Stesura Seveso Archivio Italiano di Urologia e Andrologia 2023; 95, 1 ORIGINAL PAPER genetic predisposition and environmental influence, as for dietary habits (3, 4). Besides, it is known to be associ- ated with a wide spectrum of comorbidities such as obe- sity (5), arterial hypertension (6), diabetes mellitus (7), metabolic syndrome (8) and increased likelihood of developing chronic kidney disease, especially in second- ary forms of systemic diseases (9). It was also shown that patients with urolithiasis have an increased risk of car- diovascular events (10) and vascular calcifications (11), highlighting the systemic involvement of this condition. Kidney stones develop attached to either Randall’s plaques (sub-epithelial interstitial deposits of calcium phosphate on the renal papillae), or stone plugs (crystal deposits in the terminal collecting ducts) (12). Both these can be seen on the papillary surfaces. What promotes plaque formation is not well understood. It has been sug- gested that idiopathic calcium oxalate stones normally develop on Randall’s plaques and that secondary forms of stones are mainly formed from plugs (12). A better understanding of both etiology and pathogenesis of the different forms of nephrolithiasis is fundamental to prevent recurrences with a more personalized and cause- specific medical treatment. The improved optical uretero- renoscopic inspection techniques may make the evalua- tion of renal papilla not only possible but hopefully able to produce a large amount of new data and evidence as to the pathogenesis of stones (13). Recently, a renal papil- lary appearance scoring system was proposed, in order to better characterize and to standardize the visual inspec- tion of renal papillae (PPLA score) (14). Although it could certainly be a useful tool for improving reproducibility in the description of pathological findings in different patients and centers, at this moment the potential impli- cations of this score on kidney stone risk factors are not well understood. The aim of this study is therefore to investigate the asso- ciation between the main risk factors for kidney stone recurrence and the endoscopic papillary evaluation score (PPLA) in a cohort of patients with nephrolithiasis. The association between PPLA and subsequent recurrence was also investigated. Objectives: The aim of this study is to investi- gate the association between the urinary metabolic milieu and kidney stone recurrence with a validated papillary evaluation score (PPLA). Materials and methods: We prospectively enrolled 30 stone for- mers who underwent retrograde intrarenal surgery procedures. Visual inspection of the accessible renal papillae was performed to calculate PPLA score, based on the characterization of ductal plugging, surface pitting, loss of papillary contour and Randall’s plaque extension. Stone compositions, 24h urine collections and kidney stone events during follow-up were collected. Relative supersaturation ratios (RSS) for calcium oxalate (CaOx), brushite and uric acid were calculated using EQUIL-2. PPLA score > 3 was defined as high. Results: Median follow-up period was 11 months (5, 34). PPLA score was inversely correlated with BMI (OR 0.59, 95% CI 0.38, 0.91, p = 0.018), type 2 diabetes (OR 0.04, 95% CI 0.003, 0.58, p = 0.018) and history of recurrent kidney stones (OR 0.17, 95% CI 0.04, 0.75, p = 0.019). The associations between PPLA score, diabetes and BMI were not confirmed after excluding patients with uric acid stones. Higher PPLA score was associated with lower odds of new kidney stone events during follow-up (OR 0.15, 95% CI 0.02, 1.00, p = 0.05). No other significant correla- tions were found. Conclusions: Our results confirm the lack