Our results suggest that the type of endoscopic papillary injury is associated with the type of stone and with certain disorders in urinary chemistry. This suggests that different mechanisms are responsible for these different endoscopic papillary injuries.
Coe et al. (17) hypothesized that the direct contact of a plug blocking Bellini’s duct in an environment with hypercalciuric urine favors the formation of HAP and calcium oxalate stones, although this relationship has not been demonstrated previously. Our results are consistent with this hypothesis. In particular, we observed that intratubular calcification and papillary crater each had significant associations with the type of lithiasis, in that they were more prevalent in patients with COD and CP stones. Moreover, we found that Randall’s Plaque was mainly associated with COM calculi.
We also found that intratubular calcification was significantly associated with urinary calcium concentration. This result confirms that Bellini’s duct must be exposed to supersaturated urine for the formation of HAP stones (pH > 6) and to hypercalciuria for the formation of an intratubular obstruction. When this deposit reaches the end of Bellini's duct and contacts the urine, it can induce the development of COD or COD + HAP calculi.
On the other hand, Randall’s plaque was mainly associated with COM calculi that developed in renal cavities. It is important to consider that typical calculi of papillary COM are generated on Randall’s plaque, which originates from internal lesions of intrapapillary tissue (8). These are small stones that are usually expelled spontaneously. Consequently, this type of calculus does not require surgery. However, all the stones examined in the present study required RIRS for elimination because they were larger, developed on the most distal part of Bellini’s ducts, and had fast growth due to the existence of hypercalciuria and sometimes high urinary pH. Therefore, we expected that none of the included patients had typical COM papillary calculi. We did observe the presence of Randall’s plaques, which in principle are related to the formation of COM stones. However, recent studies showed that not all of Randall's plaques generate papillary COM calculi (8).
In fact, Randall’s plaque seems to occur without symptoms in most individuals, and stone formation only occurs when there are large numbers of these plaques (8). It is thus possible that the small number of Randall’s plaque lesions and their total area in these patients were insufficient to lead to the development of papillary COM stones. We did not evaluate the percentage of surface affected by Randall’s plaque. However, other studies reported that the surface affected by Randall’s plaque was 7.4% in those who developed papillary calculi, but only 0.5% in those who did not develop calculi (20–26).
We found that Randall’s plaque was significantly associated with hypocitraturia (p = 0.005) and that urinary calcium concentration was significantly lower than those detected in the presence of intratubular calcification and / or renal crater. These data are consistent with the current understanding that a deficiency of stone inhibitors and normocalciuria can lead to the development of COM calculi (8). Thus, citrate inhibits the crystallization of oxalate and calcium phosphate, preventing the formation of the lithiasic core and posterior growth. Interestingly, regardless of the type of injury, the presence of uric acid stones is more likely when the urinary pH is below 5.5, and the presence of HAP stones is more likely when the urinary pH is above 6.0 (27–29).
There were some limitations in our study. First, we only described the experience of 41 patients at a single center. Second, the identification of papillary injury was somewhat subjective, even though we used previously described criteria to define the different types of injuries. Third, we did not consider the severity of papillary injuries, and only considered the presence or absence of a lesion. Another possible limitation is that there may have been some overlap in the different types of lesions if they were at different stages of disease progression. For example, we found an association of intratubular calcification with papillary crater. This can occur if lithiasis begins in an intratubular calcification, but detachment of the calculus from the renal papilla leads to the formation of a papillary crater (Fig. 4).
Our study identified several significant relationships of endoscopic papillary injuries with the type of stone and urine chemistry. The characterization of a papillary endoscopic injury may help a urologist to better understand the underlying mechanism of stone formation in individual patients. Further studies with larger numbers of patients are needed to confirm this hypothesis.