Identification of Resolvin D1 and Protectin D1 as Potential Therapeutic Agents for Treating Kidney Stones.

Intrarenal calcium oxalate (CaOx) crystals induce renal tubular epithelial cell (TEC) inflammatory and oxidative injury. This study is aimed at exploring potential therapeutic lipid components in kidney stones because lipids are involved in the development of several diseases and indicate the risk of kidney stones. Serum specimens were collected from 35 kidney stone patients and 35 normal controls. The lipid components in serum were measured, and differences were analyzed. The documented biological importance was comprehensively reviewed to identify lipids that differed significantly between the two groups to find potential agents associated with kidney stones. CaOx nephrocalcinosis mouse model was established to examine the therapeutic effects of specific lipids on CaOx deposition and CaOx-induced oxidative renal injury. Several lipids with significantly different levels were present in the serum of patients with stones and normal controls. Resolvin D1 (RvD1) (4.93-fold change, P < 0.001) and protectin D1 (PD1) (5.06-fold change, P < 0.001) were significantly decreased in the serum of patients with kidney stones, and an integrative review suggested that these factors might be associated with inflammatory responses, which is a crucial mechanism associated with stone damage. The administration of RvD1 and PD1 significantly inhibited kidney CaOx deposition and suppressed CaOx-induced renal tubular cell inflammatory injury and necrosis in a CaOx nephrocalcinosis mouse model. Furthermore, RvD1 and PD1 facilitated the expression of the oxidative indicator superoxide dismutase 2 (SOD2), inhibited NADPH oxidase 2 (NOX2) expression, and diminished intracellular reactive oxygen species (ROS) levels. This study preliminarily elucidated the role of lipids in kidney stones. The inhibitory effects of RvD1 and PD1 on oxidative damage induced by CaOx deposition provide a promising perspective for kidney stone treatment strategies.

Urinary tetrahydroaldosterone is associated with circulating FGF23 in kidney stone formers.

The spectrum of diseases with overactive renin-angiotensin-aldosterone system (RAS) or elevated circulating FGF23 overlaps, but the relationship between aldosterone and FGF23 remains unclarified. Here, we report that systemic RAS activation sensitively assessed by urinary tetrahydroaldosterone excretion is associated with circulating C-terminal FGF23. We performed a retrospective analysis in the Bern Kidney Stone Registry, a single-center observational cohort of kidney stone formers. Urinary excretion of the main aldosterone metabolite tetrahydroaldosterone was measured by gas chromatography-mass spectrometry. Plasma FGF23 concentrations were measured using a C-terminal assay. Regression models were calculated to assess the association of plasma FGF23 with 24 h urinary tetrahydroaldosterone excretion. We included 625 participants in the analysis. Mean age was 47 ± 14 years and 71% were male. Mean estimated GFR was 94 ml/min per 1.73 m2. In unadjusted analyses, we found a positive association between plasma FGF23 and 24 h urinary tetrahydroaldosterone excretion (ß: 0.0027; p = 4.2 × 10-7). In multivariable regression models adjusting for age, sex, body mass index and GFR, this association remained robust (ß: 0.0022; p = 2.1 × 10-5). Mineralotropic hormones, 24 h urinary sodium and potassium excretion as surrogates for sodium and potassium intake or antihypertensive drugs did not affect this association. Our data reveal a robust association of RAS activity with circulating FGF23 levels in kidney stone formers. These findings are in line with previous studies in rodents and suggest a physiological link between RAS system activation and FGF23 secretion.

Genetically Predicted Lifelong Circulating 25(OH)D Levels are Associated With Serum Calcium Levels and Kidney Stone Risk.