of efficacy of PPLA score in phenotyping patients affected by kidney stone disease or in predicting the risk of stone recurrence. Larger, long-term studies need to be performed to clarify the role of PPLA on the risk of stone recurrence. KEY WORDS: Kidney stones; Retrograde intrarenal surgery; Stone recurrence; Management; Stone phenotype. Submitted 19 July 2022; Accepted 20 August 2022 INTRODUCTION Nephrolithiasis is a medical condition characterized by a high prevalence in the general population and high recur- rence rates (1), causing an elevated annual expenditure reaching up to $10 billion in the United States (2). Kidney stone disease pathogenesis is multifactorial, including Determinants of renal papillary appearance in kidney stone formers: An in-depth examination Matteo Bargagli 1, 2, Francesco Pinto 3, Rossella De Leonardis 1, Mauro Ragonese 3, Angelo Totaro 3, Salvatore Recupero 4, Matteo Vittori 5, PierFrancesco Bassi 1, 3, Giovanni Gambaro 6, Pietro Manuel Ferraro 1, 2 1 Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italia; 2 U.O.S. Terapia Conservativa della Malattia Renale Cronica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia; 3 U.O.C. Clinica Urologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia; 4 U.O.C. Urologia, Ospedale Fatebenefratelli, Rome, Italy; 5 Department of Urology, San Carlo di Nancy Hospital, Rome, Italy; 6 Renal Unit, Department of Medicine, University-Hospital of Verona, Verona, Italy. DOI: 10.4081/aiua.2023.10748 Summary Archivio Italiano di Urologia e Andrologia 2023; 95, 1 M. Bargagli, F. Pinto, R. De Leonardis, et al. MATERIALS AND METHODS Study population We prospectively enrolled all patients undergoing retro- grade intrarenal surgery (RIRS) procedures for kidney stones at the U.O.C. Clinica Urologica, Fondazione Policlinico Universitario A. Gemelli IRCCS from May 2018 to September 2019. All patients were stone-free after RIRS procedure. Additional inclusion criteria were age ≥ 18 years and signed informed consent. At study initia- tion, all patients were naïve for dietary advice and med- ical treatment for kidney stone recurrence. All procedures performed in studies involving human par- ticipants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or compa- rable ethical standards. The study was approved by the Bioethics Committee of the Fondazione Policlinico Univer sitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy (ID n° 2349). Informed consent was obtained from all individual participants included in the study. Data collection and measurements Patients included in this study performed a baseline visit after RIRS procedure at the nephrology stone clinic, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, followed by a 1-year telephonic interview for investi- gating incident kidney stone events. Either a visible spon- taneous passage of stone, evidence of kidney stones at any instrumental exam or new kidney stones removal proce- dure, were considered as a recurrence and the variable “overall recurrent kidney stone disease at the end of the study” was generated accordingly. For each patient, demographic and anthropometric information (sex, age, height, weight), clinical data regarding stone disease (history of sympto- matic stone events, family history of kidney stones, solitary kidney), self-reported comorbidities (hypertension, dia- betes, cardiovascular diseases, bone fractures), a physical examination and office blood pressure measurements were recorded. Standardized urine analyses (urine pH, daily uri- nary excretion of calcium, phosphate, magnesium, sodium, potassium, creatinine, urea, citrate, uric acid and oxalate) were conducted. Stones were routinely collected during RIRS procedures, in