Three-dimensional computed tomography-based resection process map for robot-assisted partial nephrectomy: propensity score matching of a single-center retrospective study.

BACKGROUND AND OBJECTIVES: We aimed to examine the effect of preoperative three-dimensional (3D) computed tomography (CT)-based resection process map (RPM) imaging on the outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We retrospectively analyzed 177 patients (RPM group, n = 92; non-RPM group, n = 85) who underwent this surgery between November 2012 and April 2022. Patient-specific contrast-enhanced CT images were used to construct an RPM, a 3D representation of the kidney showing the planned tumor resection and a 5 mm safety margin. Outcome analyses were performed using propensity score matching. The primary endpoint was the trifecta achievement rate. RESULTS: We extracted 90 cases. The trifecta achievement rate showed no significant differences between the RPM (73.3%) and non-RPM groups (73.3%). However, the RPM group had fewer Grade 3 and higher complications (0.0% vs. 13.3%, p = 0.026). The da Vinci Xi (OR 3.38, p = 0.016) and tumor diameter (OR 0.95, p = 0.013) were independent factors affecting trifecta achievement in multivariate analysis. Using RPM imaging was associated with the absence of Grade 3 and higher perioperative complications (OR 5.33, p = 0.036) in univariate analysis. CONCLUSIONS: Using preoperative 3D CT-based RPM images before RAPN may not affect trifecta achievement, but may reduce serious complication occurrence by providing detailed information on tumor resection.

Using fosfomycin to prevent infection following ureterorenoscopy in response to shortage of cephalosporins: a retrospective preliminary study.

BACKGROUND: In 2019, the shortage of cefazolin led to the demand for cefotiam and cefmetazole exceeding the supply. The Department of Nephro-urology at Nagoya City University Hospital used fosfomycin as a substitute for perioperative prophylaxis. This retrospective preliminary study evaluated the efficacy of fosfomycin and cefotiam for preventing infections following ureterorenoscopy. METHODS: The study included 182 patients who underwent ureterorenoscopy between January 2018 and March 2021). Perioperative antibacterial treatment with fosfomycin (n = 108) or cefotiam (n = 74) was administered. We performed propensity score matching in both groups for age, sex, preoperative urinary catheter use, and preoperative antibiotic treatment. RESULTS: The fosfomycin and cefotiam groups (n = 69 per group) exhibited no significant differences in terms of patients' median age, operative duration, preoperative urine white blood cell count, preoperative urine bacterial count, and the rate of preoperative antibiotic treatment. In the fosfomycin and cefotiam groups, the median duration of postoperative hospital stay was 3 and 4 days, respectively; the median maximum postoperative temperature was 37.3 °C and 37.2 °C, respectively. The fosfomycin group had lower postoperative C-reactive protein levels and white blood cell count than the cefotiam group. However, the frequency of fever > 38 °C requiring additional antibiotic administration was similar. CONCLUSIONS: During cefotiam shortage, fosfomycin administration enabled surgeons to continue performing ureterorenoscopies without increasing the complication rate.

Defining a learning curve for urology trainees to achieve renal access without complications in endoscopic combined intrarenal surgery.

OBJECTIVES: There is a lack of data on the number of surgeries required for endoscopic combined intrarenal surgery (ECIRS). Accordingly, we aimed to identify the learning curve for ECIRS performed by multiple surgeons. METHODS: We included 296 patients who underwent ECIRS at our university hospital between 2016 and 2021. A learning curve for percutaneous nephrolithotomy side was calculated considering urology-resident surgeons. The learning curve was retrospectively analyzed for surgical time, renal puncture time, stone-free rate, and complications and corrected for age, body mass index, stone size, computed tomography value, cumulative number of surgeries, and stone location. RESULTS: This study included cases performed by 32 surgeons, including 30 residents and 2 attending surgeons. The median number of surgeries performed by the residents and attending surgeons prior to this study was 4.5 and 90, respectively. The median number of surgical procedures performed during the training period was seven. The surgical time of the residents decreased as the number of cases increased, reaching a median surgical time of 111 min for the attending surgeons after 16.4 cases. Renal puncture time was achieved in 20.1 cases. Complications related to renal access were observed in 13.0% (34 patients), Clavien-Dindo grade II in 1.9% (5 patients), and grade III or higher in 0.8% (2 patients). Comparing the first to fifth cases with the 21st and subsequent cases, the complication rate improved from 35% to 13%. CONCLUSION: Our study demonstrated that ECIRS training provided 16-20 cases with a learning curve to achieve acceptable surgical outcomes.

Maternal family history of urolithiasis is associated with earlier age of onset of stone disease.

PURPOSE: To evaluate the impact of detailed family history on the severity of disease and age of onset in patients with urolithiasis. METHODS: Prospectively collected data from a single institution between October 2015 and December 2020 were analyzed. Our primary endpoint was the number of patients experiencing at least one recurrent stone during the follow-up period. RESULTS: Of 1566 patients analyzed, 603 (39%) reported at least one family member with a history of stones. The percentage of patients experiencing at least one recurrent stone event was higher in patients with a family history of stones (38%) compared to those without a family history of stones (28%) over a median follow-up period of 8 months (p = 0.001). On multivariate analysis, the presence of any family history of urolithiasis increased risk of recurrent stone events (odds ratio [OR] 1.62, p < 0.001). The presence of both a first- and a second-degree relative with urolithiasis was associated with higher odds for a recurrent stone event (OR 2.17; p = 0.003) and a younger age of onset for stones, (OR 3.32; < 0.001). A maternal-side relative with stones conferred a higher odds ratio for younger age of first onset of stones (OR 2.93; p < 0.001). CONCLUSION: Any family history of kidney stone disease imparts an increased risk of recurrent stone event and an earlier age of onset for urolithiasis. The presence of both first- and second-degree relatives or a maternal-side relative with kidney stones may be a predictor for an earlier age of onset for urolithiasis.

An Update of In Vivo Application of Artificial Intelligence and Robotics for Percutaneous Nephrolithotripsy: Results from a Systematic Review.

PURPOSE OF REVIEW: Kidney puncture is a key step in percutaneous nephrolithotomy (PCNL). Ultrasound/fluoroscopic-guided access to the collecting systems is commonly used in PCNL. Performing a puncture is often challenging in kidneys with congenital malformations or complex staghorn stones. We aim to perform a systematic review to examine data on in vivo applications, outcomes, and limitations of using artificial intelligence and robotics for access in PCNL. RECENT FINDINGS: The literature search was performed on November 2, 2022, using Embase, PubMed, and Google Scholar. Twelve studies were included. 3D in PCNL is useful for image reconstruction but also in 3D printing with definite benefits seen in improving anatomical spatial understanding for preoperative and intraoperative planning. 3D model printing and virtual and mixed reality allow for an enhanced training experience and easier access which seems to translate into a shorter learning curve and better stone-free rate compared to standard puncture. Robotic access improves the accuracy of the puncture for ultrasound- and fluoroscopic-guided access in both supine and prone positions. The potential advantage robotics are using artificial intelligence to do remote access, reduced number of needle punctures, and less radiation exposure during renal access. Artificial intelligence, virtual and mixed reality, and robotics may play a key role in improving PCNL surgery by enhancing all aspects of a successful intervention from entry to exit. There is a gradual adoption of this newer technology into clinical practice but is yet limited to centers with access and the ability to afford this.

Clinical characteristics of Raoultella ornithinolytica bacteremia and antimicrobial susceptibility of Raoultellaornithinolytica.

Raoultella ornithinolytica (R. ornithinolytica) is a gram-negative rod that was considered related to Klebsiella oxytoca and was classified as R. ornithinolytica in 2001. R. ornithinolytica is known as a histamine-producing bacterium that causes mackerel poisoning. Although only few clinical cases of R. ornithinolytica infection in humans have been reported, the number of diagnosed cases is expected to increase owing to the advancements in identification methods. In the present study, we performed a retrospective analysis of cases of R. ornithinolytica infection detected at our hospital. From September 2019 to July 2021, 62 specimens positive for R. ornithinolytica were obtained after removing duplicates. The clinical courses of these cases were investigated retrospectively based on electronic medical records. Of the 62 specimens, 24 were sputum, 19 were urine, three were stool, six were blood, four were bile, and six were other specimens. All the six blood culture specimens in which R. ornithinolytica was detected were from male patients, and the causative diseases were cholangitis in four cases and complicated pyelonephritis in two cases. Of these, two patients with cholangitis succumbed to death due to the worsening of underlying cancer. Identification of R. ornithinolytica is reportedly difficult, and some instruments may misidentify it as Klebsiella oxytoca. The prognosis of R. ornithinolytica infection has been reported to be good when susceptible drugs are used. However, high mortality rates were also reported despite the use of these drugs, suggesting the need for further investigation of clinical features of R. ornithinolytica infection.

Hemoglobin and neutrophil levels stratified according to International Metastatic Renal Cell Carcinoma Database Consortium risk predict the effectiveness of ipilimumab plus nivolumab in patients with advanced metastatic renal cell carcinoma.

OBJECTIVE: To identify biomarkers associated with the effectiveness of ipilimumab plus nivolumab against advanced metastatic renal cell carcinoma. METHODS: We retrospectively analyzed the data of 75 patients treated with ipilimumab plus nivolumab at seven hospitals between August 2018 and April 2021. Prognostic biomarkers were assessed prior to initiating treatment with ipilimumab plus nivolumab. Median overall survival and progression-free survival were examined using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of disease progression. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors most important for predicting disease progression were determined using classification and regression tree analysis. RESULTS: Median overall survival and progression-free survival were longer in the intermediate IMDC risk group than in the poor IMDC risk group (overall: not reached vs. 18.3 months; progression-free: not reached vs. 13.5 months). The multivariate analysis identified poor IMDC risk as a risk factor for disease progression (hazard ratio 2.61, 95% confidence interval: 1.05-6.51). Based on the results of the classification and regression tree analysis, the cohort was divided into non-anemia, anemia + neutro-Low, and anemia + neutro-High groups. Median overall survival and progression-free survival were longer in the non-anemia and anemia + neutro-Low groups than in the anemia + neutro-High group (overall: not reached vs. 29.3 months vs. 4.3 months: progression-free: not reached vs. 29.0 months vs. 3.9 months). CONCLUSION: Hemoglobin and neutrophil levels may represent crucial biomarkers for predicting the effectiveness of ipilimumab plus nivolumab therapy in patients with renal cell carcinoma.

Elevated eosinophils proportion as predictor of immune-related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma.

OBJECTIVES: Ipilimumab and nivolumab treatment against advanced and metastatic renal cell carcinoma (RCC) causes severe and lethal immune-related adverse events (irAEs). Predicting irAEs might improve clinical outcomes, however no practical biomarkers exist. This study examined whether eosinophils could be effective biomarkers for ≥grade 2 irAEs in RCC. METHODS: We retrospectively analyzed 75 patients with RCC treated with ipilimumab and nivolumab between August 2018 and March 2021 in a multicenter study. Eosinophils were examined before and 2 weeks after treatment, and immediately after irAEs development. The optimal cut-off value for ≥grade 2 irAEs was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were undertaken to identify predictors of ≥grade 2 irAEs. RESULTS: Two weeks after treatment, eosinophils were significantly upregulated in patients who had experienced ≥grade 2 irAEs than in those who had not experienced irAEs (mean, 5.7% vs. 3.2%; p < 0.05). The optimal cut-off value for eosinophils against ≥grade 2 irAEs was 3.0% (area under the curve = 0.69). In multivariate analyses, an eosinophil level ≥ 3.0% was a risk factor for ≥grade 2 irAEs (odds ratio 4.18, 95% confidence interval 1.16-15.1). The eosinophil level 2 weeks after treatment was upregulated by the onset of any type of irAEs including endocrine, gastrointestinal, pulmonary and skin disorders. CONCLUSIONS: An increased eosinophil level 2 weeks after treatment might be an effective biomarker for ≥grade 2 irAEs in patients with RCC treated with ipilimumab and nivolumab.

