Nephrolithiasis Associated with Nephrocalcinosis Is Primarily Composed of Carbonate Apatite.

INTRODUCTION: This study was designed to determine the mineral composition of calculi in nephrocalcinosis with nephrolithiasis, diagnose the underlying disease, and monitor the course of renal function in patients with nephrocalcinosis-nephrolithiasis. METHODS: Renal calculi extruded in a series of 8 patients with nephrocalcinosis were analysed using Fourier transmission infrared spectrometry. In 4 patients, next-generation sequencing using a nephrocalcinosis-nephrolithiasis panel was performed to determine the nature of the underlying disease. In addition, longitudinal analysis of renal function was performed in all patients. RESULTS: Seven patients revealed carbonate apatite as the sole constituent of renal calculi. One patient showed a mixed composition of dicalcium phosphate dihydrate/carbonate apatite at first analysis yet in subsequent episodes also had calculi composed of pure carbonate apatite. Further molecular analysis displayed distal renal tubular acidosis in 2 of 4 patients who consented to sequencing. No known genetic defect could be found in the other two cases. In line with prior reports, decline of renal function was dependent on underlying disease. Distal renal tubular acidosis revealed a progressive course of renal failure, whereas other causes showed stable renal function in long term analysis. CONCLUSION: Nephrocalcinosis with nephrolithiasis is a rare condition with heterogeneous aetiology. Yet mineral composition of renal calculi predominantly consisted of pure carbonate apatite. This uniform finding is similar to subcutaneous calcifications of various origins and might propose a general principle of tissue calcification. Progressive decline of renal function was found in distal renal tubular acidosis, whereas other conditions remained stable over time.

Machine learning models for screening clinically significant nephrolithiasis in overweight and obese populations.

PURPOSES: Our aim is to build and evaluate models to screen for clinically significant nephrolithiasis in overweight and obesity populations using machine learning (ML) methodologies and simple health checkup clinical and urine parameters easily obtained in clinics. METHODS: We developed ML models to screen for clinically significant nephrolithiasis (kidney stone > 2 mm) in overweight and obese populations (body mass index, BMI ≥ 25 kg/m2) using gender, age, BMI, gout, diabetes mellitus, estimated glomerular filtration rate, bacteriuria, urine pH, urine red blood cell counts, and urine specific gravity. The data were collected from hospitals in Kaohsiung, Taiwan between 2012 and 2021. RESULTS: Of the 2928 subjects we enrolled, 1148 (39.21%) had clinically significant nephrolithiasis and 1780 (60.79%) did not. The testing dataset consisted of data collected from 574 subjects, 235 (40.94%) with clinically significant nephrolithiasis and 339 (59.06%) without. One model had a testing area under curve of 0.965 (95% CI, 0.9506-0.9794), a sensitivity of 0.860 (95% CI, 0.8152-0.9040), a specificity of 0.947 (95% CI, 0.9230-0.9708), a positive predictive value of 0.918 (95% CI, 0.8820-0.9544), and negative predictive value of 0.907 (95% CI, 0.8756-0.9371). CONCLUSION: This ML-based model was found able to effectively distinguish the overweight and obese subjects with clinically significant nephrolithiasis from those without. We believe that such a model can serve as an easily accessible and reliable screening tool for nephrolithiasis in overweight and obesity populations and make possible early intervention such as lifestyle modifications and medication for prevention stone complications.

Children With Type 1 Spinal Muscular Atrophy Are at Increased Risk for Nephrolithiasis.

