Management of urinary stones: state of the art and future perspectives by experts in stone disease.

AIM: To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024. Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity. Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents. Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture). Diagnostic work up:  Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies. PROPHYLAXIS: Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most "high-risk" patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at "high-risk" forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched. FUTURE RESEARCH: Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters, assessment of stone composition by evaluation of endoscopic images and prediction of outcomes of stone treatments. The synergy between urologists, nephrologists, and scientists in basic kidney stone research will enhance the depth and breadth of investigations, leading to a more comprehensive understanding of kidney stone formation.

Correlation research demonstrates that an inflammatory diet is a risk factor for calcium oxalate renal stone formation.

BACKGROUND AND AIMS: Previous studies have demonstrated associations between the Dietary Inflammatory Index (DII®), an analytical tool which evaluates the inflammatory potential of the diet according to the pro- and anti-inflammatory properties of its components, and renal stone formation. However, these have not comprehensively addressed important parameters such as stone type, gender, DII scores in stone formers (SFs) and healthy controls (Cs) and associations of DII with urine and blood chemistries. These were adopted as the survey parameters for the present study, the purpose of which was to test whether the contributory role of an inflammatory diet on stone formation could be further confirmed. METHODS: 97 calcium oxalate (CaOx) SFs and 63 Cs, matched for age and gender each completed a semi-quantitative food frequency questionnaire from which nutrient composition was computed. These data were used to calculate the DII® score. To control the effect of energy intake, energy-adjusted DII scores were calculated per 1000 kcal consumed (E-DII™). A single blood sample and two consecutive overnight (8h) urine samples were collected from a subset (n = 59 SFs and n = 54 Cs) of the overall number of particpants (n = 160). These were analysed for renal stone risk factors. Data were analysed using regression models fit in R software. RESULTS: E-DII scores were found to fit the data better than DII, so they were used throughout. E-DII scores were significantly more positive (more pro-inflammatory) in SFs than in controls in the combined gender group (-0.34 vs. -1.73, p < 0.0001) and separately in males (-0.43 vs. -1.78, p = 0.01) and females (-0.26 vs. - 1.61, p = 0.05). In blood, a significant negative correlation was seen between E-DII and HDL cholesterol. In urine significant positive correlations were seen between E-DII and each of calcium (ρ = 0.25, p = 0.02), phosphate (ρ = 0.48, p < 0.001), magnesium (ρ = 0.33, p < 0.0001) and uric acid (ρ = 0.27, p = 0.004) concentrations. A significant negative correlation was seen between E-DII and urinary volume ρ = -0.27, p = 0.003). There was no correlation between E-DII scores and the relative supersaturations of urinary CaOx, calcium phosphate (brushite) and uric acid. CONCLUSIONS: Our findings provide hitherto unreported quantitative evidence in support of the notion that the diet of calcium oxalate renal stone patients is significantly more pro-inflammatory than that of healthy controls.

Fifty years of basic and clinical renal stone research: have we achieved major breakthroughs? A debate.

PURPOSE OF REVIEW: After 50 years of basic and clinical renal stone research, it is appropriate to evaluate whether breakthroughs have been achieved and if so, how they may be harnessed to combat stone disease therapeutically and prophylactically. RECENT FINDINGS: Regarding stone therapeutics and prophylaxis, recent innovative studies are sparse. Researchers have resorted to publishing articles derived from data mining. Stone incidence and prevalence have increased during the past 50 years, suggesting the absence of any major breakthroughs. However, new sciences and technologies have created fresh opportunities. Information technology stores huge epidemiological databases leading to identification of new risk factors. Genetic coding has prompted identification of monogenic diseases associated with urolithiasis. Genome-wide association studies in combination with epigenomics, transcriptomics, proteomics, and metabolomics are providing new insights. High-throughput and culture-independent techniques promise to define the impact of microbiome on stone formation while artificial intelligent techniques contribute to diagnosis and prediction of treatment outcomes. These technologies, as well as those which are advancing surgical treatment of stones represent major breakthroughs in stone research. SUMMARY: Although efforts to cure stones have not yielded major breakthroughs, technological advances have improved surgical management of this disease and represent significant headway in applied stone research.