A Randomized, Single-Blind Clinical Trial Comparing Robotic-Assisted Fluoroscopic-Guided with Ultrasound-Guided Renal Access for Percutaneous Nephrolithotomy.

PURPOSE: We conducted a randomized, single-blind clinical trial comparing the surgical outcomes of robotic-assisted fluoroscopic-guided (RAF group) and ultrasound-guided (US group) renal access in mini-percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: We recruited patients who underwent mini-PCNL with ureteroscopic assistance for large renal stones between January 2020 and May 2021. Block randomization was performed using online software. Automated needle target with x-ray was used for fluoroscopic-guided renal access in the RAF group. PCNL was performed by residents using a pneumatic lithotripsy system with 16.5Fr/17.5Fr tracts. The primary outcome was single puncture success, and the secondary outcomes were stone-free rate, complication rate, parameters measured during renal access and fluoroscopy time. RESULTS: In total, 71 patients (35 in US group, 36 in RAF group) were enrolled. No difference was seen in the single puncture success rate between the US and RAF groups (34.3% and 50.0%, p=0.2). In 14.3% cases in the US group vs no cases in the RAF group, the resident was unable to obtain access due to difficult targeting (p=0.025). The mean number of needle punctures was significantly fewer, and the median duration of needle puncture was shorter in the RAF group (1.83 vs 2.51 times, p=0.025; 5.5 vs 8.0 minutes, p=0.049, respectively). The stone-free rate at 3 months after surgery was 83.3% and 70.6% in the RAF and US groups, respectively (p=0.26). Multivariate analysis revealed that RAF guidance reduced the mean number of needle punctures by 0.73 times (p=0.021). CONCLUSIONS: RAF renal access in mini-PCNL may have further potential applications in this field.

Efficacy of ultrasound monitoring during extracorporeal shock wave lithotripsy: A multi-institutional propensity score-matched study.

OBJECTIVES: To evaluate the efficacy of ultrasound-assisted monitoring during shock wave lithotripsy for kidney and proximal ureteral calculi. METHODS: We retrospectively reviewed 535 patients who initially underwent shock wave lithotripsy for renal or proximal ureteral calculi between January 2012 and December 2021. The patients were divided into the X-ray group (n = 294) and ultrasound plus X-ray group (n = 241) based on the methods of targeting and monitoring calculi during shock wave lithotripsy. Because of differences in patient backgrounds, 1:1 propensity score-based matching was performed. The primary endpoint was the stone-free rate. RESULTS: In the final 1:1 matched cohort, 192 kidney stone cases and 162 proximal ureteral stone cases were analyzed. For patients with kidney calculi, the stone-free rate of the ultrasound plus X-ray group was significantly higher than that of the X-ray group (66.7% vs. 47.9%; P = 0.013). In the multivariate analysis, a large stone area (odds ratio 2.37), lower caliceal stones (odds ratio 3.37), and X-ray monitoring alone (odds ratio 0.49) were independently associated with shock wave lithotripsy failure. For patients with proximal ureteral stones, there was no significant difference in the stone-free rate between the ultrasound plus X-ray group and X-ray group (71.6% and 58.0%, respectively; P = 0.100). During the multivariate analysis, high computed tomography attenuation (odds ratio 2.31) and large stone area (odds ratio 2.18) were independent factors associated with residual stones after shock wave lithotripsy. CONCLUSIONS: Ultrasound-assisted monitoring may contribute to a higher stone-free rate for patients with kidney calculi, but not for those with proximal ureteral calculi.