OBJECTIVE: To assess whether lifelong higher circulating 25-hydroxyvitamin D [25(OH)D] levels increase serum calcium levels and kidney stone disease (KSD) risk. METHODS: Summary data for KSD were obtained from the UK biobank genome-wide association study (6536 cases and 388 508 controls). We acquired summary data for 25(OH)D from 120 618 Europeans and another large-scale analysis (443 734 Europeans) for primary and secondary analysis. Random-effect inverse-variance weighted (IVW) and 7 additional sensitivity analyses were applied. Next, multivariable Mendelian randomization (MVMR) was performed by introducing data for serum calcium levels. RESULTS: Genetic predisposition for a 1-SD higher 25(OH)D level was associated with increased serum calcium levels (IVW; beta, 0.014; 95% CI, 0.010-0.018; P = 7.64E-10). Genetically predicted higher circulating 25(OH)D levels were associated with increased the risk of KSD, with per 1-SD odds ratios (ORs) of 1.47 (95% CI, 1.22-1.77; P = 5.49E-05) and 1.36 (95% CI, 1.03-1.80; P = 0.029) using the IVW and MVMR-Egger methods, respectively. In secondary analysis, similar results were found: 25(OH)D was associated with an increased risk of KSD in univariate Mendelian randomization (IVW; OR 1.71; 95% CI, 1.26-2.32; P = 0.001) and MVMR (OR 1.43; 95% CI, 1.16-1.76; P < 0.001) analyses. Most sensitivity analyses were consistent with the primary results, both for the primary and secondary analyses. CONCLUSIONS: Our study supports that higher genetically predicted lifelong circulating 25(OH)D levels are associated with higher calcium levels and KSD risk. The effects of 25(OH)D on KSD were partially attenuated-but still significant-in MVMR.

Higher Triglyceride-Glucose Index Is Associated With Increased Likelihood of Kidney Stones.

Aims: We aimed to assess the association between triglyceride-glucose (TyG) index and kidney stones in US adults. Methods: Data were obtained from the 2007-2014 National Health and Nutrition Examination Survey (NHANES). Participants aged ≥18 years who were not pregnant and provided complete data about TyG index and kidney stones were included in the analysis. Weighted multivariable regression analysis and subgroup analysis were preformed to estimate the independent relationship between TyG index and nephrolithiasis and recurrence. Results: A total of 20,972 participants were included with the mean TyG index of 8.71 ± 0.72. The prevalence rates of nephrolithiasis and recurrence were 9.30% and 3.17% overall and increased with the higher TyG index tertiles (Nephrolithiasis: Tertile 1, 6.98%; Tertile 2, 9.15%; Tertile 3, 11.98%, p < 0.01; Recurrence: Tertile 1, 1.84%; Tertile 2, 3.27%; Tertile 3, 4.50%, p < 0.01). Each unit increase in TyG index was associated with 12% and 26% higher odds of nephrolithiasis [odds ratio (OR) = 1.12; 95% CI: 1.02-1.22; p = 0.02] and recurrence (OR = 1.26; 95% CI: 1.08-1.46; p < 0.01). Interaction tests indicated no significant effect of gender, age, body mass index, hypertension, and diabetes on this association between TyG index and kidney stones. Conclusions: Higher TyG index was associated with an increased likelihood of nephrolithiasis and recurrence. Considering TyG index is a reliable indicator of insulin resistance (IR). Treatment and management of IR at a younger age may improve or alleviate the occurrence and recurrence of kidney stones.

An agnostic study of associations between ABO and RhD blood group and phenome-wide disease risk.

Background: There are multiple known associations between the ABO and RhD blood groups and disease. No systematic population-based studies elucidating associations between a large number of disease categories and blood group have been conducted. Methods: Using SCANDAT3-S, a comprehensive nationwide blood donation-transfusion database, we modeled outcomes for 1217 disease categories including 70 million person-years of follow-up, accruing from 5.1 million individuals. Results: We discovered 49 and 1 associations between a disease and ABO and RhD blood groups, respectively, after adjustment for multiple testing. We identified new associations such as a decreased risk of kidney stones and blood group B as compared to blood group O. We also expanded previous knowledge on other associations such as pregnancy-induced hypertension and blood groups A and AB as compared to blood group O and RhD positive as compared to negative. Conclusions: Our findings generate strong further support for previously known associations, but also indicate new interesting relations. Funding: Swedish Research Council.