Conflicts of interest and the risk of bias are inevitable in urolithiasis research.

This review examines data from stone conferences and research journals to assess whether justifiable concerns exist about possible bias in urolithiasis research and if so, how they can be minimized. Conflict of interest (COI) policies of two major urological congresses and three symposia dedicated to stone research were reviewed. Disclosure slides were viewed in webcasts and were evaluated for robustness and speaker compliance with respect to policy. Additionally, disclosure and COI policies of ten Science Citation Index (SCI)-approved journals were assessed and compared with actual declarations in published papers on urolithiasis. It was observed that disclosure and conflict declarations are frequently conflated in congresses and journals. Differences between the two ideologies appear to be ignored or unappreciated. Disclosures in the major urological meetings revealed a high percentage of financial relationships with industry. In dedicated stone conferences, more than two-thirds of speakers failed to display a declaration slide. Both scenarios generate questions about objectivity. Disclosure and COI statements in journals varied widely in format, detail and content. It is concluded that there exists a misinformed and incorrect perception in urolithiasis research that disclosure of potential COIs somehow validates a study as being objective and unbiased. Current policies and practices at conferences and in published papers create a setting in which concerns of bias prevail. Changes, including the establishment of a universal policy, insistence of independent and explicit declarations of disclosures and conflicts, implementation of sanctions for transgression and the introduction of intensive scrutiny by reviewers are required to minimize doubts.

Composition and inhibitory properties of endogenous urinary GAGS are different in subjects from two race groups with different occurrence rates of kidney stones: Pilot studies provide unique evidence in support of an inhibitory role for this group of compounds.

BACKGROUND: Calcium oxalate (CaOx) kidney stone disease is common in South African whites (W) but is rare in the black population (B). The possible role of endogenous urinary glycosaminoglycans (GAGs) has not been previously investigated in this context. AIM: To determine concentration, composition, structure and CaOx crystal-inhibiting properties of this group of compounds in ultrafiltered urine of healthy subjects from both groups. MATERIALS AND METHODS: GAGS were isolated from 24 h urine samples and were quantified and characterized by sequential precipitation, Bradford protein assay, high performance liquid chromatography, and anion exchange high performance chromatography. CaOx crystal inhibition was determined in ultrafiltered urinary fractions to which purified GAGS (PG) from each group (PGB and PGW) had been added. Nucleation, growth and aggregation were measured by Coulter particle counting, spectrophotometric assay and [14C]-oxalate deposition. RESULTS: Higher concentrations of chondroitin sulfate (CS) were found in PGB than in PGW. PGB inhibited crystallization to a greater extent than PGW. CONCLUSIONS: We attribute the stronger inhibitory effect of PGB to its higher content of CS and suggest that the superior inhibition of CaOx crystallization by PGB relative to PGW might be a contributory factor in accounting for the lower stone occurrence rate in B.

Seeking consistency for the role of urinary macromolecules and glycosaminoglycans in calcium oxalate crystallization processes pertaining to the risk of renal stone formation using a multi-faceted basic science approach.

BACKGROUND: The roles of urinary macromolecules (UMMs) in calcium oxalate (CaOx) renal stone formation have not been consistently established. AIM: To unravel these roles using a multi-faceted, multi-technique approach employing a wide range of experimental variables on a rotational basis in strategically chosen combinations. METHODS: Endogenous urinary glycosaminoglycans (GAGs) were investigated in fractions obtained after ultrafiltration of pooled human urine (HU). Exogenous GAGs (chondroitin sulphate, CS, and hyaluronic acid, HA) were studied in artificial (AU) and in individual HUs. Experiments were conducted in a batch crystallizer and in a mixed suspension, mixed product removal flow system. Crystallization was quantitatively followed using Coulter multisizer and flow cytometer techniques. Crystal aggregation in the presence and absence of exogenous CS and HA was measured by Zeta potential and crystal sedimentation. RESULTS: Total UMMs (endogenous) and individual GAGs (exogenous) consistently promoted CaOx crystallization and disaggregation. Evidence of UMM-UMM and UMM-solution synergistic effects was consistently observed for achieving modulation of crystallization processes. CONCLUSIONS: Total UMMs, the main modulatory component of which is GAGs, are promoters of CaOx crystal nucleation and inhibitors of CaOx crystal aggregation. These results allow researchers to disregard alternative roles that have been advocated in such studies.

