Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study.

More than 20 years have passed since the identification of SLC3A1 and SLC7A9 as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the presence of modulatory factors influencing cystinuria severity. In 2016, a second renal cystine transporter, AGT1, encoded by the SLC7A13 gene, was discovered. Although it was discarded as a causative gene for cystinuria, its possible effect as a modulatory gene remains unexplored. Thus, we analyzed its function in mouse models of cystinuria, screened the SLC7A13 gene in 34 patients with different lithiasic phenotypes, and functionally characterized the identified variants. Mice results showed that AGT1/rBAT may have a protective role against cystine lithiasis. In addition, among the four missense variants detected in patients, two exhibited a 25% impairment in AGT1/rBAT transport. However, no correlation between SLC7A13 genotypes and lithiasis phenotypes was observed in patients, probably because these variants were found in heterozygous states. In conclusion, our results, consistent with a previous study, suggest that AGT1/rBAT does not have a relevant effect on cystinuria patients, although an impact in patients carrying homozygous pathogenic variants cannot be discarded.

Cystinuria: clinical practice recommendation.

Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the low solubility of cystine at normal urinary pH. We developed clinical practice recommendation for diagnosis, surgical and medical treatment, and follow-up of patients with cystinuria. Elaboration of these clinical practice recommendations spanned from June 2018 to December 2019 with a consensus conference in January 2019. Selected topic areas were chosen by the co-chairs of the conference. Working groups focusing on specific topics were formed. Group members performed systematic literature review using MEDLINE, drafted the statements, and discussed them. They included geneticists, medical biochemists, pediatric and adult nephrologists, pediatric and adult urologists experts in cystinuria, and the Metabolic Nephropathy Joint Working Group of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN members. Overall 20 statements were produced to provide guidance on diagnosis, genetic analysis, imaging techniques, surgical treatment (indication and modalities), conservative treatment (hydration, dietetic, alkalinization, and cystine-binding drugs), follow-up, self-monitoring, complications (renal failure and hypertension), and impact on quality of life. Because of the rarity of the disease and the poor level of evidence in the literature, these statements could not be graded. This clinical practice recommendation provides guidance on all aspects of the management of both adults and children with cystinuria, including diagnosis, surgery, and medical treatment.

Information and consensus document for the detection and management of chronic kidney disease.

Chronic kidney disease (CKD) is a major public health problem worldwide that affects more than 10% of the Spanish population. CKD is associated with high comorbidity rates, poor prognosis and major consumption of health system resources. Since the publication of the last consensus document on CKD seven years ago, little evidence has emerged and few clinical trials on new diagnostic and treatment strategies in CKD have been conducted, apart from new trials in diabetic kidney disease. Therefore, CKD international guidelines have not been recently updated. The rigidity and conservative attitude of the guidelines should not prevent the publication of updates in knowledge about certain matters that may be key in detecting CKD and managing patients with this disease. This document, also prepared by 10 scientific associations, provides an update on concepts, clarifications, diagnostic criteria, remission strategies and new treatment options. The evidence and the main studies published on these aspects of CKD have been reviewed. This should be considered more as an information document on CKD. It includes an update on CKD detection, risk factors and screening; a definition of renal progression; an update of remission criteria with new suggestions in the older population; CKD monitoring and prevention strategies; management of associated comorbidities, particularly in diabetes mellitus; roles of the Primary Care physician in CKD management; and what not to do in Nephrology. The aim of the document is to serve as an aid in the multidisciplinary management of the patient with CKD based on current recommendations and knowledge.

A urinary stone from the early medieval site of Riner, Catalonia.

