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.

Association of Vitamin D Levels With Kidney Volume in Autosomal Dominant Polycystic Kidney Disease (ADPKD).

Vitamin D possesses renoprotective effects beyond mineral metabolism, potentially reducing arterial blood pressure and inflammation and vitamin D enzymes (CYP24A1 and CYP27B1) as well as vitamin D receptor (VDR) contribute to its homeostasis. In the present study, we aimed to determine vitamin D association with kidney volume, blood pressure parameters and inflammatory markers in ADPKD. This cross-sectional study, conducted from August 2011 through May 2016, evaluated 25(OH)D, 1,25(OH)2D and other hormonal/biochemical serum and urinary parameters, inflammatory markers and monocyte expression of VDR, CYP24A1, CYP27B1 in 74 ADPKD patients. The height-adjusted total kidney volume (htTKV) was determined by MRI and blood pressure (BP) measured through 24-h ambulatory BP monitoring (ABPM).Vitamin D insufficiency was present in 62% of patients and CYP24A1 was overexpressed in this group, raising a hypothesis of 25(OH)D increased catabolism. Serum 25(OH)D levels and VDR expression were negatively correlated with htTKV as was VDR with IL-6, IL-10, CRP, and NFκB. A multiple linear regression analysis with htTKV as dependent variable, including hypertension, CRP, eGFR, age, time since diagnosis, VDR, and 25(OH)D adjusted for season of the year showed that only the first three parameters were independent predictors of the former. There has been no association of serum 25(OH)D and VDR expression with ABPM parameters. Present findings suggested that low levels of serum 25(OH)D and VDR expression are associated with a higher kidney volume in ADPKD patients, but do not represent independent risk factors for htTKV.

Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia

ABSTRACT Objective To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. Subjects and methods We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. Results We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. Conclusion The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).

Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia.

OBJECTIVE: To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. SUBJECTS AND METHODS: We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. RESULTS: We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. CONCLUSION: The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).

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.

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.

Pain determinants of pain in autosomal dominant polycystic kidney disease / Determinantes de dor em pacientes com doença renal policística autossômica dominante

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.

A dor é o sintoma mais comum relatado pelos pacientes com doença renal policística autossômica dominante (DRPAD), acometendo aproximadamente 60% dos casos, e podendo resultar de hemorragia renal, cálculos, infecções do trato urinário, ruptura do cisto, ou devido ao estiramento da cápsula ou à tração do pedículo renal. Recentemente, investigamos padrões de dor em pacientes com DRPAD usando uma versão traduzida de um questionário de dor específico para a população com DRPAD. O questionário revelou que 67% dos pacientes com DRPAD apresentaram algum tipo de dor. As conclusões do estudo enfatizaram que a dor apareceu no início do curso de ADPKD, quando os pacientes ainda exibiam função renal preservada. O presente estudo, através de uma análise de regressão múltipla, revelou que o volume renal (risco nove vezes maior) e a nefrolitíase (risco quatro vezes maior) foram os fatores determinantes mais importantes para a dor em pacientes com DRPAD com função renal preservada, após ajustes para a presença de hipertensão arterial e duração da doença.

Anxiety, depression, and quality of life in patients with familial glomerulonephritis or autosomal dominant polycystic kidney disease.

INTRODUCTION: Psychological aspects and quality of life are often evaluated in patients under renal replacement therapy, but studies about anxiety, depression, and quality of life in familial renal diseases are lacking. OBJECTIVES: To evaluate the frequency of anxiety, depression, and quality of life (QOL) and their eventual associations with the main laboratory, clinical, socioeconomic, and cultural parameters in familial glomerulonephritis (GN) or autosomal dominant polycystic kidney disease (ADPKD). METHODS: Ninety adult patients (52 familial GN and 38 ADPKD) completed the questionnaires of State Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and QOL-Short-Form SF-36, and were also submitted to a short interview. RESULTS: Moderate anxiety was detected in both groups. Depression was found in 34.6% of familial GN and 60.5% of ADPKD patients. Anxiety and depression were more associated with female gender in familial GN, and with poorer schooling in ADPKD. Patients of both groups presented two quality of life unfavorable dimensions: emotional role function and general health perception. In addition, quality of life was worse among females, unmarried, and Caucasian subjects, and those individuals with a poorer educational level. CONCLUSION: The use of these instruments allows one to appreciate the frequency and levels of anxiety, depression, and quality of life in patients with familial renal diseases that could affect their compliance to treatment. These findings can contribute to planning a better multidisciplinary assistance to such groups of patients.