BACKGROUND: Nephrolithiasis is not a well-documented condition in children with spinal muscular atrophy (SMA). It is possible that this condition was underestimated before the era of nusinersen because of a much shorter life expectancy. We present our observational data on nephrolithiasis and its possible risk factors in children with type 1 SMA. METHODS: We retrospectively reviewed the charts of 20 children with genetically confirmed type 1 SMA. Thirteen patients (aged 9 to 55 months) who underwent urinary tract ultrasonography were included in the study. Medical records were retrospectively reviewed for demographic and clinical characteristics, ultrasound results, and metabolic abnormalities. RESULTS: Seven children (54%) had nephrolithiasis; 5 had multiple stones and two had a single stone. Two patients had microlithiasis (<3 mm), three had a stone in the size of 3 to 5 mm, and one had a stone in the size of more than 8 mm. Two patients with nephrolithiasis had urinary tract abnormalities. Patients with nephrolithiasis were more likely to have a history of urinary tract infections (UTIs) (P = 0.048) and higher urine specific gravity (P = 0.014) than patients without nephrolithiasis. Five of seven children with nephrolithiasis had a urine metabolic evaluation; all had hypercalciuria, three had hyperuricosuria, but none had hyperoxaluria, hypocitraturia, or hypomagnesemia. CONCLUSION: Children with SMA type 1 are at an increased risk for nephrolithiasis. Hypercalciuria and high urine specific gravity appear to be the most common risk factors for the occurrence of nephrolithiasis. In addition, UTI is more common in patients with type 1 SMA with nephrolithiasis.

Low Potassium Intake: A Common Risk Factor for Nephrolithiasis in Patients with High Blood Pressure.

Hypertension (Htn) is a crucial cause of cardio-vascular and chronic kidney disease. Moreover, it is an independent risk factor for nephrolithiasis (NL). A diet rich in vegetables and fruits is indicated for both Htn and NL prevention, and the 24-h urinary potassium excretion can be used as a warning light for adherence. The aim of this study is to demonstrate the association between urinary potassium excretion and recurrent nephrolithiasis among patients affected by Htn. We have analyzed medical records of 119 patients affected by Htn and NL (SF-Hs) referring to Bone and Mineral Metabolism laboratory and 119 patients affected by Htn but without NL (nSF-Hs) referring to Hypertension and Organ Damage Hypertension related laboratory, both in Federico II University of Naples. The potassium 24-h urinary levels in SF-Hs were significantly lower compared to nSF-Hs. This difference was confirmed by the multivariable linear regression analysis in the unadjusted model and adjusted model for age, gender, metabolic syndrome, and body mass index. In conclusion, a higher potassium urinary excretion in 24-h is a protective factor against NL in patients affected by Htn and dietary interventions can be considered for kidney protection.

Associations between grain intake and hospitalized nephrolithiasis in Chinese adults: a case-control study.

Introduction: nephrolithiasis is one of the most common urological disorders. Grains are essential staple foods worldwide. This study aimed to investigate the associations between whole grains and refined grains intake, and hospitalized nephrolithiasis in a Chinese population. Methods: the patients and healthy participants were enrolled in the Shenyang sub-cohort of Tianjin Chronic Low-Grade Systemic Inflammation and Health Cohort Study. After selecting and matching by age (±one year) and sex using a 1 : 2 ratio, a total of 666 participants (222 patients and 444 healthy controls) were included. Whole grains and refined grains intake was measured using a validated self-administered food frequency questionnaire. Multivariate conditional logistic regression analysis was used to evaluate the associations between whole grains and refined grains intake with hospitalized nephrolithiasis. Results: after multivariable adjustments, a higher intake of whole grains was inversely associated with hospitalized nephrolithiasis. Compared to participants with the lowest tertile of whole grains intake, the adjusted odds ratio (OR) and 95% confidence interval (CI) of hospitalized nephrolithiasis for participants in the highest tertile was 0.58 (0.26, 0.81) (P for trend = 0.020). In contrast, a higher intake of refined grains was positively associated with nephrolithiasis. Compared to participants with the lowest tertile of refined grains intake, the adjusted OR (95% CI) of hospitalized nephrolithiasis for participants in the highest tertile was 3.75 (1.48, 9.52) (P for trend = 0.006). The results were consistent in both genders. Conclusion: the consumption of whole grains was found to be negatively associated with hospitalized nephrolithiasis, while the consumption of refined grains was positively associated with hospitalized nephrolithiasis. Therefore, a substitution of whole grains for refined grains consumption may assist in hospitalized nephrolithiasis prevention.

