Effects of thiazides and new findings on kidney stones and dysglycemic side effects.

Thiazide and thiazide-like diuretics (thiazides) belong to the most frequently prescribed drugs worldwide. By virtue of their natriuretic and vasodilating properties, thiazides effectively lower blood pressure and prevent adverse cardiovascular outcomes. In addition, through their unique characteristic of reducing urine calcium, thiazides are also widely employed for the prevention of kidney stone recurrence and reduction of bone fracture risk. Since their introduction into clinical medicine in the early 1960s, thiazides have been recognized for their association with metabolic side effects, particularly impaired glucose tolerance, and new-onset diabetes mellitus. Numerous hypotheses have been advanced to explain thiazide-induced glucose intolerance, yet underlying mechanisms remain poorly defined. Regrettably, the lack of understanding and unpredictability of these side effects has prompted numerous physicians to refrain from prescribing these effective, inexpensive, and widely accessible drugs. In this review, we outline the pharmacology and mechanism of action of thiazides, highlight recent advances in the understanding of thiazide-induced glucose intolerance, and provide an up-to-date discussion on the role of thiazides in kidney stone prevention.

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.

Thiazides for kidney stone recurrence prevention.

PURPOSE OF REVIEW: Kidney stones are the most common condition affecting the kidney, and characterized by a high rate of recurrence. Thiazide and thiazide-like diuretics (thiazides) are commonly prescribed to prevent the recurrence of kidney stones. This review offers a comprehensive up-to-date assessment of the evidence supporting the use of thiazides for kidney stone recurrence prevention, highlights potential harms associated with treatment, and identifies areas of knowledge that require further investigation. RECENT FINDINGS: The clinical routine to prescribe thiazides for kidney stone prevention has recently been challenged by the findings of the large NOSTONE trial that failed to show superiority of hydrochlorothiazide at doses up to 50 mg daily over placebo in preventing a composite of clinical or radiological recurrence in patients at high risk of recurrence. Yet, adverse events such as new onset diabetes mellitus and gout were more common in patients receiving hydrochlorothiazide compared to placebo. As demonstrated by a novel meta-analysis presented in this review encompassing all randomized placebo-controlled trials with thiazide monotherapy, current trial evidence does not indicate that thiazide monotherapy is significantly better than placebo in preventing kidney stone recurrence. SUMMARY: Given the limited efficacy and possible adverse effects, we advocate for a restrictive use of thiazides for kidney stone recurrence prevention. Clearly, there remains a high unmet medical need for effective, targeted therapies to prevent recurrence of kidney stones.

Prevalence and characteristics of genetic disease in adult kidney stone formers.

BACKGROUND: Molecular mechanisms of kidney stone formation remain unknown in most patients. Previous studies showed high a heritability of nephrolithiasis, but data on prevalence and characteristics of genetic disease in unselected adults with nephrolithiasis are lacking. This study was conducted to fill this important knowledge gap. METHODS: We performed whole exome sequencing in 787 participants of the Bern Kidney Stone Registry, an unselected cohort of adults with ≥ 1 past kidney stone episode (KSF), and 114 non-stone-forming individuals (NKSF). An exome-based panel of 34 established nephrolithiasis genes was analyzed and variants assessed according to ACMG criteria. Pathogenic (P) or likely pathogenic (LP) variants were considered diagnostic. RESULTS: Mean age of KSF was 47±15 years, and 18% were first time KSF. A Mendelian kidney stone disease was present in 2.9% (23 of 787) of KSF. The most common genetic diagnoses were cystinuria (SLC3A1, SLC7A9; n=13), Vitamin D-24 hydroxylase deficiency (CYP24A1; n=5) and primary hyperoxaluria (AGXT, GRHPR, HOGA1; n=3). 8.1% (64 of 787) of KSF were monoallelic for LP/P variants predisposing to nephrolithiasis, most frequently in SLC34A1/A3 or SLC9A3R1 (n=37), CLDN16 (n=8) and CYP24A1 (n=8). KSF with Mendelian disease had a lower age at the first stone event (30±14 years vs. 36±14 years, p=0.003), were more likely to have cystine stones (23.4% vs. 1.4%) and less likely to have calcium oxalate monohydrates stones (31.9% vs. 52.5%) compared to KSF without genetic diagnosis. The phenotype of KSF with variants predisposing to nephrolithiasis was subtle and showed significant overlap with KSF without diagnostic variants. In NKSF, no Mendelian disease was detected, and LP/P variants were significantly less prevalent compared to KSF (1.8% vs. 8.1%). CONCLUSION: Mendelian disease is uncommon in unselected adult KSF, yet variants predisposing to nephrolithiasis are significantly enriched in adult KSF.