Efficacy of fosfomycin in preventing infection after endoscopic combined intrarenal surgery in periods of limited supply of first- and second-generation cephalosporins.

OBJECTIVES: In March 2019, cefazolin was unavailable owing to difficulty in procuring the active ingredient. Furthermore, the supply of alternative drugs, such as cefotiam and cefmetazole, was limited. In the Department of Nephro-Urology, fosfomycin-based drugs are used as substitutes for cefazolin, which is a perioperative prophylactic antibacterial drug. Herein, we investigated the effectiveness of fosfomycin sodium and cefotiam in preventing infection after endoscopic combined intrarenal surgery as a retrospective preliminary study. METHODS: A total of 200 patients who underwent endoscopic combined intrarenal surgery at our department between August 2017 and January 2021 were included. The patients were administered cefotiam (n = 95) or fosfomycin (n = 105) as perioperative antibacterial agents. There were no significant differences in the median age or surgery time between the cefotiam and fosfomycin groups. Propensity score matching was performed to match the preoperative urine bacterial counts of both groups. Sixty-eight patients were selected from each group. RESULTS: The median postoperative hospital stay duration was 4 days for the two groups. The median maximum postoperative temperatures were 37.5 and 37.4°C, respectively. There were no significant differences between the maximum postoperative temperatures in both groups. Furthermore, there were no differences between the groups regarding the white blood cell counts, C-reactive protein levels, and aspartate aminotransferase and alanine aminotransferase levels postoperatively, as well as in terms of postoperative fever requiring additional antibiotics. CONCLUSIONS: During a period of difficulty in acquiring cefazolin and cefotiam, the use of fosfomycin allowed us to continue with the procedure without increased clinical complications.

Comparison of the safety and efficacy between the prone split-leg and Galdakao-modified supine Valdivia positions during endoscopic combined intrarenal surgery: A multi-institutional analysis.

OBJECTIVES: To evaluate the safety and efficacy of the prone split-leg and the Galdakao-modified supine Valdivia positions during endoscopic combined intrarenal surgery. METHODS: A multi-institutional, retrospective cohort study was conducted between January 2014 and December 2018. The stone-free and complication rates were compared between the prone split-leg and the Galdakao-modified supine Valdivia positions. Anatomical variations were evaluated using contrast-enhanced computed tomography imaging. RESULTS: In total, 118 and 100 patients underwent endoscopic combined intrarenal surgery in the prone split-leg and Galdakao-modified supine Valdivia positions, respectively. Renal punctures in the prone split-leg position were predominantly executed through the lower calyces (78.0%), whereas those in the Galdakao-modified supine Valdivia position were primarily performed through the middle calyces (64.0%; P < 0.001). Surgical duration in the prone split-leg position was significantly shorter than that in the Galdakao-modified supine Valdivia position (106.5 vs 126.0 min; P = 0.0459). There were no significant differences in the stone-free rate between the two positions (78.8% vs 76.0%; P = 0.629). Incidences of urinary tract injury (P = 0.033) and febrile urinary tract infection (23.7% vs 10.0%; P = 0.011) in the prone split-leg position were significantly higher than that in the Galdakao-modified supine Valdivia position. The tilt of the major renal axis was significantly greater in the prone position than the corresponding values in the oblique position (19.4° vs 8.5°; P = 0.019). CONCLUSIONS: Anatomical variation might result in the differences of renal puncture calyx. Endoscopic combined intrarenal surgery in the Galdakao-modified supine Valdivia position may bring equal stone-free status, with a longer surgical time but fewer complications including febrile urinary tract infection and urinary tract injury than the prone split-leg position.

Ureteroscopy-assisted puncture for ultrasonography-guided renal access significantly improves overall treatment outcomes in endoscopic combined intrarenal surgery.

