Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?

Adipose Tissue Denervation Blunted the Decrease in Bone Formation Promoted by Obesity in Rats.

The impact of obesity upon bone metabolism is controversial since both beneficial or harmful effects have been reported. Bone remodeling is modulated by the central nervous system through cytokines, hormones and neuromodulators. The present study aimed to evaluate the effects evoked by bilateral retroperitoneal white adipose tissue (rWAT) denervation (Dnx) upon bone mineral metabolism and remodeling in an experimental model of obesity in rats. Male Wistar rats were fed during 18 weeks with high-fat diet (HFD) or standard diet (SD) as controls, and rWAT Dnx or Sham surgery was performed at the 14th week. Biochemical and hormonal parameters, bone histomorphometry, rWAT and hypothalamus protein and gene expression were analyzed. The HFD group presented decreased bone formation parameters, increased serum and bone leptin and FGF23, increased serum and hypothalamic neuropeptide Y (NPY) and decreased serum 1,25-dihydroxyvitamin D3 and PTH. After rWAT Dnx, bone markers and histomorphometry showed restoration of bone formation, and serum and hypothalamic NPY decreased, without alteration in leptin levels. The present study shows that the denervation of rWAT improved bone formation in obese rats mediated by a preferential reduction in neurohormonal actions of NPY, emphasizing the relevance of the adipose tissue-brain-bone axis in the control of bone metabolism in obesity.

COVID-19: The impact on urolithiasis treatment in Brazil

ABSTRACT Introduction: It has been more than a year since the first case of Covid-19 was diagnosed in Brazil, and its most problematic feature is the oversaturation of the healthcare system capacity. Urolithiasis is a disease that requires timely and appropriate management. The present study aimed to evaluate the impact of the pandemic in hospital admissions for urolithiasis in the Brazilian public healthcare system. Materials and Methods: In this cross-sectional study, hospital admissions were obtained from the Brazilian Public Health Information system. All hospital admissions associated with urolithiasis diagnosis (ICD-10 N20) between March 2017 and February 2021 were analyzed. Results: During the COVID-19 outbreak, there was a significant decrease in hospital admissions (p<0.0001). More than 20.000 patients probably did not have the opportunity to undergo their surgeries. The impact of the COVID-19 outbreak on women's admissions was significantly more intense than for men, reducing from 48.91% to 48.36% of the total (p=0.0281). The extremes of age seemed to be more affected, with patients younger than 20 years and older than 60 years having a significant reduction in access to hospital services (p=0.033). Conclusions: In conclusion, we have noticed a considerable reduction in overall admissions for the treatment of urolithiasis in the Brazilian public healthcare system during the first year of the Covid-19 pandemic. Women and individuals older than 60 years were especially affected. In contrast, we noted a rise in urgent procedures, comparing with the average of the corresponding period of the three previous years. Recovery plans will be needed while returning to activities to handle the impounded surgical volume.

Urinary Citrate Is Associated with Kidney Outcomes in Early Polycystic Kidney Disease.

Low urinary citrate and crystal deposition accelerated cystogenesis in an experimental model of polycystic kidney disease (PKD).Hypocitraturia, frequently observed in patients with autosomal dominant PKD (ADPKD) could contribute to disease progression.Present findings suggest lower urinary citrate in early PKD was associated with faster eGFR decline and worse kidney survival.

Kidney organoids generated from erythroid progenitors cells of patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Kidney organoids have been broadly obtained from commercially available induced pluripotent stem cells (iPSCs); however, it has been a great challenge to efficiently produce renal organoid models from patients with autosomal dominant polycystic kidney disease (ADPKD) that recapitulate both embryogenesis and the mechanisms of cystogenesis. METHODS: Blood erythroid progenitors (EPs) from two ADPKD patients and one healthy donor (HC) was used as a comparative control to normalize the many technical steps for reprogramming EPs and for the organoids generation. EPs were reprogrammed by an episomal vector into iPSCs, which were differentiated into renal tubular organoids and then stimulated by forskolin to induce cysts formation. RESULTS: iPSCs derived from EPs exhibited all characteristics of pluripotency and were able to differentiate into all three germ layers. 3D tubular organoids were generated from single cells after 28 days in Matrigel. HC and ADPKD organoids did not spontaneously form cysts, but upon forskolin stimulation, cysts-like structures were observed in the ADPKD organoids but not in the HC-derived organoids. CONCLUSION: The findings of this study showed that kidney organoids were successfully generated from the blood EP cells of ADPKD patients and a healthy control donor. This approach should contribute as a powerful tool for embryonic kidney development model, which is able to recapitulate the very early pathophysiological mechanisms involved in cytogenesis.