The impact of vitamin D deficiency on clinical, biochemical and metabolic parameters in primary hyperparathyroidism.

BACKGROUND: It has been suggested that vitamin D deficiency is associated with worse clinical outcomes in primary hyperparathyroidism (PHPT). We aimed to evaluate the relationship between vitamin D deficiency and clinical, biochemical and metabolic parameters in PHPT patients. METHODS: A total of 128 patients with biochemically confirmed PHPT were included. Patients were categorized as vitamin D deficient if 25-OH vitamin D was <50nmol/L, or normal if vitamin D was ≥50nmol/L. Biochemical parameters, bone mineral densitometry (BMD), and urinary tract and neck ultrasonography were assessed. RESULTS: In the study group, 66 (51.6%) patients had vitamin D deficiency and 60 (48.4%) had normal vitamin D levels. Nephrolithiasis and osteoporosis were found in 26.6% and 30.5% of subjects, respectively. The prevalence of metabolic syndrome (MetS), obesity (BMI≥30kg/m2) and hypertension (HTN) were higher in the vitamin D deficient group when compared to the normal group (p=0.04, p=0.01 and p=0.03, respectively). There was no difference regarding the presence of nephrolithiasis and osteoporosis between the groups. The mean adenoma size was similar in both groups. CONCLUSIONS: Vitamin D deficiency was not associated with osteoporosis, nephrolithiasis, adenoma size or biochemical parameters in PHPT. However, vitamin D deficiency may be a risk factor for developing HTN and MetS in PHPT.

Correlates of nephrolithiasis in US black women: data from the black women's health study.

Nephrolithiasis is a common urologic condition and a significant source of patient morbidity and healthcare expenditure. There are few epidemiologic studies of kidney stones focusing exclusively on Black women. We retrospectively assessed the prevalence and correlates of self-reported kidney stones within the Black Women's Health Study (BWHS). Descriptive statistics and multivariable logistic regression models were used to explore factors associated with nephrolithiasis. As of the 2005 follow-up questionnaire, a cumulative total of 1063 women among 43,178 reported ever being diagnosed with kidney stones for a prevalence of 2.64%. Women with a history of nephrolithiasis were older, slightly heavier, and were more likely to have a comorbid condition (e.g., type-2 diabetes, gallstones), drink alcohol, and consume a Western-style diet. A history of gallstone disease was associated with an odds ratio (OR) of 3.59 (95% confidence interval (CI) 3.09-4.17). The OR for consuming ≥ 7 alcoholic beverages/week, compared to none was 0.61 (0.39-0.94), while the OR for high adherence to the Western diet, compared to low adherence was 1.53 (1.23-1.90). Our findings are consistent with previous studies of primarily white populations relating lifestyle-associated risk factors with nephrolithiasis. Despite their lower prevalence of kidney stones, it is important to focus on vulnerable populations such as Black women given their disproportionate burden of metabolic conditions (e.g., obesity, diabetes) related to kidney stone disease.

Outcomes of live renal donors with a history of nephrolithiasis; A systematic review.

