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1.
Int Braz J Urol ; 45(6): 1249-1259, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31808414

RESUMO

OBJECTIVE: Urinary stones with oxalate composition can cause kidney failure. Recent findings evidenced that probiotics are effective in reducing oxalate absorption in these subjects based on their high colonic absorption levels at baseline. The purpose of this study was to evaluate the effect of the simultaneous use of oxalate-degrading bacteria, Urtica dioica and T. terrestris extract in reducing urinary oxalate. MATERIALS AND METHODS: Anti-urolithiatic activity of Urtica dioica and T. terrestris extract and pro-biotic by using ethylene glycol induced rat model. In this study, 4 strains of Lactobacillus and 2 strains of Bifidobacterium and also 2 strains of L. paracasei (that showed high power in oxalate degrading in culture media) were used. Male Wistar rats were divided into four groups (n=6). The rats of group-I received normal diet (positive control group) and groups-II (negative control group), III, IV rats received diet containing ethylene glycol (3%) for 30 days. Groups III rats re-ceived Urtica dioica and T. terrestris extract. Groups IV rats received extracts + probiotic for 30 days. FINDINGS: The results show that the use of herbal extracts (Urtica dioica and T. terrestris) redu-ced the level of urinary oxalate and other parameters of urine and serum. Also, the accumulation of calcium oxalate crystals in the kidney tissue was significantly reduced. CONCLUSION: Considering that the formation of calcium oxalate crystals can cause inflammation and tissue damage in the kidney, the use of herbal extracts with oxalatedegrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.


Assuntos
Hiperoxalúria/prevenção & controle , Oxalatos/urina , Extratos Vegetais/farmacologia , Probióticos/farmacologia , Tribulus/química , Urtica dioica/química , Animais , Nitrogênio da Ureia Sanguínea , Cálcio/análise , Creatinina/análise , Cálculos Renais/prevenção & controle , Cálculos Renais/urina , Túbulos Renais/química , Masculino , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo
2.
BMC Cancer ; 19(1): 967, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623580

RESUMO

BACKGROUND: Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their treatment. The presence of pancreatic metastases in patients with metastatic renal carcinoma, often confers a more favourable prognosis and as a consequence this patient group may be exposed to such treatments for more prolonged periods of time. However, the development of renal failure may also be a consequence of the cancer itself rather than its treatment. CASE PRESENTATION: We present an 84-year-old patient receiving the tyrosine kinase inhibitor (TKI) pazopanib for metastatic renal carcinoma who developed oxalate nephropathy as a consequence of pancreatic exocrine insufficiency resulting from pancreatic metastases. CONCLUSIONS: This case demonstrates the importance of investigating unexpected toxicities and highlights the potential consequences of pancreatic insufficiency and its sequelae in patients with pancreatic metastases.


Assuntos
Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/patologia , Insuficiência Pancreática Exócrina/complicações , Falência Renal Crônica/etiologia , Neoplasias Renais/complicações , Neoplasias Renais/patologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/secundário , Acetatos/uso terapêutico , Idoso de 80 Anos ou mais , Compostos de Cálcio/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Falência Renal Crônica/terapia , Neoplasias Renais/tratamento farmacológico , Masculino , Oxalatos/urina , Neoplasias Pancreáticas/tratamento farmacológico , Pancrelipase/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Diálise Renal , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Resultado do Tratamento
3.
JAMA Intern Med ; 179(4): 542-551, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30830167

RESUMO

Importance: Oxalate is a potentially toxic terminal metabolite that is eliminated primarily by the kidneys. Oxalate nephropathy is a well-known complication of rare genetic disorders and enteric hyperoxaluria, but oxalate has not been investigated as a potential contributor to more common forms of chronic kidney disease (CKD). Objective: To assess whether urinary oxalate excretion is a risk factor for more rapid progression of CKD toward kidney failure. Design, Setting, and Participants: This prospective cohort study assessed 3123 participants with stages 2 to 4 CKD who enrolled in the Chronic Renal Insufficiency Cohort study from June 1, 2003, to September 30, 2008. Data analysis was performed from October 24, 2017, to June 17, 2018. Exposures: Twenty-four-hour urinary oxalate excretion. Main Outcomes and Measures: A 50% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD). Results: This study included 3123 participants (mean [SD] age, 59.1 [10.6] years; 1414 [45.3%] female; 1423 [45.6%] white). Mean (SD) eGFR at the time of 24-hour urine collection was 42.9 (16.8) mL/min/1.73 m2. Median urinary excretion of oxalate was 18.6 mg/24 hours (interquartile range [IQR], 12.9-25.7 mg/24 hours) and was correlated inversely with eGFR (r = -0.13, P < .001) and positively with 24-hour proteinuria (r = 0.22, P < .001). During 22 318 person-years of follow-up, 752 individuals reached ESRD, and 940 individuals reached the composite end point of ESRD or 50% decline in eGFR (CKD progression). Higher oxalate excretion was independently associated with greater risks of both CKD progression and ESRD: compared with quintile 1 (oxalate excretion, <11.5 mg/24 hours) those in quintile 5 (oxalate excretion, ≥27.8 mg/24 hours) had a 33% higher risk of CKD progression (hazard ratio [HR], 1.33; 95% CI, 1.04-1.70) and a 45% higher risk of ESRD (HR, 1.45; 95% CI, 1.09-1.93). The association between oxalate excretion and CKD progression and ESRD was nonlinear and exhibited a threshold effect at quintiles 3 to 5 vs quintiles 1 and 2. Higher vs lower oxalate excretion (at the 40th percentile) was associated with a 32% higher risk of CKD progression (HR, 1.32; 95% CI, 1.13-1.53) and 37% higher risk of ESRD (HR, 1.37; 95% CI, 1.15-1.63). Results were similar when treating death as a competing event. Conclusions and Relevance: Higher 24-hour urinary oxalate excretion may be a risk factor for CKD progression and ESRD in individuals with CKD stages 2 to 4.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Oxalatos/urina , Insuficiência Renal Crônica/urina , Adulto , Idoso , Biomarcadores/urina , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Adulto Jovem
4.
Int Urol Nephrol ; 51(4): 601-608, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30783888

RESUMO

PURPOSE: To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. METHODS: Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. RESULTS: The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI - 23.71, - 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (- 2.8; 95% CI - 4.9, - 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. CONCLUSION: ALLN-177 reduced 24-h UOx excretion, and was well tolerated. The results of this pilot study provided justification for further investigation of ALLN-177 in patients with secondary hyperoxaluria. TRIAL REGISTRATION: Clinicaltrials.gov NCT02289755.


Assuntos
Carboxiliases/uso terapêutico , Hiperoxalúria/tratamento farmacológico , Hiperoxalúria/urina , Oxalatos/urina , Administração Oral , Adulto , Idoso , Carboxiliases/administração & dosagem , Dieta , Terapia Enzimática , Feminino , Humanos , Hiperoxalúria/complicações , Cálculos Renais/complicações , Masculino , Pessoa de Meia-Idade
5.
Nutrients ; 11(2)2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30678344

RESUMO

Green tea is widely used as a ''healthy'' beverage due to its high level of antioxidant polyphenol compounds. However tea is also known to contain significant amount of oxalate. The objective was to determine, in a cross-sectional observational study among a population of 273 hypercalciuric stone-formers referred to our center for metabolic evaluation, whether daily green tea drinkers (n = 41) experienced increased stone risk factors (especially for oxalate) compared to non-drinkers. Stone risk factors and stone composition were analyzed according to green tea status and sex. In 24-h urine collection, the comparison between green tea drinkers and non-drinkers showed no difference for stone risk factors such as urine oxalate, calcium, urate, citrate, and pH. In females, the prevalence of calcium oxalate dihydrate (COD) and calcium phosphate stones, assessed by infrared analysis (IRS) was similar between green tea drinkers and non-drinkers, whereas prevalence of calcium oxalate monohydrate (COM) stones was strikingly decreased in green tea drinkers (0% vs. 42%, p = 0.04), with data in accordance with a decreased oxalate supersaturation index. In males, stone composition and supersaturation indexes were similar between the two groups. Our data show no evidence for increased stone risk factors or oxalate-dependent stones in daily green tea drinkers.


Assuntos
Dieta/estatística & dados numéricos , Cálculos Renais/epidemiologia , Chá , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácido Cítrico/urina , Estudos Transversais , Feminino , Humanos , Concentração de Íons de Hidrogênio , Cálculos Renais/urina , Masculino , Pessoa de Meia-Idade , Oxalatos/urina , Fatores de Risco , Ácido Úrico/urina , Urinálise , Adulto Jovem
6.
Urolithiasis ; 47(3): 243-254, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29947993

RESUMO

In rats, we recently showed how a chronic metabolic acidosis simultaneously reduced urinary oxalate excretion and promoted oxalate secretion by the distal colon leading to the proposition that acid-base disturbances may trigger changes to renal and intestinal oxalate handling. The present study sought to reproduce and extend these observations using the mouse model, where the availability of targeted gene knockouts (KOs) would offer future opportunities to reveal some of the underlying transporters and mechanisms involved. Mice were provided with a sustained load of acid (NH4Cl), base (NaHCO3) or the carbonic anhydrase inhibitor acetazolamide (ATZ) for 7 days after which time the impacts on urinary oxalate excretion and its transport by the intestine were evaluated. Mice consuming NH4Cl developed a metabolic acidosis but urinary oxalate was only reduced 46% and not statistically different from the control group, while provision of NaHCO3 provoked a significant 2.6-fold increase in oxalate excretion. For mice receiving ATZ, the rate of urinary oxalate excretion did not change significantly. Critically, none of these treatments altered the fluxes of oxalate (or chloride) across the distal ileum, cecum or distal colon. Hence, we were unable to produce the same effects of a metabolic acidosis in mice that we had previously found in rats, failing to find any evidence of the 'gut-kidney axis' influencing oxalate handling in response to various acid-base challenges. Despite the potential advantages offered by KO mice, this model species is not suitable for exploring how acid-base status regulates oxalate handling between the kidney and intestine.