The blood types that many people are familiar with, such as O-negative or AB-positive, are determined by two systems of antigens or proteins on the surface of the red blood cells: the ABO system and the RhD system. The ABO system types people's blood as A, B or AB if they have A and/or B antigens, or as type O if they have neither; while the RhD system provides the positive or negative label depending on whether or not the RhD antigen is present. Previous studies have found that some ABO blood groups are linked to increased risk and severity of a variety of conditions, including blood clots in veins, bleeding disorders and gastric ulcers. Despite the known influence that blood groups can have on disease, the connection has not been fully studied in many conditions, particularly for RhD status. Knowing the differences in risk and disease severity between different populations could help clinicians identify individuals that they need to monitor more closely and include blood group information in prediction models. To fill this gap in information, Dahlén et al. systematically looked for relationships between diseases and blood groups using records from 5.1 million people on a Swedish national blood donation-transfusion database. Examining 1,217 disease categories revealed that the vast majority did not appear to have a connection to either the ABO or RhD systems of classifying blood. However, the analysis identified 49 diseases with links to ABO blood types and one linked to RhD status. One notable finding was that people with blood group B have an decreased risk of kidney stones. The distribution of blood groups varies significantly around the world, so this relationship between disease and blood group may in part explain regional differences in disease occurrence. In the future, identifying relationships with blood groups may help to better understand the underlying biological mechanisms of diseases and lead to new avenues of research.

Sex Differences of Kidney Stone Urine Risk Factors after Roux-en-Y Gastric Bypass.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) is a bariatric surgical procedure that is associated with higher risk of kidney stones after surgery. We examined urine composition in 18 men and women before and after RYGB to examine differences in kidney stone risk. METHODS: Three 24-h urine collections were performed before and 1 year after RYGB. We analyzed mean urinary values for pre- and post-RYGB collections and compared men and women. RESULTS: Seven men and eleven women completed pre- and post-RYGB urine collections. Pre-RYGB, men had higher calcium oxalate supersaturation (CaOx SS) (7.0 vs. 5.0, p = 0.04) compared with women. Post-RYGB, women had higher urine CaOx SS (13.1 vs. 4.6, p = 0.002), calcium phosphate supersaturation (1.04 vs. 0.59, p = 0.05), and lower urine volumes (1.7 vs. 2.7L, p < 0.001) compared with men. DISCUSSION/CONCLUSION: There are important differences in urine composition by sex that may contribute to higher kidney stone risk in women after RYGB compared with men.

Gender differences in acute stone admissions - should we have a lower threshold for treatment in female patients?

OBJECTIVES: To examine the gender-related differences in the presentation, management and outcomes of patients admitted with acute renal colic at our institution. PATIENTS AND METHODS: A retrospective analysis of 231 consecutive patients requiring inpatient admission for acute renal colic between October 2015 and March 2018. For each admission, data on demographics, admission blood results, stone characteristics, management and outcomes were collected. Differences between genders were compared using the chi-squared and Student's t-test. RESULTS: Gender distribution was 35% female: 65% male. There was no significant difference in age, American Society of Anesthesiologists Physical Status Classification grade or history of diabetes. Women had a higher admission C-reactive protein level (89.3 vs 32.9 mg/L, P < 0.001) and neutrophil count (10.0 vs 8.8 × 109 /L, P = 0.04) than men. They also had more positive cultures (34.1% vs 6.0%, P < 0.001) and were more likely to require percutaneous nephrostomy insertion (9.8% vs 0.7%, P = 0.005). Women had more intensive therapy unit (ITU) admissions (12.2% vs 0.6%, P < 0.001) and longer lengths of stay (4.4 vs 1.8 days, P < 0.001) than men. There was no mortality in our series. CONCLUSION: In the present study, women admitted with acute renal colic were more likely to have an associated infection than men and require rapid decompression. Although there was no difference in mortality, women experienced greater morbidity as evidenced by the higher rate of ITU admissions and longer length of stay. These differences are important to consider when assessing the suitability of conservative management for female patients.

Generation and characterization of a novel rat model of primary hyperoxaluria type 1 with a nonsense mutation in alanine-glyoxylate aminotransferase gene.

