowing masses to progress to the final endpoints of cardiac death and kidney failure. Future articles will address specific and unique aspects of kidney care that are needed for a whole-health model for CKD patients. This is a model of early recognition and intervening, establishing each patient’s level of readiness for assessment and lifestyle intervention.  The learning process is intended for its role in inspiring the patient’s understanding and need to take the journey.

 

References

  1. Foque, Denis et al. Adherence to ketoacids/essential amino acids – supplemented low protein diets and new indications for patients with CKD. BMC Nephrology 2016; 17:63.
  2. Centers for Disease Control and Prevention. National Chronic Kidney Disease Fact Sheet, 2017. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2017.
  3. Coresh, Josef et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third national health and nutrition examination survey. American Journal of Kidney Diseases; 2003; 41(1); 1-12.
  4. Chronic Renal Disease, Paul L. Kimmel and Mark E. Rosenberg. 2015.
  5. Xin hui Wang et al. The Aging Kidney- Increased Susceptibility to Nephrotoxicity. International Journal of Molecular Science 2014; 15(9), 15358-76.
  6. Berger, Kat and Moeller, Marcus Mechanisms of Epithelial Repair and Regeneration after Acute Kidney Injury. Seminars in Nephrology. July 2014; 3(4): 394-403.
  7. Olivier, wouter et al. Early CKD: Diagnosis, management, and models of care. National Review of Nephrology : 2015Aug;11(8):491-502.
  8. Brenner & Rector’s The Kidney 10thEdition, 2015 edited byMaarten Taal, Glenn Chertow, Philip Marsden, Karl Skorecki, Alan Yu, and Barry Brenner
  9. Bland, Jeffrey. Chronic Kidney Disease: The Gut-Kidney Connection. Integrative Medicine a Clinicians Journal. 2017Feb; 16:1, p14-16.
  10. Buhner, Stephen . ”Balance: The Kidneys, Urinary Tract, and Adrenal Glands. Vital Man.
  11. Williams, Anne ND. In Hypertension, Kidneys are Often “Villians,” Not Victims. Holistic Primary Care 8/24/2015.
  12. Vaziri, Nosratola et al. Effect of Uremia on Structure and Function of Immune System. Journal of Renal Nutrition; 22(1); Jan 2012: 149-156.

Additional References

  1. Choi,Michael J  CKD for Primary Care Practitioners: Can We Cut to the Chase Without Too Many Shortcuts? American Journal of Kidney Disease. 2016; 67(6): 826-829.
  2. ADA Revises Standards of Care, Medscape Educational Clinical Briefs, September 2017
  3. Greger,Michael MD. “Treating Chronic Kidney Disease with Food” Nutritionfacts.org, 3/21/16.
  4. Cataldi, Luigi, MD. .The Kidney Through the Ages: Proceeding of the 8thInternational Workshop of Neonatal Nephrology, April 6-8,1998, Rome Italy Il Pediatra XX
  5. Minich,Deanna M. and Bland,Jeffrey S. . Review Article: Personalized Lifestyle Medicine: Relevance for Nutrition and Lifestyle Recommendations. The Scientific World Journal. Volume 2013 (2013), Article ID 129841
  6. Rankin,Gary,editor. Renal Toxicology – Epidemiology and Mechanisms.  International Journal of Molecular Science, Special Issue, 2014, 15(11).
  7. Mishima,Aikan et al. Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS–based metabolomics approach. Kidney International. 2017 Sept, 92(3); 634-645.
  8. Cupisti, Adamasco et al. Nutritional Support in the tertiary care of patients affected by chronic renal insufficiency: report of a step wise personalized pragmatic approach. BMC Neph 2016; 17:124.
  9. Nash, Danielle et al. Improving Care for Patient with or at Risk for CKD Using EMR Interventions: A pragmatic Cluster–Randomized Trial Protocol. Can J Kidney Health Dis 2017.

 

About the Author

 

Robin Rose MD, FNP, RN, has practiced small town holistic family medicine for many years, integrating a variety modalities.

A particular interest in chronic disease has flowered into a focus on the epidemic of chronic kidney disease as a portal to long-term healing.