Urine and stone analysis for the investigation of the renal stone former: a consensus conference.

The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places.

Comparison of Supersaturation Outputs from Different Programs and Their Application in Testing Correspondence with Kidney Stone Composition.

Introduction: Relative supersaturation (SS) for calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid (UA) has been used for assessing urinary crystallization and estimated by programs, including EQUIL, Joint Expert Speciation System (JESS), and Lithorisk. We compared outputs from these programs and their correspondence with stone composition. Materials and Methods: SS of CaOx, CaP, and UA, using EQUIL, JESS, and Lithorisk were calculated from stone-forming patients. Pearson correlation coefficients were used to ascertain the correspondence between the outputs. Fractional regression models evaluated the relationship between SS and the percentage of each compound in the stones. Results: Two hundred eleven patients were included. Pearson correlation coefficients for CaOx (r ≥ 0.96), CaP (r ≥ 0.99), and UA SS (r ≥ 0.99) showed a high correspondence between all programs. We observed a significant correspondence between CaOx SS and the percentage of CaOx dihydrate in the stone (p < 0.001), as well as between the percentage of brushite and apatite and CaP SS. UA SS showed the strongest correspondence with the percentage of UA in the stones (p < 0.001). Conclusions: Good correlation between EQUIL, JESS, and Lithorisk was observed and good correspondence with stone composition. The magnitude of the association demonstrated by fractional regression models supports evidence for applying SS in clinical practice.

The Efficacy of Polyunsaturated Fatty Acids as Protectors against Calcium Oxalate Renal Stone Formation: A Review.

In the pathogenesis of hypercalciuria and hyperoxaluria, n-6 polyunsaturated fatty acids (PUFAs) have been implicated by virtue of their metabolic links with arachidonic acid (AA) and prostaglandin PGE2. Studies have also shown that n-3 PUFAs, particularly those in fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-can serve as competitive substrates for AA in the n-6 series and can be incorporated into cell membrane phospholipids in the latter's place, thereby reducing urinary excretions of calcium and oxalate. The present review interrogates several different types of study which address the question of the potential roles played by dietary PUFAs in modulating stone formation. Included among these are human trials that have investigated the effects of dietary PUFA interventions. We identified 16 such trials. Besides fish oil (EPA+DHA), other supplements such as evening primrose oil containing n-6 FAs linoleic acid (LA) and γ-linolenic acid (GLA) were tested. Urinary excretion of calcium or oxalate or both decreased in most trials. However, these decreases were most prominent in the fish oil trials. We recommend the administration of fish oil containing EPA and DHA in the management of calcium oxalate urolithiasis.

Exploring the Potential Relationship Between Phytate Ingestion, Urinary Phytate Excretion, and Renal Stone Risk in a Unique Human Model: No Hard Evidence in Support of Phytate as a Stone Inhibitor.

OBJECTIVE: Dietary phytate (IP6) enjoys a reputation as an inhibitor of calcium renal stone formation, although there are very few human studies to support this notion. In South Africa, urolithiasis occurs in the white (W) but is rare in the black (B) population. We undertook this unique human model to further investigate the IP6 theory. METHODS: Healthy W and B males completed baseline food-frequency recall questionnaires. Dietary intake of IP6 was restricted for 18 days. An IP6 dietary supplement was ingested on days 15-18. Twenty-four-hour urinary phytate and other urinary components were determined. Relative supersaturations of calcium salts were calculated. The urinary metastable limit (MSL) of calcium oxalate (CaOx) and its crystallisation kinetics were determined experimentally. RESULTS: Habitual dietary intake of IP6 and its urinary excretion were significantly higher in B than in W (1650 ± 202 vs. 640 ± 134 mg/d, P = .0002 and 1.13 ± 0.12 vs. 0.75 ± 0.13 µM, P <.05, respectively). In B, urinary phytate decreased significantly after 15 days of IP6 restriction, but in W, its excretion remained constant. After supplementation, urinary IP6 increased significantly in both groups reaching levels commensurate with the baseline value in B. No significant differences occurred in B in any of the routine urinary risk factors throughout the trial. However, in W, urinary citrate excretion increased on day 18 relative to day 0. There were no significant intragroup or intergroup changes in relative supersaturation, metastable limit, or crystallization kinetics. CONCLUSIONS: Despite notable differences in the renal handling of ingested IP6, there were no changes in any of the well-established urinary risk factors for calcium renal stone formation in either of our uniquely different test groups. We conclude that, in the absence of hard evidence, claims that IP6 is a stone inhibitor remain unproven.