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.

Thiazides Attenuate Insulin Secretion Through Inhibition of Mitochondrial Carbonic Anhydrase 5b in ß -Islet Cells in Mice.

SIGNIFICANCE STATEMENT: Thiazide diuretics (thiazides) are among the most widely prescribed drugs worldwide, but their use is associated with glucose intolerance and new-onset diabetes mellitus. The molecular mechanisms remain elusive. Our study reveals that thiazides attenuate insulin secretion through inhibition of the mitochondrial carbonic anhydrase isoform 5b (CA5b) in pancreatic ß cells. We furthermore discovered that pancreatic ß cells express only one functional carbonic anhydrase isoform, CA5b, which is critical in replenishing oxaloacetate in the mitochondrial tricarboxylic acid (TCA) cycle (anaplerosis). These findings explain the mechanism for thiazide-induced glucose intolerance and reveal a fundamental role of CA5b in TCA cycle anaplerosis and insulin secretion in ß cells. BACKGROUND: Thiazide diuretics are associated with glucose intolerance and new-onset diabetes mellitus. Previous studies demonstrated that thiazides attenuate insulin secretion, but the molecular mechanisms remain elusive. We hypothesized that thiazides attenuate insulin secretion via one of the known molecular thiazide targets in ß cells. METHODS: We performed static insulin secretion experiments with islets of wild-type, Sodium/chloride co-transporter (NCC) (SLC12A3), and sodium-driven chloride/bicarbonate exchanger (NDCBE) (SLC4A8) knock-out (KO) mice and with murine Min6 cells with individual knockdown of carbonic anhydrase (CA) isoforms to identify the molecular target of thiazides in ß cells. CA isoform 5b (CA5b) KO mice were then used to assess the role of the putative thiazide target CA5b in ß -cell function and in mediating thiazide sensitivity in vitro and in vivo . RESULTS: Thiazides inhibited glucose- and sulfonylurea-stimulated insulin secretion in islets and Min6 cells at pharmacologically relevant concentrations. Inhibition of insulin secretion by thiazides was CO 2 /HCO 3- -dependent, not additive to unselective CA inhibition with acetazolamide, and independent of extracellular potassium. By contrast, insulin secretion was unaltered in islets of mice lacking the known molecular thiazide targets NCC or NDCBE. CA expression profiling with subsequent knockdown of individual CA isoforms suggested mitochondrial CA5b as a molecular target. In support of these findings, thiazides significantly attenuated Krebs cycle anaplerosis through reduction of mitochondrial oxaloacetate synthesis. CA5b KO mice were resistant to thiazide-induced glucose intolerance, and thiazides did not alter insulin secretion in CA5b KO islets. CONCLUSIONS: Thiazides attenuate insulin secretion via inhibition of the mitochondrial CA5b isoform in ß cells of mice.