Assuntos
Acidose/metabolismo , Mucosa Intestinal/metabolismo , Cálculos Renais/metabolismo , Rim/metabolismo , Oxalatos/metabolismo , Acetazolamida/administração & dosagem , Acidose/induzido quimicamente , Acidose/urina , Cloreto de Amônio/toxicidade , Animais , Inibidores da Anidrase Carbônica/administração & dosagem , Anidrases Carbônicas/metabolismo , Modelos Animais de Doenças , Feminino , Homeostase/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Rim/efeitos dos fármacos , Cálculos Renais/urina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxalatos/urina , Ratos , Eliminação Renal/efeitos dos fármacos , Especificidade da Espécie
7.
World J Urol ; 37(3): 561-566, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30039387

RESUMO

PURPOSE: Cranberry supplements are commonly used as a natural deterrent to urinary tract infection. However, one small study (n = 5) which showed an increase in urinary oxalate levels following cranberry supplementation has led to its use with caution among patients susceptible to nephrolithiasis. Furthermore, most commonly available cranberry tablet preparations contain vitamin C, which has been independently shown to increase urinary oxalate excretion. The aim of this study is to investigate the influence of cranberry supplementation on urinary oxalate excretion. METHODS: Fifteen participants were randomised to receive cranberry tablets alone or cranberry tablets containing vitamin C. Tablets were taken at the manufacturers recommended dosage for a period of 14 days. Participants provided a 24 h urine collection at trial entry and day 14. Urinary variables were compared to assess for changes in oxalate levels. RESULTS: The median age was 27 years (21-43). There was no difference in the 24 h urine volume pre or post commencement of cranberry tablets (1.7 vs 2 L, p = 0.07). An increase in median urinary oxalate excretion was observed in participants taking both cranberry-only tablets (0.10 mmol/day) and tablets containing vitamin C (1.15 mmol/day). CONCLUSION: Dietary supplementation with cranberry increases urinary oxalate excretion and should be avoided in patients at risk of urolithiasis.


Assuntos
Ácido Ascórbico/farmacologia , Suplementos Nutricionais , Nefrolitíase/urina , Oxalatos/urina , Preparações de Plantas/farmacologia , Eliminação Renal/efeitos dos fármacos , Vaccinium macrocarpon , Vitaminas/farmacologia , Adulto , Feminino , Humanos , Masculino , Fatores de Risco , Adulto Jovem
8.
Urolithiasis ; 47(3): 255-261, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29959478

RESUMO

Previous studies have suggested that ω-3 and ω-6 polyunsaturated fatty acid (PUFA) composition in plasma and red blood cell (RBC) total phospholipids plays a role in urolithiasis. Our aim was to test the robustness of this dogma by retrospectively comparing baseline profiles of these parameters in subjects from high- and low-stone-risk groups. The documented difference in stone occurrence in white (relatively common) (W) and black (rare) (B) subjects prompted us to select these groups as the high-low risk model for the study. Blood and urine samples were obtained from ten subjects in each group and were analysed for PUFAs and stone risk factors, respectively. Concentrations of linoleic acid (LA), eicosadienoic acid (EDA) and arachidonic acid (AA) in plasma and or/RBC total phospholipids were significantly higher in B. Differences in other PUFA profiles were also observed. There was no inter-group difference in AA/LA ratios. Urinary oxalate was significantly higher while urinary phosphate was significantly lower in B. We speculate that elevated AA in B might arise because of a possibly enhanced elongation of LA to EDA, as well as an enhanced ∆-8-desaturation of EDA to dihomo-gamma-linolenic acid (DGLA), which is the immediate precursor of AA. Alternatively, we speculate that the ∆-5-desaturation step of DGLA to AA might be more highly activated in this group. Irrespective of the mechanism, our observed inter-group differences in phospholipid PUFA composition are in conflict with previously published dogma which relates PUFA characteristics to high- and low-stone risk.