Successful urinary discrimination between calcium oxalate kidney stone patients and healthy subjects using 1 H NMR spectroscopy: Suggestion of a possible link to protein content.

Stone formation in the urinary tract is a multifactorial world-wide disease afflicting between 8 and 20% of population groups in different geographical locations. Discrimination between stone formers and healthy persons on the basis of urine composition remains a crucial goal among researchers. Since 1 H NMR is able to monitor the metabolic function of the kidney we applied it to the urine of 60 stone formers (34 females, 26 males) and 38 healthy persons (14 females, 24 males). Spectra were normalized relative to an internal standard and integrated over 37 consecutive regions. The resulting data were subjected to principal component and canonical discriminant analysis. Excellent discrimination between patient and controls for both genders was achieved, with all the data falling within the 95% confidence interval. The most important variables allowing for this inter-group separation correspond to those associated with protein signals. We therefore speculate that the discrimination between patients and controls may be due to the presence or absence of macromolecular stone promoters and/or inhibitors. This supports numerous in vitro studies demonstrating that urinary macromolecules play significant roles in stone formation and prevention. Our finding that 1 H NMR analysis of urine differentiates between stone formers and healthy persons represents an important breakthrough for rapid screening of individuals who are at risk for this disease.

Theoretical and laboratory investigations of the effects of hydroxyproline ingestion on the metabolic and physicochemical risk factors for calcium oxalate kidney stone formation in a small group of healthy subjects.

PURPOSE: Dietary hydroxyproline may be involved in the endogenous synthesis of oxalate. Glycolate, produced during the metabolism of hydroxyproline, may exert physicochemical effects on urinary calcium by virtue of its dihydroxycarboxylic acid structure. The aim of this study was to investigate these possible stone-risk scenarios. METHODS: We modelled the effect of different glycolic acid concentrations on ionized calcium (iCa2+) and relative supersaturation (RSS) of calcium oxalate (CaOx) using the program JESS. Thereafter, three healthy white males and two healthy black males ingested 30 g gelatin for 3 days. 24-h urines were collected at baseline and after completion of the protocol. Urines were analysed for physicochemical risk factors and for iCa2+ and glycolic acid. Speciation concentrations and RSS values were calculated. RESULTS: Theoretical modelling showed that binding between calcium and glycolate does not occur and that iCa2+ and RSS CaOx are unaffected. However, after ingestion of hydroxyproline, iCa2+ decreased significantly. Urinary pH and glycolate increased significantly. Oxalate excretion and RSS CaOx did not change CONCLUSIONS: We attribute the decrease in iCa2+ to increases in the concentrations of several Ca-phosphate species, the formation of which is due to the increase in pH. We speculate that the absence of an increase in oxalate excretion despite an increase in glycolate excretion may be due to the mixed racial composition of our test group in which some pathways may be preferred to others. Our findings alert stone researchers to the importance of measuring urinary pH in their workup of subjects and to select racially homogenous groups for investigation.

Potential thermodynamic and kinetic roles of phytate as an inhibitor of kidney stone formation: theoretical modelling and crystallization experiments.

