Biomarker & Lifestyle Clues Associated with Kidney Stones

Some blood biomarkers and related clues are associated with the potential causes of kidney stones, also known as nephrolithiasis or urolithiasis.

The kidneys and lungs are responsible for maintaining the body's acid-base balance. The lungs excrete volatile acidic carbon dioxide, while the kidneys excrete non-volatile metabolic acids and reabsorb alkaline bicarbonate. These help keep blood pH at an optimal 7.35 – 7.45. Low-grade metabolic acidosis and overt metabolic acidosis (serum bicarbonate below 22 mmol/L) increase the risk of kidney stone formation (Wieers 2024).

The most common kidney stones are composed of calcium oxalate, followed by calcium phosphate, uric acid, struvite, and cystine (Chmiel 2023).

Kidney stone formation is associated with a significantly increased risk of cardiovascular disease, likely related to underlying mechanisms, including vascular calcification, oxidative stress, endothelial dysfunction, and cholesterol-induced pathology (Muschialli 2024). Kidney stone formation has been associated with a 20-24% increased risk of CVD, myocardial infarction, and stroke (Saenz-Medina 2022).

Therapeutic approaches to endothelial dysfunction. Endothelial therapy can be achieved with primary endothelial therapy for prevention of healthy endothelial function by controlling cardiovascular risk factors and secondary endothelial therapy for to improve dysfunctional endothelial homeostasis by treating underlying cardiovascular risk factors and cardiovascular disease. CV, cardiovascular; PAOD, peripheral arterial occlusive disease.

Source: Park, Kyoung-Ha, and Woo Jung Park. “Endothelial Dysfunction: Clinical Implications in Cardiovascular Disease and Therapeutic Approaches.” Journal of Korean medical science vol. 30,9 (2015): 1213-25. doi:10.3346/jkms.2015.30.9.1213 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY)­­ license (https://creativecommons.org/licenses/by/4.0/).

Kidney stone risk is increased by:

Biomarkers

• Low serum bicarbonate, especially below 22 mmol/L (mEq/L) (Wieers 2024)
• Elevated neutrophil:lymphocyte ratio (NLR) above 1.72 (Mao 2021)
• Low serum magnesium, especially 2.07 mg/dL (0.85 mmol/L) or below (Wu 2020)
• Elevated systemic immune-inflammatory index (SII) above 330 x 10⁹/L, primarily in adults under age 50, with an SII based on neutrophils, lymphocytes, and platelets (Di 2023)
• Elevated C-reactive protein, especially above 4.6 mg/L (Liang 2024)
• Elevated serum uric acid, especially above 7.0 mg/dL (Tanaka 2017)
• Low serum glutamine (associated with a high dietary acid load) (Wieers 2024)
• Urinary factors: hypercalciuria, hyperoxaluria, hypomagnesuria, hypercystinuria, hypocitraturia (Nojaba 2023)

Lifestyle and other factors

• Family history or past history of kidney stones (Nojaba 2023)
  Antibiotic use, dysbiosis, and high-dose vitamin C intake in susceptible individuals (Chmiel 2023)  
• Increased abundance of GI Bacteroides and Prevotella (Zhao 2021)    
• An acid-forming diet, e.g., a Western-style diet high in animal protein, processed foods, and excess sodium chloride (Wieers 2024).
• A diet high in oxalates and low in calcium (Nojaba 2023)
• Low fluid intake (Nojaba 2023)
• Increased oxalate absorption, especially due to malabsorption (Nojaba 2023)
• Urinary tract infections (Nojaba 2023)
• Acidic urine pH below 5.5 (Nojaba 2023)
• Heavy metal toxicity (Yen 2018)
• Oxidative stress and endothelial dysfunction (Saenz-Medina 2022)
• Obesity, metabolic syndrome, diabetes mellitus, hypertension, high intake of salt, animal protein, and added sugar (Di 2023, Khan 2016)

Kidney stone risk is decreased by:

Biomarkers

• Optimal serum magnesium, especially 2.31 mg/dL (0.95 mmol/L) or above (Wu 2020)
• Maintaining optimal vitamin A, B6, D, and magnesium status (Chmiel 2023)

Lifestyle and other factors

• Alcohol intake was associated with a reduced risk of kidney stones (Wei 2024)
• Vegan/vegetarian diets high in fruits and vegetables (Wieers 2024)
• Calcium supplements can bind oxalate, reduce its absorption, and reduce associated kidney stone risk (Nojaba 2023)
  
  

Source: Wieers, Michiel L A J et al. “Dietary acid load in health and disease.” Pflugers Archiv : European journal of physiology, 10.1007/s00424-024-02910-7. 29 Jan. 2024, doi:10.1007/s00424-024-02910-7 This article is licensed under a Creative Commons Attribution 4.0 International License

Optimal Takeaways

• Consume an alkalizing plant-based diet derived from whole unprocessed foods with minimal added salt and sugar
• Minimize animal protein intake
• Maintain adequate hydration with purified water that contains adequate alkalizing minerals
• Maintain a healthy weight, blood pressure, and blood glucose level
• Avoid heavy metals and toxins
• Maintain a healthy gastrointestinal microbiome
• Minimize inflammation
• Alkalize the urine, especially in high-risk individuals

Want to Learn More?

CLICK HERE to learn more about Alkalizing the Urine

References

Chmiel, John A et al. “Vitamins as regulators of calcium-containing kidney stones - new perspectives on the role of the gut microbiome.” Nature reviews. Urology vol. 20,10 (2023): 615-637. doi:10.1038/s41585-023-00768-5

Di, Xingpeng et al. “Association between the systemic immune-inflammation index and kidney stone: A cross-sectional study of NHANES 2007-2018.” Frontiers in immunology vol. 14 1116224. 21 Feb. 2023, doi:10.3389/fimmu.2023.1116224

Khan, Saeed R et al. “Kidney stones.” Nature reviews. Disease primers vol. 2 16008. 25 Feb. 2016, doi:10.1038/nrdp.2016.8

Liang, Dan et al. “The association between C-reactive protein levels and the risk of kidney stones: a population-based study.” BMC nephrology vol. 25,1 39. 27 Jan. 2024, doi:10.1186/s12882-024-03476-3

Mao, Weipu et al. “Neutrophil-lymphocyte ratio acts as a novel diagnostic biomarker for kidney stone prevalence and number of stones passed.” Translational andrology and urology vol. 10,1 (2021): 77-86. doi:10.21037/tau-20-890

Muschialli, Luke et al. “Epidemiological and biological associations between cardiovascular disease and kidney stone formation: A systematic review and meta-analysis.” Nutrition, metabolism, and cardiovascular diseases : NMCD vol. 34,3 (2024): 559-568. doi:10.1016/j.numecd.2023.09.011

Nojaba, Leila. and Nilmarie Guzman. “Nephrolithiasis.” StatPearls, StatPearls Publishing, 8 August 2023.

Saenz-Medina, Javier et al. “Endothelial Dysfunction: An Intermediate Clinical Feature between Urolithiasis and Cardiovascular Diseases.” International journal of molecular sciences vol. 23,2 912. 14 Jan. 2022, doi:10.3390/ijms23020912

Tanaka, Yoshimi et al. “The influence of serum uric acid on renal function in patients with calcium or uric acid stone: A population-based analysis.” PloS one vol. 12,7 e0182136. 31 Jul. 2017, doi:10.1371/journal.pone.0182136

Wei, Baian et al. “Association between drinking status and risk of kidney stones among United States adults: NHANES 2007-2018.” BMC public health vol. 24,1 820. 15 Mar. 2024, doi:10.1186/s12889-024-18307-1

Wieers, Michiel L A J et al. “Dietary acid load in health and disease.” Pflugers Archiv : European journal of physiology, 10.1007/s00424-024-02910-7. 29 Jan. 2024, doi:10.1007/s00424-024-02910-7

Wu, Jing et al. “Association Between Serum Magnesium and the Prevalence of Kidney Stones: a Cross-sectional Study.” Biological trace element research vol. 195,1 (2020): 20-26. doi:10.1007/s12011-019-01830-3

Yen, Yunhe et al. “Heavy Metal Components in Blood and Urinary Stones of Urolithiasis Patients.” Biological trace element research vol. 185,2 (2018): 266-274. doi:10.1007/s12011-018-1253-x

Zhao, Enyang et al. “Intestinal dysbacteriosis leads to kidney stone disease.” Molecular medicine reports vol. 23,3 (2021): 180. doi:10.3892/mmr.2020.11819