Thiazide and thiazide-like diuretics in nephrolithiasis / Diuréticos tiazídicos e tiazídicos-like na nefrolitíase

Abstract 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.

Resumo Diuréticos tiazídicos e tiazídicos-like são amplamente usados para o tratamento da hipercalciúria em pacientes com formação de cálculos. Embora os efeitos dos diferentes tiazídicos devam ser relativamente semelhantes em termos de prevenção da recorrência do cálculo, sua potência e efeitos colaterais podem ser diferentes. No entanto, há poucos dados sobre os efeitos metabólicos e ósseos desses agentes em pacientes com nefrolitíase recorrente com hipercalciúria. O objetivo deste artigo de atualização foi comparar nossa experiência quanto ao uso de tiazídicos e tiazídicos-like com a publicada na literatura atual, no que diz respeito às suas propriedades anticalciúricas e consequente redução da formação de cálculos recorrentes. Discutimos também seu impacto na massa óssea e potenciais efeitos colaterais.

Dietary pattern analysis among stone formers: resemblance to a DASH-style diet / Análise do padrão alimentar de pacientes litiásicos: similaridades com o padrão de dieta DASH

Abstract Recent epidemiological studies have shown that dietary patterns may have a more persistent impact on the risk of stone formation than single nutrients of the diet. Dietary Approaches to Stop Hypertension (DASH), a low-sodium and fruits/vegetables-rich diet, has been associated with a lower risk of nephrolithiasis, due to altered urinary biochemistry. This observational study aimed to investigate whether the dietary pattern of stone formers (SF) resembled a DASH-diet and its influence on urinary lithogenic parameters. Anthropometric data, fasting serum sample, 24-h urine samples, and a 3-day food intake record under an unrestricted diet were obtained from 222 SF and compared with 136 non-SF subjects (controls). The DASH-diet food portions were determined from the food records whereas intakes of sodium chloride (NaCl) and protein (protein equivalent of nitrogen appearance, PNA) were estimated from 24-hr urinary sodium and urea. A dietary profile close to a DASH-diet was not observed in any of the groups. NaCl intake and PNA were significantly higher in SF versus non-SF (12.0 ± 5.2 v.s. 10.1 ± 3.4 g/day, p = 0.01 and 1.8 ± 0.1 v.s. 1.4 ± 0.1 g/kg/day, p = 0.03). SF exhibited a positive correlation of NaCl intake and PNA with urinary calcium, oxalate and uric acid, and of PNA with urinary sodium. SF consumed more vegetables and legumes, but less fruits and low-fat dairy items than non-SF. The present series presented a dietary profile characterized by low calcium and high salt and protein contents, not reflecting an ideal DASH-style diet pattern.

Resumo Estudos epidemiológicos recentes mostraram que os padrões alimentares podem ter um impacto mais persistente sobre o risco de formação de cálculos do que apenas os nutrientes da dieta. A dieta DASH (Dietary Approaches to Stop Hypertension), uma dieta pobre em sódio e rica em frutas/vegetais, tem sido associada a um menor risco de nefrolitíase, devido às alterações metabólicas urinárias. Este estudo observacional teve como objetivo investigar se o padrão alimentar de pacientes litiásicos (Lit) se assemelhava a uma dieta estilo DASH e sua influência nos parâmetros litogênicos urinários. Dados antropométricos, amostra de soro em jejum, amostras de urina de 24 horas e um registro de ingestão alimentar de 3 dias sob dieta irrestrita foram obtidos de 222 Lit e comparados com 136 indivíduos não-Lit (controles). As porções de alimentos do padrão de dieta DASH foram determinadas a partir dos registros alimentares, enquanto a ingestão de cloreto de sódio (NaCl) e proteína (Equivalente Protéico do Aparecimento de Nitrogênio Urinário, PNA) foram estimadas a partir da uréia e sódio urinários de 24 horas. Um perfil alimentar próximo a uma dieta estilo DASH não foi observado em nenhum dos grupos. A ingestão de NaCl e PNA foram significativamente maiores nos Lit versus não-Lit (12,0 ± 5,2 v.s. 10,1 ± 3,4 g/dia, p = 0,01 e 1,8 ± 0,1 v.s. 1,4 ± 0,1 g/kg/dia, p = 0,03). Os Lit exibiram uma correlação positiva entre a ingestão de NaCl e PNA com cálcio, oxalato e ácido urinários, e de PNA com sódio urinário. Os Lit consumiram mais vegetais e leguminosas, mas menos frutas e lácteos com teor reduzido de gordura do que os não-Lit. A presente série apresentou um padrão alimentar caracterizado por reduzido consumo de cálcio e elevado em sal e proteínas, não refletindo um padrão ideal de dieta DASH.