Kidney stone formation is governed by thermodynamic (supersaturation) and kinetic (crystal nucleation, growth, aggregation) mechanisms. We adopted a dual theoretical and experimental approach to investigate the potential role of urinary phytate in this regard. Thermodynamic constants for eight protonated phytate species and seven calcium-phytate complexes were determined by potentiometry and incorporated into the speciation program JESS. Urine was collected from 16 heathy males and their urine compositions were used as input for JESS. Phytate concentration was varied during modelling. No statistically significant decreases in Ca2+ concentrations or in supersaturation values were predicted by JESS. Crystallization experiments were then performed in pooled urine. Endogenous phytate concentration was determined using a metal-dye assay. The pool was dosed with various concentrations of phytate to achieve final concentrations equivalent to those used for modelling. Experiments showed that phytate had no effects on Ca2+ concentrations (as predicted by our theoretical modelling), metastable limits or crystal nucleation and growth kinetics. However, crystal aggregation kinetics was inhibited. We speculate that HPhy-11, small amounts of which were revealed by modelling, may bind to crystal surfaces and inhibit aggregation. We conclude that phytate exerts a kinetic, but not a thermodynamic inhibitory effect on crystallization in urine.

Correction to: Different effects of γ-linolenic acid (GLA) supplementation on plasma and red blood cell phospholipid fatty acid composition and calcium oxalate kidney stone risk factors in healthy subjects from two race groups with different risk profiles pose questions about the GLA-arachidonic acid-oxaluria metabolic pathway: pilot study.

The authors would like to add the following paragraph in the acknowledgement section of the original version of the paper.

Correction to: Testing the dogma that total phospholipid fatty acid composition of blood plays a role in kidney stone pathogenesis, using a high-low risk human model: results from a pilot study.

The authors would like to add the following paragraph in the acknowledgement section of the original version of the paper.

Testing the dogma that total phospholipid fatty acid composition of blood plays a role in kidney stone pathogenesis, using a high-low risk human model: results from a pilot study.

Previous studies have suggested that ω-3 and ω-6 polyunsaturated fatty acid (PUFA) composition in plasma and red blood cell (RBC) total phospholipids plays a role in urolithiasis. Our aim was to test the robustness of this dogma by retrospectively comparing baseline profiles of these parameters in subjects from high- and low-stone-risk groups. The documented difference in stone occurrence in white (relatively common) (W) and black (rare) (B) subjects prompted us to select these groups as the high-low risk model for the study. Blood and urine samples were obtained from ten subjects in each group and were analysed for PUFAs and stone risk factors, respectively. Concentrations of linoleic acid (LA), eicosadienoic acid (EDA) and arachidonic acid (AA) in plasma and or/RBC total phospholipids were significantly higher in B. Differences in other PUFA profiles were also observed. There was no inter-group difference in AA/LA ratios. Urinary oxalate was significantly higher while urinary phosphate was significantly lower in B. We speculate that elevated AA in B might arise because of a possibly enhanced elongation of LA to EDA, as well as an enhanced ∆-8-desaturation of EDA to dihomo-gamma-linolenic acid (DGLA), which is the immediate precursor of AA. Alternatively, we speculate that the ∆-5-desaturation step of DGLA to AA might be more highly activated in this group. Irrespective of the mechanism, our observed inter-group differences in phospholipid PUFA composition are in conflict with previously published dogma which relates PUFA characteristics to high- and low-stone risk.

Short-Term Changes in Urinary Relative Supersaturation Predict Recurrence of Kidney Stones: A Tool to Guide Preventive Measures in Urolithiasis.

PURPOSE: Kidney stone disease is characterized by a relatively high rate of recurrence. In our study we analyzed the association between relative supersaturation and the risk of stone recurrence. Additionally, we examined the association between the risk of recurrence and changes in relative supersaturation and urinary composition after 1 week of medical treatment. MATERIALS AND METHODS: We performed a post hoc analysis of data from a previously published randomized controlled trial comparing the effect of 2 diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Baseline and followup 24-hour urine parameters were used to calculate the relative supersaturation of calcium oxalate, calcium phosphate and uric acid using the EQUIL2, JESS and LithoRisk computer programs. Cox models were used to calculate the estimated association between each baseline relative supersaturation, and 1-week changes and the risk of recurrence during followup. RESULTS: During a 5-year followup 35 patients (34%) experienced recurrence. A reduction in calcium oxalate relative supersaturation at 1 week was significantly associated with a lower risk of recurrence using the EQUIL2 calculation (for every 10% reduction from baseline HR 0.92, 95% CI 0.86-1.00, p = 0.044). However, there was no association for relative supersaturation calculated by other methods or for the relative supersaturation of other salts. Changes in the 24-hour urine excretion of citrate, potassium and magnesium were significantly associated with a risk of recurrence. CONCLUSIONS: In recurrent stone formers with hypercalciuria baseline values and changes in the relative supersaturation of calcium oxalate may be associated with the risk of recurrence. Changes in urinary citrate, potassium and magnesium following dietary intervention may also be predictive.