Ansiedade, depressão e qualidade de vida em pacientes com glomerulonefrite familiar ou doença renal policística autossômica dominante / Anxiety, depression, and quality of life in patients with familial glomerulonephritis or autosomal dominant polycystic kidney disease

INTRODUÇÃO: Aspectos psicológicos, transtornos psiquiátricos e qualidade de vida são frequentemente avaliados em pacientes em terapia renal substitutiva. Entretanto, não existem estudos que analisem ansiedade, depressão e qualidade de vida especificamente em pacientes portadores de doenças renais familiares. OBJETIVO: Avaliar a frequência de traços e estados ansiosos e depressivos e qualidade de vida, verificando as possíveis relações com os principais achados laboratoriais, clínicos, socioeconômicos e culturais de pacientes portadores de glomerulonefrites (GN) familiares ou de doença renal policística autossômica dominante (DRPAD). MÉTODOS: Noventa pacientes adultos (52 GN familiares e 38 DRPAD) foram avaliados utilizando Inventário de Ansiedade Traço-Estado (IDATE), Inventário de Depressão Beck (Beck) e Questionário de Qualidade de Vida Short Form-36 (SF-36), além de uma breve entrevista. RESULTADOS: Observou-se ansiedade moderada em ambos os grupos, depressão em 34,6 por cento das GN e em 60,5 por cento das DRPAD. De um modo geral, ansiedade e depressão associaram-se mais ao gênero feminino na GN familiar e ao pior nível educacional na DRPAD. Pacientes de ambos os grupos apresentaram duas dimensões mais afetadas no que se refere à qualidade de vida, o aspecto emocional e a percepção geral do estado de saúde. Além disso, o SF-36 revelou que na presente amostra, a qualidade de vida foi pior para o sexo feminino, e para pacientes de cor branca, com baixa escolaridade e sem parceiros estáveis. CONCLUSÃO: Os questionários aplicados permitiram identificar frequência e graus de ansiedade, depressão e comprometimento da qualidade de vida nos pacientes com doença renal familiar, que poderiam afetar a aderência desses pacientes ao tratamento. Esses achados podem contribuir para o planejamento de um melhor atendimento multidisciplinar para ambas as doenças.

INTRODUCTION: Psychological aspects and quality of life are often evaluated in patients under renal replacement therapy, but studies about anxiety, de>pression, and quality of life in familial renal diseases are lacking. OBJECTIVES: To evaluate the frequency of anxiety, depression, and quality of life (QOL) and their eventual associations with the main laboratory, clinical, socioeconomic, and cultural parameters in familial glomerulonephritis (GN) or autosomal dominant polycystic kidney disease (ADPKD). METHODS: Ninety adult patients (52 familial GN and 38 ADPKD) completed the questionaires of State Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and QOL-Short-Form SF-36, and were also submitted to a short interview. RESULTS: Moderate anxiety was detected in both groups. Depression was found in 34.6 percent of familial GN and 60.5 percent of ADPKD patients. Anxiety and depression were more associated with female gender in familial GN, and with poorer schooling in ADPKD. Patients of both groups presented two quality of life unfavorable dimensions: emotional role function and general health perception. In addition, quality of life was worse among females, unmarried, and Caucasian subjects, and those individuals with a poorer educational level. CONCLUSION: The use of these instruments allows one to appreciate the frequency and levels of anxiety, depression, and quality of life in patients with familial renal diseases that could affect their compliance to treatment. These findings can contribute to planning a better multidisciplinary assistance to such groups of patients.

Tradução, adaptação cultural e aplicação de um questionário de dor para pacientes com doença renal policística / Translation, cultural adaptation and aplication of a pain questionnaire for patients with polycystic kidney disease

INTRODUÇÃO: A dor é um sintoma comum em pacientes com doença renal policística autossômica dominante (DRPAD), acometendo em torno de 60 por cento dos casos. OBJETIVO: Traduzir para o português, realizar a adaptação cultural e aplicar um questionário específico de dor, desenvolvido e já validado para população americana com DRPAD. PACIENTES E MÉTODO: Realizada por uma equipe multidisciplinar a partir da versão original traduzida, a adaptação cultural implicou em poucas alterações como substituição de palavras por sinônimos ou supressão de termos não comumente utilizados em nossa cultura. Foram feitas modificações em 12 das 46 questões propostas, visando melhor compreensão pelos pacientes. Houve equivalência entre esta adaptação e a posterior retrotradução. RESULTADOS: A forma final do questionário, aplicada em 97 pacientes com DRPAD (64F/33M, 35 ± 12 anos) acompanhados no Ambulatório de Rins Policísticos da Universidade Federal de São Paulo, mostrou que 65 (67 por cento) apresentavam dores isoladas ou associadas em várias localizações, mais frequentemente lombar (77 por cento), seguida de abdominal (66 por cento), cefaleia (15 por cento) e torácica (4 por cento). O questionário revelou que depois do antecedente familiar, a dor foi o segundo fator a contribuir para o diagnóstico de DRPAD nesta população (55 por cento e 22 por cento dos casos, respectivamente). DISCUSSÃO: Dados clínicos e laboratoriais dos prontuários médicos mostraram que pacientes com dor apresentavam volume renal e tamanho do maior cisto significantemente maiores do que os sem dor. CONCLUSÕES: Concluimos que a utilização de um questionário de dor especifico para população com DRPAD propiciou melhor caracterização deste sintoma, assim como sua relação com as complicações associadas que ocorrem comumente nesta população.