OBJECTIVES: To assess the impact and availability of ureteroscopy-assisted puncture for percutaneous renal access during ultrasonography-guided miniaturized (mini)-endoscopic combined intrarenal surgery for large volume renal and/or proximal ureteral stones. METHODS: We conducted a multi-institutional retrospective cohort study for urolithiasis treatment. Data from a total of 313 patients who underwent mini-endoscopic combined intrarenal surgery to treat renal and/or ureteral stones between January 2016 and April 2020 were collected. We compared the outcomes between ultrasonography-guided mini-endoscopic combined intrarenal surgery with and without ureteroscopy-assisted puncture (ureteroscopy-assisted puncture(+) group [n = 126] and ureteroscopy-assisted puncture(-) group [n = 187] group, respectively). The primary outcome was requirement for additional surgical intervention. Secondary outcomes were stone-free rate, complications and total procedure, fluoroscopy, hospital stay, and postoperative ureteral stent placement durations. RESULTS: The ureteroscopy-assisted puncture(+) group had a lower additional surgical intervention rate and a higher stone-free rate immediately after and 3 months after surgery than the ureteroscopy-assisted puncture(-) group (5.6% vs 19.7%, P < 0.001; 82.5% vs 65.8%, P = 0.001; 59.5% vs 44.6%, P = 0.011). The median total procedure, fluoroscopy, and postoperative ureteral stent placement durations were 18 min, 3 min, and 5 days shorter, respectively, in the ureteroscopy-assisted puncture(+) group. Multivariate analyses showed that ureteroscopy-assisted puncture was associated with a decreased risk of additional surgical intervention (odds ratio 0.31, P = 0.011) and postoperative infection (odds ratio 0.34, P = 0.003) and decreased total procedure (estimate = -11 min; P = 0.011), fluoroscopy (estimate = -3 min; P = 0.034), and postoperative ureteral stent placement (estimate = -8 days; P = 0.011) durations. Female patients and those with smaller stone volumes or without hydronephrosis were identified as ideal ureteroscopy-assisted puncture candidates. CONCLUSIONS: Ureteroscopy-assisted puncture during mini-endoscopic combined intrarenal surgery could provide favorable surgical outcomes, especially in female patients without collecting system obstruction.

Fatty acid-binding protein 4 downregulation drives calcification in the development of kidney stone disease.

Nephrolithiasis is a significant source of morbidity, and its incidence has increased significantly over the last decades. This rise has been attributed to concurrent increasing rates of obesity, associated with a 3-time risk of developing NL. To date, the mechanism by which obesity is linked to stone formation has not been elucidated. We aimed to utilize a transcriptomics approach to discover the missing link between these two epidemic diseases. We investigated gene expression profiling of nephrolithiasis patients by two RNA-sequencing approaches: comparison between renal papilla tissue with and without the presence of calcified Randall's plaques (RP), and comparison between the papilla, medulla, and cortex regions from within a single recurrent stone forming kidney. Results were overlaid between differently expressed genes found in the patient cohort and in the severely lithogenic kidney to identify common genes. Overlay of these two RNA-sequencing datasets demonstrated there is impairment of lipid metabolism in renal papilla tissue containing RP linked to downregulation of fatty acid binding protein (FABP) 4. Immunohistochemistry of human kidney specimens and microarray analysis of renal tissue from a nephrolithiasis mouse model confirmed that FABP4 downregulation is associated with renal stone formation. In a FABP4 knockout mouse model, FABP4 deficiency resulted in development of both renal and urinary crystals. Our study revealed that FABP4 plays an important, previously unrecognized role in kidney stone formation, providing a feasible mechanism to explain the link between nephrolithiasis and metabolic syndrome.

Low bone mineral density is a potential risk factor for symptom onset and related with hypocitraturia in urolithiasis patients: a single-center retrospective cohort study.