The clinical outcomes of kidney donors with a prior history of nephrolithiasis are poorly defined. We conducted a systematic review assessing the post-donation clinical outcomes of kidney donors with a history of nephrolithiasis. Electronic databases (Ovid and Embase) were searched between 1960 and 2021 using key terms and Medical Subject Headings (MeSH) - nephrolithiasis, renal stones, renal transplantation and renal graft. Articles included conference proceedings and journal articles and were not excluded based on patient numbers. Primary outcome was donor stone-related event. Secondary outcomes were renal function upon follow-up or post-operative nephrectomy complications. In summary, 340 articles were identified through database search. We identified 14 studies (16 cohorts) comprising 432 live donors followed up for a median of 26 months post live kidney donation. Six donors donated the stone-free kidney whilst 23 live donors had bilateral stones. Mean stone size was 4.2 ± 1.4 mm (1-16) with average follow up duration of 21.1 months (1-149). Twelve studies provided primary outcome (n = 138 patients) and eight (n = 348) for secondary outcomes. One donor had a stone-related event upon follow up. A total of 195 patients had eGFR <60 upon follow up. However, they were not significantly different when compared to renal function of live donors that didn't have pre-donation nephrolithiasis. Many of the studies couldn't provide long term follow up, coupled with limited data regarding the nature of the pre-donation stone disease. In conclusion, this systematic review shows that we have very limited information upon which to base recommendation regarding pre-donation risk of post-donation complications. Longer term follow up is required and lifelong follow up with live donor registries will aid further understanding.

Obesity Is Positively Associated and Alcohol Intake Is Negatively Associated with Nephrolithiasis.

The current research investigated the impacts of smoking, alcohol consumption, and obesity on the development of nephrolithiasis. We included ≥40-year-old Koreans from the Korean National Health Insurance Service-Health Screening Cohort. A total of 28,395 nephrolithiasis patients were compared with 113,580 control participants. Previous histories of smoking, alcohol consumption, and obesity were examined before the presence of nephrolithiasis. Conditional logistic regression analysis was performed to estimate the odds ratios (ORs) of smoking, alcohol consumption, and obesity for nephrolithiasis. Further analyses were conducted, according to age, sex, smoking, alcohol consumption, and obesity. The current smoking status was not linked with the presence of nephrolithiasis. Alcohol consumption was linked with a lower likelihood of the presence of nephrolithiasis (adjusted OR (aOR) = 0.89, 95% confidence intervals (CI) = 0.86−0.92, p < 0.001). Being obese was associated with a greater likelihood of the presence of nephrolithiasis ((95% CI) = 1.27 (1.22−1.31) < 1.42 (1.37−1.46) < 1.59 (1.47−1.71) for overweight < obese I < obese II). The relation of alcohol consumption and obesity with nephrolithiasis was consistent in the subgroups. The presence of nephrolithiasis was positively linked with obesity and negatively linked with alcohol consumption.

Cistinuria como causa de litiasis urinaria / Cystinuria as a cause of urolithiasis

La cistinuria es una enfermedad genética que provoca un defecto de reabsorción de cistina, causando como manifestación principal litiasis urinarias que pueden llegar a ser de gran tamaño. Es importante tratarla desde temprana edad porque puede comportar importantes comorbilidades. (AU)

Cystinuria is a genetic disease that causes impaired cystine reabsorption. Its main manifestation is urolithiasis, in some cases producing very large stones. It is important to treat it from an early age because it can lead to important comorbidities. (AU)

Stones left unturned: Missed opportunities to diagnose primary hyperparathyroidism in patients with nephrolithiasis.

BACKGROUND: Nephrolithiasis is a sequela of primary hyperparathyroidism and an indication for parathyroidectomy. The prevalence of primary hyperparathyroidism in patients with nephrolithiasis is 3% to 5%; however, recent studies suggest that many hypercalcemic patients with nephrolithiasis never undergo workup for primary hyperparathyroidism. Our goal is to evaluate primary hyperparathyroidism screening rates at a tertiary academic health institution and identify opportunities to increase referral rates in patients presenting with nephrolithiasis. METHODS: We retrospectively reviewed 15,725 patients across an academic health system who presented with nephrolithiasis between 2012 and 2020. Calcium levels measured within 6 months of presentation were identified, and those with hypercalcemia (≥10.3 mg/dL) were reviewed if parathyroid hormone levels were measured. Patients with primary hyperparathyroidism were evaluated to see if they were referred to a specialist for treatment. RESULTS: Of 15,725 patients presenting with nephrolithiasis, 12,420 (79%) had calcium levels measured; 630 patients (4.0%) were hypercalcemic, and 207 (33%) had parathyroid hormone levels measured. Patients were more likely to have parathyroid hormone levels sent if they were older, had higher calcium levels, or presented to an outpatient clinic (P = .028, P = .002, P < .001). We identified 89 patients (0.6%) with primary hyperparathyroidism, of which only 35 (39%) were referred for treatment. CONCLUSION: The proportion of patients presenting with nephrolithiasis ultimately diagnosed with primary hyperparathyroidism was significantly lower than others have reported. Additionally, a substantial number of patients with nephrolithiasis did not have calcium and/or parathyroid hormone levels measured. These missed opportunities for diagnosis are critical as early definitive management of primary hyperparathyroidism can prevent recurrent nephrolithiasis and other primary hyperparathyroidism-related end organ effects.