INTRODUCTION: Pain is a common symptom in patients with autosomal dominant polycystic kidney disease (ADPKD), affecting around 60 percent of cases. OBJECTIVE: Translate a pain questionnaire developed and validated for ADPKD in USA into Portuguese and to perform its cultural adaptation and apply it. METHOD: The cultural adaptation performed by a panel of experts resulted in small changes consisting of words substitution by synonyms or deletion of terms not commonly used in our culture in 12 out of the 46 questions posed, to solve patients difficulties in understanding the questionnaire. RESULTS: There has been equivalence between the adapted form of the instrument with the back-translation. The final form of the questionnaire applied in 97 patients with ADPKD (64F/33M, 35 ± 12 years) showed that 65 (67 percent) had isolated or associated pain in multiple locations , more often at lumbar region (77 percent), followed by abdominal (66 percent), headache (15 percent) and chest (4 percent). The questionnaire revealed that after family history, pain was the second factor contributing to the diagnosis of ADPKD in this population (55 percent and 22 percent of cases, respectively). DISCUSSION: Clinical and laboratory data from medical records showed that patients referring pain had renal volume and size of the largest cyst significantly higher than those without pain. CONCLUSION: We conclude that the use of a specific pain questionnaire for ADPKD population provided a better characterization of this symptom, as well as its relationship with the associated complications that commonly occur in this setting.

How to avoid discontinuation of antihypertensive treatment: The experience in São Paulo, Brazil.

OBJECTIVES: To evaluate the importance of providing guidelines to patients via active telephone calls for blood pressure control and for preventing the discontinuation of treatment among hypertensive patients. INTRODUCTION: Many reasons exist for non-adherence to medical regimens, and one of the strategies employed to improve treatment compliance is the use of active telephone calls. METHODS: Hypertensive patients (n=354) who could receive telephone calls to remind them of their medical appointments and receive instruction about hypertension were distributed into two groups: a) "uncomplicated" - hypertensive patients with no other concurrent diseases and b) "complicated" - severe hypertensive patients (mean diastolic ≥ 110 mmHg with or without medication) or patients with comorbidities. All patients, except those excluded (n=44), were open-block randomized to follow two treatment regimens ("traditional" or "current") and to receive or not receive telephone calls ("phone calls" and "no phone calls" groups, respectively). RESULTS: Significantly fewer patients in the "phone calls" group discontinued treatment compared to those in the "no phone calls" group (4 vs. 30; p<0.0094). There was no difference in the percentage of patients with controlled blood pressure in the "phone calls" group and "no phone calls" group or in the "traditional" and "current" groups. The percentage of patients with controlled blood pressure (<140/90 mmHg) was increased at the end of the treatment (74%), reaching 80% in the "uncomplicated" group and 67% in the "complicated" group (p<0.000001). CONCLUSION: Guidance to patients via active telephone calls is an efficient strategy for preventing the discontinuation of antihypertensive treatment.

Translation, cultural adaptation and aplication of a pain questionnaire for patients with polycystic kidney disease.

INTRODUCTION: Pain is a common symptom in patients with autosomal dominant polycystic kidney disease (ADPKD), affecting around 60% of cases. OBJECTIVE: Translate a pain questionnaire developed and validated for ADPKD in USA into Portuguese and to perform its cultural adaptation and apply it. METHOD: The cultural adaptation performed by a panel of experts resulted in small changes consisting of words substitution by synonyms or deletion of terms not commonly used in our culture in 12 out of the 46 questions posed, to solve patients difficulties in understanding the questionnaire. RESULTS: There has been equivalence between the adapted form of the instrument with the back-translation. The final form of the questionnaire applied in 97 patients with ADPKD (64F/33M, 35 ± 12 years) showed that 65 (67%) had isolated or associated pain in multiple locations , more often at lumbar region (77%), followed by abdominal (66%), headache (15%) and chest (4%). The questionnaire revealed that after family history, pain was the second factor contributing to the diagnosis of ADPKD in this population (55% and 22% of cases, respectively). DISCUSSION: Clinical and laboratory data from medical records showed that patients referring pain had renal volume and size of the largest cyst significantly higher than those without pain. CONCLUSION: We conclude that the use of a specific pain questionnaire for ADPKD population provided a better characterization of this symptom, as well as its relationship with the associated complications that commonly occur in this setting.

