Olmesartan (Benicar) and kidney disease

As a matter of course, markers of kidney function including blood urea nitrogen (BUN) and creatinine will fluctuate while a patient is on the Marshall Protocol (MP).

There is a tendency for some physicians to become alarmed by these fluctuations, particularly if a patient has kidney disease. However, for the vast majority of patients these test results are an expected part of the healing process. In fact, a wide range of research shows that olmesartan is therapeutic for kidney disease.

One study found that hemodialysis patients who had high serum values of urea nitrogen (BUN) were less likely to have the acute infection, Helicobacter pylori.¹⁾ This suggests that temporary markers of kidney stress such as BUN may correlate with a robust and successful immune response.

In a 2011 study appearing in Kidney International, Agarwal et al. gave 16 patients with chronic kidney disease daily doses of paricalcitol, an orally active vitamin D receptor activator.²⁾ The vitamin D analog was stopped after four days, and measurements were continued for three. Researchers found that subjects' serum creatinine significantly increased at a rate of 0.010 mg/dl/day and urine creatinine at a rate of 17.6 mg/day. Researchers also found a small increase in blood levels of BUN.

In conclusion, VDR activation may alter creatinine metabolism. An increase in creatinine generation may lead to an increase in serum creatinine and, if eGFR is used to measure kidney function, it may give the appearance that kidney function is declining when truly it may not be altered.

Rajiv Agarwal et al.

This in vivo study is significant as it confirms several key aspects of the Marshall Protocol:³⁾

• Patients with kidney disease on a treatment designed to stimulate the VDR can expect their measures of creatinine to increase.
• The strategy of waiting-out abnormal creatinine values, rather than trying to intervene, is the most sensible approach currently available.
• A more valid method for measuring kidney function is the 24hr creatinine clearance test, rather than the calculated eGFR.

Typically, the levels of BUN - a measure of the amount of nitrogen in the blood that comes from urea, a substance removed by the kidneys - to come back elevated, as bacterial endotoxins cause nitric oxide and subsequently more nitrogen to be generated in the inflamed tissues. Levels of creatinine - a breakdown product of phosphate that is filtered by the kidneys - may also become elevated after people start the MP. This is not unusual, as most short courses of antibiotics aimed at killing classical bacteria also cause spikes in BUN and creatinine. According to the study site, maintaining a level of creatinine 10-20% higher than normal indicates the kidneys are functioning adequately while the MP is inducing immunopathology to resolve kidney inflammation.

The important thing to keep in mind is that these markers fall back into range as the disease resolves and the Th1 pathogens are eradicated. Remaining on olmesartan despite fluctuations in markers of kidney and liver function is therapeutic and a necessary part of the healing process.

In the patient with an increase in serum creatinine concentration, decreasing the dose of [the ARB]… will cause the serum creatinine concentration to return to the original baseline. Unfortunately, such an approach is not optimal for the long-term preservation of renal function and should be discouraged.

Biff Palmer, Nephrology at the University of Texas Southwestern ⁴⁾

“Creatine in meat is converted to creatinine on cooking, which is absorbed, causing significant increases in serum creatinine. This could impact management, as threshold for commencing and withdrawing certain medications and expensive investigations is defined by eGFR. eGFR calculated using fasting serum creatinine would be a better reflection of kidney function” ⁵⁾

Subclinical - that is to say, undetected or undetectable - kidney disease is common in patients with Th1 diseases, and this is no less true of MP patients. Inflammation in the kidney and liver tend to be “silent.” Before beginning the MP, the kidneys are inflamed because they are infected with the Th1 pathogens. Patients tend to be largely unaware of the problem because their immune system, which has been weakened by the pathogens, doesn’t kill enough of the pathogens to cause a rise in bacterial byproducts that would be picked up on a blood test.

Once patients activate the innate immune system with olmesartan and begin rapidly killing the Th1 pathogens, the resulting immunopathology causes a rise in bacterial death, the effects of which are finally high enough to show up on lab tests.

According to a 2008 commentary appearing in Nature:

Vitamin D receptor (VDR) activation has a beneficial influence on the progression of experimental renal insufficiency, and reduced renal tissue renin expression may play a role in this process.

Ilkka H. Pörsti ⁶⁾

MP patients with kidney inflammation and their healthcare practitioners should be extremely comforted by the fact that the patient is taking olmesartan. This is due to the great number of studies, which have found that olmesartan and other ARBs protect the kidneys from the effects of inflammation and cytokine damage.

The benefits of olmesartan on patients with kidney inflammation include

• decreased insulin resistance, fewer symptoms of the metabolic syndrome, and decreased inflammation in patients with chronic kidney disease.⁷⁾
• decreased (intra)renal vascular resistance, increased renal perfusion, and significantly reduced oxidative stress in patients with type 2 diabetes⁸⁾
• protection of the kidneys in diabetic nephropathy ⁹⁾
• offer a survival benefit in hemodialysis patients, may help in preservation of renal function in predialysis patient, and affect the tissue repair process, reducing renal fibrosis¹⁰⁾
• prevention of the onset of microalbuminuria in patients with Type 2 diabetes^{11) 12) 13) 14)}

High-dose ARB treatment in patients with chronic renal disease is not associated with any clinically significant long-term negative effects on serum creatinine or potassium and is thus an important therapeutic modality with which to achieve further reductions in urinary protein excretion.

Alan J. Weinberg, et al. ¹⁵⁾

The effects of ARBs, in general, on people with kidney inflammation include:

• improved patient prognosis in non-diabetic chronic kidney diseases with mild-to-moderate renal dysfunction.¹⁶⁾
• effectiveness in controlling UAE [urinary albumin excretion] in cases in which blood pressure is not well controlled, implying that ARBs have renoprotective actions independent of changes in blood pressure.
• ability to actively control proteinuria and stabilize kidney function in children, providing an alternative to more toxic therapies, especially corticosteroids, in children with glomerular disorders such as those associated with obesity.¹⁷⁾
• formation of a dosage-dependent, anti-inflammatory effect on the kidneys that is mediated by suppression of NF-kappaBA protein that stimulates the release of inflammatory cytokines in response to infection activation and chemokine expression.¹⁸⁾
• ability to retard the progression of advanced renal insufficiency.¹⁹⁾
• effective slowing of the progression of chronic allograft nephropathy (CAN)²⁰⁾

Olmesartan also has additional beneficial effects for organs and systems beyond the kidneys.

.Olmesartan Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome by Suppressing Tubular Expression of TGFβ.

Ability to affect the local renin-angiontensin sytem (RAS) and thus improve renal injury and function in a rat model of potentially progressive glomerulosclerosis.²¹⁾

Ability of Olmesartan to ameliorate renal injury and fibrosis in rats when taken at ultrahigh doses.²²⁾