Influence of socioeconomic disparities, temperature and humidity in kidney stone composition.

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.

Caffeine Accelerates Cystic Kidney Disease in a Pkd1-Deficient Mouse Model.

BACKGROUND/AIMS: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and growth, leading to end-stage renal disease. A higher kidney volume is predictive of a more accelerated decline in renal function. This study aimed to examine the effects of caffeine, a phosphodiesterase inhibitor, on the progression of cystic kidney disease in a mouse model orthologous to human disease (Pkd1cond/cond:Nestincre). METHODS: Caffeine was administered to male cystic (CyCaf) and noncystic (NCCaf) mice (Pkd1cond/cond) from conception and at the postweaning period through 12 weeks of life (3 mg/d), while control animals consumed water (CyCtrl and NCCtrl). Renal ultrasonography was performed at 10 weeks of life to calculate total kidney volume and cystic index. At the end of the protocol, blood and urine samples were collected for biochemical analysis, and animals were euthanized. Kidneys were harvested to obtain renal tissue for determinations of adenosine 3´5´-cyclic monophosphate (cAMP) by an enzymatic immunoassay kit and phosphorylated extracellular signal-regulated kinase (p-ERK) by Western blotting. Renal fibrosis (picrosirius staining), renal cell proliferation (ki-67 immunohistochemistry) and apoptotic rates (TUNEL analysis) were also determined. RESULTS: At 12 weeks, CyCaf mice exhibited higher serum urea nitrogen, renal cystic index, total kidney volume, kidney cell proliferation, apoptosis and fibrosis compared with CyCtrl mice. Serum cystatin C was significantly higher in CyCaf than in NCCaf and NCCtrl mice. CyCaf mice had higher total kidney weight than all other groups but not higher heart and liver weight. The levels of cAMP and p-ERK did not differ among the groups. CONCLUSION: Caffeine consumption from conception through 12 weeks led to increased cystic index and total kidney volume and worsened renal function in Pkd1-deficient cystic mice, suggesting that high consumption of caffeine may contribute to a faster progression of renal disease in ADPKD.

Influence of nutritional status, laboratory parameters and dietary patterns upon urinary acid excretion in calcium stone formers / Influência do estado nutricional e dos parâmetros laboratoriais e dietéticos sobre a excreção urinária ácida em pacientes portadores de litíase cálcica

ABSTRACT Introduction: Obesity and Metabolic Syndrome (MS) are associated with low urinary pH and represent risk factors for nephrolithiasis, especially composed by uric acid. Acidogenic diets may also contribute to a reduction of urinary pH. Propensity for calcium oxalate precipitation has been shown to be higher with increasing features of the MS. Objective: A retrospective evaluation of anthropometric and body composition parameters, MS criteria and the dietary patterns of overweight and obese calcium stone formers and their impact upon urinary pH and other lithogenic parameters was performed. Methods: Data regarding anthropometry, body composition, serum and urinary parameters and 3-days dietary records were obtained from medical records of 102(34M/68F) calcium stone formers. Results: A negative correlation was found between urinary pH, waist circumference and serum uric acid levels (males). The endogenous production of organic acids (OA) was positively correlated with triglycerides levels and number of features of MS (males), and with glucose, uric acid and triglycerides serum levels, and number of features of MS (females). No significant correlations were detected between Net Acid Excretion (NAE) or Potential Renal Acid Load of the diet with any of the assessed parameters. A multivariate analysis showed a negative association between OA and urinary pH. Conclusion: The endogenous production of OA and not an acidogenic diet were found to be independently predictive factors for lower urinary pH levels in calcium stone formers. Hypercalciuric and/or hyperuricosuric patients presented higher OA levels and lower levels of urinary pH.