Primary hyperoxaluria type 1 (PH1) is a severe inherited disorder caused by a genetic defect in alanine-glyoxylate aminotransferase (AGXT), which results in recurrent urolithiasis and renal failure. Animal models that precisely reflect human PH1 phenotypes are lacking. We aimed to develop a novel PH1 rat model and study the mechanisms involved in PH1 deterioration. One cell stage Sprague-Dawley embryos were injected with the CRISPR/Cas9 system to introduce a Q84X mutation in Agxt. Liver tissues were harvested to determine Agxt expression. Urine oxalate, crystals, and electrolyte levels in AgxtQ84X and wild-type (WT) littermates were evaluated. Kidney tissues were used for Pizzolato staining and kidney injury evaluation. Data showed that Agxt mRNA and protein were absent in AgxtQ84X rats. At 4 and 24 wk, AgxtQ84X rats displayed 2.1- and 2.9-fold higher urinary oxalate levels, respectively, compared with WT littermates. As a result, calcium oxalate (CaOx) crystals in urine were revealed in all AgxtQ84X rats but in none of the WT rats. We also observed bladder stones in 36.4% of AgxtQ84X rats, of which 44.4% had renal CaOx deposition. Moreover, the elevated serum urea and creatinine levels indicated the impaired renal function in AgxtQ84X rats. Further investigation revealed significantly increased expression of inflammation-, necroptosis-, and fibrosis-related genes in the kidneys of AgxtQ84X rats with spontaneous renal CaOx deposition, indicating that these pathways are involved in PH1 deterioration. Collectively, these results suggest that this rat model has broad applicability in mechanistic studies and innovative therapeutics development for PH1 and other kidney stone diseases.NEW & NOTEWORTHY Primary hyperoxaluria type 1 is a severe inherited disorder that results in recurrent urolithiasis and renal failure. We generated an alanine-glyoxylate aminotransferase (Agxt)Q84X nonsense mutant rat model that displayed an early onset of hyperoxaluria, spontaneous renal CaOx precipitation, bladder stone, and kidney injuries. Our results suggest an interaction of renal CaOx crystals with the activation of inflammation-, fibrosis-, and necroptosis-related pathways. In all, the AgxtQ84X rat strain has broad applicability in mechanistic studies and the development of innovative therapeutics.

Oxalobacter formigenes reduce the risk of kidney stones in patients exposed to oral antibiotics: a case-control study.

This is the first prospective study to investigate the association between kidney stones, bone mineral density, serum testosterone, colon cancer and O. formigenes colonization. 40 kidney stone patients and 85 controls were enrolled. O. formigenes colonization was established. BMD was examined from T- and Z-scores using dual energy absorptiometry. O. formigenes was found in 28 of 40 cases and 80 of 85 controls. BMD was significantly reduced in patients (p < 0.05). The evaluation revealed a significant association between lowered O. formigenes colonization and low testosterone. Urinary calcium and oxalates levels were greater in patient. Serum testosterone and urinary citrate concentrations was reduced in patients with a significant difference. Also an association between O. formigenes and colon cancer was noted. Absence of O. formigenes might stand for a pathogenic factor in calcium oxalate stone, low bone mineral density, low testosterone levels and also colon cancer, when antibiotics are prescribed generously.

Polyfluoroalkyl chemicals and the risk of kidney stones in US adults: A population-based study.

