Chronic Kidney Disease

Dr Todd Born ND reviews current understandings of this increasingly common problem. The definition and classification of chronic kidney disease (CKD) guidelines were introduced by the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) in 2002, and were subsequently adopted with minor modifications by the international guideline group Kidney Disease Improving Global Outcomes (KDIGO) in 2004.[1]

 

These CKD guidelines shifted the concept of kidney disease from that of an uncommon life-threatening condition requiring care by nephrologists to that of a common condition with a range of severity meriting attention by general internists, and demanding strategies for prevention, early detection, and management.[2]  The guidelines had a major effect on clinical practice, research, and public health, but also generated substantial controversy.[3]

 

Chronic kidney disease (CKD) is a worldwide public health problem. In the United States, the prevalence of end-stage renal disease (ESRD) is increasing.[4]  The number of patients enrolled in the ESRD Medicare-funded program has increased from approximately 10,000 beneficiaries in 1973, to 86,354 in 1983, and to 615,899 as of December 31, 2011.[5]

 

Patients with ESRD consume a disproportionate share of healthcare resources. The total cost of the ESRD program in the US was approximately $49.3 billion in 2011. Medicare costs per person per year were more than $75,000 overall, ranging from $32,922 for transplant patients to $87,945 for those receiving hemodialysis therapy.[6]

 

Data from the UK Renal Registry indicate that there were 41,776 adult patients alive on renal replacement therapy (RRT) in the UK at the end of 2005, a prevalence for adults of 694 per million population (pmp).  Information relating to the UK population prevalence of stage 3–5 CKD comes from a large primary care study (practice population 162,113) suggesting an age standardised prevalence of stage 3–5 CKD of 8.5% (10.6% in females and 5.8% in males).[7]

 

According to a 2009 study in the Journal of Epidemiology and Community Health[8], the overall prevalence of CKD stages 1–5, in England were 14% in males and 13% in females.  Only 1.5% of males and 1.3% of females reported being told by a doctor they had CKD.  If you are really interested in reading more about CKD in the UK, in 2008 the Royal College of Physicians published “Chronic Kidney Disease, National clinical guideline for early identification and management in adults in primary and secondary care.”

 

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) workgroup has defined CKD as the following [1], which has been accepted internationally:[9]

• The presence of markers of kidney damage for three or more months, as defined by structural or functional abnormalities of the kidney, with or without decreased glomerular filtration rate (GFR), that can lead to decreased GFR, manifest by either pathological abnormalities or other markers of kidney damage, including abnormalities in the composition of blood or urine, or abnormalities in imaging tests.

OR

• The presence of GFR <60 mL/min per 1.73 m2 for three or more months with or without other signs of kidney damage, as described above.

 

Based upon representative samples of the United States population, the following studies have estimated the prevalence of CKD in the general population through measurement of markers of kidney damage such as elevated serum creatinine concentration, decreased estimated GFR (eGFR), and presence of albuminuria, including microalbuminuria.

 

The purpose of CKD staging is to guide management, including stratification of risk for progression and complications of CKD. Risk stratification is used as a guide to inform appropriate treatments and the intensity of monitoring and patient education.[10]  In patients who are diagnosed with CKD using the criteria described above, staging of the CKD is done according to:[11]

 

• Cause of disease
• Six categories of GFR (G stages)
• Three categories of albuminuria (A stages)

 

Staging patients with CKD according to cause, GFR, and albuminuria enhances risk stratification for the major complications of CKD.

 

It can be difficult to ascertain the cause of kidney disease. In clinical practice, CKD is most often discovered as decreased eGFR during the evaluation and management of other medical conditions

 

GFR — The GFR (G-stages) follow the original CKD classification scheme:[12]^,[13]

• G1 − GFR >90 mL/min per 1.73 m2
• G2 − GFR 60 to 89 mL/min per 1.73 m2
• G3a − GFR 45 to 59 mL/min per 1.73 m2
• G3b − GFR 30 to 44 mL/min per 1.73 m2
• G4 − GFR 15 to 29 mL/min per 1.73 m2
• G5 − GFR <15 mL/min per 1.73 m2 or treatment by dialysis

 

In general, the presence of the following risk factors for CKD should provoke formal testing for CKD:[14]

• History of diabetes, cardiovascular disease, hypertension, hyperlipidemia, obesity, metabolic syndrome, smoking, human immunodeficiency virus (HIV) or hepatitis C virus infection, and malignancy
• Family history of kidney disease
• Treatment with potentially nephrotoxic drugs

 

All patients who have risk factors for CKD should be screened with both a urine test for albumin in a first morning or a random “spot” urine sample and a blood test for creatinine to estimate GFR. The preferred screening strategy for albuminuria is measurement of the urine albumin-to-creatinine ratio in an untimed urinary sample.

 

Depending upon the presence of particular risk factors, additional testing, such as renal ultrasonography, may be required, for example, in patients with a family history of polycystic kidney disease (PKD). The K/DOQI clinical practice guidelines for CKD, as well as other K/DOQI guidelines, can be accessed through the NKF’s web site (www.kidney.org/professionals/kdoqi/guidelines.cfm).

 

For people with disabilities, and ongoing mental health challenges, as well or independent of chronic kidney disease, the team at advocates for health have compiled this useful resourse. (http://sunrisehouse.com/addiction-demographics/physically-disabled/)

 

Once the diagnosis is established and the cause and/or potentially reversible factors are identified and treated, CKD should be staged according to the classification proposed by the NKF-K/DOQI Clinical Practice Guidelines for Evaluation, Classification, and Stratification of CKD and subsequently revised.

