Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate.

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. METHODS: We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 ml/min per 1.73m². The outcomes were CKD-related complications (hypertension, anaemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. RESULTS: The study included 49 558 participants (50.3% women, 49.7% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modelling eGFR as a natural spline revealed varied significance thresholds between sexes for anaemia and hyperparathyroidism. Additionally, the eGFR-hyperphosphatemia association was more pronounced in men. We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR in women). CONCLUSIONS: Research shows sex disparities in most CKD-related complications. Men develop anaemia and hyperparathyroidism earlier, women show steeper anaemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

24-Hour Urinary Chemistries and Kidney Stone Risk.

RATIONALE & OBJECTIVE: Most previous studies of the relationship between urinary factors and kidney stone risk have either assumed a linear effect of urinary parameters on kidney stone risk or implemented arbitrary thresholds suggesting biologically implausible "all-or-nothing" effects. In addition, little is known about the hierarchy of effects of urinary factors on kidney stone risk. This study evaluated the independent associations between urine chemistries and kidney stone formation and examined their magnitude and shape. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We analyzed 9,045 24-hour urine collections from 6,217 participants of the Health Professionals Follow-Up Study and Nurses' Health Studies I and II. EXPOSURES: Urine volume and pH, and concentrations of calcium, citrate, oxalate, potassium, magnesium, uric acid, phosphorus, and sodium. OUTCOME: Incident symptomatic kidney stones. ANALYTICAL APPROACH: Multivariable logistic regression analysis incorporating restricted cubic splines to explore potentially non-linear relationships between urinary factors and the risk of forming a kidney stone. Optimal inflection point analysis was implemented for each factor and dominance analysis was performed to establish the relative importance of each urinary factor. RESULTS: Each urinary factor was significantly associated with stone formation except for urine pH. Higher urinary levels of calcium, oxalate, phosphorus, and sodium were associated with a higher risk of stone formation, whereas higher urine volume, uric acid, citrate, potassium, and magnesium were associated with a lower risk. The relationships were substantially linear for urine calcium, uric acid, and sodium. In contrast, the magnitudes of the relationships were modestly attenuated at levels above the inflection points for urine oxalate, citrate, volume, phosphorus, potassium, and magnesium. Dominance analysis identified three categories of factors' relative importance: higher (calcium, volume and citrate), intermediate (oxalate, potassium and magnesium) and lower (uric acid, phosphorus and sodium). LIMITATIONS: Predominantly white participants, lack of information on stone composition. CONCLUSIONS: Urine chemistries have complex relationships and differential relative associations with the risk of kidney stone formation.

Epidemiological and biological associations between cardiovascular disease and kidney stone formation: A systematic review and meta-analysis.

AIMS: Previous studies find kidney stone formers (KSF) are at greater risk of developing cardiovascular disease (CVD). The underlying mechanisms are poorly understood, and many clinicians are unaware of this connection. We will: DATA SYNTHESIS: Our systematic review is registered with PROSPERO (ID CRD42021251477). We searched epidemiological and biological data. The epidemiological search generated 669 papers, narrowed down to 15. There were 4,259,869 participants (230,720 KSFs). KSF was associated with 25% higher risk of coronary artery disease (CAD) (95% confidence interval (CI): 15, 35%), 17% higher risk of stroke/transient ischemic attacks (TIA) (CI:10, 25%) and 39% higher risk of arterial disease (AD) (CI: 17 65%). Significant heterogeneity was found. Female-identifying KSFs had a higher risk of stroke (ratio = 1.10) and CAD (1.20). The biological search generated 125 papers, narrowed down to 14. Potential underlying mechanisms were extracted and discussed, including intimal/medial vascular calcification, oxidative stress via osteopontin (OPN), cholesterol-induced pathology, and endothelial dysfunction. CONCLUSIONS: There is a significant association between KSF and CVD, supporting the consideration of KSF as a systemic, calcium-mediated disease. Clinicians will benefit from being aware of this connection.

Circulating metabolites associated with kidney function decline and incident CKD: a multi-platform population-based study.