The potential nephrotoxicity of polyfluoroalkyl chemicals (PFCs) have received extensive attention. However, the relationship between PFCs and the risk of kidney stones remain unclear. This study aimed to examine the level of PFCs in the US population and its relationship with the risk of kidney stones. We investigated the serum levels of six PFCs in 8453 adult participants (≥20 years) from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016, including perfluorodecanoic acid (PFDE), perfluorohexane sulfonic acid (PFHS), 2-(N-methyl-perfluorooctane sulfonamido) acetate (MPAH), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUA), and perfluorododecanoic acid (PFDO). Logistic regression model was used to evaluate the correlation between PFCs and kidney stones. Of the 8453 participants, 787 self-reported a history of kidney stones. After adjusting for gender, age, race, education, marital status, body mass index (BMI), hypertension, diabetes and estimated glomerular filtration rate (eGFR), we found that total PFCs and PFHS were positively correlated with the risk of kidney stones. Compared with the lowest tertile, the odds ratios with 95% confidence intervals (CI) with increasing tertiles were 1.30 (95% CI,1.08-1.59, p = 0.007) and 1.25 (95 CI%,1.00-1.52, p = 0.024) for total PFCs and 1.24 (95 CI%,1.03-1.51, p = 0.032), and 1.35 (95 CI,1.10-1.68, p = 0.005) for PFHS. Our study shows that total PFCs and PFHS were associated with an increased risk of kidney stones.

A different perspective on the filtration barrier after kidney stone formation: An immunohistochemical and biochemical study.

The aim of this study is to investigate whether the filtration barrier is affected by experimental kidney stone formation. Thirty-two rats divided into 4 equally groups (n = 8) at random. Group I control; Group II 1% ethylene glycol; Group III 1% Ethylene glycol + 0.25% Ammonium chloride; Group IV 1% Ethylene glycol + 0.5% Ammonium chloride group. Tissues applied hematoxylin-eosin, periodic-acid-Schiff, Pizzolato's staining. Immunohistochemically stained with integrin α3ß1, type IV collagen, laminin, nephrin, CD2-associated protein (CD2AP) and podocin to show the filtration barrier structure. The TUNEL method was used for apoptosis. The amount of calcium, magnesium, creatinine and uric acid in urine and blood samples, also urine microprotein determined. Stones were formed in all experimental groups. Urine calcium, creatinine, uric acid levels decreased, magnesium levels were not changed. No statistically significant change was observed in blood serum results and TUNEL analysis. Immunohistochemical results showed an increase in nephrin, podocin, CD2AP, laminin and a decrease in integrin α3ß1 and type IV collagen. Consequently, there is an increase in the expression densities of the proteins incorporated in the structure to prevent loss of functionality in the cellular part supporting the structure against a weakening of the basement membrane structure in the glomerular structure in which urine is filtered.

Utility of blood tests in screening for metabolic disorders in kidney stone disease.

OBJECTIVES: To determine the clinical utility of blood tests as a screening tool for metabolic abnormalities in patients with kidney stone disease. SUBJECTS AND METHODS: Clinical and biochemical data from 709 patients attending the Oxford University Hospitals NHS Foundation Trust for assessment and treatment of kidney stones were prospectively collected between April 2011 and February 2017. Data were analysed to determine the utility of serum calcium, parathyroid hormone (PTH), urate, chloride, bicarbonate, potassium and phosphate assays in screening for primary hyperparathyroidism, normocalcaemic hyperparathyroidism, hyperuricosuria, distal renal tubular acidosis (dRTA) and hypercalciuria. RESULTS: An elevated serum calcium level was detected in 2.3% of patients. Further investigations prompted by this finding resulted in a diagnosis of primary hyperparathyroidism in 0.2% of men and 4.6% of women for whom serum calcium was recorded. An elevated serum PTH level in the absence of hypercalcaemia was detected in 15.1% of patients. Of these patients, 74.6% were vitamin D-insufficient; no patients were diagnosed with normocalcaemic hyperparathyroidism. Hyperuricosuria was present in 21.6% of patients and hypercalciuria in 47.1%. Hyperuricaemia was not associated with hyperuricosuria, nor was hypophosphataemia associated with hypercalciuria. No patient was highlighted as being at risk of dRTA using serum chloride and bicarbonate as screening tests. CONCLUSION: This study indicates that individuals presenting with renal calculi should undergo metabolic screening with a serum calcium measurement alone. Use of additional blood tests to screen for metabolic disorders is not cost-effective and may provide false reassurance that metabolic abnormalities are not present. A full metabolic assessment with 24-h urine collection should be undertaken in recurrent stone formers and in those at high risk of future stone disease to identify potentially treatable metabolic abnormalities.

Analysis of Primary Hyperparathyroidism Screening Among US Veterans With Kidney Stones.