The role of urinary supersaturations for lithogenic salts in the progression of autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is associated with significant risk of forming kidney stones, especially those made of calcium oxalate and uric acid, compared with the general population. Since crystals are able to activate the inflammasome and lead to cell injury, crystalluria might worsen ADPKD natural history, acting as a third hit. METHODS: The Bern ADPKD registry is a prospective observational cohort study. Height-adjusted total kidney volume (ht-TKV) was measured at baseline and every 3 years. Twenty-four hour urinary solute excretions collected at baseline and eGFR measurements over time were included in this analysis. Twenty-four hour urinary supersaturations (SS) for calcium oxalate, calcium phosphate and uric acid were calculated using EQUIL-2. Linear regression models were used to assess linear and non-linear associations between slopes of ht-TKV and eGFR with SSs and 24 h urinary solute excretions. RESULTS: Seventy-seven participants (mean age 45.0 [SD 12.9] years, eGFR 76.4 [28.3] mL/min/1.73 m2) were included, with a median follow-up of 4 years. The median slopes of ht-TKV and eGFR were 3.9 percent/year and 2.9 mL/min/1.73 m2/year, respectively. SS for uric acid showed a direct, linear association (p value for linearity 0.035) with ht-TKV slope. When analyzing individual components, urinary uric acid, ammonium, magnesium and sulfate were all directly associated with ht-TKV slope. Urinary sulfate was also directly associated with eGFR slope. CONCLUSIONS: Uric acid supersaturation and several other urinary components are identified as predictors of cyst growth in patients with ADPKD. Future studies with a dedicated design are needed to investigate the pathophysiological mechanisms underlying these associations.

Tolvaptan treatment is associated with altered mineral metabolism parameters and increased bone mineral density in ADPKD patients.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a unique bone and mineral phenotype. The impact of tolvaptan treatment on mineral metabolism and bone mineral density (BMD) is unknown. METHODS: We conducted an analysis in the Bern ADPKD Registry, a prospective observational cohort study. Mineral metabolism parameters were measured at baseline and every 12 months thereafter. BMD was determined by dual-energy X-ray absorptiometry at baseline and after 3 years. Multivariable mixed-effects regression models were applied to assess changes in mineral metabolism parameters and BMD associated with tolvaptan treatment. RESULTS: A total of 189 participants (122 without and 67 with subsequent tolvaptan treatment) were included in the analysis. During follow-up, tolvaptan treatment was associated with increased BMD at the femoral neck {ß = 0.092 [95% confidence interval (CI) 0.001-0.183], P = .047}. In addition, tolvaptan treatment was associated with higher plasma magnesium [ß = 0.019 (95% CI 0.001-0.037), P = .037], bicarbonate [ß = 0.972 (95% CI 0.242-1.702), P = .009] and urine pH [ß = 0.214 (95% CI 0.056-0.372), P = .008] and lower parathyroid hormone [ß = -0.191 (95% CI -0.328 to -0.053), P = .006], 1,25(OH)D3 [ß = -0.126 (95% CI -0.235 to -0.164), P = .024] and fractional urinary magnesium excretion [ß = -0.473 (95% CI -0.622 to -0.324), P < .001]. CONCLUSIONS: Chronic tolvaptan treatment is associated with increased femoral BMD and significant changes in both mineral metabolism and acid-base parameters in ADPKD patients.

Urinary metabolic profile and stone composition in kidney stone formers with and without heart disease.

OBJECTIVE: Kidney stone disease seems to be associated with an increased risk of incident cardiovascular outcomes; the aim of this study is to identify differences in 24-h urine excretory profiles and stone composition among stone formers with and without cardiovascular disease (CVD). METHODS: Data from patients attending the Department of Renal Medicine's metabolic stone clinic from 1995 to 2012 were reviewed. The sample was divided according to the presence or absence of CVD (myocardial infarction, angina, coronary revascularization, or surgery for calcified heart valves). Univariable and multivariable regression models, adjusted for age, sex, BMI, hypertension, diabetes, eGFR, plasma bicarbonate and potential renal acid load of foods were used to investigate differences across groups. RESULTS: 1826 patients had available data for 24-h urine analysis. Among these, 108 (5.9%) had a history of CVD. Those with CVD were older, have higher prevalence of hypertension and diabetes and lower eGFR. Univariable analysis showed that patients with CVD had significantly lower 24-h urinary excretions for citrate (2.4 vs 2.6 mmol/24 h, p = 0.04), magnesium (3.9 vs 4.2 mmol/24 h, p = 0.03) and urinary pH (6.1 vs 6.2, p = 0.02). After adjustment for confounders, differences in urinary citrate and magnesium excretions remained significant. No differences in the probability of stone formation or stone compositions were found. CONCLUSIONS: Stone formers with CVD have lower renal alkali excretion, possibly suggesting higher acid retention in stone formers with cardiovascular comorbidities. Randomized clinical trials including medications and a controlled diet design are needed to confirm the results presented here.

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.

The Role of Diet in Bone and Mineral Metabolism and Secondary Hyperparathyroidism.

Bone disorders are a common complication of chronic kidney disease (CKD), obesity and gut malabsorption. Secondary hyperparathyroidism (SHPT) is defined as an appropriate increase in parathyroid hormone (PTH) secretion, driven by either reduced serum calcium or increased phosphate concentrations, due to an underlying condition. The available evidence on the effects of dietary advice on secondary hyperparathyroidism confirms the benefit of a diet characterized by decreased phosphate intake, avoiding low calcium and vitamin D consumption (recommended intakes 1000-1200 mg/day and 400-800 UI/day, respectively). In addition, low protein intake in CKD patients is associated with a better control of SHPT risk factors, although its strength in avoiding hyperphosphatemia and the resulting outcomes are debated, mostly for dialyzed patients. Ultimately, a consensus on the effect of dietary acid loads in the prevention of SHPT is still lacking. In conclusion, a reasonable approach for reducing the risk for secondary hyperparathyroidism is to individualize dietary manipulation based on existing risk factors and concomitant medical conditions. More studies are needed to evaluate long-term outcomes of a balanced diet on the management and prevention of secondary hyperparathyroidism in at-risk patients at.

Seasonality of acute kidney injury in a tertiary hospital academic center: an observational cohort study.

BACKGROUND: The aim of our study was to describe seasonal trends of acute kidney injury (AKI) and its relationship with weather conditions in a hospitalized population. METHODS: We retrospectively collected demographic (age, sex), clinical (ICD-9-CM codes of diagnosis discharge) and laboratory data (creatinine values) from the inpatient population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS between January 2010 and December 2014 with inclusion of all patients ≥18 years with at least two values available for creatinine. The outcome of interest was AKI development, defined according to creatinine kinetics criteria. The exposures of interest were the months and seasons of the year; air temperature and humidity level were also evaluated. Log-binomial regression models adjusted for age, sex, eGFR, comorbidities, Charlson/Deyo index score, year of hospitalization were used to estimate risk ratios (RR) and 95% confidential intervals (CI). RESULTS: A total of 64,610 patients met the inclusion criteria. AKI occurred in 2864 (4.4%) hospital admissions. After full adjustment, winter period was associated with increased risk of AKI (RR 1.16, 95% CI 1.05, 1.29, p=0.003). Lower air temperature and higher humidity level were associated with risk of AKI, however in multivariable-adjusted models only higher humidity level showed a significant and independent association. CONCLUSIONS: AKI is one of the most common complications of hospitalized populations with a defined seasonal pattern and a significant increase in incidence during wintertime; weather conditions, particularly higher humidity level, are independent predictors of AKI and could partially justify the observed seasonal variations.

Dietetic and lifestyle recommendations for stone formers. / Consejos dietéticos y de estilo de vida en pacientes con litiasis urinarias.