Background: Investigation of circulating metabolites associated with kidney function and chronic kidney disease (CKD) risk could enhance our understanding of underlying pathways and identify new biomarkers for kidney function. Methods: We selected participants from the population-based Rotterdam Study with data on circulating metabolites and estimated glomerular filtration rate based on serum creatinine (eGFRcreat) available at the same time point. Data on eGFR based on serum cystatin C (eGFRcys) and urine albumin-to-creatinine ratio (ACR) were also included. CKD was defined as eGFRcreat <60 ml/min per 1.73 m2. Data on circulating metabolites (ntotal = 1381) was obtained from the Nightingale and Metabolon platform. Linear regression, linear mixed, and Cox proportional-hazards regression analyses were conducted to study the associations between metabolites and kidney function. We performed bidirectional two-sample Mendelian randomization analyses to investigate causality of the identified associations. Results: We included 3337 and 1540 participants with data from Nightingale and Metabolon, respectively. A total of 1381 metabolites (243 from Nightingale and 1138 from Metabolon) were included in the analyses. A large number of metabolites were significantly associated with eGFRcreat, eGFRcys, ACR, and CKD, including 16 metabolites that were associated with all four outcomes. Among these, C-glycosyltryptophan (HR 1.50, 95%CI 1.31;1.71) and X-12026 (HR 1.46, 95%CI 1.26;1.68) were most strongly associated with CKD risk. We revealed sex differences in the associations of 11-ketoetiocholanolone glucuronide and 11-beta-glucuronide with the kidney function assessments. No causal associations between the identified metabolites and kidney function were observed. Conclusion: Our study indicates that several circulating metabolites are associated with kidney function which are likely to have potential as biomarkers, rather than as molecules involved in the pathophysiology of kidney function decline.

Erythrocyte membrane fluidity: A novel biomarker of residual cardiovascular risk in type 2 diabetes.

AIMS: Improving the composition of circulating fatty acids (FA) leads to a reduction in cardiovascular diseases (CVD) in high-risk individuals. The membrane fluidity of red blood cells (RBC), which reflects circulating FA status, may be a valid biomarker of cardiovascular (CV) risk in type 2 diabetes (T2D). METHODS: Red blood cell membrane fluidity, quantified as general polarization (GP), was assessed in 234 subjects with T2D, 86 with prior major CVD. Based on GP distribution, a cut-off of .445 was used to divide the study cohort into two groups: the first with higher GP, called GEL, and the second, defined as lower GP (LGP). Lipidomic analysis was performed to evaluate FA composition of RBC membranes. RESULTS: Although with comparable CV risk factors, the LGP group had a greater percentage of patients with major CVD than the GEL group (40% vs 24%, respectively, p < .05). Moreover, in a logistic regression analysis, a lower GP value was independently associated with the presence of macrovascular complications. Lipidomic analysis showed a clear shift of LGP membranes towards a pro-inflammatory condition due to higher content of arachidonic acid and increased omega 6/omega 3 index. CONCLUSIONS: Increased membrane fluidity is associated with a higher CV risk in subjects with T2D. If confirmed in prospective studies, membrane fluidity could be a new biomarker for residual CV risk assessment in T2D.

Predictive models in chronic kidney disease: essential tools in clinical practice.

PURPOSE OF REVIEW: The integration of risk prediction in managing chronic kidney disease (CKD) is universally considered a key point of routine clinical practice to guide time-sensitive choices, such as dialysis access planning or counseling on kidney transplant options. Several prognostic models have been developed and validated to provide individualized evaluation of kidney failure risk in CKD patients. This review aims to analyze the current evidence on existing predictive models and evaluate the different advantages and disadvantages of these tools. RECENT FINDINGS: Since Tangri et al. introduced the Kidney Failure Risk Equation in 2011, the nephrological scientific community focused its interest in enhancing available algorithms and finding new prognostic equations. Although current models can predict kidney failure with high discrimination, different questions remain unsolved. Thus, this field is open to new possibilities and discoveries. SUMMARY: Accurately informing patients of their prognoses can result in tailored therapy with important clinical and psychological implications. Over the last 5 years, the number of disease-modifying therapeutic options has considerably increased, providing possibilities to not only prevent the kidney failure onset in patients with advanced CKD but also delay progression from early stages in at-risk individuals.

Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes.

OBJECTIVE: We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. METHODS: We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. RESULTS: The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. CONCLUSIONS: SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits.

Determinants of Kidney Failure in Primary Hyperoxaluria Type 1: Findings of the European Hyperoxaluria Consortium.