Importance: Approximately 3% to 5% of patients with kidney stones have primary hyperparathyroidism (PHPT), a treatable cause of recurrent stones. However, the rate of screening for PHPT in patients with kidney stones remains unknown. Objectives: To estimate the prevalence of parathyroid hormone (PTH) testing in veterans with kidney stones and hypercalcemia and to identify the demographic, geographic, and clinical characteristics of veterans who were more or less likely to receive PTH testing. Design, Setting, and Participants: This cohort study obtained Veterans Health Administration (VHA) health records from the Corporate Data Warehouse for veterans who received care in 1 of the 130 VHA facilities across the United States from January 1, 2008, through December 31, 2013. Historical encounters, medical codes, and laboratory data were assessed. Included patients had diagnostic or procedural codes for kidney or ureteral stones, and excluded patients were those with a previous serum PTH level measurement. Data were collected from January 1, 2006, to December 31, 2014. Data analysis was conducted from June 1, 2019, to January 31, 2020. Exposures: Elevated serum calcium concentration measurement between 6 months before and 6 months after kidney stone diagnosis. Main Outcomes and Measures: Proportion of patients with a serum PTH level measurement and proportion of patients with biochemical evidence of PHPT who underwent parathyroidectomy. Results: The final cohort comprised 7561 patients with kidney stones and hypercalcemia and a mean (SD) age of 64.3 (12.3) years. Of these patients, 7139 were men (94.4%) and 5673 were white individuals (75.0%). The proportion of patients who completed a serum PTH level measurement was 24.8% (1873 of 7561). Across the 130 VHA facilities included in the study, testing rates ranged from 4% to 57%. The factors associated with PTH testing included the magnitude of calcium concentration elevation (odds ratio [OR], 1.07 per 0.1 mg/dL >10.5 mg/dL; 95% CI, 1.05-1.08) and the number of elevated serum calcium concentration measurements (OR, 1.08 per measurement >10.5 mg/dL; 95% CI, 1.06-1.10) as well as visits to both a nephrologist and a urologist (OR, 6.57; 95% CI, 5.33-8.10) or an endocrinologist (OR, 4.93; 95% CI, 4.11-5.93). Of the 717 patients with biochemical evidence of PHPT, 189 (26.4%) underwent parathyroidectomy within 2 years of a stone diagnosis. Conclusions and Relevance: This cohort study found that only 1 in 4 patients with kidney stones and hypercalcemia were tested for PHPT in VHA facilities and that testing rates varied widely across these facilities. These findings suggest that raising clinician awareness to PHPT screening indications may improve evaluation for parathyroidectomy, increase the rates of detection and treatment of PHPT, and decrease recurrent kidney stone disease.

Glycemic Status, Insulin Resistance, and the Risk of Nephrolithiasis: A Cohort Study.

RATIONALE & OBJECTIVE: The effect of glycemic status on nephrolithiasis risk remains controversial. This study sought to examine the association of glycemic status and insulin resistance with incident nephrolithiasis. STUDY DESIGN: A retrospective cohort study. SETTING & PARTICIPANTS: 278,628 Korean adults without nephrolithiasis who underwent a comprehensive health examination between 2011 and 2017. EXPOSURES: Glucose level, glycated hemoglobin level, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). OUTCOME: Nephrolithiasis ascertained using abdominal ultrasound. ANALYTICAL APPROACH: A parametric proportional hazard model was used to estimate adjusted HRs and 95% CIs. We explored prespecified potential sex differences in the association of glycemic status and incident nephrolithiasis. RESULTS: During a median follow-up of 4.2 years, 6,904 participants developed nephrolithiasis. Associations between levels of glycemic status and incident nephrolithiasis were examined separately in men and women (P for interaction = 0.003). Among men, multivariable-adjusted HRs for incident nephrolithiasis comparing glucose levels of 90-99, 100-125, and ≥ 126 mg/dL were 1.10 (95% CI, 1.01-1.19), 1.11 (95% CI, 1.02-1.21), and 1.27 (95% CI, 1.10-1.46), respectively, while HRs for incident nephrolithiasis comparing glycated hemoglobin levels of 5.7%-5.9%, 6.0%-6.4%, and 6.5%-<5.7% were 1.03 (95% CI, 0.96-1.10), 1.18 (95% CI, 1.07-1.31), and 1.20 (95% CI, 1.06-1.37), respectively. The HR for incident nephrolithiasis comparing the highest HOMA-IR quintile to the lowest quintile was 1.18 (95% CI, 1.06-1.31). Among women, no apparent association was found between glycemic status and nephrolithiasis risk. LIMITATIONS: Glucose tolerance testing and computed tomography assessment for nephrolithiasis were not available. CONCLUSIONS: Higher glycemic values, even within the normoglycemic range, and HOMA-IR were positively associated with increased risk for nephrolithiasis, associations that were only observed among men. Insulin resistance and hyperglycemia may contribute to the development of nephrolithiasis, particularly among men.