Nutrition is tightly associated with the risk of stone events. A part from genetic predisposition, a correct and balanced diet might prevent incident kidney stones. Several studies analyzed each dietary component and different diets to better understand their impact on stone recurrence. Fluids: High fluids intake is the most important factor for preventing kidney stones disease and for every 200 mL of water, the risk of stones is reduced by 13%. Soft drinks seems to be associated to a greater risk of stone events, whereas caffeine and citrus fruits juice are not. Calcium: Normally calcium intake with diet does not exceed 1.2 g/day. A balanced consumption of dairy products is capable of reducing oxalate intestinal absorption and urinary excretion compared to low calcium diet, being protective for stone disease. Oxalate: The exact amount of oxalate contained in different foods is difficult to estimate for its variability, even in the same aliment. In addition, the amount of oxalate consumed was shown to be only a minor risk factor for stone disease, whereas its intestinal absorption is strongly influenced by external factors, such as calcium intake. Dietary oxalate restriction is advisable only in patients with known elevated consumption. Sodium: High sodium intake is both associated with hypertension, heart disease and stone risk. Increased sodium consumption is directly associated to hypercalciuria in both calcium stone formers and healthy subjects. Although dietary sodium restriction to recommended values is always desirable in stone formers, it is difficult to achieve for its broad use in food preparation. Proteins: Animal proteins are associated to increased risk for stone formation, whereas vegetable and dairy proteins are not. Increased meat intake was associated to acidic urine pH, negative calcium balance and reduced anti-lithogenic urinary solutes excretion.Fruits and vegetables: Alkalizing foods are one of the most important factors for stone protection. Their consumption increases anti-lithogenic solutes as citrate, potassium and magnesium. A diet rich in fruits and vegetables is strongly recommended for stone formers. Uric acid: Elevated meat consumption is either associated to increased purine metabolism and acid load, favoring uric acid nephrolithiasis by reducing urine pH and increasing urinary excretion of uric acid, especially in patients affected by metabolic syndrome and diabetes.In conclusion, the most effective diet for stone protection is rich in fruits and vegetables, low in animal proteins and salt, with balanced dairy product consumption and obviously, with elevated fluid intake. These characteristics make vegetarian and Mediterranean diets protective and useful for stone formers, whereas western diet is at risk for stone formation.

La nutrición está fuertemente asociada al riesgo de episodios litiásicos. Aparte de la predisposición genética, una dieta correcta y balanceada podría prevenir la incidencia de litiasis renal. Varios estudios han analizado cada componente de la dieta y diferentes dietas para entender mejor su impacto sobre la recurrencia litiásica. Líquidos: Una alta ingesta de fluidos es el factor más importante para la prevención de la enfermedad litiásicay por cada 200 mL de agua, el riesgo de litiasis se reduce un 13%. Los refrescos parecen estar asociados a un mayor riesgo de eventos litiásicos, mientras que la cafeina y los zumos de cítricos no lo están. Calcio: Normalmente la ingesta diaria de calcio con la dieta no excede los 1,2 g. Un consumo balanceado de productos lácteos es capaz de reducir la absorción intestinal y la excreción urinaria de oxalato si lo comparamos con una dieta pobre en calcio, siendo protector para la enfermedad litiásica. Oxalato: La cantidad exacta de oxalato en las diferentes comidas es difícil de estimar debido a su variabilidad, incluso en el mismo alimento. Además, se demostró que la cantidad de oxalato ingerido era solo un factor de riesgo menor para la enfermedad litiásica, mientras que  su absorción intestinal está fuertemente influenciada por factores externos como la ingesta de calcio. La restricción de oxalato en la dieta se aconseja solamente en pacientes con aumento probado en su consumo. Sodio: Una ingesta elevada de sodio se asocia tanto con la hipertensión como con la enfermedad cardiaca y el riesgo de litiasis. El consumo elevado de sodio está directamente asociado con la hipercalciuria, tanto en litiásicos cálcicos como en sujetos sanos. Aunque la restricción dietética de sodio a los valores recomendadoses deseable en los pacientes litiásicos, es difícil de conseguir debido al alto uso de sodio en la preparación de las comidas.Proteinas: Las proteinas animales están asociadas a un riesgo aumentado para la formación de litiasis, mientras que las vegetales y las de productos lácteos no. Un aumento de consumo de carne se ha asociado a un pH urinario ácido, balance de calcio negativo y reducciónde la excrección urinaria de solutos anti-litogénicos.Frutas y vegetales: Las comidas alcalinizantes son uno de los factores más importantes para la protección ante la litiasis. Su consumo aumenta los solutos anti-litogénicos como el citrato, potasio y magnesio. Una dieta rica en frutas y vegetales es muy recomendable para los pacientes litiásicos. Acido úrico: Un consumo elevado de carne está asociado tanto a un aumento de metabolismo de las purinas como a la carga ácida, favoreciendo la nefrolitiasis úrica al reducir el pH urinario y aumentar la excreción urinaria de ácido úrico, especialmente en pacientes afectados por el síndrome metabólico y diabetes.En conclusión, la dieta más efectiva para proteger contrala litiasis es la rica en frutas y vegetales, pobre en  proteinas animales y sal, con un consumo balanceado de productos lácteos y, obviamente, con una alta ingesta de líquidos. Estas características hacen que las dietas vegetarianas y la mediterránea sean protectoras y útiles para los pacientes litiásicos, mientras que la dieta occidental sea una dieta de riesgo para la formación de litiasis.