RESUMO Introdução: A obesidade e a Síndrome Metabólica (SM) se associam a pH urinário ácido e representam fatores de risco para litíase renal, especialmente a úrica. Dietas acidogênicas também podem contribuir para a redução do pH urinário. Já foi demonstrado maior risco de precipitação de oxalato de cálcio em proporção aos critérios de SM. Objetivo: Avaliar retrospectivamente o impacto de parâmetros antropométricos, composição corporal, critérios de SM e padrão alimentar sobre o pH urinário e outros parâmetros litogênicos em pacientes com sobrepeso e obesos com litíase cálcica. Métodos: Foram coletados dados de antropometria, composição corporal, exames séricos e urinários, e registros alimentares (3 dias) de 102 (34M/68F) pacientes com litíase cálcica. Resultados: O pH urinário se correlacionou negativamente com a circunferência da cintura e ácido úrico sérico (homens). A produção endógena de ácidos orgânicos (AO) se correlacionou positivamente com os triglicérides séricos e o número de critérios de SM (homens), e com glicemia, ácido úrico, triglicérides e número de critérios para SM (mulheres). Não se observaram correlações significantes entre a excreção renal líquida de ácidos (NAE) e o potencial de carga ácida renal (PRAL) da dieta com nenhum dos parâmetros avaliados. Na análise de regressão multivariada, os AO apresentaram associação negativa significante com o pH urinário. Conclusão: A produção endógena de AO, e não um padrão de dieta acidogênica, foi o fator determinante independente para menores níveis de pH urinário em pacientes com litíase cálcica. Pacientes com hipercalciúria e/ou hiperuricosúria apresentaram maiores valores de AO e menores de pH urinário.

Bone turnover after bariatric surgery

ABSTRACT Objective The aim of the present study was to evaluate parameters of bone and mineral metabolism after bariatric surgery. Subjects and methods This sectional study included data from medical records from 61 bariatric surgery (BS) patients (minimum period of 6 months after the procedure) and from 30 class II and III obese patients as a control group (Cont), consisting of daily dietary intake of macronutrients, calcium and sodium, serum 25(OH)D and parathyroid hormone (PTH) and other biochemical serum and urinary parameters. Bone alkaline phosphatase (BAP), leptin, fibroblast growth factor-23 (FGF-23) and deoxypyridinoline (DPYD) were determined from available banked serum and urinary samples. Results Mean body mass index (BMI), median energy, carbohydrate, protein and sodium chloride consumption were significantly lower in the BS versus Cont, but calcium and lipids were not. No significant differences were found in ionized calcium, 25(OH)D, PTH and fibroblast growth factor 23 (FGF-23) between groups. Mean serum BAP was significantly higher for BS versus Cont and had a positive correlation with time after the surgical procedure. Mean serum leptin was significantly lower and median urinary DPYD higher in BS versus Cont. Conclusion The present study showed an increase in bone markers of both bone formation and resorption among bariatric patients up to more than 7 years after the surgical procedure, suggesting that an increased bone turnover persists even at a very long-term follow-up in such patients.

Bone turnover after bariatric surgery.

OBJECTIVE: The aim of the present study was to evaluate parameters of bone and mineral metabolism after bariatric surgery. SUBJECTS AND METHODS: This sectional study included data from medical records from 61 bariatric surgery (BS) patients (minimum period of 6 months after the procedure) and from 30 class II and III obese patients as a control group (Cont), consisting of daily dietary intake of macronutrients, calcium and sodium, serum 25(OH)D and parathyroid hormone (PTH) and other biochemical serum and urinary parameters. Bone alkaline phosphatase (BAP), leptin, fibroblast growth factor-23 (FGF-23) and deoxypyridinoline (DPYD) were determined from available banked serum and urinary samples. RESULTS: Mean body mass index (BMI), median energy, carbohydrate, protein and sodium chloride consumption were significantly lower in the BS versus Cont, but calcium and lipids were not. No significant differences were found in ionized calcium, 25(OH)D, PTH and fibroblast growth factor 23 (FGF-23) between groups. Mean serum BAP was significantly higher for BS versus Cont and had a positive correlation with time after the surgical procedure. Mean serum leptin was significantly lower and median urinary DPYD higher in BS versus Cont. CONCLUSION: The present study showed an increase in bone markers of both bone formation and resorption among bariatric patients up to more than 7 years after the surgical procedure, suggesting that an increased bone turnover persists even at a very long-term follow-up in such patients.

N-acetylcysteine protects against star fruit-induced acute kidney injury.