The effect of an oral sodium phosphate load on parathyroid hormone and fibroblast growth factor 23 secretion in normo- and hypercalciuric stone-forming patients.

BACKGROUND & AIMS: Abnormalities of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) secretion may cause calcium-phosphate (Ca-P) metabolism disorders in nephrolithiasis. Post-phosphate-load alterations in serum Ca, P and PTH, phosphaturia and calciuria enable monitoring hormonal regulation of Ca-P homeostasis. Our study aimed to determine differences in: 1.selected Ca-P metabolism parameters between healthy and kidney-stone-forming individuals, 2.PTH and FGF23 secretion induced by sodium-phosphate-load(NaP-load) in patients with/without hypercalciuria, 3.secretion of Ca-P related hormones in patients with low and normal/high serum concentrations of 25-hydroxyvitamin D3 (25OHD3). METHODS: Sodium phosphates NaH2PO4/Na2HPO4-100mmol were administered orally for five days in 19 hypercalciuric [urinary Ca(U-Ca) 6.5 ± 1.7 mmol/d]-HSF, 35 normocalciuric (2.5±1 mmol/d)-NSF stone-forming patients and 19 controls (U-Ca 2.5 ± 1.4 mmol/d)-CG. On days 1 and 5 PTH-,FGF23-,Ca-,P were determined before and after NaP-load. The areas under PTH, FGF23 curves (AUC) were calculated. U-Ca, urinary phosphate (U-P) and sodium (U-Na) were also determined. RESULTS: Following NaP-load, patients and controls exhibited expected alterations in Ca-P homeostasis. Despite changes in phosphate and PTH, no differences in FGF23 concentrations were observed. Patients differed from controls in having higher AUCPTH, calciuria and natriuresis, taking longer for PTH and P to normalize and lack of correlation between AUCPTH and phosphaturia. Post-NaP-load hypocalciuric effect of PTH secretion in NSF was less pronounced than in CG. In the HSFs, the hypocalciuric effect was more pronounced than in NSFs, but insufficient to correct hypercalciuria. In all stone-formers with low 25OHD3 concentrations, the AUCFGF23 was significantly increased on first (1215 ± 605vs766 ± 315 p = 0.0457) and fifth days (1211 ± 641vs777 ± 299 p = 0.041) of NaP-load, compared to normal/high 25OHD3-patients. Hypercalciuric patients with low 25OHD3 concentrations had greater AUCPTH5 than those with normal/high 25OHD3 (1005 ± 401vs835 ± 220 p = 0.0341). CONCLUSIONS: Compared to controls, kidney-stone-forming patients exhibited enhanced PTH secretion after NaP-load. The HSFs showed a more pronounced hypocalciuric effect than NSFs, but insufficient to correct hypercalciuria. In hypercalciuric stone-formers with low 25OHD3, FGF23 engagement in hyperphosphatemia reduction increased.

Papillary vs non-papillary access during percutaneous nephrolithotomy: Retrospective, match-paired case-control study.