Assuntos
Ácidos Graxos Insaturados/sangue , Cálculos Renais/etiologia , Fosfolipídeos/química , Grupo com Ancestrais do Continente Africano , Grupo com Ancestrais do Continente Europeu , Ácidos Graxos Insaturados/química , Voluntários Saudáveis , Humanos , Cálculos Renais/sangue , Cálculos Renais/urina , Masculino , Oxalatos/urina , Projetos Piloto , Estudos Retrospectivos , Fatores de Risco , África do Sul
9.
Urology ; 124: 310.e9-310.e14, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30412704

RESUMO

OBJECTIVE: To test the effect of calcium and vitamin B6 therapies on urinary oxalate excretion in a rodent model of enteric hyperoxaluria after Roux-en Y gastric bypass (RYGB) surgery. METHODS: Obese male Sprague-Dawley rats underwent sham (n = 7) or RYGB (n = 10). Animals were maintained on low oxalate (1.5%) and fat (10%; LOF), normal calcium (0.6 %) diet for 8 weeks and then completed a 2-phase crossover metabolic study. In the first 2-week phase, animals were fed a Low oxalate and fat (LOF), high calcium (2.4%; HC) diet. After a 2-week washout, rats were fed a LOF/normal calcium diet highly enriched with vitamin B6. Urine was collected before and after each intervention. Plasma pyridoxal 5'-phosphate (PLP) and metabolites were measured baseline and 11 weeks after sham or RYGB. RESULTS: Compared to baseline, sham animals on LOF/HC diet doubled their urinary calcium excretion but not oxalate. RYGB animals on LOF/HC diet decreased urinary oxalate excretion 28% (P = .001) without a significant rise in urinary calcium. Vitamin B6 supplementation decreased RYGB urinary oxalate by approximately 15% (P = .06), and serum PLP explained 63% of urinary oxalate variability. CONCLUSION: Based on the findings in this model, calcium supplementation appears to be a reasonable therapy to decrease urinary oxalate in RYGB patients who maintain a low fat and oxalate diet. Serum PLP had a fair correlation to urinary oxalate excretion and may be a useful screening tool in hyperoxaluric RYGB patients. Further experimental human studies after RYGB are necessary to determine whether these commonly employed supplements truly provide a benefit in enteric hyperoxaluria.


Assuntos
Cálcio/uso terapêutico , Suplementos Nutricionais , Derivação Gástrica , Hiperoxalúria/tratamento farmacológico , Hiperoxalúria/urina , Oxalatos/urina , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/urina , Vitamina B 6/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Animais , Modelos Animais de Doenças , Derivação Gástrica/efeitos adversos , Hiperoxalúria/etiologia , Masculino , Complicações Pós-Operatórias/etiologia , Ratos , Ratos Sprague-Dawley
10.
Int Urol Nephrol ; 51(2): 279-284, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30515733

RESUMO

PURPOSE: Magnesium plays numerous vital roles in human's body. It is known as a protective factor in stone formation by binding to oxalate in the intestinal and urinary system, and decreasing its absorption and crystallization, respectively. Due to controversies about the association between the 24-h urine magnesium and other urine metabolites in different studies, this study was designed to find a clear answer to this question. METHODS: In this retrospective cross-sectional study, data from 24-h urinalysis of the calcium stone-forming (CSF) patients were assessed. The correlation between 24-h urine (24-U) magnesium to creatinine ratio (Mg/Cr) with other 24-U metabolites to creatinine ratio was assessed, using Spearman correlation test. The association between 24-U magnesium and 24-U oxalate was also studied in a multivariate logistic regression model. RESULTS: Among 965 patients, the level of Mg/Cr showed a direct association with all other 24-U metabolite to Cr ratio (p-value < 0.001 for all analyses). The result of multivariate regression analysis showed that the higher quartile of 24-U oxalate (> 47 mg/24 h) increased the odds of 24-U magnesium more than 75 mg/24 h (data median) (OR 1.89, 95% CI 1.14-3.13) comparing with the lower quartile of 24-U oxalate (≤ 26 mg/24 h). CONCLUSIONS: In a routine dietary habit, since rich sources of magnesium contain a high amount of oxalate at the same time, it is not surprising that magnesium level in 24-h urinalysis showed a direct association with 24-h urine oxalate.


Assuntos
Cálcio , Cálculos Renais , Rim , Magnésio , Eliminação Renal , Adulto , Cálcio/metabolismo , Cálcio/urina , Correlação de Dados , Creatinina/análise , Estudos Transversais , Feminino , Humanos , Concentração de Íons de Hidrogênio , Irã (Geográfico)/epidemiologia , Rim/metabolismo , Rim/fisiopatologia , Cálculos Renais/química , Cálculos Renais/epidemiologia , Cálculos Renais/metabolismo , Cálculos Renais/urina , Magnésio/metabolismo , Magnésio/urina , Masculino , Pessoa de Meia-Idade , Oxalatos/metabolismo , Oxalatos/urina , Estudos Retrospectivos , Urinálise/métodos
11.
Nat Commun ; 9(1): 5454, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30575740