Parathyroidectomy for nephrolithiasis in primary hyperparathyroidism: Beneficial but not a panacea.

BACKGROUND: Nephrolithiasis is a classic indication for parathyroidectomy in primary hyperparathyroidism patients; however, the effects of parathyroidectomy on nephrolithiasis recurrence are not well studied. The aim was to determine effect of parathyroidectomy on time to first nephrolithiasis recurrence and recurrence rate per patient-years. METHODS: A retrospective cohort study of patients diagnosed with primary hyperparathyroidism and at least one episode of nephrolithiasis was performed. The patients were divided into observation, presurgery, and postsurgery groups. Endpoints were time to first recurrence of nephrolithiasis and average recurrence rate per patient-years. RESULTS: The cohort was comprised of 1,252 patients. In addition, 334 (27%) patients underwent parathyroidectomy and 918 (73%) were observed. The surgical and nonsurgical groups differed significantly in age, sex, Charlson, calcium, and primary hyperparathyroidism level. Overall recurrence rate was 31.3%. The 5-, 10-, and 15-year recurrence-free survival rates were 74.4%, 56.3%, 49.5%, respectively (presurgery), 82.4%, 70.9%, 62.8%, respectively (postsurgery; P < .0001), and 86.3%, 77.7%, and 70.6%, respectively (observation). The presurgery group had an increased risk of first recurrence compared with the observation group (hazard ratio 1.89; 95% confidence interval, 1.44-2.47). The average recurrence rates among all surgical patients who recurred were 1 event per 4.3 patient-years presurgery versus 1 event per 6.7 patient-years postsurgery (P = .0001). CONCLUSION: Recurrent nephrolithiasis is a significant problem in patients with primary hyperparathyroidism. Parathyroidectomy prolongs the time to first recurrence and decreases the number of re-recurrences over time but does not eliminate recurrences. Observation may also be a reasonable approach in selected patients.

Renal complications and quality of life in postsurgical hypoparathyroidism: a case-control study.

PURPOSE: Conventional therapy (calcium and activated vitamin D) does not restore calcium homeostasis in patients with chronic hypoparathyroidism (HypoPT) and is associated with renal complications and reduced quality of life (QoL). The aim of this study was to evaluate in a case-control, cross-sectional study, the rate of renal complications and QoL in two sex- and age-matched cohort of patients with differentiated thyroid cancer with (n = 89) and without (n = 89) chronic post-operative HypoPT (PoHypoPT) and their relationship with the biochemical control of the disease. METHODS: Serum and urinary parameters, renal ultrasound and QoL were assessed by SF-36 and WHO-5 questionnaires. RESULTS: Forty-three (48.3%) PoHypoPT patients reported symptoms of hypocalcemia. Twenty-six (29.2%) patients were at target for all 6 parameters, 46 (51.6%) for 5. The most frequently unmet targets were gender-specific 24-h urinary calcium (44.9%) and serum calcium (37.1%). Serum phosphate, magnesium and 25(OH)D were in the normal range in > 90% of patients. Renal calcifications were found in 26 (29.2%) patients, with no correlation with 24-h urinary calcium. eGFR did not differ between patients and controls. Conversely, patients had a significant higher rate of renal calcifications and a lower SF-36, but not WHO-5, scores. SF-36 scores did not differ between PoHypoPT patients who were, or not, hypocalcemic. CONCLUSIONS: Our study shows that the rate of renal calcifications was higher in patients with PoHypoPT than in those without. This finding, together with the reduced QoL and the presence of hypocalcemic symptoms in about half patients, underscores that the treatment of chronic HypoPT with conventional therapy is suboptimal.