OBJECTIVE: The most crucial steps of percutaneous nephrolithotomy (PCNL) are the percutaneous access and dilation of the access route. Recent literature suggests that papillary access to renal calyx is the accepted method. Despite this rule, we do not always make papillary puncture and we puncture wherever we can to achieve stone-free status and reduce unnecessary access. In this study, we present our results with papillary vs non-papillary access in patients with a kidney stone. MATERIAL AND METHODS: Two hundred and seven patients with non-papillary access and 69 patients with papillary access who had similar demographics (age, body mass index (BMI), stone size) were selected with pair match analysis (3:1). Preoperative and postoperative data were collected from the patient's chart. Operative time (from starting surgery to nephrostomy tube), drop-in hematocrit level, transfusion rate, duration of hospital stay, perioperative and postoperative complications (Clavien-Dindo Classification) and stone-free status (no or < 3 mm residual stone) were also evaluated in both groups. RESULTS: The mean operative time was similar in between two groups. The mean hematocrit decreases not differ between the two groups (p = 0.56). In papillary group, only 2 patients (3.2%) required transfusion and only one patient (1.4%) in the non-papillary group had a transfusion with no statistically significant difference (p = 0.43). The overall complication rates were 7.1% in the papillary group and 7.2% in the non-papillary group (p = 0.89). Postoperative mean creatinine level was similar between the two groups.  Conclusions: In this study, we found that non-papillary access is a feasible option for PCNL in the terms of stone-free status and complication rates.

Comparative metabolism of schaftoside in healthy and calcium oxalate kidney stone rats by UHPLC-Q-TOF-MS/MS method.

Schaftoside is a flavone-C-glycoside isolated from Herba Desmodii Styracifolii with valuable anti-kidney stones efficacies. In this study, a six-step strategy was first developed to detect and identify the metabolites in plasma, urine, bile, feces and rat intestinal bacteria samples of healthy and model rats administrated with schaftoside using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). The number and the relative peak area of metabolites in healthy rats and model rats were compared, and it was noticed that metabolites in bio-samples of healthy and model rats both had obvious differences. A total of 28 metabolites of schaftoside in healthy rats and 30 metabolites in model rats were initially indentified. The relative peak area of the parent drug and every metabolite in model rat plasma samples were larger than those in healthy rat plasma. Those metabolites with high blood concentrations might be beneficial for the treatment of calcium oxalate stones in the kidney. The results are valuable and important for understanding the metabolic process of schaftoside in clinical application, and especially the metabolism study in calcium oxalate kidney stone model rats could provide a beneficial reference for the further search of effective substances associated with the treatment of kidney stones.

Postoperative renal functional changes assessed by 99mTc-DTPA scintigraphy and predictive factors after miniaturized percutaneous nephrolithotomy and retrograde intrarenal surgery: An observational 1-year follow-up study.

Purpose: We evaluated the comparative effect of miniaturized percutaneous nephrolithotomy (mini-PCNL) and retrograde intrarenal surgery (RIRS) on perioperative kidney function by use of diethylenetriamine penta-acetic acid (99mTc-DTPA) scintigraphy and identified significant predictors associated with deterioration or amelioration of renal function after surgery. Materials and Methods: All 70 patients who underwent mini-PCNL or RIRS between 2012 and 2016 were monitored by 99mTc-DTPA scintigraphy preoperatively. Patients with abnormal renal function were monitored from 3 to 12 months postoperatively. Logistic regression analyses were conducted to estimate the predictors of aggravated renal dysfunction and improvement. Results: The difference in preoperative renal function between the contralateral and the operative side was >10% in 57 patients (81.4%). Among those in the group with abnormal renal function, 40 (70.2%), 10 (17.5%), and 7 (12.3%) patients showed stability, deterioration, and improvement in renal function at postoperative year 1, respectively. Functional changes did not differ according to the type of surgery. A high level of serum creatinine preoperatively (p=0.060) and a history of previous stone procedures (p=0.051) showed borderline significance for prediction of deterioration in renal function. Conclusions: RIRS and mini-PCNL had similar effects and favorable outcomes on renal function during a 1-year follow-up period. High baseline serum creatinine levels and a history of procedures warrant careful attention.