Article published in The Townsend Letter, June 2020
The views expressed in this article are not The Townsend Letter’s, they are those of the author. This article is not intended to be viewed as medical advice. Please check with your health care provider before starting to take any herbal supplements.
It has long been known that the most common cause of mortality in kidney patients is not kidney failure directly but secondary heart disease. As more is understood about the mechanisms of secondary heart disease, it becomes clear that inflammation is a major contributor to degeneration in kidney patients, not just in cardiac health but with vascular calcification, premature aging, telomere shortening, mitochondrial dysfunction, muscle wasting, and osteoporosis. Historically, strategies to address chronic kidney disease have focused on preserving filtration and also renal replacement therapy with dialysis and transplants to avoid uremic toxicity. Additionally, addressing inflammation may also go a long way to improving the long-term prognosis of kidney patients.
Urine contains at least 3,079 different waste products, as revealed by the latest cataloguing of uremic compounds. Of these compounds 1,453 come from the human metabolism. Seventy-two are made from bacteria and another 2,282 come from diet, drugs, cosmetics or environmental exposure (some compounds belong to more than one group). The kidneys handle any water-soluble material the body needs to get rid of. Creatinine has been determined to be the most steady, stable indicator of a uremic state. When creatinine is high, other uremic waste products are also present in the blood.1
For most kidney patients only creatinine and BUN are tested. Sometimes uric acid is also tested if the patient is experiencing symptoms of gout. High uric acid itself can cause injury to kidneys through inflammation fibroblast expansion and Endothelin-1 expression.2 Uric acid crystals can even settle in the heart.3 However, uric acid may not be the biggest culprit as allopurinol therapy, in one study, did not improve cardiovascular outcomes in patients.4
Unfortunately, the most worrisome uremic waste products are not tested; and most kidney patients are not followed by a cardiologist. Also, the usual markers of inflammation—CRP and ESR—are generally not tested. With most kidney patients, a shortened life span is usually the outcome; but it doesn’t have to be this way. By understanding the link between uremia and inflammation, kidney patients can take steps to reduce their cardiovascular risk.
Inflammatory markers are present with early stage kidney disease but increase as the kidneys lose the ability to filter waste. A study published in 2017 looked at patients undergoing cardiac bypass surgery. Patients were divided into three groups: (1) with creatinine under 1.3 mg/dl (control group), (2) with creatinine between 1.3 and 2.0 (early chronic kidney disease) and (3) patients with creatinine >2.0 (advanced chronic kidney disease). Both the early stage kidney patients and the later stage kidney patients showed high levels of proinflammatory markers, while marked calcification of the blood vessels was seen with advanced kidney disease.5
Uremic toxins in the blood are in constant contact with the endothelium of vascular tissue. A 2019 study looked at the effect of uremic serum on cultured human endothelial cells and measured the levels of expression of molecules associated with vascular injury and repair. Monocyte chemoattractant protein 1 (MCP-1) was markedly increased in sera from uremic patients with diabetes as well as sera from uremic patients with hypertension. MCP-1 caused endothelial injury and inflammation. Sera from diabetic patients also included an increase in vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1), which are initiators of the vascular repair process. VEGF and SDF-1 were not elevated in the sera from patients who reached end stage renal disease due to hypertension, suggesting that the cause of renal failure can be a factor in expression of inflammatory markers.6