order to obtain composition analysis, using Fourier-transform infrared spectroscopy. The creati- nine-based CKD-EPI equation was used to obtain the esti- mated glomerular filtration rate (eGFR). Among the meta- bolic evaluation parameters, the main one is represented by supersaturation for calcium oxalate, calcium phosphate and uric acid, representing the propensity of urine to form those crystals. Urine relative supersaturation ratios (RSS) for calcium oxalate monohydrate, brushite and undissociated uric acid were calculated by the EQUIL2 program (15). Visual inspection of the accessible renal papillae during RIRS procedures was performed in order to calculate a score of papillary appearance (PPLA score). PPLA score is based on the characterization of 4 ordinal variables (ductal plugging, surface pitting, loss of papillary contour and Randall’s plaque extension), representing worsening pic- tures of renal involvement. PPLA score is an ordinal vari- able and it ranges from a minimum of 0 to a maximum of 8, produced by the sum of 4 components; each sub-com- ponent is an ordinal variable with 3 levels (from 0 to 2). In this study, the modified version of PPLA score was used, considering Randall’s plaque extension as an ordinal numeric variable (Table 1) (16). All the images were eval- Table 1. PPLA score system for renal papillae (16). Score 0 1 2 Ductal plugging 0 plaque deposits/ ≤ 5 plaque deposits/ > 5 plaque deposits/ dilated ducts dilated ducts dilated ducts Surface pitting None ≤ 25% papillary surface > 25% papillary surface Loss of contour None Depressed Flattened Randall’s plaque extension Low Medium High Table 2. Baseline characteristics of the study cohort. Characteristic Participants (n = 30) Males 19 (63) Age, years 60.2 (12) SBP, mmHg 130 (10) DBP, mmHg 83 (5) Body Mass Index, kg/m2 25.8 (4) eGFR creatinine Equation CKD-EPI 2009, mL/min per 1.73 m2 84.2 (19) Arterial hypertension 14 (47) Diabetes 3 (10) Cardiovascular disease 6 (20) Bone fractures 2 (7) Hyperparathyroidism 1 (3) Positive family history for kidney stones 11 (37) History of recurrent kidney stones 10 (33) Solitary kidney 1 (3) 1-year kidney stone recurrence 9 (30) PPLA score subgroups (0-6) 0 1 (3) 1 1 (3) 2 7 (23) 3 4 (13) 4 5 (17) 5 9 (30) 6 3 (10) High PPLA score (> 3) 17 (57) RSS for calcium oxalate 35.52 (20.20, 64.31) RSS for calcium phosphate 0.42 (0.23, 1.82) RSS for uric acid 1.03 (0.77, 1.89) Urine pH 5.5 (5.0, 6.0) Urine calcium, mg/day 183 (122, 283) Urine phosphate, mg/day 770 (600-988) Urine uric acid, mg/day 450 (326, 552) Urine citrate, mg/day 427.1 (177.35, 614.7) Urine oxalate, mg/day 19.5 (15.0, 26.8) Urine creatinine, g/day 1.2 (1.0, 1.7) Urine sodium, mEq/day 145.9 (138.3, 191.0) Urine potassium, mEq/day 59.4 (48.0, 78.0) Urine magnesium, mg/day 100.0 (80.2, 120.0) Urine volume, mL/day 2,000 (1,550, 2,400) Hypercalciuria 6 (20) Hyperoxaluria 2 (7) Hypocitraturia 11 (37) Calcium oxalate stones 17 (57) Urate stones 3 (9) Calcium phosphate stones 0 Mixed calcium oxalate and urate stones 5 (17) Mixed calcium oxalate and calcium phosphate stones 8 (26) Archivio Italiano di Urologia e Andrologia 2023; 95, 1 Renal papillary appearance in stone formers uated one by one from 4 expert surgeons (> 50 flexible ureteroscopy for renal stones) and 5 junior surgeons (< 50 procedures performed). All the graders evaluated the videos of the papillae using the same video system and were allowed to review the video more than one time. Moreover, the percentage of agreement for the single item was evaluated in the two subgroups of surgeons and among senior graders, to ensure inter-grader concordance. Hypercalciuria was considered as urine calcium excretion > 250 mg/24h for women and 300 mg/24h