RESUMO

CRISPR/Cas9 technology offers novel approaches for the development of new therapies for many unmet clinical needs, including a significant number of inherited monogenic diseases. However, in vivo correction of disease-causing genes is still inefficient, especially for those diseases without selective advantage for corrected cells. We reasoned that substrate reduction therapies (SRT) targeting non-essential enzymes could provide an attractive alternative. Here we evaluate the therapeutic efficacy of an in vivo CRISPR/Cas9-mediated SRT to treat primary hyperoxaluria type I (PH1), a rare inborn dysfunction in glyoxylate metabolism that results in excessive hepatic oxalate production causing end-stage renal disease. A single systemic administration of an AAV8-CRISPR/Cas9 vector targeting glycolate oxidase, prevents oxalate overproduction and kidney damage, with no signs of toxicity in Agxt1-/- mice. Our results reveal that CRISPR/Cas9-mediated SRT represents a promising therapeutic option for PH1 that can be potentially applied to other metabolic diseases caused by the accumulation of toxic metabolites.


Assuntos
Oxirredutases do Álcool/antagonistas & inibidores , Sistemas CRISPR-Cas , Terapia Genética/métodos , Hiperoxalúria Primária/terapia , Oxalatos/urina , Oxirredutases do Álcool/genética , Animais , Modelos Animais de Doenças , Edição de Genes , Células HEK293 , Humanos , Masculino , Camundongos , Nefrocalcinose/prevenção & controle
12.
Curr Mol Med ; 18(7): 436-447, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30539697

RESUMO

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an inherited disease caused by mutations in alanine-glyoxylate aminotransferase (AGXT). It is characterized by abnormal metabolism of glyoxylic acid in the liver leading to endogenous oxalate overproduction and deposition of oxalate in multiple organs, mainly the kidney. Patients of PH1 often suffer from recurrent urinary tract stones, and finally renal failure. There is no effective treatment other than combined liver-kidney transplantation. METHODS: Microinjection was administered to PH1 rats. Urine samples were collected for urine analysis. Kidney tissues were for Western blotting, quantitative PCR, AGT assays and histological evaluation. RESULTS: In this study, we generated a novel PH1 disease model through CRISPR/Cas9 mediated disruption of mitochondrial localized Agxt gene isoform in rats. Agxt-deficient rats excreted more oxalate in the urine than WT animals. Meanwhile, mutant rats exhibited crystalluria and showed a slight dilatation of renal tubules with mild fibrosis in the kidney. When supplied with 0.4% ethylene glycol (EG) in drinking water, mutant rats excreted greater abundance of oxalate and developed severe nephrocalcinosis in contrast to WT animals. Significantly elevated expression of inflammation- and fibrosisrelated genes was also detected in mutants. CONCLUSION: These data suggest that Agxt-deficiency in mitochondria impairs glyoxylic acid metabolism and leads to PH1 in rats. This rat strain would not only be a useful model for the study of the pathogenesis and pathology of PH1 but also a valuable tool for the development and evaluation of innovative drugs and therapeutics.


Assuntos
Sistemas CRISPR-Cas , Modelos Animais de Doenças , Hiperoxalúria Primária , Nefrocalcinose , Transaminases/deficiência , Animais , Glioxilatos/metabolismo , Hiperoxalúria Primária/genética , Hiperoxalúria Primária/patologia , Hiperoxalúria Primária/urina , Mitocôndrias/genética , Mitocôndrias/metabolismo , Nefrocalcinose/genética , Nefrocalcinose/patologia , Nefrocalcinose/urina , Oxalatos/urina , Ratos , Ratos Transgênicos
13.
Nutrients ; 10(10)2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30332783

RESUMO

The purpose of this study was to determine the effects of consumption of different cocoa-derived products on uric acid crystallization in urine of 20 healthy volunteers. Participants were requested to select the specific diet that they wished to follow during the 12 h prior to collection of urine. The only restriction was that the diet could not include any product with cocoa, coffee, or caffeine. On the first day, each volunteer followed their selected diet, and an overnight 12 h urine sample was collected as the baseline urine. After seven days on an unrestricted diet, each volunteer repeated the same diet with 20 g of milk chocolate, chocolate powder, or dark chocolate during breakfast and another 20 g during dinner. Overnight 12 h urine samples were then collected. Urine volume, pH, oxalate, creatinine, uric acid, theobromine, and a uric acid crystallization test were determined for each sample. The results for all 20 patients show that uric acid crystallization was significantly lower following the consumption of chocolate powder or dark chocolate relative to baseline or following the consumption of milk chocolate. The results indicated that increased concentrations of urinary theobromine reduced the risk of uric acid crystallization.