Introduction: Primary hyperoxaluria type 1 (PH1) has a highly heterogeneous disease course. Apart from the c.508G>A (p.Gly170Arg) AGXT variant, which imparts a relatively favorable outcome, little is known about determinants of kidney failure. Identifying these is crucial for disease management, especially in this era of new therapies. Methods: In this retrospective study of 932 patients with PH1 included in the OxalEurope registry, we analyzed genotype-phenotype correlations as well as the impact of nephrocalcinosis, urolithiasis, and urinary oxalate and glycolate excretion on the development of kidney failure, using survival and mixed model analyses. Results: The risk of developing kidney failure was the highest for 175 vitamin-B6 unresponsive ("null") homozygotes and lowest for 155 patients with c.508G>A and c.454T>A (p.Phe152Ile) variants, with a median age of onset of kidney failure of 7.8 and 31.8 years, respectively. Fifty patients with c.731T>C (p.Ile244Thr) homozygote variants had better kidney survival than null homozygotes (P = 0.003). Poor outcomes were found in patients with other potentially vitamin B6-responsive variants. Nephrocalcinosis increased the risk of kidney failure significantly (hazard ratio [HR] 3.17 [2.03-4.94], P < 0.001). Urinary oxalate and glycolate measurements were available in 620 and 579 twenty-four-hour urine collections from 117 and 87 patients, respectively. Urinary oxalate excretion, unlike glycolate, was higher in patients who subsequently developed kidney failure (P = 0.034). However, the 41% intraindividual variation of urinary oxalate resulted in wide confidence intervals. Conclusion: In conclusion, homozygosity for AGXT null variants and nephrocalcinosis were the strongest determinants for kidney failure in PH1.

Recommendations for the management of hyperkalemia in patients receiving renin-angiotensin-aldosterone system inhibitors.

Hyperkalemia is common in clinical practice and can be caused by medications used to treat cardiovascular diseases, particularly renin-angiotensin-aldosterone system inhibitors (RAASis). This narrative review discusses the epidemiology, etiology, and consequences of hyperkalemia, and recommends strategies for the prevention and management of hyperkalemia, mainly focusing on guideline recommendations, while recognizing the gaps or differences between the guidelines. Available evidence emphasizes the importance of healthcare professionals (HCPs) taking a proactive approach to hyperkalemia management by prioritizing patient identification and acknowledging that hyperkalemia is often a long-term condition requiring ongoing treatment. Given the risk of hyperkalemia during RAASi treatment, it is advisable to monitor serum potassium levels prior to initiating these treatments, and then regularly throughout treatment. If RAASi therapy is indicated in patients with cardiorenal disease, HCPs should first treat chronic hyperkalemia before reducing the dose or discontinuing RAASis, as reduction or interruption of RAASi treatment can increase the risk of adverse cardiovascular and renal outcomes or death. Moreover, management of hyperkalemia should involve the use of newer potassium binders, such as sodium zirconium cyclosilicate or patiromer, as these agents can effectively enable optimal RAASi treatment. Finally, patients should receive education regarding hyperkalemia, the risks of discontinuing their current treatments, and need to avoid excessive dietary potassium intake.

International comparison and time trends of first kidney transplant recipient characteristics across Europe: an ERA Registry study.

BACKGROUND: The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe. METHOD: The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year. RESULTS: In total, 99 543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries. CONCLUSION: We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased.

Effects of PCSK9 inhibition on glucose metabolism and ß-cell function in humans: a pilot study.

