Calcium oxalate is the most prevalent type of kidney stone, and patients diagnosed with this condition receive the same treatment, irrespective of proportion of COM and COD in their stone [4]. However, we hypothesized that demographic and metabolic factors associated with varying proportion of COM and COD components might vary. In line with our hypothesis, we noted significant correlation between decreased age, decreased BMI, increased urine pH, and the supersaturation of several metabolites (increased CaOx, increased brushite, and decreased UA) with the proportion of COD in CaOx stones. These findings provide a potential to modify some of these factors thereby influencing treatment choice or at least laying a foundation for future research.
We observed an increased risk of having a significant percentage of COD (≥ 20%) in CaOx stones in patients with younger age, lower BMI, higher urine pH, higher urinary potassium, and increased supersaturation of CaOx and brushite. Patients with CaOx stones most commonly present in the fifth decade of life [4]. However, we found that patients with higher proportion of COD stones were significantly younger and had a lower BMI. Our findings are consistent with previous studies that also demonstrated a higher prevalence of COD stones in younger individuals, with age differences ranging from 6 to 10.6 years between CaOx subtypes [4, 11, 12]. Additionally, the present study revealed no significant correlation between the proportion of CaOx stones and gender or the presence of chronic diseases, consistent with the findings of Bamberger et al who used ≥ 80% of predominant subtypes component as a cut-off for dividing patients between COM and COD subtypes. In their study involving 157 patients, no significant associations were observed between these factors and CaOx stone subtypes [12]. However, this remains equivocal as Pierratos and colleagues previously reported an association between COM stones and male patients [11].
Urine pH, which can be influenced by multiple factors such as dietary choices, renal function, and medications, plays a crucial role in determining the composition of kidney stones [9]. Our study revealed a significant association between alkaline urine and COD stones. These results are consistent with previous findings that suggest an environment favoring the formation of COD stones in the presence of elevated urine pH, while an acidic urine promotes the formation of COM stones [11, 13]. Interestingly, Taylor et al. demonstrated an inverse relationship between BMI and urine pH, which may point to a physiologic explanation for why BMI was inversely related to presence or amount of COD [14]. Nonetheless, it is important to be cautious when interpreting these findings because many of these variables may influence one another or may not be truly independent.
Interestingly, increasing total 24-hour urinary potassium was associated with a decrease in likelihood of having a significant percentage of COD in a patient’s stone composition. However, this finding may be affected by diet and medication use and its implications are difficult to explain. Additionally, differences between CaOx subtypes and many other components of the 24-hour urine test including calcium, citrate, oxalate, and others were not found to be related to the presence of COM or COD. Our findings echo those of Guerra and colleagues who noted that pure CaOx stones with ≤ 25% COD had few associated urinary metabolic abnormalities [13]. However, these authors and others have reported associations between hypercalciuria and COD stones, as well as between hypocitraturia and hyperoxaluria with COM stones utilizing a higher cutoff limit for classifying subtypes of CaOx stones [11–13]. Notably, Otto et al. conducted a study analyzing patients with CaOx stones and found that age was a key factor influencing 24-hour urine results, with older individuals showing greater hyperoxaluria and lower urinary pH [15]. We used cutoff value for COD component as ≥ 20% in our study. This might influence the results of our study and explain differences noted between our results and those of other authors [11–13]. It is relevant to note that Omar and coworkers found no difference in sensitivity, specificity, and accuracy of the 24-hour urine supersaturation in predicting stone composition with different cut-off values of predominant stone component (≥ 60%, ≥ 70%, ≥ 80% and ≥ 90%) [16].
Regarding the relationship of CaOx stones with 24-hour urinary supersaturations, we found that the supersaturation of both CaOx and brushite were high in patients with a significant amount of COD or as the proportion of COD increased. This is consistent with earlier research, which demonstrated that pure CaOx stones are associated with an increased supersaturation of CaOx and brushite, with the latter being more closely associated with COD stones [11, 13]. Additionally, our study revealed an inverse association between the proportion of COD present in a specimen and UA supersaturation. This finding may be confounded by the robust increase in urinary pH in patients with a higher proportion of COD, as urine becomes alkaline, the UA supersaturation decreases.
Our study has certain limitations inherent to its retrospective design that warrant acknowledgment. Most of the stones were collected after endoscopic procedures for stone removal. There is a theoretical possibility that the proportion of COD component might have been dusted and thereby not collected for chemical analysis. Since most stones were not sent intact for chemical analysis, the final stone composition report of stone fragments may not represent that of the original intact stone. The exclusion of multiple patients due to unavailability of 24-hour urine tests during the required period reduced the statistical power of our study. Moreover, as a single-institution study, caution must be exercised when generalizing the results to other geographic regions, as nephrolithiasis is influenced by regional factors. Additionally, the absence of information regarding medications and compliance limits some of our findings, especially pertaining to metabolic changes in the 24-hour urine collections.
However, we feel we validated existing findings in the literature while also making several novel observations, further highlighting the notion that treating different situations with a uniform approach may be inadequate. For instance, patients with COD stones may derive less benefit from potassium citrate compared to those with COM stones due to their elevated urine pH. Additionally, weight loss guidance may hold greater significance for patients with COM stones than for those with COD stones. These findings underscore the need for further research to explore subtype-specific treatment approaches for CaOx stones and assess their impact on patient outcomes. By tailoring treatment strategies to the specific subtypes, we can optimize management and enhance the overall care of patients with CaOx stones. Furthermore, our study offers valuable guidance for patient management even in the absence of a 24-hour urine risk profile.