Prospective long-term evaluation of incomplete distal renal tubular acidosis in idiopathic calcium nephrolithiasis diagnosed (treated) by low-dose NH4CL loading – gender prevalences and impact of alkali treatment

Purpose Prospective evaluation of the prevalence of incomplete distal renal tubular acidosis (idRTA) in idiopathic calcium stone formers (ICSF) diagnosed by half-dose ammonium chloride loading (NH4Cl, 0.05 g/kg body weight/day) and impact of alkali treatment of idRTA. Methods Evaluation of 386 consecutive idiopathic calcium stone formers (ICSF) (280 males, 106 females) for idRTA. If screening fasting urine pH was > 5.80, 1-day NH4Cl loading was performed without severe adverse effects. Normally, urine pH falls below 5.45. Results Sixty-four idiopathic calcium stone formers exhibited idRTA, one complete dRTA. Prevalence was higher in women (25.4%) than in men (13.6%). Thus, for more equilibrated comparisons, we formed pairs of 62 idiopathic calcium stone formers (ICSF) with and 62 without idRTA, matched for gender, age, BMI and serum creatinine. Idiopathic calcium stone formers with idRTA more often had hypercalciuria (p < 0.025) and urine citrate < 2 mmol/d (p < 0.05), formed calcium phosphate stones more frequently, exhibited higher numbers of stones/year (1.4 ± 1.5 vs. 0.9 ± 0.8, p = 0.034) and 2.5 times more intrarenal calcifications (4.6 ± 5.9 vs. 1.8 ± 3.6, p = 0.002). All idiopathic calcium stone formers with idRTA were recommended chronic alkali therapy. After 4–15 years of follow-up, stone events /years follow-up (stone passage or urologic intervention) were higher in patients non-adherent to alkali therapy (0.61 ± 0.92) than in patients adherent to treatment (0.11 ± 0.21, p = 0.006). Conclusion Incomplete distal renal tubular acidosis is 1.8-fold more prevalent among female idiopathic calcium stone formers, predicts more stone recurrences, predisposes to calcium phosphate stones and is associated with 2.5 times more intrarenal calcifications vs. non-idRTA patients. Chronic alkali treatment reduces clinical stone recurrences by 5.5 times. Graphical abstract

Diet-Derived Antioxidants and Risk of Kidney Stone Disease: Results From the NHANES 2007–2018 and Mendelian Randomization Study

We aimed to explore the associations between diet-derived antioxidants and kidney stone disease (KSD) risk in this study. We performed weighted multivariable-adjusted logistic regression to assess the associations between the six main diet-derived antioxidants and the risk of KSD by using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Then, we used the Mendelian randomization (MR) approach to verify the causal relationships between circulating antioxidants levels and KSD risk. Genetic tools were extracted from published genome-wide association studies (GWAS). Summary data for KSD was from the FinnGen study and UK biobank. Inverse variance weighted (IVW) was the primary analysis. The 26,438 participants, including 2,543 stone formers, were included for analyses. There were no significant associations between retinol, vitamin B6, vitamin C, vitamin E, and lycopene intake with the risk of KSD across all the quartile categories. Similarly, pooled odds ratio (OR) for KSD risk in genetically predicted per unit change were 1.25 (95% CI: 0.39, 4.02; p = 0.712), 1.14 (95% CI: 0.84, 1.53; p = 0.400), 0.75 (95% CI: 0.52, 1.10; p = 0.141), 1.66 (95% CI: 0.80, 3.46; p = 0.178), 1.27 (95% CI: 0.29, 5.62; p = 0.756), and 0.92 (95% CI: 0.76, 1.12; p = 0.417) for retinol, β-carotene, vitamin B6, vitamin C, α-tocopherol, and lycopene, respectively. The above estimates were replicated in the secondary analyses using UK biobank data. Our study did not support a causal association between circulating antioxidants levels and KSD risk. However, these findings should be verified in larger sample-size MR due to the pleiotropy and other limitations.

Medical management for the prevention of kidney stones

The alarming fact is that approximately one out of every 10 of us will have a kidney stone during our lifetime. The increasing prevalence and associated costs of kidney stones have resulted in it being one of the most commonly encountered and impactful medical conditions. Contributing factors include, but are not limited to, diet, climate, genetics, medications, activity and underlying medical conditions. Symptoms generally parallel stone size. Treatment varies from supportive to procedural (invasive and non-invasive). Prevention remains the best way to avoid this condition especially given the high recurrence rate. First time stone formers require counselling regarding dietary adjustments. Certain risk factors ultimately require a more in-depth metabolic investigation, especially if stones are recurrent. Ultimately, management is defined by stone composition. Where appropriate, we review both pharmacologic and non-pharmacologic options. Pivotal to successful prevention is patient education and the encouragement of compliance with the appropriate regimen.