for men, hyperuricosuria as urine uric acid excretion > 750 mg/24h for women and 800 mg/24h for men, hyperox- aluria as urine oxalate excretion > 45 mg/24h and hypoc- itraturia as urine citrate excretion < 320 mg/24h (17). Statistical analysis Continuous variables were reported as medians with 25th and 75th percentiles or means with standard deviation (SD) and categorical variables were reported as counts with per- centages. PPLA score > 3 was defined as high. The inter- observer surgeon concordance among all 10 investigators and between the median values of the two subgroups (junior vs senior) was analysed by the Kendall coefficient of concordance. Ordinal logistic regression was used to analyse the association between stone risk factors (hyper- tension, diabetes, body mass index, cardiovascular dis- ease, history of recurrent kidney stones, family history of kidney stones, RSS for calcium oxalate, calcium phosphate and uric acid, urine pH, urinary excretions of calcium, oxalate, citrate, uric acid and urine volume) and PPLA and its components (ductal plugging, surface pitting, loss of papillary contour, Randall’s plaque extension). The analy- ses were repeated after modelling PPLA as lower (≤ 3) and higher (> 3) using logistic regression models. The associa- tion between PPLA and 1-year kidney stone recurrence was analysed with logistic regression models. Statistical tests were two-sided and a p-value < 0.05 was considered statistically significant. Statistical analyses were performed using the software Stata version 16 (StataCorp, College Station, TX, USA). RESULTS A total of 30 stone formers were enrolled in this study. Mean age was 60.2 (SD 12.4) years and most patients were males (n = 19, 63%). Overall, 47% were hypertensive (n = 14), 10% were diabetic (n = 3), 20% presented cardiovas- cular comorbidities (n = 6). As regards kidney stone dis- ease, 33% had a positive history of recurrence (n = 10) and 37% had a positive family history of stones (n = 11). Stone composition analysis, available in 23 patients (69%), revealed that calcium oxalate stones were the most frequent (56.5%), followed by mixed calcium oxalate and calcium phosphate stones (26.1%) (Table 2). Overall, 20% of the study sample had hypercalciuria (n = 6), 37% hypocitraturia (n = 11) and 7% hyperoxaluria (n = 2). The most frequent total PPLA score was 5 (n = 9, 30%) and 57% of patients had a PPLA score > 3 (n = 17). Concordance between surgeon groups in the evaluations of plugging, pitting, loss of papillary contour and Randall’s plaque extension were 86%, 73%, 72% and 80%, respectively. Among senior surgeons concordance was even higher with a percentage of 91%, 80%, 76% and 85% agreement. The Kendal coefficient of concor- dance was 0.93 among senior surgeons and 0.88 com- paring the two groups of senior and junior surgeons. PPLA score was inversely correlated with BMI (Odds Ratio [OR] 0.59, 95% confidence interval [CI] 0.38, 0.91, p = 0.018), type 2 diabetes mellitus (OR 0.04, 95% CI 0.003, 0.58, p = 0.018) and history of recurrent kidney stones (OR 0.17, 95% CI 0.04, 0.75, p = 0.019) (Table 3). The associ- ations between type 2 diabetes and BMI with PPLA score were not confirmed after excluding patients with uric acid stones. Among the PPLA components, Randall’s plaque Table 3. Association between PPLA score and risk factors for kidney stones or stone recurrence. PPLA score High PPLA score (> 3) Variable No Odds Ratio 95% CI p-value No Odds Ratio 95% CI p-value Hypertension 30 0.42 0.11, 1.57 0.197 30 0.34 0.08, 1.52 0.159 Diabetes 30 0.04 0.003, 0.58 0.018* 30 0.33 0.99, 1.09 0.069 Body Mass Index, kg/m2 30 0.59 0.38, 0.91 0.018* 30 0.78 0.61, 0.99 0.039 Cardiovascular disease 30 0.98 0.21, 