Naturopathic approaches to diabetic kidney disease

Townsend Letter for Doctors and Patients, May, 2007 by Alex Tan, Jacob Leone

This article presents naturopathic treatments for diabetic kidney disease, also known as diabetic nephropathy. From the outset, it should be emphasized that controlling blood sugar and hypertension are the two most important and indispensable strategies in treating diabetic nephropathy. Because there are many resources available covering naturopathic treatments for hyperglycemia and hypertension, they will not be covered here. Instead, this article will focus on specific dietary, lifestyle, and supplement regimens that have been shown to reduce morbidity and mortality in diabetic nephropathy.

Background

Diabetic nephropathy is a common complication in type 1 and type 2 diabetes (20-40% incidence among diabetics) and is one of the leading causes of end-stage renal disease (ESRD) in the US. (1) It is estimated that 50% of type 1 diabetics with overt nephropathy will have ESRD in seven to ten years, (2) and the time course may be shorter among type 2 diabetics. (3) ESRD, when untreated with dialysis or a kidney transplant, has a high mortality rate.

The earliest clinical sign of nephropathy is the detection of albumin in the urine (>30 mg/day but <300 mg/day); this is the microalbuminuria stage. Overt nephropathy typically happens five to ten years after the onset of microalbuminuria (4) and is characterized by persistent presence of albumin in the urine of >300 mg/day and decline in kidney function as measured by glomerular filtration rate (GFR). (5) Diabetic retinopathy is highly associated with nephropathy (60-90% rate of comorbidity), (6) and the absence of the former should increase suspicion that the nephropathy may have other causes.

The key change in diabetic nephropathy is an increase in extracellular material, such as thickening of the glomerular basement membrane, expansion of the mesangium, and signs of glomerular fibrosis. Although the exact causes are unknown, elevated blood glucose is associated with glomerular basement membrane thickening, (7) while glomerular hypertension is associated with sclerosis. (8) Inflammatory cytokines such as transformation growth factor beta (TGF-b) (9) and NF-KappaB10 also play a role by upregulating cellular hypertrophy and fibrinogenesis. (1)

Allopathically, the mainstays of treatment include the following: (1) blood sugar control; and (2) blood pressure control, preferably with ACE inhibitors and/or angiotensin II receptor antagonists. In terms of diet, the recommendation is protein restriction to 0.8-1.0 g/kg/d. (11) (Note that patients on dialysis may have higher protein requirements.) (12)

Prevention

It is best to treat nephropathy during the microalbuminuria stage. Once overt nephropathy sets in, the pathologic changes in the glomerulus are most likely irreversible. (13) Three tests for microalbuminuria screening are available: (1) random spot urinary albumin-to-creatinine ratio (preferred method); (2) 24-hour urine microalbuminuria test; (3) other timed--e.g., four-hour or overnight--urine collection. (14)

The American Diabetes Association (ADA) recommends annual screening for microalbuminuria among type 1 diabetics starting at five years after initial diabetes diagnosis. All type 2 diabetics should be screened yearly, starting at diagnosis, and during pregnancy. Additionally, serum creatinine should be measured at least yearly to estimate GFR in all adults with diabetes whether or not there is albuminuria. (15)

Diet & Lifestyle Interventions

A carbohydrate-restricted, low-dietary-iron, polyphenol-enriched diet (CR-LIPE) has been shown to (1) reduce death or renal transplant by nearly 50%; and (2) reduce doubling of serum creatinine by half (Table 1). This is based on a controlled study done by Faccini & Saylor in 2002, (16) where subjects were type 2 diabetics with confirmed renal disease (N=191) and mean follow-up time was 3.9 years.

Features of the CR-LIPE diet include the following:

* A 50% reduction of carbohydrates from the previous level of intake

* Replacement of iron rich red meats (beef and pork) with iron poor white meats (poultry and fish) and with protein-enriched food items known to inhibit iron absorption, e.g., dairy, eggs, and soy

* Elimination of all beverages except tea, water, red wine, and milk Tea was highly recommended. Red wine was not to exceed 150 ml with lunch and 150 ml with dinner. Milk was recommended for breakfast. Outside mealtimes, water was the only approved beverage.

* Exclusive use of polyphenol-enriched extra-virgin olive oil for both dressing and frying

* Except for carbohydrate restriction, this diet was fed ad libitum (up to the discretion of subjects).

The control group ate a standard protein restricted (0.8g/kg/d) diet, iso-caloric for ideal body weight maintenance. When the macronutrient profiles of the CR-LIPE vs. control diet were analyzed, it was shown that the CR-LIPE diet resulted in significantly less carbohydrates (35% vs. 65%), more protein (25-30% vs. 10%), and slightly more fat (30% vs. 25%).

The authors postulate that the key mechanism explaining these life-saving benefits is the fivefold reduction in serum ferritin (as a measure of body iron stores) due to reduced iron intake, absorption inhibition by milk, polyphenols, and tannins in tea. Iron in high amounts has been linked with oxidative stress, while iron depletion is linked with insulin sensitization. Low carbohydrate intake is also associated with a reduction in risk factors for morbidities associated with diabetes such as decreasing hyperlipidemia, insulinemia, and glycemia.