BACKGROUND: Patients with urolithiasis have a lower bone mineral density (BMD) than those without stones, suggesting a potential correlation between calcium stone formation and bone resorption disorders, including osteopenia and osteoporosis. METHODS: To investigate the influence of BMD on clinical outcomes in urolithiasis, we performed a single-center retrospective cohort study to analyze patients with urolithiasis who underwent both BMD examination and 24-h urine collection between 2006 and 2015. Data from the national cross-sectional surveillance of the Japanese Society on Urolithiasis Research in 2015 were utilized, and additional data related to urinary tract stones were obtained from medical records. The primary outcome was the development of stone-related symptoms and recurrences during follow-up. A total of 370 patients were included in this 10-year study period. RESULTS: Half of the patients had recurrent stones, and the two-thirds were symptomatic stone formers. While only 9% of patients had hypercalciuria, 27% and 55% had hyperoxaluria and hypocitraturia, respectively. There was a positive correlation between T-scores and urinary citrate excretion. Both univariate and multivariate analyses demonstrated that female sex was associated with recurrences (odds ratio = 0.44, p = 0.007), whereas a T-score < - 2.5 and hyperoxaluria were associated with symptoms (odds ratio = 2.59, p = 0.037; odds ratio = 0.45, p = 0.01; respectively). CONCLUSION: These results revealed that low T-scores might cause symptoms in patients with urolithiasis, suggesting the importance of BMD examination for high-risk Japanese patients with urolithiasis having hypocitraturia.

Brown adipocytes and ß3-stimulant-induced brown-like adipocytes contribute to the prevention of renal crystal formation.

According to recent studies, kidney stones are associated with metabolic syndrome. We focused on brown adipocytes and ß3-stimulant-induced brown-like adipocytes to investigate how these adipocytes influence kidney stone disease. For the interscapular brown adipose tissue (iBAT) removal experiment, mice were subjected to either iBAT removal or sham operation (X-BAT group or sham group), and, after 3 wk, renal crystal deposition was induced by intra-abdominal injection of glyoxylate (GOX) for 6 days. For the ß3-stimulant experiment, mice were administered intra-abdominal injections of the ß3-stimulant (ß3-group) or saline (control group) for 6 days. Thereafter, renal crystal deposition was induced by intra-abdominal injection of GOX for 6 days. iBAT removal decreased the expression of Sod1 and increased that of chemokine (C-C motif) ligand 2 (Ccl2), EGF module-containing mucin-like receptor 1 (Emr1), and tumor necrosis factor (Tnf) in the kidneys. Renal crystal deposition was 2.06-fold higher in the X-BAT group than in the sham group. The ß3-stimulant caused differentiation of white adipocytes into brown-like adipocytes. In the kidneys of the ß3-group, the expression of Ccl2 and Emr1 decreased and that of Sod1 increased. Renal crystal deposition was 0.17-fold lower in the ß3-group than in the control group. In summary, iBAT removal promoted kidney inflammation and renal crystal formation. ß3-Stimulant-induced brown-like adipocytes reduced inflammation and improved antioxidant action in the kidneys, which suppressed renal crystal formation. This is the first report on the therapeutic role of brown and brown-like adipocytes for kidney stone formation.

Active Phagocytosis and Diachronic Processing of Calcium Oxalate Monohydrate Crystals in an in vitro Macrophage Model.