Assuntos
Chocolate , Ingestão de Alimentos/fisiologia , Ácido Úrico/química , Adulto , Idoso , Cafeína , Café , Creatinina/urina , Cristalização , Dieta/métodos , Feminino , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Oxalatos/urina , Teobromina/urina , Ácido Úrico/urina , Adulto Jovem
14.
Microbiol Res ; 215: 65-75, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30172310

RESUMO

Increased intestinal absorption of oxalate causes hyperoxaluria, a major risk factor for kidney stone disease. Intestinal colonization of recombinant probiotic bacteria expressing oxalate-degrading gene (OxdC) is an effective therapeutic option for recurrent calcium oxalate (CaOx) stone disease. Therefore, we aimed to develop food-grade probiotic L. plantarum secreting OxdC using lactococcal group II intron, Ll.LtrB and evaluate its oxalate degradation ability in vivo. Male Wistar albino rats were divided into four groups. The rats of group I received normal rat chow and drinking water. Groups II, III and IV rats received 5% potassium oxalate containing diet for 28 days. Groups III and IV rats received L. plantarum and food-grade recombinant L. plantarum respectively from 15 to 28 days. Biochemical parameters and crystalluria were analysed in 24 h urine samples. At the end of experimental period, rats were sacrificed; intestine and kidneys were dissected out for colonization studies and histopathological analysis. Herein, we found that the administration of recombinant probiotics significantly reduced the urinary oxalate, calcium, urea, and creatinine levels in rats of group IV compared to group II. Furthermore, colonization studies indicated that recombinant probiotics have gastrointestinal transit and intestinal colonization ability similar to that of wild-type bacteria. In addition, gene expression studies revealed down-regulation of OPN and KIM-1 among group IV rats. Histopathological analysis showed less evidence of nephrocalcinosis in group IV rats. In conclusion, the study demonstrates that food-grade L. plantarum secreting OxdC is capable of degrading intestinal oxalate and thereby prevent CaOx stone formation in experimental rats.


Assuntos
Carboxiliases/genética , Carboxiliases/farmacologia , Hiperoxalúria/tratamento farmacológico , Intestinos/microbiologia , Lactobacillus plantarum/enzimologia , Lactobacillus plantarum/genética , Oxalatos/metabolismo , Probióticos/farmacologia , Alanina Racemase , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cálcio/urina , Oxalato de Cálcio/metabolismo , Carboxiliases/metabolismo , Moléculas de Adesão Celular/genética , Creatinina/urina , Modelos Animais de Doenças , Expressão Gênica , Genes Bacterianos/genética , Instabilidade Genômica , Hiperoxalúria/induzido quimicamente , Hiperoxalúria/prevenção & controle , Hiperoxalúria/urina , Mucosa Intestinal/metabolismo , Íntrons/genética , Rim/metabolismo , Rim/patologia , Cálculos Renais/induzido quimicamente , Cálculos Renais/tratamento farmacológico , Cálculos Renais/prevenção & controle , Cálculos Renais/urina , Masculino , Mutagênese , Nefrocalcinose/patologia , Oxalatos/química , Oxalatos/urina , Ácido Oxálico/metabolismo , Probióticos/administração & dosagem , Probióticos/metabolismo , DNA Polimerase Dirigida por RNA/genética , DNA Polimerase Dirigida por RNA/metabolismo , Ratos , Ratos Wistar , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Ureia/urina
16.
Int Urol Nephrol ; 50(9): 1583-1589, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30039216

RESUMO

PURPOSE: The primary goal of this pilot study was to evaluate metabolic characteristics and to examine the impact of diet in patients with primary hyperoxaluria (PH) under controlled, standardized conditions. METHODS: Four patients with genetically confirmed PH collected 24 h urines on their habitual, self-selected diets and on day 1, 6, 7, 8, and 11 under controlled, standardized conditions. The [13C2]oxalate absorption, calcium, and ammonium chloride loading tests were performed. RESULTS: While none of the patients had abnormal findings from the calcium loading test, incomplete distal renal tubular acidosis (RTA) was diagnosed in each of the four patients. Dietary intervention resulted in a significant decrease in urinary oxalate expressed as molar creatinine ratio (mmol/mol) between 30 and 40% in two of four patients. The evaluation of dietary records revealed a high daily intake of oxalate-rich foods as well as gelatin-containing sweets and meat products, rich sources of hydroxyproline, under the habitual, self-selected diets of the two responders. Intestinal oxalate hyperabsorption of 12.4% in one of the two patients may have additionally contributed to the increased urinary oxalate excretion under the individual diet. CONCLUSIONS: Our pilot data indicate that patients with PH may benefit from a restriction of dietary oxalate and hydroxyproline intake. Further research is needed to define the role of distal RTA in PH and to evaluate the hypothesis of an acquired acidification defect.