 

This classification is based on laboratory evaluation of the severity of kidney disease, association of level of kidney function with complications, and stratification of risks for loss of kidney function and development of cardiovascular disease (CVD). The K/DOQI classification also includes an action plan for each stage of the disease.

 

The frequency of testing for CKD in high-risk groups has not been rigorously studied, and recommendations are opinion-based. The National Kidney Disease Education Program (NKDEP) of the National Institutes of Health (NIH) recommends yearly testing among diabetic patients.

Hypertensive patients should be tested at diagnosis, upon initiation of therapy, and every three years thereafter. Individuals with a family history of CKD should be tested every three years. Individuals with other risk factors may be tested less frequently.[15]

 

Although the blood urea nitrogen (BUN) also varies inversely with the GFR, it is generally less useful than the serum creatinine because the BUN can change independently of the GFR.

 

Because of the problems with changes in creatinine production and secretion, other endogenous compounds have been evaluated in an effort to provide a more accurate estimation of GFR including symmetric dimethylarginine[16] and cystatin C.

 

The best studied is cystatin C, a low molecular weight protein that is a member of the cystatin superfamily of cysteine protease inhibitors.  The serum cystatin C concentration may correlate more closely with the GFR than the serum creatinine concentration.[17]  Although cystatin C has been purported to be unaffected by gender, age or muscle mass, higher cystatin C levels have now been associated with male gender, greater height and weight, and higher lean body mass.  Cystatin C levels increase sharply with age.[18]

 

The general management of the patient with CKD involves the following issues:[19]

• Treatment of reversible causes of renal failure
• Preventing or slowing the progression of renal disease
• Treatment of the complications of renal failure
• Adjusting drug dosages when appropriate for the level of eGFR
• Identification and adequate preparation of the patient in whom renal replacement therapy will be required

 

A wide range of disorders may develop as a consequence of the loss of renal function. These include disorders of fluid and electrolyte balance, such as volume overload, hyperkalemia, metabolic acidosis, and hyperphosphatemia, as well as abnormalities related to hormonal or systemic dysfunction, such as anorexia, nausea, vomiting, fatigue, hypertension, anemia, malnutrition, hyperlipidemia, and bone disease. Attention needs to be paid to all of these issues.

 

Once the patient has reached the stage of near end-stage renal disease (eGFR less than 15 mL/min per 1.73 m2), signs and symptoms related to uremia begin to occur, such as malnutrition, anorexia, nausea, vomiting, fatigue, sexual dysfunction, platelet dysfunction, pericarditis, and neuropathy.

 

When to send to a specialist?  Current guidelines state the following:[20]

• Urine albumin-to-creatinine ratio (ACR) >300 mg/g (34 mg/mmol)
• Haematuria not secondary to urological conditions
• Inability to identify a presumed cause of CKD
• eGFR decline of more than 30% in fewer than four months without an obvious explanation
• Difficult to manage complications such as anemia requiring erythropoietin therapy, and abnormalities of bone and mineral metabolism requiring phosphorus binders or vitamin D preparations
• Serum potassium greater than 5.5 meq/L
• Difficult to manage drug complications
• Patients under the age of 18 years
• Resistant hypertension

 

There is a nice 2010 article in the Natural Medicine Journal on dietary suggestions in CKD.[21]  Regarding fluid intake, “My Doctor Said I Should Drink a Lot! Recommendations for Fluid Intake in Patients with Chronic Kidney Disease” in the Clinical Journal of the American Society of Nephrology is quite helpful.[22]

 

Protein intake should be adjusted to 0.8 to 1.0 g/kg/day of high biological value protein.  Some recommend 0.56 to 0.75 g/kg/day, with 0.35 g/kg/day of high biological value protein.  The protein intake is increased by 1.0 g/day of high biological value protein for each gram per day of urinary protein loss. This is performed under close supervision and dietary counseling.[23]^,[24]

 

The following nutrients have proven efficacy in the treatment of CKD, ESRD and their respective co-morbidities.

• L-carnitine:  500-2,000 mg daily[25]
• Essential or branched-chain amino acids[26]
• Folic acid:  10 mg daily[27]
• Vitamin B12:  1000 mcg, once a week[28]
• Thiamin: 50-200 mg daily[29]
• Zinc:  50 mg daily[30]
  • Balance with copper at this dose:  About 3 mg daily
• Vitamin C:  50-100 mg daily[31]
  • Periodically measure oxalate levels[32]
• N-Acetylcysteine:  600 mg twice daily[33]
• Omega 3 essential fatty acids:  1.8 g/day of EPA + 1.2 g/day of DHA[34]
• Selenium:  200 mcg three times a week[35]
• Coenzyme Q10:  60 mg three times daily[36]

 

Botanical medicines:

• Camellia sinensis (decaf green tea)[37]
• Urtica seed[38]
• Rheum palmatum:  1 gram daily[39]
• Lespedeza capilata; Parietaria judaica (1000-1500 mg daily):[40]
• Astragalus:[41]  15 grams daily
• Cordyceps:[42]  1 gram three times daily
• Ganoderma lucidum:[43]^,[44]  750-1100 mg daily
• Tribulus terrestris:[45]
• Silybum marianum:[46]  140 mg three times daily
• Pre and Probiotics[47]

 

Exposure to high levels of lead and cadmium have also been shown to have adverse effects on kidney function.[48]^,[49]

 

Conclusions

Given the aforementioned information, along with the degree of disease burden in industrialized nations and in conjunction with the ramifications of chronic renal disease, CAM therapies can and may play a crucial role in preventing and mitigating the disease processes.

 References