4.68 0.979 30 0.71 0.12, 4.30 0.713 History of recurrent kidney stones 30 0.17 0.04, 0.75 0.019* 30 0.08 0.01, 0.53 0.009 Positive family history for kidney stones 30 1.83 0.48, 6.98 0.379 30 1.58 0.34, 7.22 0.559 1-year kidney stone recurrence 27 0.81 0.48, 1.37 0.426 27 0.15 0.02, 1.00 0.050* Overall recurrent kidney stone disease 30 0.10 0.02, 0.48 0.004* 30 0.03 0.01, 0.28 0.001* RSS for CaOx 30 1.01 0.99, 1.03 0.529 30 1.00 0.95, 1.06 0.948 RSS for Brushite 20 0.94 0.64, 1.37 0.726 20 0.54 0.23, 1.26 0.153 RSS for Uric acid 7 0.97 0.65, 1.45 0.887 7 Not estimatable Urinary excretion of calcium, mg/day 29 1.001 1.00, 1.01 0.657 29 1.00 1.00, 1.01 0.294 Urinary excretion of oxalate, mg/day 30 0.95 0.90, 1.01 0.098 30 0.97 0.91, 1.03 0.330 Urinary excretion of citrate, mg/day 30 1.00 1.00, 1.01 0.493 30 1.00 1.00, 1.00 0.934 Urinary excretion of uric acid, mg/day 7 1.00 0.99, 1.01 0.488 7 1.00 0.99, 1.01 0.815 Urinary excretion of sodium, mEq/day 28 0.98 0.96, 1.00 0.050* 28 0.97 0.93, 1.01 0.150 Urinary volume, mL/day 30 0.81 0.19, 3.43 0.774 30 0.48 0.09, 2.53 0.385 Urine pH 30 1.10 0.41, 2.93 0.853 30 1.84 0.53, 6.38 0.337 Archivio Italiano di Urologia e Andrologia 2023; 95, 1 M. Bargagli, F. Pinto, R. De Leonardis, et al. extension was inversely associated with history of recurrent kidney stones (OR 0.03, 95% CI 0.003, 0.23, p = 0.001) (Table 4). No other significant correlations were found between PPLA components and kidney stone risk factors. After a median follow-up period of 11 months (5, 34), 30% of patients reported a new symptomatic kidney stone event (n = 9). Higher PPLA score was directly asso- ciated with lower odds of new kidney stone events dur- ing follow-up (OR 0.15, 95% CI 0.02, 1.00, p = 0.050) and reduced likelihood of overall recurrent kidney stone disease at the end of the study (OR 0.03, 95% CI 0.01, 0.28, p = 0.001). DISCUSSION Novel methods capable of predicting the risk of stone recurrence and to better understand stone phenotype aetiology based on intra-renal crystals deposition are missing. In addition, three different hypotheses regarding the pathophysiology of stone formation have been pro- posed. The first hypothesis is Randall’s plaque formation, with deposition of calcium phosphate crystals in form of apatite inside interstitial parenchyma. The second regards free solute crystallization for urine stasis and the third implies renal tubules crystal deposition as the nucleation factor for stone formation (18). Recently, endoscopic visualization of the accessible portion of renal papillae and collecting duct system were applied for differentiat- ing these pathways, creating a promising additional tool for future evaluation of recurrent stone formers (14). Afterwards, a score of papillary appearance was created to study the association between stone phenotypes, urinary solute excretions and the description and quantification of either Randall’s plaque, Bellini duct plugging, focal erosion of papillary surface (pitting) and loss of papillary contour extensions (16). It can be then hypothesized that PPLA score and its sub- scores might be of help in differentiating patients with the same stone composition, urinary lithogenic risk profile or recurrence risk but with diverse papillary aspects, per- haps reflecting multiple concomitant pathogenesis of nephrolithiasis. For these reasons, the use of PPLA score was recently recommended in all patients who undergo ureteroscopy (19). However, evidence on the association between PPLA score, stone composition and urinary solute excretions is conflicting. In a previous study, Kuo et al. analyzed 14 stone formers, firstly showing the asso- ciation between higher urinary calcium excretion, urine pH and urine volume on Randall’s plaque extension (20), whereas analyzing larger cohorts of stone formers, Linnes et al. (21) and Pless et al. (22) did not confirm this associ- ation. In addition, Sabaté Arroyo et al. showed both increased frequency of intratubular calcification and pap- illary crater in patients with calcium oxalate dihydrate and calcium phosphate stones and a correlation between higher urinary calcium excretion and low urinary citrate excretion with papillary crater and Randall’s plaque extension, respectively (23). In the present study, hypercalciuria and hypocitraturia were the most frequent 24-h urine abnormalities, reflect- ing data of the most common urinary lithogenic risk pro- file in the general population (24, 25). Although we did not report any significant association between PPLA score or sub-scores and stone composition, RSS for calcium oxalate, brushite and uric acid or urinary lithogenic risk profile, both diabetes and BMI were found to be inverse- ly correlated to PPLA score. However, after excluding patients with uric acid stones, the former correlations were not confirmed. The association between increased risk for incident kidney stones and obesity, BMI and dia- betes has been known for a long time (26). Both type 2 diabetes mellitus and obesity share similar pathogenesis Table 4. Association between each PPLA sub-score (ductal plugging, surface pitting, loss of papillary contour, Randall’s plaque extension) and risk factors for kidney stones or stone recurrence. Ductal plugging Surface pitting Loss of papillary contour Randall’s plaque extension Variable No OR (95% CI) p-value OR (95% CI) p-value OR (95% CI) p-value OR (95% CI) p-value Hypertension 30 0.27 (0.06, 1.17) 0.080 0.77 (0.18, 3.34) 0.728 0.53 (0.10, 2.74) 0.448 1.02 (0.23, 4.48) 0.980 Diabetes 30 0.32 (0.32, 0.35) 0.294 0.17 (0.01, 2.15) 0.171 0.09 (0.01, 1.17) 0.065 0.00 (0.31, 3.43) 0.995 BMI 30 0.91 (0.76, 1.10) 0.328 0.83 (0.68, 1.02) 0.079 0.91 (0.74, 1.13) 0.393 0.86 (0.69, 1.07) 0.174 Cardiovascular disease 30 1.12 (0.19, 6.59) 0.904 0.68 (0.12, 3.99) 0.670 0.88 (0.13, 6.12) 0.894 2.12 (0.30, 14.82) 0.447 History of recurrent kidney stones 30 0.32 (0.07, 1.41) 0.131 0.64 (0.13, 3.06) 0.575 0.33 (0.06, 1.88) 0.213 0.03 (0.00, 0.23) 0.001* Familiarity for kidney stones 30 1.88 (0.44, 8.10) 0.395 2.40 (0.48, 11.93) 0.285 0.68 (0.13, 3.60) 0.648 1.27 (0.28, 5.87) 0.757 1-year kidney stone recurrence 27 0.37 (0.09, 1.41) 0.145 0.50 (0.11, 2.27) 0.369 2.25 (0.41, 12.38) 0.351 0.67 (0.14, 3.21) 0.619 Overall recurrent kidney stone disease 30 0.13 (0.03, 0.65) 0.013* 0.21 (0.04, 1.07) 0.061 0.48 (0.92, 2.51) 0.385 0.10 (0.17, 0.62) 0.013* RSS for CaOx 30 1.01 (0.98, 1.03) 0.618 1.00 (0.98, 1.03) 0.802 1.00 (0.97, 1.03) 0.870 1.03 (0.99, 1.06) 0.122 RSS for Brushite 20 0.97 (0.66, 1.43) 0.870 0.97 (0.71, 1.32) 0.829 0.81 (0.57, 1.15) 0.229 1.00 (0.71, 1.41) 0.990 RSS for Uric acid 5 2.95 (0.03, 317.29) 0.650 0.01 (0.00, 22.90) 0.235 1.30 (0.58, 2.90) 0.526 1.95 (0.31, 27.19) 0.675 Urinary excretion of calcium, mg/day 29 1.01 (1.00, 1.01) 0.138 1.00 (1.00, 1.01) 0.683 1.00 (0.99, 1.00) 0.209 1.00 (1.00, 1.01) 0.641 Urinary excretion of oxalate, mg/day 30 0.98 (0.93, 1.04) 0.559 0.95 (0.89, 1.02) 0.134 0.95 (0.89, 1.02) 0.157 0.99 (0.93, 1.06) 0.826 Urinary excretion of citrate, mg/day 30 1.00 (1.00, 1.00) 0.797 1.00 (0.99, 1.00) 0.147 1.00 (0.99, 1.00) 0.187 1.00 (1.00, 1.01) 0.173 Urinary excretion of uric acid, mg/day 7 1.00 (0.99, 1.01) 0.993 0.99 (0.98, 1.00) 0.138 1.00 (0.99, 1.01) 0.455 1.04 (0.97, 1.12) 0.284 Urinary excretion of sodium, mEq/day 28 0.98 (0.96, 1.01) 0.180 0.98 (0.96, 1.00) 0.102 0.98 (0.96, 1.00) 0.101 0.99 (0.97, 1.02) 0.530 Urinary volume, mL/day 30 0.78 (0.179, 3.45) 0.748 1.49 (0.30, 7.53) 0.629 0.59 (0.10, 3.40) 0.551 0.56 (0.10, 2.99) 0.496 Urine pH 30 1.62 (0.53, 4.93) 0.400 1.18 (0.37, 3.82) 0.777 0.26 (0.06, 1.06) 0.060 1.47 (0.46, 4.68) 0.512 Archivio Italiano di Urologia e Andrologia 2023; 95, 1 Renal papillary appearance in stone formers (27), being part of the metabolic syndrome, which is tightly associated to insulin resistance (28). Insulin resist- ance results in acidic urine pH and defective renal pro- duction of ammonia, increasing the likelihood of devel- oping uric acid kidney stones (8). Notably, with a correct urinary alkalization, it is possible to reduce or even dis- solve previously formed uric acid stones, provided the absence of combined uric acid and calcium stone compo- sition (29). Thus, the association between higher BMI, type 2 diabetes and lower PPLA score, may be driven by uric acid nephrolithiasis, since it was no longer significant after restriction to calcium stone formers. However, there were too few uric acid stone formers in our cohort to con- firm these observations. In this study on a prospective cohort of 30 stone formers, the association between PPLA score and the risk of 1-year kidney stone recurrence was investigated for the first time. We demonstrated an inverse association between high PPLA score and the odds of stone recurrence after a median follow-up time of 11 months. Patients enrolled in this study were naïve for dietary advice and medical treat- ment for kidney stone disease. After RIRS procedure, they underwent a work-up and dietary/medical management based on the results of 24h urine collections as well as their medical history; hence this data might reflect a more intensive medical management in the subgroup of patients with more severe pathological findings at papil- lary visualization. Limitations of this study are the small sample size and low number of uric acid stone formers. Overall, this evidence confirms the validity of advanced instrumental exams as a supplementary tool in medical and surgical management of kidney stones (30). Future, larger studies with a systematic assessment of stone recur- rence are needed to confirm our findings. CONCLUSIONS In conclusion, our results confirm the lack of efficacy of PPLA score in phenotyping patients affected by kidney stone disease or in predicting the risk of stone recurrence. 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Changes in renal papil- lary density after hydration therapy in calcium stone formers. BMC Urol. 2018; 18:101. Correspondence Matteo Bargagli, MD matteo.bargagli@unicatt.it Pietro Manuel Ferraro, MD MSC PHD FERA (Corresponding Author) pietromanuel.ferraro@unicatt.it U.O.S. Terapia Conservativa della Malattia Renale Cronica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS & Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italia Largo Agostino Gemelli 8, 00168, Roma (Italy) Francesco Pinto, MD francesco.pinto@unicatt.it Mauro Ragonese, MD mauro.ragonese@unicatt.it Angelo Totaro, MD angelo.totaro@policlinicogemelli.it PierFrancesco Bassi, MD pierfrancesco.bassi@unicatt.it U.O.C. Clinica Urologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma (Italy) Rossella De Leonardis, MD rosselladeleonardis95@gmail.com Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma (Italy) Salvatore Recupero, MD salvatoremarcorecupero@gmail.com U.O.C. Urologia, Ospedale Fatebenefratelli, Rome (Italy) Matteo Vittori, MD mvittori@gvmnet.it Department of Urology, San Carlo di Nancy Hospital, Rome (Italy) Giovanni Gambaro, MD giovanni.gambaro@univr.it Renal Unit, Department of Medicine, University-Hospital of Verona, Verona (Italy) Conflict of interest: The authors declare no potential conflict of interest.