BACKGROUND: Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect. MATERIALS AND METHODS: Male Wistar rats received SF juice (4 mL/100 g body weight) by gavage after a 12 h fasting and water deprivation. Fasting and water deprivation continued for 6 h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n = 6): received tap water; SF + NAC (n = 6): received NAC (4.8 g/L) in drinking water for 48 h after gavage; and Sham (n = 6): no interventions. After 48 h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments. RESULTS: SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy. CONCLUSIONS: Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI.

Treatment of patients with uric acid stones.

Uric acid nephrolithiasis and unduly acidic urinary pH are both considered a renal manifestation of insulin resistance but the underlying mechanisms for the development of low urinary pH and the propensity for uric acid stone formation are not completely elucidated. Nevertheless, excessive dietary acid intake, increased endogenous acid production and/or defective NH4+ excretion play an important role, among other factors. The main principles of therapy for uric acid nephrolithiasis are aimed at urinary alkalinization through diet modification or pharmacologic agents, increase of urinary volume, and less importantly at the reduction of uric acid excretion.

Adult presentation of Bartter syndrome type IV with erythrocytosis / Apresentação tardia de síndrome de Bartter tipo IV com eritrocitose

Abstract Bartter syndrome comprises a group of rare autosomal-recessive salt-losing disorders with distinct phenotypes, but one unifying pathophysiology consisting of severe reductions of sodium reabsorption caused by mutations in five genes expressed in the thick ascending limb of Henle, coupled with increased urinary excretion of potassium and hydrogen, which leads to hypokalemic alkalosis. Bartter syndrome type IV, caused by loss-of-function mutations in barttin, a subunit of chloride channel CLC-Kb expressed in the kidney and inner ear, usually occurs in the antenatal-neonatal period. We report an unusual case of late onset presentation of Bartter syndrome IV and mild phenotype in a 20 years-old man who had hypokalemia, deafness, secondary hyperparathyroidism and erythrocytosis.

Resumo A síndrome de Bartter compreende um grupo raro de doenças autossômicas recessivas perdedoras de sal, decorrentes de mutações em genes expressos na porção ascendente espessa da alça de Henle, com fenótipos distintos, porém fisiopatogenia única, que consiste em redução severa da reabsorção de sódio, e aumento da excreção urinária de hidrogênio e potássio, levando à alcalose hipocalêmica. A síndrome de Bartter tipo IV, causada por mutações com perda de função da bartina, uma subunidade do canal de cloro CLC-Kb expressa no rim e ouvido interno, geralmente se apresenta nos períodos ante e neonatal. No presente relato, descreve-se um caso não usual de síndrome de Bartter tipo IV com apresentação tardia e fenótipo atenuado, diagnosticado por análise molecular, em um homem adulto de 20 anos que se apresentava com hipocalemia, surdez, hiperparatireoidismo secundário e eritrocitose.

Litíase urinária e gestação / Urolithiasis and pregnancy

A litíase urinária é frequentemente diagnosticada durante a gestação. O diagnóstico de nefrolitíase assintomática durante a gestação não requer medidas adicionais, apenas o seguimento do pré-natal normal. Contudo, quando ocorre cólica renal ou complicações decorrentes da litíase urinária, medidas adicionais tornam-se necessárias. Nestes eventos, mais comuns nos últimos meses de gestação, há particularidades relacionadas ao quadro clínico, diagnóstico e tratamento específicos para esta população de pacientes. O presente artigo tem como objetivo revisar estes aspectos de litíase urinária na gestação à luz do conhecimento atual e da experiência pessoal dos autores.

The diagnosis of urolithiasis during pregnancy is common, even though no additional measures are required in asymptomatic cases. Renal colic or complications of urinary lithiasis occur more frequently during the last months of pregnancy, and there are several particularities for the diagnosis and treatment of this subset of women. The present manuscript aim to review the current knowledge concerning this subject and present authors personal experience.

Exercise capacity in polycystic kidney disease.

