Metabolic investigation in patients with nephrolithiasis / Investigação metabólica em pacientes com nefrolitíase

ABSTRACT: Objective: To evaluate the prevalence of metabolic disorders associated with nephrolithiasis in a female population. Methods: A retrospective study on 1,737 patients with evidence of recent formation of renal stones, being 54% females. The laboratory investigation consisted of at least two samples of blood and 24-hour urine to assess calcium, uric acid, citrate and creatinine levels, qualitative cystinuria, urinary pH following fasting and 12-hour water restriction, urine culture, serum creatinine and parathyroid hormone. Results: The most frequent alterations were hypercalciuria (40.9%), urinary tract infection (23.2%), hypocitraturia (22.4%), low urinary volume (20.5%) and hyperuricosuria (16%). Conclusion: The most frequent metabolic alterations in females were hypocitraturia, urinary tract infection, low urinary volume and hyperuricosuria.

RESUMO Objetivo: Avaliar a prevalência dos distúrbios metabólicos associados à nefrolitíase em uma população feminina. Métodos: Foi realizado um estudo retrospectivo em 1.737 pacientes com evidência de formação recente de cálculos renais, sendo 54% do sexo feminino. A avaliação laboratorial constou de duas ou mais amostras de sangue e urina de 24 horas com dosagens de cálcio, ácido úrico, citrato e creatinina cistinúria qualitativa, pH urinário em jejum e restrição hídrica de 12 horas, urocultura, creatinina e paratormônio séricos. Resultados: As alterações mais encontradas foram hipercalciúria (40,9%), infecção do trato urinário (23,2%), hipocitratúria (22,4%), baixo volume urinário (20,5%) e hiperuricosúria (16%). Conclusão: As alterações metabólicas mais frequentes na população feminina foram hipocitratúria, infecção do trato urinário, baixo volume urinário e hiperuricosúria.

Urinary oxalate, citrate, and gamma glutamyl transferase alterations after administration of Cynodon dactylon extract in cats

Urinary oxalate and citrate are the key factors in caox urolithiasis of cats and Gamma Glutamyl Transferase is a good test for assessment of kidney damage. Favorable effects of Cynodon dactylon on calcium oxalate stone formation have recently been proved in rats. The present study was designed to investigate the alteration of urinary oxalate, citrate, and GGT after administration of the hydroalcoholic extract of Cynodon dactylon to experimental hyperoxaluric cats. No scientific study has been done so far to demonstrate the beneficial effect of this plant in cats. 13 mature male cats were randomly divided into 3 groups: group A received standard diet and drinking water while, group B and C also received ethylene glycol at sub-toxic dose [130 mg/kg] daily for 30 days. Group C received hydroalcoholic extract of C.dactylon [400 mg/kg] from day 0 to 30, as well. