Kidney Stones and High Triglycerides

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by

Andre Broussard, D.C.
in

In an article published in the journal Urology, the authors found that people with high triglycerides were at an increased risk for kidney stone recurrence.  Furthermore, they think that high triglycerides may represent a therapeutic target that could reduce recurrent kidney stones in this patient population. ~ Dr. Broussard

Hypertriglyceridemia Is Associated With Increased Risk for Stone Recurrence in Urolithiasis

October 06, 2014

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  • This Korean study evaluated the correlation between stone formers and serum lipid levels. Following 321 patients over 2 years, the authors found that stone formers with hypertriglyceridemia (HT) had significantly higher urinary calcium, sodium, uric acid, magnesium, and potassium excretions than stone formers. Recurrent stone formation was found in 46% of the HT group compared with 30% of the non-HT group (P = .005), and HT was independently associated with stone recurrence.
  • HT represents a therapeutic target that could reduce recurrent stones in this patient population.

– Gautam Jayram, MD

Written by MargaretS. Pearle MD, PhD

Stone disease has increasingly been associated with systemic conditions such as hypertension,1 diabetes,2 and coronary artery disease,3 leading some to postulate a cause-and-effect relationship. A common thread in some of these conditions is obesity/weight gain and metabolic syndrome. Indeed, a number of investigators have demonstrated a relationship between stone disease and metabolic syndrome, with the number of features of metabolic syndrome correlating positively with the prevalence of self-reported or radiographically detected kidney stones.4,5 In some cases, the associations are derived from population-based studies, without knowledge of stone composition or urinary stone risk factors. However, some investigators have attempted to correlate components of the metabolic syndrome with specific derangements in urinary analytes in the hope of identifying the specific urinary risk associated with these conditions.6

In a recent retrospective study, Kang and colleagues sought to determine the effect of the various forms of dyslipidemia on specific urinary stone risk factors as well as on stone recurrence in a group of recurrent stone formers.7 When adjusted for other confounding factors, they found no correlation between lipid profile and 24-hour urinary analytes, but they did find that the status of particular dyslipidemic states (hypertriglyceridemia, low HDL cholesterolemia, and high LDL cholesterolemia) impacted some urinary stone risk factors. Furthermore, hypertriglyceridemia was found to be an independent risk factor for stone recurrence. These findings help us to understand the impact of individual dyslipidemic states on particular urinary stone risk factors. However, the authors were unable to adequately control for important confounding factors such as severity of stone disease, age, BMI, hypertension, and diabetes. As such, the independent effects of these conditions are not entirely clear.

In the case of uric acid stones, the pathophysiology relating to the association with metabolic syndrome has begun to be elucidated. Insulin resistance leads to impaired ammoniagenesis in the renal proximal tubule and increased production of endogenous acid, resulting in reduced buffering capacity and acidic urine, the primary risk factor for uric acid stone formation.8 The pathophysiologic mechanisms responsible for the association of dyslipidemia, hypertension, or cardiovascular disease with calcium stone disease are less clear. It remains to be determined which, if any, of these associations are truly causal or if stone disease is simply another manifestation of the same metabolic abnormalities that arise from obesity.

References

  1. Borghi L, Meschi T, Guerra A, et al. Essential arterial hypertension and stone disease. Kidney Int. 1999;55(6):2397-2406. http://www.nature.com/ki/journal/v55/n6/full/4490816a.html
  2. Taylor EN, Stampfer MJ, Curhan GC. Diabetes mellitus and the risk of nephrolithiasis. Kidney Int. 2005;68(3):1230-1235. http://www.nature.com/ki/journal/v68/n3/full/4496203a.html
  3. Ferraro PM, Taylor EN, Eisner BH, et al. History of kidney stones and the risk of coronary heart disease. JAMA. 2013;310(4):408-415. http://jama.jamanetwork.com/article.aspx?articleid=1719741
  4. West B, Luke A, Durazo-Arvizu RA, et al. Metabolic syndrome and self-reported history of kidney stones: the National Health and Nutrition Examination Survey (NHANES III) 1988-1994. Am J Kidney Dis. 2008;51(5):741-747. http://211.144.68.84:9998/91keshi/Public/File/16/51-5/pdf/1-s2.0-S0272638608000620-main.pdf
  5. Jeong IG, Kang T, Bang JK, et al. Association between metabolic syndome and the presence of kidney stones in a screened population. Am J Kidney Dis. 2011;58(3):383-388. http://www.sciencedirect.com/science/article/pii/S0272638611007402
  6. Torricelli FC, De SK, Gebreselassie S, et al. Dyslipidemia and kidney stone risk. J Urol. 2014;191(30):667-672. http://www.jurology.com/article/S0022-5347%2813%2905454-2/abstract
  7. Sakhaee K. Recent advances in the pathophysiology of nephrolithiasis. Kidney Int. 2009;75(6):585-595. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088505/

Abstract

OBJECTIVE
To assess the influence of dyslipidemia on urinary lithogenic metabolites and stone recurrence in stone formers.

MATERIALS AND METHODS
We retrospectively selected 321 patients with urolithiasis who had been followed up for >24 months between 2004 and 2009. Fasting blood samples were taken, and serum lipid profiles were measured. All subjects also underwent 24-hour urinary metabolic evaluation and stone analysis. The radiographic appearance of new stones was defined as stone recurrence.

RESULTS
There was no significant correlation between lipid profiles and 24-hour urine metabolites (all P >.05). Stone formers with hypertriglyceridemia had significantly higher urinary calcium, sodium, uric acid, magnesium, and potassium excretions. Only in a subgroup of uric acid stone, hypertriglyceridemia was significantly associated with decreased urinary pH. Those with low high-density lipoprotein (HDL) cholesterolemia had higher urinary sodium, magnesium, and potassium excretions, whereas those with high low-density lipoprotein (LDL) cholesterolemia had lower urinary sodium excretion. Stone analysis revealed that uric acid stones were more commonly found in patients with hypertriglyceridemia and low-HDL cholesterolemia. After a median follow-up of 35.0 months, 109 patients (34% of cohort) had stone recurrence. Stone recurrence was more common in the hypertriglyceridemia group compared with the normal triglyceridemia group (45.9% vs 29.7%; P = .005). The multivariate Cox regression model revealed that hypertriglyceridemia is associated independently with stone recurrence (hazard ratio, 1.857; 95% confidence interval, 1.211-2.847; P = .005). Kaplan-Meier curves showed similar results.

CONCLUSION
Our study showed that serum lipid profile is associated with urine metabolic alterations. More importantly, hypertriglyceridemia is independently associated with increased risk for stone recurrence in patients with urolithiasis.

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