BACKGROUND: We previously discovered that renal macrophages (Mφs) phagocytose renal calcium oxalate monohydrate (COM) crystals. This study investigated the processing of engulfed crystals using in vitro models. METHODS: J774.1 mouse Mφs were exposed to COM crystals and observed for 24 h using polarized light microscopy with/without cytochalasin B (CB), an inhibitor of phagocytosis, to confirm active crystal phagocytosis. LysoTracker and immunohistochemical staining using transmission electron microscopy for lysosomal-associated membrane protein 1 were used to confirm engulfed COM crystal uptake into lysosomes. Diachronic tracking of specific Mφs was performed to capture the entire course of engulfed COM crystal processing using polarized light microscopy. Follow-up studies of fluorescent COM (f-COM) crystals using imaging cytometry were performed in the presence and absence of nigericin to dissipate the pH gradient in acidic organelles. RESULTS: Phagocytosis rates increased with COM density and were significantly lower in cells treated with CB (p < 0.01). We observed that engulfed crystals colocalized within lysosomes of the Mφs; moreover, diachronic observation indicated that the engulfed COM crystals were subdivided during Mφ division and eliminated by the 7th day of culture. Additionally, imaging cytometry showed that the fluorescence level of f-COM crystals in the nigericin (-) group after 48 h was significantly lower than that in the nigericin (+) group. CONCLUSIONS: This study confirmed active phagocytosis and lysosomal processing of engulfed COM crystals by Mφs. This discovery is expected to contribute to the development of future drugs that enhance the COM crystal phagocytic ability of Mφs.

Identification of new urinary risk markers for urinary stones using a logistic model and multinomial logit model.

BACKGROUND: Risk assessment for urinary stones has been mainly based on urinary biochemistry. We attempted to identify the risk factors for urinary stones by statistically analyzing urinary biochemical and inflammation-related factors. METHODS: Male participants (age, 20-79 years) who visited Nagoya City University Hospital were divided into three groups: a control group (n = 48) with no history of stones and two stone groups with calcium oxalate stone experience (first-time group, n = 22; recurring group, n = 40). Using 25-µL spot urine samples, we determined the concentrations of 18 candidate urinary proteins, using multiplex analysis on a MagPix® system. RESULTS: In univariate logistic regression models classifying the control and first-time groups, interleukin (IL)-1a and IL-4 were independent factors, with significantly high areas under the receiver operating characteristic curve (1.00 and 0.87, respectively, P < 0.01 for both). The multivariate models with IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) showed higher areas under the receiver operating characteristic curve (0.93) compared to that for the univariate model with IL-4. In the classification of control, first-time, and recurrence groups, accuracy was the highest for the multinomial logit model with IL-4, GM-CSF, IL-1b, IL-10, and urinary magnesium (concordance rate 82.6%). CONCLUSIONS: IL-4, IL-1a, GM-CSF, IL-1b, and IL-10 were identified as urinary inflammation-related factors that could accurately distinguish control individuals from patients with urinary stones. Thus, the combined analysis of urinary biochemical data could provide an index that more clearly evaluates the risk of urinary stone formation.

Helper T-cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques.

OBJECTIVES: To elucidate the difference in the lithogenesis of calcium oxalate and calcium phosphate stones. METHODS: Renal papillary tissues were obtained from 23 idiopathic calcium oxalate and seven calcium phosphate stone patients who had undergone endoscopic lithotripsy. Samples were individually collected from two different regions in each patient: the papillary mucosa containing Randall's plaque and mucosa not containing Randall's plaque. A microarray analysis was carried out on those tissues to compare their gene expression patterns. Furthermore, a causal pathway analysis comparing their differences was carried out. RESULTS: Cluster analysis showed that gene expression profiles of calcium phosphate stone patients markedly differed from those of calcium oxalate stone patients. Disease and function analysis showed that Randall's plaque-containing tissues of calcium phosphate stone-forming patients had significantly higher movement and migration of mononuclear leukocytes, and lower tendency toward infection and lymph node formation than Randall's plaque-containing tissues of calcium oxalate stone formers. Additional pathway analysis showed increased immune cell signaling in calcium phosphate formers, such as the helper T cell 1 and 2 pathways, which was confirmed by their messenger ribonucleic acid expression. CONCLUSIONS: The present results show the upregulation of helper T-cell signaling pathways in Randall's plaque-containing papillae in calcium phosphate, but not in calcium oxalate stone formers. Thus, helper T-cell immune responses and the related inflammatory processes seem to lead to the formation of calcium phosphate stones on Randall's plaques.