Calcium and Vitamin D Supplementation and Their Association with Kidney Stone Disease: A Narrative Review

Kidney stone disease is a multifactorial condition influenced by both genetic predisposition and environmental factors such as lifestyle and dietary habits. Although different monogenic polymorphisms have been proposed as playing a causal role for calcium nephrolithiasis, the prevalence of these mutations in the general population and their complete pathogenetic pathway is yet to be determined. General dietary advice for kidney stone formers includes elevated fluid intake, dietary restriction of sodium and animal proteins, avoidance of a low calcium diet, maintenance of a normal body mass index, and elevated intake of vegetables and fibers. Thus, balanced calcium consumption protects against the risk for kidney stones by reducing intestinal oxalate availability and its urinary excretion. However, calcium supplementation given between meals might increase urinary calcium excretion without the beneficial effect on oxalate. In kidney stone formers, circulating active vitamin D has been found to be increased, whereas higher plasma 25-hydroxycholecalciferol seems to be present only in hypercalciuric patients. The association between nutritional vitamin D supplements and the risk for stone formation is currently not completely understood. However, taken together, available evidence might suggest that vitamin D administration worsens the risk for stone formation in patients predisposed to hypercalciuria. In this review, we analyzed and discussed available literature on the effect of calcium and vitamin D supplementation on the risk for kidney stone formation.

Effects of COVID-19 pandemics on urinary metabolites in kidney stone patients: our kidney stone prevention clinic experience

Background The dietary habits and lifestyle changes during the COVID-19 pandemic could affect the urinary risk factors in kidney stone formers. In this study, we investigated the effects of the COVID-19 pandemic on 24-h urine metabolites, as a surrogate for dietary intake, in patients with kidney stones, in Tehran, Iran. Methods We evaluated the medical records of all patients with urolithiasis who visited in our stone prevention clinic from the beginning of COVID-19 in Iran to 1 year later (Feb 2020–Feb 2021) and compared it with the patients’ medical records in the same period a year before COVID-19 (Feb 2019–Feb 2020). Results The results of our stone prevention clinic showed a decrease in the number of visits during COVID-19. Twenty-four-hour urine urea, sodium, and potassium were significantly lower, and 24-h urine magnesium was significantly higher during COVID-19. Higher 24-h urine oxalate was only shown in patients with the first-time visit, whereas lower 24-h urine uric acid and citrate were only shown in patients with the follow-up visits. Conclusions COVID-19 pandemics may change some of the dietary habits of the patients, including lower salt, protein, and fruit and vegetable intake. Although economic issues, restricted access, or sanitation issues may be the reason for the undesirable dietary changes, the importance of a quality diet should be discussed with all patients, as possible. Since the number of patients visited in the stone clinic was lower during COVID-19, virtual visits could be an excellent alternative to motivate patients with kidney stones.

Association between aortic calcification and the presence of kidney stones: calcium oxalate calculi in focus

Purpose The current research is aimed at analyzing the relationship between kidney stone (KS) and abdominal aortic calcification (AAC) and the relationship between KS components and AAC. Methods This is a retrospective, case–control study. Kidney stone formers (KSFs) were treated at the Department of Urology, West China Hospital, Sichuan University for urological calculus disease from January 2014 to January 2020. Matched non-stone formers (non-SFs) were drawn from the same hospital for routine health examination from January 2018 to February 2019. Research-related information was collected and reviewed retrospectively from the hospital’s computerized records. AAC were evaluated using available results of computed tomography imaging and abdominal vascular ultrasound. The relationships of AAC between KSFs and non-SFs were compared. The composition of renal calculi was analyzed by Fourier-transform infrared spectrophotometer. KSFs were divided into AAC groups and non-AAC based on AAC. The relationship of the composition of renal calculi between AAC and non-AAC were compared. The independent-sample t test, the chi-squared test and binary logistics regression were performed. Results Altogether, 4516 people were included, with 1027 KSFs and 3489 non-SFs. There were no significant differences in the laboratory parameters between KSFs and non-SFs. The association between the presence of AAC and KS was significant in multivariable model 2 [adjusting hypertension, diabetes mellitus, fasting blood glucose, uric acid, serum triglyceride (TG), serum calcium, and urine pH] (OR 5.756, 95% CI 4.616–7.177, p < 0.001). The result of KSFs showed that calcium oxalate calculi (CaOx) was significantly associated with AAC in multivariable model 3 (adjusting age, hypertension, diabetes mellitus, drinking history, smoking history, and TG) (OR 1.351, 95% CI 1.002–1.822, p = 0.048). Conclusions The current study pioneered the revelation of the relationship between CaOx and AAC. Through an elimination of the confounding factors, the study demonstrated that KS and AAC were connected.