How to avoid discontinuation of antihypertensive treatment: The experience in São Paulo, Brazil

OBJECTIVES: To evaluate the importance of providing guidelines to patients via active telephone calls for blood pressure control and for preventing the discontinuation of treatment among hypertensive patients. INTRODUCTION: Many reasons exist for non-adherence to medical regimens, and one of the strategies employed to improve treatment compliance is the use of active telephone calls. METHODS: Hypertensive patients (n=354) who could receive telephone calls to remind them of their medical appointments and receive instruction about hypertension were distributed into two groups: a) "uncomplicated" - hypertensive patients with no other concurrent diseases and b) "complicated" - severe hypertensive patients (mean diastolic >110 mmHg with or without medication) or patients with comorbidities. All patients, except those excluded (n=44), were open-block randomized to follow two treatment regimens ("traditional" or "current") and to receive or not receive telephone calls ("phone calls" and "no phone calls" groups, respectively). RESULTS: Significantly fewer patients in the "phone calls" group discontinued treatment compared to those in the "no phone calls" group (4 vs. 30; p<0.0094). There was no difference in the percentage of patients with controlled blood pressure in the "phone calls" group and "no phone calls" group or in the "traditional" and "current" groups. The percentage of patients with controlled blood pressure (<140/90 mmHg) was increased at the end of the treatment (74 percent), reaching 80 percent in the "uncomplicated" group and 67 percent in the "complicated" group (p<0.000001). CONCLUSION: Guidance to patients via active telephone calls is an efficient strategy for preventing the discontinuation of antihypertensive treatment.

Infecção urinária / Urinary tract infections

A infecção do trato urinário (ITU), uma das afecções mais frequentes nos Serviços de Saúde, possui espectro variável de apresentação clínica, abrangendo cistite, pielonefrite e bacteriúria assintomática. A severidade e recorrência das ITU estão relacionadas a fatores genéticos, hormonais e comportamentais juntamente com a virulência do micro-organismo invasor. Os autores revisitam o tema, chamando atenção para a importância do diagnóstico diferencial e trazem uma visão atualizada dos esquemas antibióticos propostos para tratamento e prevenção, segundo as últimas diretrizes internacionais. Outras modalidades terapêuticas alternativas são também abordadas.

Pneumonias / Pneumonia

A infecção do trato urinário (ITU), uma das afecções mais frequentes nos Serviços de Saúde, possui espectro variável de apresentação clínica, abrangendo cistite, pielonefrite e bacteriúria assintomática. A severidade e recorrência das ITU estão relacionadas a fatores genéticos, hormonais e comportamentais juntamente com a virulência do micro-organismo invasor. Os autores revisitam o tema, chamando atenção para a importância do diagnóstico diferencial e trazem uma visão atualizada dos esquemas antibióticos propostos para tratamento e prevenção, segundo as últimas diretrizes internacionais. Outras modalidades terapêuticas alternativas são também abordadas.

Preservation of urine samples for metabolic evaluation of stone-forming patients.

Metabolic evaluation of stone-forming (SF) patients is based on the determination of calcium, oxalate, citrate, uric acid and other parameters in 24-h urine samples under a random diet. A reliable measurement of urinary oxalate requires the collection of urine in a receptacle containing acid preservative. However, urinary uric acid cannot be determined in the same sample under this condition. Therefore, we tested the hypothesis that the addition of preservatives (acid or alkali) after urine collection would not modify the results of those lithogenic parameters. Thirty-four healthy subjects (HS) were submitted to two non-consecutive collections of 24-h urine. The first sample was collected in a receptacle containing hydrochloric acid (HCl 6 N) and the second in a dry plastic container, with HCl being added as soon as the urine sample was received at the laboratory. Additionally, 34 HS and 34 SF patients collected a spot urine sample that was divided into four aliquots, one containing HCl, another containing sodium bicarbonate (NaHCO(3 )5 g/l), and two others in which these two preservative agents were added 24 h later. Urinary oxalate, calcium, magnesium, citrate, creatinine and uric acid were determined. Urinary parameters were also evaluated in the presence of calcium oxalate or uric acid crystals. Mean values of all urinary parameters obtained from previously acidified 24-h urine samples did not differ from those where acid was added after urine collection. The same was true for spot urine samples, with the exception of urinary citrate that presented a slight albeit significant change of 5.9% between samples in HS and 3.1% in SF. Uric acid was also not different between pre- and post-alkalinized spot urine samples. The presence of crystals did not alter these results. We concluded that post-delivery acidification or alkalinization of urine samples does not modify the measured levels of urinary oxalate, calcium, magnesium, creatinine and uric acid, and that the change on citrate was not relevant, hence allowing all parameters to be determined in a single urine sample, thus avoiding the inconvenience and cost of multiple 24-h urine sample collections.

