Evaluation of the correlation between the calcification pattern in the medullopapillary complex in the kidney and immunehistochemical markers and laboratory parameters

Introduction & Objectives: To prevent and treat nephrolithiasis, it is crucial to investigate the risk factors and pathophysiological mechanisms associated with it. Commonly acknowledged pathway for the formation of CaOx stones in idiopathic calcium oxalate stone formers (ICSF) is the Randall's plaque (RP), which is defined as: interstitial formation of calcium phosphate core in the tips of renal papillae. One theory is that proximal tubular mineral aggregates cause further downstream aggregation at the tip of the papilla, also called the 'Anderson-Carr-Randall progression'. We aimed to further examine this theory and find possible risk factors contributing to this process. Materials & Methods: 50 kidney specimens, obtained from radical nephrectomy and nephroureterectomy procedures performed between Jun-2019 and Jan-2023, were examined by micro-CT analysis. Attenuation ranges were matched with deposition characteristics on micro-CT analysis and stone-to-tissue ratio was used to determine the severity of the calcification. Patients' preoperative parameters of; blood and urine laboratory analysis and 24-h urine analysis were documented. Patients were excluded from the study if they had any disease excluding them from being an ICSF if they were to form any stone in the future. Statistics of categorical variables and scalar correlations were examined by T-test, Mann-Whitney-U, Pearson's coefficient, logistic and linear regression analysis and chi-square tests. Results: Regardless of whether a RP was existing or not, Micro-CT analysis revealed various amounts of mineral deposition in all examined renal papillae. Hypertension (HT) and age were found to be risk factors for medullar mineral aggregation. Further increasing urine volume above 1600mL/d had a negative effect on formation of proximal tubular aggregates. With the formation of RP, 24-hour urine citrate amount, presence of HT and urine volume less than 1275 ml/day were found to be significant in the regression model. Conclusions: Histopathological changes in the renal papillae begins to occur before the formation of a RP. The presence of HT and patient age increases the formation of proximal aggregates that contribute to the formation of RP. The most important risk factors for the transformation of these mineral aggregates into RP are the presence of HT, low 24-hour urine citrate and urine volume lower than 1275 ml/day. Stone disease formation can be slowed or prevented by increasing oral fluid intake, treating low citrate in the urine, and treating HT.