Background: Anti-PCSK9 monoclonal antibodies are effective in reducing LDL-C and cardiovascular events by neutralizing circulating PCSK9. PCSK9, however, is also expressed in tissues, including the pancreas, and studies on PCSK9 KO mice have shown impaired insulin secretion. Statin treatment is already known to affect insulin secretion. Our aim was to conduct a pilot study to evaluate the effect of anti-PCSK9 mAb on glucose metabolism and ß-cell function in humans. Methods: Fifteen non-diabetic subjects, candidates for anti-PCSK9 mAb therapy, were enrolled. All underwent OGTT at baseline and after 6 months of therapy. During OGTT, insulin secretion parameters were derived from C-peptide by deconvolution (ß cell glucose sensitivity). Surrogate insulin sensitivity indices were also obtained from OGTT (Matsuda). Results: Glucose levels during OGTT were unchanged after 6 months of anti-PCSK9 mAb treatment, as well as insulin and C-peptide levels. The Matsuda index remained unchanged, while ß-cell glucose sensitivity improved post-therapy (before: 85.3 ± 65.4; after: 118.6 ± 70.9 pmol min-1m-2mM-1; p<0.05). Using linear regression, we found a significant correlation between ßCGS changes and BMI (p=0.004). Thus, we compared subjects with values above and below the median (27.6 kg/m2) and found that those with higher BMI had a greater increase in ßCGS after therapy (before: 85.37 ± 24.73; after: 118.62 ± 26.83 pmol min-1m-2mM-1; p=0.007). There was also a significant correlation between ßCGS change and Matsuda index through linear regression (p=0.04), so we analyzed subjects who had values above and below the median (3.8). This subgroup analysis showed a slight though not significant improvement in ßCGS in more insulin resistant patients, (before: 131.4 ± 69.8; after: 170.8 ± 92.7 pmol min-1m-2mM-1; p=0.066). Conclusions: Our pilot study demonstrates that six-month treatment with anti-PCSK9 mAb improves ß-cell function, and does not alter glucose tolerance. This improvement is more evident in patients with greater insulin-resistance (low Matsuda) and higher BMI.

Diagnostic policies on nephrolithiasis/nephrocalcinosis of possible genetic origin by Italian nephrologists: a survey by the Italian Society of Nephrology with an emphasis on primary hyperoxaluria.

BACKGROUND: Primary hyperoxaluria is a genetic disorder of the metabolism of glyoxylate, the precursor of oxalate. It is characterized by high endogenous production and excessive urinary excretion of oxalate, resulting in the development of calcium oxalate nephrolithiasis, nephrocalcinosis, and, in severe cases, end-stage kidney disease and systemic oxalosis. Three different forms of primary hyperoxaluria are currently known, each characterized by a specific enzymatic defect: type 1 (PH1), type 2 (PH2), and type 3 (PH3). According to currently available epidemiological data, PH1 is by far the most common form (about 80% of cases), and is caused by a deficiency of the hepatic enzyme alanine:glyoxylate aminotransferase. METHODS: A survey on rare forms of nephrolithiasis and nephrocalcinosis with a focus on primary hyperoxaluria in the setting of Italian Nephrology and Dialysis Centers, using an online questionnaire, was recently conducted by the Project Group "Rare Forms of Nephrolithiasis and Nephrocalcinosis" of the Italian Society of Nephrology, with the aim of assessing the impact and management of this disorder in clinical practice in Italy. RESULTS: Forty-five public and private Italian Centers participated in the survey, and responses to the questionnaire were provided by 54 medical professionals. The survey results indicate that 21 out of the 45 participating Centers are managing or have managed primary hyperoxaluria patients, most of whom are on dialysis, or are recipients of kidney transplants. CONCLUSIONS: The data of this survey indicate the need to implement genetic testing in suspected cases of primary hyperoxaluria, not only in the setting of dialysis or transplantation, but also with the aim of encouraging early diagnosis of PH1, which is the only type of primary hyperoxaluria for which specific drug therapy is currently available.

Associations between Net Gastrointestinal Alkali Absorption, 24-Hour Urine Lithogenic Factors, and Kidney Stones.