Dietary Oxalate Intake and Kidney Outcomes.

Oxalate is both a plant-derived molecule and a terminal toxic metabolite with no known physiological function in humans. It is predominantly eliminated by the kidneys through glomerular filtration and tubular secretion. Regardless of the cause, the increased load of dietary oxalate presented to the kidneys has been linked to different kidney-related conditions and injuries, including calcium oxalate nephrolithiasis, acute and chronic kidney disease. In this paper, we review the current literature on the association between dietary oxalate intake and kidney outcomes.

Urinary Lithogenic Risk Profile in ADPKD Patients Treated with Tolvaptan.

BACKGROUND AND OBJECTIVES: Nephrolithiasis is a common health problem in autosomal dominant polycystic kidney disease (ADPKD) and significantly contributes to patient morbidity. Recently, Tolvaptan has been introduced for the treatment of ADPKD, but whether it is associated with alterations of the urinary lithogenic risk profile remains unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted an analysis of participants enrolled in the Bern ADPKD registry, a prospective observational cohort study. Twenty-four-hour urine analyses were performed at baseline and then at yearly follow-ups. Relative supersaturation ratios for calcium oxalate, brushite, and uric acid were calculated with the program EQUIL2. Unadjusted and multivariable mixed-effects linear regression models, adjusted for age, sex, body mass index, eGFR, net acid excretion, and height-adjusted total kidney volume, were used to assess the association of Tolvaptan with urinary parameters relevant for kidney stone formation. The maximum individual follow-up time was 3 years, median follow-up time 1.9 years, and cumulative follow-up time 169 years. RESULTS: In total, 125 participants (38 with and 87 without Tolvaptan treatment) were included in the analysis. In multivariable analysis, Tolvaptan treatment was associated [adjusted estimate of the difference between Tolvaptan and no Tolvaptan; 95% confidence interval (CI)] with lower urine relative supersaturation ratios for calcium oxalate (-0.56; 95% CI, -0.82 to -0.3; P<0.001), brushite (-0.33; 95% CI, -0.54 to -0.11; P=0.004), and uric acid (-0.62; 95% CI, -0.88 to -0.37; P<0.001), and with higher urine citrate in mmol/mmol creatinine per day (0.25; 95% CI, 0.05 to 0.46; P=0.02) and calcium in mmol/mmol creatinine per day (0.31; 95% CI, 0.09 to 0.53; P=0.006) excretion. In addition, Tolvaptan treatment was associated with lower net acid excretion in mEq/mmol creatinine per day (-0.54; 95% CI, -0.90 to -0.17; P=0.004) and higher net gastrointestinal alkali absorption in mEq/mmol creatinine per day (0.57; 95% CI, 0.26 to 0.88; P<0.001). CONCLUSIONS: Tolvaptan treatment is associated with a significantly improved urinary lithogenic risk profile in patients with ADPKD.

Risk of Kidney Stones: Influence of Dietary Factors, Dietary Patterns, and Vegetarian-Vegan Diets.

Nephrolithiasis is a common medical condition influenced by multiple environmental factors, including diet. Since nutritional habits play a relevant role in the genesis and recurrence of kidney stones disease, dietary manipulation has become a fundamental tool for the medical management of nephrolithiasis. Dietary advice aims to reduce the majority of lithogenic risk factors, reducing the supersaturation of urine, mainly for calcium oxalate, calcium phosphate, and uric acid. For this purpose, current guidelines recommend increasing fluid intake, maintaining a balanced calcium intake, reducing dietary intake of sodium and animal proteins, and increasing intake of fruits and fibers. In this review, we analyzed the effects of each dietary factor on nephrolithiasis incidence and recurrence rate. Available scientific evidence agrees on the harmful effects of high meat/animal protein intake and low calcium diets, whereas high content of fruits and vegetables associated with a balanced intake of low-fat dairy products carries the lowest risk for incident kidney stones. Furthermore, a balanced vegetarian diet with dairy products seems to be the most protective diet for kidney stone patients. Since no study prospectively examined the effects of vegan diets on nephrolithiasis risk factors, more scientific work should be made to define the best diet for different kidney stone phenotypes.