Assuntos
Hiperoxalúria Primária/dietoterapia , Hiperoxalúria Primária/urina , Oxalatos/administração & dosagem , Oxalatos/urina , Acidose Tubular Renal/diagnóstico , Adolescente , Adulto , Cálcio/administração & dosagem , Cálcio/urina , Criança , Creatinina/urina , Dieta , Registros de Dieta , Humanos , Hidroxiprolina/administração & dosagem , Absorção Intestinal , Túbulos Renais Distais , Masculino , Pessoa de Meia-Idade , Projetos Piloto
17.
BMC Vet Res ; 14(1): 225, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-30045718

RESUMO

BACKGROUND: Protein concentration and quality in cat food can vary considerably, and the impact on feline urine composition and nutrient supply is of high practical relevance. In the present study, 6 canned diets with varying protein concentrations and qualities were fed to 10 healthy adult cats. Protein quality in the diet differed depending on the amount of collagen-rich ingredients. Hydroxyproline concentrations were 2.56-4.45 g/kg dry matter in the high quality and 3.76-9.44 g/kg dry matter in the low quality diets. Protein levels were 36.2, 43.3 and 54.9% in the high quality and 36.7, 45.0 and 56.1% in the low quality groups. Each diet was fed for 6 weeks, using a randomized cross-over design. In the last 2 weeks of each feeding period, urine and faeces of the cats were collected. RESULTS: Renal calcium (Ca), oxalate (Ox) and citrate excretion were unaffected by the dietary protein concentration, possibly mediated by a high urine volume (24.2-34.2 ml/kg bodyweight (BW)/day) in all groups. However, renal Ox excretion was lower when the high quality diets were fed (P = 0.013). Urinary relative supersaturation (RSS) with calcium oxalate (CaOx) was low in general, but reduced in the high quality groups (P = 0.031). Urinary RSS values for magnesium ammonium phosphate (MAP) were high (2.64-5.00) among all groups. Apparent digestibility of crude protein and most minerals was unaffected by the different diets. Feed intake was higher in the low quality groups (P = 0.026), but BW of the cats did not differ depending on dietary protein quality. BW of the cats increased with increasing dietary protein concentrations (P = 0.003). CONCLUSION: In conclusion, a high protein canned diet might not be a specific risk factor for CaOx urolith formation in cats. In contrast, all diets resulted in high RSS MAP values, which might be critical concerning MAP crystallization. Protein quality had a minor, but significant impact on urine composition, necessitating further research on this subject. A lower energy supply when feeding a low protein quality can be assumed. Changes in BW were only small and require a careful interpretation.


Assuntos
Ração Animal/análise , Gatos/urina , Proteínas na Dieta/química , Ração Animal/normas , Animais , Cálcio/urina , Gatos/metabolismo , Ácido Cítrico/urina , Colágeno/análise , Digestão , Metabolismo Energético , Hidroxiprolina/análise , Oxalatos/urina
18.
Pediatr Nephrol ; 33(8): 1443-1446, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29705963

RESUMO

BACKGROUND: Primary hyperoxaluria type 3 (PH3) is a recently described cause of childhood renal calculi. It results from mutations in the HOGA1 gene and most cases have been diagnosed after clinical ascertainment, exclusion of other genetic hyperoxalurias and mutation testing. Metabolite testing has not been widely applied but holds promise for the rapid screening and diagnosis of patients who are not specifically suspected to have PH3. CASE-DIAGNOSIS/TREATMENT: Two cases presented with renal calculi. Urine metabolite testing by tandem mass spectrometry was performed as part of the routine diagnostic work-up for this condition. Both had significantly increased levels of the PH3 urine marker 4-hydroxyglutamate and related metabolites. The diagnosis of PH3 was confirmed by the finding of bi-allelic damaging HOGA1 mutations. CONCLUSIONS: Urine screening by tandem mass spectrometry is a rapid, high-throughput test that can detect PH3 cases that may otherwise not be diagnosed.


Assuntos
Glutamatos/urina , Hiperoxalúria Primária/diagnóstico , Ácidos Cetoglutáricos/urina , Cálculos Renais/etiologia , Oxalatos/urina , Adolescente , Feminino , Glutamatos/metabolismo , Humanos , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/genética , Hiperoxalúria Primária/urina , Lactente , Ácidos Cetoglutáricos/metabolismo , Cálculos Renais/terapia , Cálculos Renais/urina , Litotripsia , Masculino , Metabolômica/métodos , Oxo-Ácido-Liases/genética , Oxo-Ácido-Liases/metabolismo , Recidiva , Espectrometria de Massas em Tandem
19.
Urologiia ; (1): 48-52, 2018 Mar.
Artigo em Russo | MEDLINE | ID: mdl-29634134

