The mechanism of CaOx stone formation is not yet completely clear, but Randall’s plaque theory is the main hypothesis of stone formation [3]. Randall’s plaque is defined as calcium phosphate deposits lying under the papillary epithelium which may serve as a nidus for CaOx deposition and eventual stone formation. Increased excretion of urinary calcium, phosphate, and oxalate as well as decreased excretion of citrate is thought to contribute to intra-tubular crystal formation. However, the exact mechanism behind interstitial crystal formation and subsequent stone formation remains unclear [4].
Randall’s plaque has been extensively histopathologically investigated in patients who underwent percutaneous nephrolithotomy [3, 5]. Following histological analysis of Randall’s plaque, the next step was to show that calcification of the renal papillary area observed by endoscopy is a risk factor for stone recurrence [6]. However, this method requires an invasive examination. A study followed to determine whether CT values of the renal papillary region could be predicted for stone recurrence by simple CT. Several authors have therefore attempted to measure the HU of renal papillae by means of unenhanced CT with the hypothesis that localized calcifications such as Randall’s plaque increase the radiologic density of tissues. In 2008, Eisner et al. first reported that the CT attenuation value of renal papilla in 17 patients with stones was significantly higher than that in non-stone-forming controls [1]. A later study also demonstrated that CT values of renal papilla in the stone-bearing kidney and in the contralateral kidney in 90 patients with stones were significantly higher than those in non-stone forming controls [2]. Interestingly, these two studies showed that the CT attenuation values of the renal papilla in patients with calculi were higher than those in all renal papillae in healthy subjects, regardless of the presence or absence of calculi, the healthy side, or the affected side. These results not only support that Randall’s plaque can be detected as higher CT attenuation values, they also imply that Randall’s plaque is formed by systemic rather than by local changes.
Ciudin et al. reported the clinical significance of CT attenuation value of renal papillae [7,8,9,10]. CT values of renal papillae in patients with calcium stones were higher than those in healthy subjects, but they were also higher on CT before the development of stones [8]. High CT attenuation values were demonstrated to not be the result of calcium stone formation, but rather they represent the cause of calcium stones, which supports Randall’s plaque theory. They also followed up 187 patients who were treated for calcium stones and found to be stone free and found that renal papillary CT values were significantly higher in patients with recurrent stones than in those without recurrence [10].
In the current study, we focused on only calcium oxalate stone formers and divided them into two groups according to the CT attenuation value of real papillae: the low-HU group (< 38.9) and the high-HU group (≥ 38.9). We wanted to ascertain whether the CT attenuation value is associated with the clinical course of patients with calcium stones. Although the HU value of renal papillae was not correlated with disease severity (multiple stone formers), recurrence rate in the high-HU value group was significantly higher than that of the low-HU value group (0.10 events/person/year [IQR 0–0.45] vs. 0 events/person/year [IQR 0–0.27], p = 0.03). Multivariable logistic regression model revealed that high-HU value was an independent predictor of stone recurrence (odds ratio [OR] 1.90, 95% CI 1.00–3.64, p = 0.04) as well as medical prophylaxis (OR 3.01, 95% CI 1.23–7.35, p = 0.01). The results that the use of medical prophylaxes had a positive impact on stone recurrence might be because they are applied to patients who were thought to be at higher risk of recurrence.
Another unique feature of our study was the relationship between renal papillary CT values and 24-hour urine chemistries. Although only one previous study reported the relationship between renal papillae CT attenuation values and 24-hour urine chemistry [11], there was no correlation between papillary density and hypercalciuria. We also found no significant difference in daily urinary calcium excretion or AP (CaOx) index between the high and low renal papillary CT groups.
There are several limitations in regard to our study. First, the number of patients was small, and more patients are required to reach a stronger conclusion. Second, we targeted only patients with calcium stones, and many previous studies have examined not only patients with calcium stones, but also healthy controls. Third follow up period was rather short (3.5–4.0 years). Longer term observations will yield more accurate results.
However, our study showed that measurement of HU of renal papillae is useful for not only screening of future stone patients within the general public, but also in the establishment of follow-up plans for present patients with stones after treatment.
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