BACKGROUND: Reports about exercise performance in autosomal dominant polycystic kidney disease (ADPKD) are scarce. We aimed to evaluate exercise capacity and levels of nitric oxide and asymmetric dimethylarginine (ADMA) in normotensive patients with ADPKD. STUDY DESIGN: Prospective controlled cohort study. SETTING & PARTICIPANTS: 26 patients with ADPKD and 30 non-ADPKD control participants (estimated glomerular filtration rate>60 mL/min/1.73 m2, aged 19-39 years, and blood pressure [BP]<140/85 mmHg). We excluded smokers, obese people, and individuals with associated diseases. PREDICTOR: ADPKD versus control. OUTCOMES: Exercise capacity and nitric oxide and ADMA levels in response to exercise. MEASUREMENTS: Cardiopulmonary exercise testing and serum and urinary nitric oxide, plasma ADMA, and BP levels before and after exercise. RESULTS: Mean basal systolic and diastolic BP, estimated glomerular filtration rate, and age did not differ between the ADPKD and control groups (116±12 vs. 110±11 mmHg, 76±11 vs 71±9 mmHg, 113±17 vs. 112±9.6 mL/min/1.73 m2, and 30±8 vs. 28.9±7.3 years, respectively). Peak oxygen uptake and anaerobic threshold were significantly lower in the ADPKD group than in controls (22.2±3.3 vs. 31±4.8 mL/kg/min [P<0.001] and 743.6±221 vs. 957.4±301 L/min [P=0.01], respectively). Postexercise serum and urinary nitric oxide levels in patients with ADPKD were not significantly different from baseline (45±5.1 vs. 48.3±4.6 µmol/L and 34.7±6.5 vs. 39.8±6.8 µmol/mg of creatinine, respectively), contrasting with increased postexercise values in controls (63.1±1.9 vs. 53.9±3.1 µmol/L [P=0.01] and 61.4±10.6 vs. 38.7±5.6 µmol/mg of creatinine [P=0.01], respectively). Similarly, whereas postexercise ADMA level did not change in the ADPKD group compared to those at rest (0.47±0.04 vs. 0.45±0.02 µmol/L [P=0.6]), it decreased in controls (0.39±0.02 vs. 0.47±0.02 µmol/L [P=0.006]), as expected. A negative correlation between nitric oxide and ADMA levels after exercise was found in only the control group (r = -0.60; P<0.01). LIMITATIONS: Absence of measurements of flow-mediated dilatation and oxidative status. CONCLUSIONS: We found lower aerobic capacity in young normotensive patients with ADPKD with preserved kidney function and inadequate responses of nitric oxide and ADMA levels to acute exercise, suggesting the presence of early endothelial dysfunction in this disease.

Determination of urinary lithogenic parameters in murine models orthologous to autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD), a genetic disease caused by mutations in PKD1 or PKD2 genes, is associated with a high prevalence of nephrolithiasis. The underlying mechanisms may encompass structural abnormalities resulting from cyst growth, urinary metabolic abnormalities or both. An increased frequency of hypocitraturia has been described in ADPKD even in the absence of nephrolithiasis, suggesting that metabolic alterations may be associated with ADPKD per se. We aimed to investigate whether non-cystic Pkd1-haploinsufficient (Pkd1(+/-)) and/or nestin-Cre Pkd1-targeted cystic (Pkd1(cond/cond):Nestin(cre)) mouse models develop urinary metabolic abnormalities potentially related to nephrolithiasis in ADPKD. 24-h urine samples were collected during three non-consecutive days from 10-12 and 18-20 week-old animals. At 10-12 weeks of age, urinary oxalate, calcium, magnesium, citrate and uric acid did not differ between test and their respective control groups. At 18-20 weeks, Pkd1(+/-) showed slightly but significantly higher urinary uric acid vs. controls while cystic animals did not. The absence of hypocitraturia, hyperoxaluria and hyperuricosuria in the cystic model at both ages and the finding of hyperuricosuria in the 18-20 week-old animals suggest that anatomic cystic distortions per se do not generate the metabolic disturbances described in human ADPKD-related nephrolithiasis, while Pkd1 haploinsufficiency may contribute to this phenotype in this animal model.

Pain determinants of pain in autosomal dominant polycystic kidney disease.

Pain is the most common symptom reported by ADPKD patients, afflicting approximately 60% of cases and may result from renal hemorrhage, calculi, urinary tract infections, cyst rupture, or due to stretching of the capsule or traction of the renal pedicle. We have recently investigated pain patterns in AD-PKD patients using a translated version of a pain questionnaire specific for AD-PKD population. The questionnaire revealed that 67% patients with ADPKD exhibited some type of pain. The findings of that study emphasized that pain appeared early in the course of ADPKD, when patients still exhibited preserved renal function. In the present study, a multivariate logistic regression analysis disclosed that renal volume (9-fold increased risk) and nephrolithiasis (4-fold increased risk) were the most important determinant factors for pain in ADPKD patients with preserved renal function, after adjustments for the presence of hypertension and duration of the disease.