RESUMO

INTRODUCTION: Urolithiasis and nephrotuberculosis, due to the similarity of the radiographic patterns, share the same differential diagnosis list. The study aimed to analyze the incidence of co-occurrence of nephrotuberculosis and urolithiasis and to determine the impact of urolithiasis on the clinical course of renal tuberculosis. MATERIAL AND METHODS: This open cohort retrospective study comprised 843 patients with renal tuberculosis and 245 patients with urolithiasis. 1088 medical records were analyzed to identify cases with co-occurrence of these two diseases and determine the clinical presentation of renal tuberculosis, urolithiasis, and the comorbid state. Also, patients with pulmonary tuberculosis (44), urogenital tuberculosis (17), and chronic nonspecific pyelonephritis (12) were tested for serum concentration of total calcium and phosphorus. RESULTS: Of 843 patients with renal tuberculosis, 39 (4.6%), had concomitant nephrolithiasis. The combination of urolithiasis with nephrotuberculosis manifested by more severe symptoms; these patients had a more than two-fold risk of tuberculosis recurrence. Except for the incidence of renal colic and dysuria, the clinical manifestations of urolithiasis and nephrotuberculosis did not differ statistically significantly. Prolonged infectious and inflammatory process in the kidneys resulted in an increase in the excretion of oxalates, which was more pronounced in patients with nonspecific pyelonephritis (p<0.05). A three-month course of antituberculosis chemotherapy resulted in a 36.2% increase in the excretion of oxalates in patients with urotuberculosis (p<0.05). Excretion of uric acid also significantly increased after a three-month intake of antituberculosis drugs. CONCLUSION: In our study, the incidence of concomitant urolithiasis and urogenital tuberculosis was low (4.6%), but comorbidity significantly complicated the clinical course of the disease and worsened the prognosis of nephrotuberculosis. Antituberculosis polychemotherapy increases the risk for formation of urinary stones. Prevention of urolithiasis in patients with urogenital tuberculosis warrants further investigation.


Assuntos
Tuberculose Renal/diagnóstico , Tuberculose Renal/epidemiologia , Urolitíase/diagnóstico , Urolitíase/epidemiologia , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Estudos de Coortes , Comorbidade , Diagnóstico Diferencial , Humanos , Oxalatos/urina , Prognóstico , Recidiva , Estudos Retrospectivos , Tomógrafos Computadorizados , Tuberculose Renal/tratamento farmacológico , Ácido Úrico/urina , Urolitíase/tratamento farmacológico
20.
Int Braz J Urol ; 44(4): 758-764, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29617079

RESUMO

Phyllanthus niruri (P.niruri) or stone breaker is a plant commonly used to reduce stone risk, however, clinical studies on this issue are lacking. OBJECTIVE: To prospectively evaluate the effect of P. niruri on the urinary metabolic parameters of patients with urinary lithiasis. MATERIALS AND METHODS: We studied 56 patients with kidney stones <10mm. Clinical, metabolic, and ultrasonography assessment was conducted before (baseline) the use of P. niruri infusion for 12-weeks (P. niruri) and after a 12-week (wash out) Statistical analysis included ANOVA for repeated measures and Tukey's/McNemar´s test for categorical variables. Significance was set at 5%. RESULTS: Mean age was 44±9.2 and BMI was 27.2±4.4kg/m2. Thirty-six patients (64%) were women. There were no significant changes in all periods for anthropometric and several serum measurements, including total blood count, creatinine, uric acid, sodium, potassium, calcium, urine volume and pH; a significant increase in urinary potassium from 50.5±20.4 to 56.2±21.8 mg/24-hour (p=0.017); magnesium/creatinine ratio 58±22.5 to 69.1±28.6mg/ gCr24-hour (p=0.013) and potassium/creatinine ratio 39.3±15.1 to 51.3±34.7mg/gCr24- hour (p=0.008) from baseline to wash out. The kidney stones decreased from 3.2±2 to 2.0±2per patient (p<0.001). In hyperoxaluria patients, urinary oxalate reduced from 59.0±11.7 to 28.8±16.0mg/24-hour (p=0.0002), and in hyperuricosuria there was a decrease in urinary uric acid from 0.77±0.22 to 0.54±0.07mg/24-hour (p=0.0057). CONCLUSIONS: P.niruri intake is safe and does not cause significant adverse effects on serum metabolic parameters. It increases urinary excretion of magnesium and potassium caused a significant decrease in urinary oxalate and uric acid in patients with hyperoxaluria and hyperuricosuria. The consumption of P.niruri contributed to the elimination of urinary calculi.


Assuntos
Cálculos Renais/metabolismo , Cálculos Renais/prevenção & controle , Phyllanthus/química , Chás de Ervas , Adulto , Análise de Variância , Cálcio/sangue , Cálcio/urina , Creatinina/sangue , Creatinina/urina , Feminino , Humanos , Cálculos Renais/diagnóstico por imagem , Magnésio/urina , Masculino , Pessoa de Meia-Idade , Oxalatos/urina , Potássio/sangue , Potássio/urina , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Sódio/sangue , Sódio/urina , Resultado do Tratamento , Ureia/sangue , Ureia/urina , Ácido Úrico/sangue , Ácido Úrico/urina , Adulto Jovem
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