Prevalence of chronic kidney disease in the Lazio region, Italy: a classification algorithm based on health information systems.

BACKGROUND: Estimating CKD prevalence is difficult. Information on CKD prevalence is rather scanty in Italy and available figures come from surveys in selected geographical areas. Administrative data have been already demonstrated to be an effective tool in estimating the epidemiological burden of diseases, however there is limited experience in literature as far as CKD is concerned. METHODS: The aim of this study is to develop an algorithm based on regional Health Administrative Databases to identify individuals with CKD and provide estimates of disease prevalence in Lazio Region (Italy); about 5.500.000 inhabitants in 2017. A population-level analysis based on a record-linkage strategy using data from Health Administrative Databases has been applied in Lazio Region. CKD cases were identified between January 1, 2012 and December 31, 2017 using Outpatient Specialist Service Information System, Hospital Discharge Registry, Ticket Exemption Registry and Drug Dispensing Registry. Age-specific and standardized prevalence rates were calculated by gender. CKD cases were classified as higher and lower severity. RESULTS: The algorithm identified 99,457 individuals with CKD (mean age 71 years, 55.8% males). The exclusive contributions of each regional source used were: 35,047 (35.2%) from Outpatient Specialist Service Information System, 27,778 (27.9%) from Hospital Discharge Registry, 4143 (4.2%) from Ticket Exemption Registry and 463 (0.5%) from Drug Dispensing Registry; 5.1% of cases were found in all databases. The standardized prevalence rate at December 31, 2017 was 1.76, 2.06% for males and 1.50% for females. The prevalence increased with age, rising from 0.33% (age 0-18) up to 14.18% (age 85+) among males and from 0.25% up to 8.18% among females. The proportion of CKD individuals with lower severity disease was 78.7% in both genders. CONCLUSIONS: The proposed algorithm represents a novel tool to monitor the burden of CKD disease, that can be used by the regional government to guide the development and implementation of evidence-based pathways of care for CKD patients. The high prevalence of people with CKD of lower severity should be carefully considered in order to promote diagnosis and optimal management at early stages.

Hyperchloremia and acute kidney injury: a retrospective observational cohort study on a general mixed medical-surgical not ICU-hospitalized population.

The aim of this observational retrospective cohort study was to analyze the association between hyperchloremia and serum chloride variation with in-hospital acute kidney injury (AKI) and mortality in a general, no-ICU hospitalized population. We performed a retrospective study on inpatient population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS between January 2010 and December 2014 with inclusion of adult patients with at least two values available for chloride, sodium and creatinine. Hyperchloremia was defined as serum chloride concentration ≥ 108 mmol/L (moderate hyperchloremia: chloremia between 108-110 mmol/L, severe hyperchloremia: chloremia > 110 mmol/L). According to the time of onset of the electrolyte disturbance, hyperchloremia was then classified as hospital acquired (HA) and community acquired (CA). In patients with HA-hyperchloremia, chloride variation (ΔCl) was calculated. In-hospital AKI was defined according to creatinine kinetics criteria occurring 48 h after hospital admission. Logistic regression analysis was used to evaluate the association between the exposures of interest and in-hospital AKI and mortality. A total of 24,912 hospital admissions met the inclusion criteria. Regression analyses showed that only severe HA-hyperchloremia was associated with increased risk of in-hospital AKI [odds ratio (OR) 2.60, 95% confidence interval (CI) 1.58, 4.30, p value < 0.001] and death (OR 3.89, 95% CI 2.11, 7.18, p value < 0.001). With increasing ΔCl, the OR of in-hospital AKI increased progressively (p value for trend = 0.005). In conclusion, severe hyperchloremia is an independent predictor for in-hospital AKI and mortality; HA-hyperchloremia is more detrimental for patient outcome; higher ΔCl from hospital admission is associated with increased risk of AKI.