Temporal Trends of Dietary Risk Factors after a Diagnosis of Kidney Stones

Diet is an important contributor to kidney stone formation, but there are limited data regarding long-term changes in dietary factors after a diagnosis of a kidney stone. We analyzed data from three longitudinal cohorts, the Health Professionals Follow-Up Study and the Nurses' Health Studies I and II, comparing changes in dietary factors in participants with and without a history of kidney stones during follow-up. The total daily intake of dietary calcium, supplemental calcium, animal protein, caffeine, fructose, potassium, sodium, oxalate, phytate, vitamin D, vitamin C, sugar-sweetened beverages, fluids, NEAP and DASH score were assessed by repeat FFQs and computed as absolute differences; a difference-in-differences (DID) approach was used to account for general temporal changes using data from participants without a history of kidney stones from the same calendar period. 184,398 participants with no history of kidney stones were included, 7,095 of whom became confirmed stone formers. Several intakes changed significantly over time in stone formers compared with non-formers, with some showing a relative increase up to 8 years later, including caffeine (DID 8.8 mg/day, 95% CI 3.4, 14.1), potassium (23.4 mg/day, 95% CI 4.6, 42.3), phytate (12.1 mg/day, 95% CI 2.5, 21.7), sodium (43.1 mg/day, 95% CI 19.8, 66.5) and fluid intake (47.1 mL/day, 95% CI 22.7, 71.5). Other dietary factors showed a significant decrease, such as oxalate (−7.3 mg/day, 95% CI −11.4, −3.2), vitamin C (−34.2 mg/day, 95% CI −48.8, −19.6), and vitamin D (−18.0 IU/day, 95% CI −27.9, −8.0). A significant reduction in sugar-sweetened beverages of −0.5 (95% CI −0.8, −0.3) and −1.4 (95% CI −1.8, −1.0) servings/week and supplemental calcium −105.1 (95% CI −135.4, −74.7) and −69.4 (95% CI −95.4, −43.4) mg/day for NHS I and NHS II, respectively intake was observed in women. Animal protein, dietary calcium, fructose intake, DASH score and NEAP did not change significantly over time. After the first episode of a kidney stone, mild and inconsistent changes were observed concerning dietary factors associated with kidney stone formation.

Sequencing the CaSR locus in Pakistani stone formers reveals a novel loss-of-function variant atypically associated with nephrolithiasis

Background Nephrolithiasis (NL) affects 1 in 11 individuals worldwide and causes significant morbidity and cost. Common variants in the calcium sensing receptor gene (CaSR) have been associated with NL. Rare inactivating CaSR variants classically cause hyperparathyroidism, hypercalcemia and hypocalciuria. However, NL and familial hypercalciuria have been paradoxically associated with select inactivating CaSR variants in three kindreds from Europe and Australia. Methods To discover novel NL-associated CaSR variants from a geographically distinct cohort, 57 Pakistani families presenting with pediatric onset NL were recruited. The CaSR locus was analyzed by directed or exome sequencing. Results We detected a heterozygous and likely pathogenic splice variant (GRCh37 Chr3:122000958A>G; GRCh38 Chr3:12228211A>G; NM_000388:c.1609-2A>G) in CaSR in one family with recurrent calcium oxalate stones. This variant would be predicted to cause exon skipping and premature termination (p.Val537Metfs*49). Moreover, a splice variant of unknown significance in an alternative CaSR transcript (GRCh37 Chr3:122000929G>C; GRCh38 Chr3:122282082G >C NM_000388:c.1609-31G >C NM_001178065:c.1609-1G >C) was identified in two additional families. Conclusions Sequencing of the CaSR locus in Pakistani stone formers reveals a novel loss-of-function variant, expanding the connection between the CaSR locus and nephrolithiasis.

Prevalence of Hypertension in Patients with Nephrolithiasis

Introduction: Kidney stone disease, also known as nephrolithiasis, is a prevalent illness that affects people of all ages and genders. Hypertension is defined as persistent elevation of systemic arterial blood pressure (systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg). Methodology: This was a prospective study conducted over a period of 3 months between February 2021 and April 2021 at the Department of General Medicine in our tertiary care center. A total of 280 patients who came to the outpatient department (OPD) were included in the study as study participants. After recording blood pressure, participants were classified as normotensives (218) and hypertensives (62). The study participants were examined for the development of kidney stone disease. In those study participants who had clinical features suggesting nephrolithiasis, the diagnosis was confirmed by Ultrasonography. Results: It was observed that 25 of 62 hypertensives and 47 of 218 normotensives developed nephrolithiasis. And there were 43 men and 29 women among the 72 stone formers. Conclusion: Our study showed a male preponderance for stone formers. And it is also evident that nephrolithiasis is more prevalent among hypertensives than normotensives though not statistically significant.