OBJECTIVE: This paper presents the differential diagnosis of a calcified mass found in the pelvic cavity of an adult male dating to the 10th century AD. MATERIALS: Skeletal remains of an adult male exhumed from the cemetery associated with the early medieval church of Riner (Solsonès, Catalonia). METHODS: The structure and composition of the mass were examined by x-ray imaging, microscopic stereoscopy and Fourier transform infrared spectrometry analysis. RESULTS: The examination reveals a light brown kidney-shaped calcification with well-defined margins, irregular hypodense zones, and several thin concentric layers. The obtained spectra showed a mixture of carbonate apatite (with a high level of carbonation) and calcite in all the sections studied. CONCLUSION: The calcification most likely corresponds to a urinary calculus of infectious origin. SIGNIFICANCE: Given the insights that urinary calculi can provide towards understanding consequences of infection and environmental conditions, this case will be of interest to other researchers wishing to initiate comparative analyses. LIMITATIONS: The discussion of the etiology of the stone is limited by the lack of preservation of certain elements such as struvite.

[Spanish bottled and tap water analysis and their relation with urinary lithiasis]. / Análisis de las aguas embotelladas y de grifo españolas y de las implicaciones de su consumo en la litiasis urinaria.

OBJECTIVE: To perform a chemical analysis of all the available waters in Spain with the idea of offering consume recommendations to lithiasic patients. MATERIAL AND METHODS: Information research of the chemical composition of Spanish tap and bottled water in publications, supermarkets and Internet. A descriptive study, and a correlation study between water components by means of Pearson test were performed. RESULTS: Information about composition from tap water of most of the main Spanish cities and 85 bottled water brands was found. A significant correlation between calcium and magnesium concentration (p = 0.0001) and high correlation between bicarbonate and sodium concentration (p = 0.0001, Pearson coefficient 0.958) was found. It is also offered water classifications according to calcium, bicarbonate, sodium and magnesium concentrations. CONCLUSION: A guideline about water election for lithiasic patients is offered according to their geographical origin and dietetic preferences, mainly lactic consume.

Tables for estimating the glomerular filtration rate using the new CKD-EPI equation from serum creatinine concentration.

Chronic kidney disease (CKD) and its complications have become a major healthcare problem, both due to the resources that are required in the final stages of the disease and to secondary complications. As such, its early diagnosis is considered to be very important nowadays. The recently published 2013 KDIGO guidelines base the definition and classification of CKD on glomerular filtration values and albuminuria as staging criteria and prognostic markers of the disease. The MDRD and MDRD-IDMS equations (when creatinine values can be traced to the reference method) are those most used, but both the 2013 KDIGO international guidelines and the new 2013 CKD consensus document, in which ten scientific societies participated under the direction of the Spanish Society of Nephrology, recommend to be replaced by the CKD-EPI equation. Our objective has been, as with previous equations, to develop tables that display the estimated glomerular filtration rate value using the CKD-EPI equation from serum creatinine concentration, age and sex, and thereby provide an instrument that facilitates the dissemination of this new equation, particularly in settings where it is not calculated automatically.

Current use of equations for estimating glomerular filtration rate in Spanish laboratories.

INTRODUCTION: In 2006 the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) and the Spanish Society of Nephrology (S.E.N.) developed a consensus document in order to facilitate the diagnosis and monitoring of chronic kidney disease with the incorporation of equations for estimating glomerular filtration rate (eGFR) into laboratory reports. The current national prevalence of eGFR reporting and the degree of adherence to these recommendations among clinical laboratories is unknown. METHODS: We administered a national survey in 2010-11 to Spanish clinical laboratories. The survey was through e-mail or telephone to laboratories that participated in the SEQC’s Programme for External Quality Assurance, included in the National Hospitals Catalogue 2010, including both primary care and private laboratories. RESULTS: A total of 281 laboratories answered to the survey. Of these, 88.2% reported on the eGFR, with 61.9% reporting on the MDRD equation and 31.6% using the MDRD-IDMS equation. A total of 42.5% of laboratories always reported serum creatinine values, and other variables only when specifically requested. Regarding the way results were presented, 46.2% of laboratories reported the exact numerical value only when the filtration rate was below 60mL/min/1.73m2, while 50.6% reported all values regardless. In 56.3% of the cases reporting eGFR, an interpretive commentary of it was enclosed. CONCLUSIONS: Although a high percentage of Spanish laboratories have added eGFR in their reports, this metric is not universally used. Moreover, some aspects, such as the equation used and the correct expression of eGFR results, should be improved.