Effects of an oxalate load on urinary oxalate excretion in calcium stone formers.

OBJECTIVE: To investigate the oxalate intake and the effect of an oxalate load on urinary oxalate excretion in calcium stone-forming (CSF) patients. DESIGN: Prospective study. SETTING: University-affiliated outpatient Renal Lithiasis Unit. PATIENTS AND CONTROLS: Seventy (70) CSF and 41 healthy subjects (HS) collected a 24-hour urine sample and were submitted to a 3-day dietary record to determine mean oxalate (Ox), calcium (Ca) and vitamin C intake. Fifty-eight (58) CSF patients were randomly selected to receive milk (N = 28) or dark (N = 30) chocolate as an oxalate load. INTERVENTION: Administration of either milk (94 mg Ox + 430 mg Ca) or dark chocolate (94 mg Ox + 26 mg Ca) for 3 days. A 24-hour urine sample was obtained before and after the load to determine calcium, oxalate, sodium, potassium, urea, and creatinine. MAIN OUTCOME MEASURE: Oxalate intake and excretion. RESULTS: CSF patients presented mean Ox intake of 98 +/- 137 mg/d, similar to that of HS (108 +/- 139 mg/d). Mean Ox and vitamin C intake was directly correlated with Ox excretion only in CSF. The consumption of dark chocolate induced a significant increase in mean urinary Ox (36 +/- 14 versus 30 +/- 10 mg/24 hr) not observed in the milk chocolate group. Thus, a 2-fold increase in Ox intake in this population of CSF patients produced a significant 20% increase in oxaluria, not observed when Ca was consumed simultaneously. CONCLUSION: The present study suggests that even small increases in Ox intake affect oxalate excretion and the mitigation of urinary oxalate increase by Ca consumption reinforces that Ca and Ox intakes for CSF patients should be in balance. Further studies are necessary to assess whether or not a 20% increase in oxaluria will lead to a higher risk of stone formation.

Infeccao do trato urinario inferior-cistite e sindrome uretral / Lower urinary tract infection-cystitis and urethral syndrome

Os autores atualizam os mais recentes conceitos fisiopatologicos(biologia celular e molecular)clinicos, e laboratoriais da infeccao urinaria nao complicada do trato urinario inferior, da cistite e da sindrome uretral. Analisam os aspectos epidemiologicos e apresentam os avancos terapeuticos destas doencas. Avaliam os diferentes esquemas de tratamento destas doencas. Avaliam os diferentes esquemas de tratamento no que diz respeito a escolha dos antimicrobianos, da dose e sua duracao: dose unica, tres, sete dias e tratamento classico. Apresentam as perspectivas nesta area, especialmente o desenvolvimento de vacinas, atualmente sendo testadas.

Avaliaçäo da saturaçäo urinária em pacientes com doença inflamatória intestinal / Evaluation of urinary saturation in patients with inflamatory bowel disease

A doença inflamatória intestinal (DII), como a doença de Crohn (DC) e a retocolite ulcerativa (RCU), pode associar-se à litogênese devido a hiperoxalúria entérica. Na avaliaçao metabólica de 12 pacientes DII (6 DC e 6 RCU), sendo 3 com litíase recente, nao se observou alteraçao significante da média de excreçao de cálcio, ácido úrico e oxalato versus pacientes com litíase (LIT) sem DII. Hipocitratúria foi evidenciada em 6112 (5O por cento) e hiperuricosúria em 3/12 (25 por cento) dos pacientes. Estes dados sugerem que pacientes DII, mesmo sem apresentar hiperoxalúria, podem expor-se a maior risco de formaçao de cálculos, devido à hiperuricosúria e também à hipocitratúria, possivelmente decorrente do quadro diarréico crônico.