Calcificación miocárdica de etiología multifactorial / Myocardial calcification with multifactorial etiology

En el presente trabajo se describe un caso de muerte súbita en una mujer de 70 años que fallece 20 días después de ser dada de alta tras ingreso por infección urinaria secundaria a litiasis renal complicada con shock séptico e insuficiencia renal y respiratoria. En el corazón se identificó una cardiopatía isquémica crónica y extensas áreas de miocardio calcificado. Además, se exponen los tipos de calcificaciones del miocardio existentes y sus causas; y se analizan aquellos factores que en el caso presentado han podido causar la calcificación del miocardio(AU)

In the present report, we describe a case of sudden death in a 70-year-old woman who died 20 days after been discharged after admission for urinary infection secondary to renal lithiasis complicated with septic shock and renal and respiratory failure. It has been identified chronic ischemic heart disease and extensive areas of calcified myocardium. Also, we review myocardial calfications subtypes and its causes, and we analyze the specifics of the presented case(AU)

Premature Senescence and Telomere Shortening Induced by Oxidative Stress From Oxalate, Calcium Oxalate Monohydrate, and Urine From Patients With Calcium Oxalate Nephrolithiasis.

Oxidative stress, a well-known cause of stress-induced premature senescence (SIPS), is increased in patients with calcium oxalate (CaOx) kidney stones (KS). Oxalate and calcium oxalate monohydrate (COM) induce oxidative stress in renal tubular cells, but to our knowledge, their effect on SIPS has not yet been examined. Here, we examined whether oxalate, COM, or urine from patients with CaOx KS could induce SIPS and telomere shortening in human kidney (HK)-2 cells, a proximal tubular renal cell line. Urine from age- and sex-matched individuals without stones was used as a control. In sublethal amounts, H2O2, oxalate, COM, and urine from those with KS evoked oxidative stress in HK-2 cells, indicated by increased protein carbonyl content and decreased total antioxidant capacity, but urine from those without stones did not. The proportion of senescent HK-2 cells, as indicated by SA-ßgal staining, increased after treatment with H2O2, oxalate, COM, and urine from those with KS. Expression of p16 was higher in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS than it was in cells treated with urine from those without stones and untreated controls. p16 was upregulated in the SA-ßgal positive cells. Relative telomere length was shorter in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS than that in cells treated with urine from those without stones and untreated controls. Transcript expression of shelterin components (TRF1, TRF2 and POT1) was decreased in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS, in which case the expression was highest. Urine from those without KS did not significantly alter TRF1, TRF2, and POT1 mRNA expression in HK-2 cells relative to untreated controls. In conclusion, oxalate, COM, and urine from patients with CaOx KS induced SIPS and telomere shortening in renal tubular cells. SIPS induced by a lithogenic milieu may result from upregulation of p16 and downregulation of shelterin components, specifically POT1, and might contribute, at least in part, to the development of CaOx KS.

The Molecular Aspect of Nephrolithiasis Development.

