Bartter syndrome is an inherited renal tubular disorder caused by a defective salt reabsorption in the thick ascending limb of loop of Henle, resulting in salt wasting, hypokalemia, and metabolic alkalosis. Mutations of several genes encoding the transporters and channels involved in salt reabsorption in the thick ascending limb cause different types of Bartter syndrome. A poor phenotype–genotype relationship due to the interaction with other cotransporters and different degrees of compensation through alternative pathways is currently reported. However, phenotypic identification still remains the first step to guide the suspicion of Bartter syndrome. Given the rarity of the syndrome, and the lack of genetic characterization in most cases, limited clinical evidence for treatment is available and the therapy is based mainly on the comprehension of renal physiology and relies on the physician’s personal experiences. A better understanding of the mutated channels and transporters could possibly generate targets for specific treatment in the future, also encompassing drugs aiming to correct deficiencies in folding or plasma membrane expression of the mutated proteins.

Introduction: Large variations in demographic, economic and environmental factors might influence the worldwide distribution of urolithiasis, but scarce data are available concerning their associations with stone composition. We aimed to evaluate the frequency and composition of kidney stones and their associations with temperature, humidity, and human development index (HDI). Materials and Methods: A total of 1,158 stones from distinct patients (47±14 years old, male/female 2:1) were included. The mean annual temperature and relative humidity of each town were considered separately. Results: Calcium oxalate monohydrate (COM) was disclosed in 38.8% of patients, calcium oxalate dihydrate (COD) in 22.1%, mixed COD/apatite in 9.4%, pure apatite in 1.9%, brushite in 1.8%, struvite in 8.3%, pure uric acid in 11.1%, mixed uric acid/COM in 5.6%, and cystine/rare types in 0.8%. Mean HDI of all pooled cities was 0.780±0.03. However, people living in HDI<0.800 regions had twice the odds of having a struvite stone versus those living in HDI>0.800 (OR=2.14, 95% CI 1.11-4.11). Furthermore, a progressive increase in the struvite stones frequency from 4.5 to 22.8% was detected from HDI>0.800 through HDI<0.700. No significant difference for other stone types was disclosed. Separate logistic regression models assessed the association of each stone composition with gender, temperature, humidity and HDI as covariates. Conclusion: Patients living in low HDI areas are more prone to develop struvite stones, possibly due to lower access to healthcare. Temperature and humidity did not represent a specific risk factor for any stone type in the present sample.

Thiazide and thiazide-like diuretics are widely used for the management of hypercalciuria among stone-forming patients. Although the effects of different thiazides should be relatively similar in terms of prevention of stone recurrence, their potency and side effects may differ. However, there is scarce data concerning the metabolic and bone effects of these agents among recurrent nephrolithiasis patients with hypercalciuria. The aim of this update article was to compare our experience in the use of thiazide and thiazide- like diuretics with that of the current literature, concerning their anticalciuric properties and consequent reduction of recurrent stone formation. Their impact on bone mass and potential side effects were also discussed.