BACKGROUND: It is not clear whether kidney stone formers have an abnormal handling of alkali and acid precursors in the gut, which might affect urine composition and ultimately stone formation. In this study, we aimed to investigate the determinants of net gastrointestinal alkali absorption and its associations with key urinary parameters in a large group of stone formers and non-stone formers. METHODS: Data were collected from three independent cohorts with at least one 24-hour urine collection. We explored potential determinants of net gastrointestinal alkali absorption and the association between net gastrointestinal alkali absorption, urinary parameters, and stone former status. Finally, we estimated the proportion of the association between urine parameters and stone former status explained by differences in net gastrointestinal alkali absorption. RESULTS: The analysis included 6067 participants (1102 men and 4965 women; 698 and 1804 of whom were stone formers, respectively). Average net gastrointestinal alkali absorption values were consistently lower in stone formers across the three cohorts (from -15.0 to -4.9 mEq/d). Age was directly associated with net gastrointestinal alkali absorption, whereas body mass index and net endogenous acid production were inversely associated. Net gastrointestinal alkali absorption was inversely associated with supersaturation for calcium oxalate, uric acid, and renal net acid excretion and directly associated with supersaturation for calcium phosphate, urine pH, and citrate. The odds of being a stone former was 15% (13%-17%) lower per 10 mEq/24 hours higher net gastrointestinal alkali absorption. Differences in net gastrointestinal alkali absorption explained a modest amount of the differences between stone formers and non-stone formers for supersaturation for calcium oxalate (6.3%) and a sizable amount for supersaturation for uric acid (15.2%), urine pH (38.3%), citrate (26.2%), and renal net acid excretion (63.4%). CONCLUSIONS: Kidney stone formers have lower net gastrointestinal alkali absorption, and this explains differences in urine composition and the likelihood of stone formation.

Determinants of renal papillary appearance in kidney stone formers: An in-depth examination.

OBJECTIVES: The aim of this study is to investi-gate the association between the urinary metabolic milieu and kidney stone recurrence with a validated papillary evaluation score (PPLA). MATERIALS AND METHODS: We prospectively enrolled 30 stone for-mers who underwent retrograde intrarenal surgery procedures. Visual inspection of the accessible renal papillae was performed to calculate PPLA score, based on the characterization of ductal plugging, surface pitting, loss of papillary contour and Randall's plaque extension. Stone compositions, 24h urine collections and kidney stone events during follow-up were collected. Relative supersaturation ratios (RSS) for calcium oxalate (CaOx), brushite and uric acid were calculated using EQUIL-2. PPLA score > 3 was defined as high. RESULTS: Median follow-up period was 11 months (5, 34). PPLA score was inversely correlated with BMI (OR 0.59, 95% CI 0.38, 0.91, p = 0.018), type 2 diabetes (OR 0.04, 95% CI 0.003, 0.58, p = 0.018) and history of recurrent kidney stones (OR 0.17, 95%CI 0.04, 0.75, p = 0.019). The associations between PPLA score, diabetes and BMI were not confirmed after excluding patients with uric acid stones. Higher PPLA score was associated with lower odds of new kidney stone events during follow-up (OR 0.15, 95% CI 0.02, 1.00, p = 0.05). No other significant correla-tions were found. CONCLUSIONS: Our results confirm the lack of efficacy of PPLA score in phenotyping patients affected by kidney stone disease or in predicting the risk of stone recurrence. Larger, long-term studies need to be performed to clarify the role of PPLA on the risk of stone recurrence.

Association analysis of 10 candidate genes causing Mendelian calcium nephrolithiasis in the INCIPE study: a South European general population cohort.

Background: Idiopathic calcium nephrolithiasis (ICN) is a common condition with a complex phenotype influenced by both environmental and genetic factors. In our study we investigated the association of allelic variants with the history of nephrolithiasis. Methods: We genotyped and selected 10 candidate genes potentially related to ICN from 3046 subjects participating in the INCIPE survey cohort (Initiative on Nephropathy, of relevance to public health, which is Chronic, possibly in its Initial stages, and carries a Potential risk of major clinical End-points), a study enrolling subjects from the general population in the Veneto region in Italy. Results: Overall, 66 224 variants mapping on the 10 candidate genes were studied. A total of 69 and 18 variants in INCIPE-1 and INCIPE-2, respectively, were significantly associated with stone history (SH). Only two variants, rs36106327 (chr20:54 171 755, intron variant) and rs35792925 (chr20:54 173 157, intron variant) of the CYP24A1 gene were observed to be consistently associated with ICN. Neither variant has been previously reported in association with renal stones or other conditions. Carriers of CYP24A1 variants showed a significant increase in the ratio of 1,25 (OH)2 vitamin D to 25 (OH) vitamin D compared with controls (P = .043). Although not associated with ICN in this study, the rs4811494 CYP24A1 variant that was reported to be causative of nephrolithiasis was very prevalent in heterozygosity (20%). Conclusion: Our data suggest a possible role for CYP24A1 variants in the risk of nephrolithiasis. Genetic validation studies in larger sample sets will be necessary to confirm our findings.