Urolithiasis is the third most common urological disease after urinary tract infections and prostate diseases, and it is characterised by an occurrence rate of about 15%, which continues to rise. The increase in the incidence of kidney stones observed in recent decades, is most likely caused by modifications in dietary habits (high content of protein, sodium and sugar diet) and lifestyle (reduced physical activity) in all industrialised countries. Moreover, men are more likely than women to be diagnosed with kidney stones. A growing body of evidence suggests that inflammation, oxidant-antioxidant imbalance, angiogenesis, purine metabolism and urea cycle disorders may play a crucial role in nephrolithiasis development. Patients with urolithiasis were characterised by an increased level of reactive oxygen species (ROS), the products of lipid peroxidation, proinflammatory cytokines as well as proangiogenic factors, compared to controls. Furthermore, it has been shown that deficiency and disorders of enzymes involved in purine metabolism and the urea cycle might be causes of deposit formation. ROS generation suggests that the course of kidney stones might be additionally potentiated by inflammation, purine metabolism and the urea cycle. On the other hand, ROS overproduction may induce activation of angiogenesis, and thus, allows deposit aggregation.

The impact of metabolic syndrome components on urinary parameters and risk of stone formation.

PURPOSE: To investigate the relationship between metabolic syndrome (MS) and urinary abnormalities in stone-forming patients. Additionally, to delineate whether severity of urinary derangements is impacted by the number of co-occurring MS components. METHODS: Stone-forming patients who underwent initial metabolic workup prior to medical intervention at a comprehensive stone clinic were retrospectively reviewed and included in the study. Patients were given a six point (0-5) Metabolic Syndrome Severity Score (MSSS) based on the number of co-occurring MS components and split into six respective groups. Baseline clinical characteristics and metabolic profiles were compared between groups. RESULTS: Four-hundred-ninety-five patients were included in the study. Median age and median BMI was 58 years and 27.26 kg/m2, respectively. Several significant metabolic differences were noted, most notably a downward trend in median urinary pH (p < 0.001) and an upward trend in median urinary supersaturation uric acid (p < 0.001) across groups as MSSS increased. Multivariate analysis demonstrated an independent association between higher MSSS and increasing number of urinary abnormalities. A second multivariate analysis revealed that all MS components except hyperlipidemia were independently associated with low urinary pH. Additionally, obesity was independently associated with the greatest number of urinary abnormalities and had the strongest association with hyperuricosuria. CONCLUSIONS: Prior research has attributed the strong association of nephrolithiasis and MS to high prevalence of UA nephrolithiasis and low urinary pH. Our findings indicate that all MS components with the exception of hyperlipidemia were independently associated with low urinary pH suggesting a mechanism independent from insulin resistance.

Results of a Gene Panel Approach in a Cohort of Patients with Incomplete Distal Renal Tubular Acidosis and Nephrolithiasis.

BACKGROUND: Distal renal tubular acidosis (dRTA) is characterized by an impairment of urinary acidification resulting in metabolic acidosis, hypokalemia, and inappropriately elevated urine pH. If not treated, this chronic condition eventually leads to nephrocalcinosis, nephrolithiasis, impaired renal function, and bone demineralization. dRTA is a well-defined entity that can be diagnosed by genetic testing of 5 genes known to be disease-causative. Incomplete dRTA (idRTA) is defined as impaired urinary acidification that does not lead to overt metabolic acidosis and therefore can be diagnosed if patients fail to adequately acidify urine after an ammonium chloride (NH4Cl) challenge or furosemide and fludrocortisone test. It is still uncertain whether idRTA represents a distinct entity or is part of the dRTA spectrum and whether it is caused by mutations in the same genes of overt dRTA. METHODS: In this cross-sectional study, we investigated a group of 22 stone formers whose clinical features were suspicious of idRTA. They underwent an NH4Cl challenge and were found to have impaired urinary acidification ability. These patients were then analyzed by genetic testing with sequencing of 5 genes: SLC4A1, ATP6V1B1, ATP6V0A4, FOXI1, and WDR72. RESULTS: Two unrelated individuals were found to have two different variants in SLC4A1 that had never been described before. CONCLUSIONS: Our results suggest the involvement of other genes or nongenetic tubular dysfunction in the pathogenesis of idRTA in stone formers. However, genetic testing may represent a cost-effective tool to recognize, treat, and prevent complications in these patients.