Different effects of γ-linolenic acid (GLA) supplementation on plasma and red blood cell phospholipid fatty acid composition and calcium oxalate kidney stone risk factors in healthy subjects from two race groups with different risk profiles pose questions about the GLA-arachidonic acid-oxaluria metabolic pathway: pilot study.

Fatty acid (FA) composition of phospholipids in plasma and red blood cells (RBC) can influence calciuria, oxaluria and renal stone formation. In this regard, the ratio of arachidonic acid (AA) and its precursor linoleic acid (LA) appears to be important. Administration of γ-linolenic acid (GLA) has been shown to increase the concentration of dihomo-gamma linoleic acid (DGLA) relative to AA indicating that it may attenuate biosynthesis of the latter. Such effects have not been investigated in race groups having difference stone occurrence rates. Black (B) and white (W) healthy males ingested capsules containing linoleic acid (LA) and GLA, for 30 days. Plasma and RBC total phospholipid (TPL) FA profiles, serum and 24 h urine biomarkers of hypercalciuria and urinary stone risk factors were determined on days 0 and 30. Data were tested for statistical significance using GraphPadInstat version 3.02. Concentration and percentage content of DGLA in plasma TPL increased in W but not in B. Arachidonic acid (AA) did not change in either group. There was no change in calcium excretion in either group but oxalate and citrate excretion increased in W. We suggest that elongation of GLA to DGLA may occur more rapidly than desaturation of DGLA to AA in W and that depressed activity of the enzyme elongase may occur in B. Calciuric and citraturic effects may be dependent on the quantity of LA or on the mass ratio of LA/GLA in the FA supplement. Questions about the mooted DGLA-AA-oxaluria pathway arise. We speculate that there exists a potential for using GLA as a conservative treatment for hypocitraturia. The observation of different responses in B and W indicates that such differences may play a role in stone formation and prevention.

Glycaemia and phosphatemia after oral glucose and maltitol ingestion in subjects from two different race groups: preliminary evidence of inter-race differences in metabolism and possible implications for urinary stone disease.

PURPOSE: Glucose (Glu) and maltitol (Mal) ingestion affect calciuria and phosphaturia. Renal phosphate leak involving hypophosphatemia is thought to be a mechanism. Inter-race differences in carbohydrate metabolism are known. We investigated the effects of Glu and Mal ingestion on glycaemia and phosphatemia in subjects from two race groups to better understand potential implications for nephrolithiasis. METHODS: Healthy black (B) (n = 8) and white (W) (n = 8) males followed a self-selected standardized diet for 7 days and a strictly controlled standardized diet on Day 8. After an overnight fast, subjects provided blood samples prior to and 30 min after ingestion of a randomly assigned solution of Glu or Mal. Blood Glu and serum phosphate were measured. Protocols were swapped after a 1-week washout period. RESULTS: Following Glu ingestion, glycaemia increased significantly in W (4.8 vs 6.2 mmol/l) but not in B (4.7 vs 5.3 mmol/l) while phosphatemia decreased significantly in B (1.16 vs 1.01 mmol/l) but not in W (1.24 vs 1.15 mmol/l). After Mal ingestion, glycaemia increased significantly in B (4.7 vs 5.2 mmol/l) but not in W (4.6 vs 5.9 mmol/l), while phosphatemia decreased significantly in W (1.24 vs 1.18 mmol/l) but not in B (1.17 vs 1.06 mmol/l). CONCLUSIONS: Our results suggest that enzymes which regulate glycolysis may be less active in B than in W, or expression of renal transcellular Glu transporters may be relatively inhibited in B. Effects on phosphatemia are carbohydrate- and race-dependent, thereby prohibiting speculation of a general algorithm linking these variables. Inter-race differences in metabolic handling of carbohydrates might impact on respective nephrolithiasis risk factors in such groups.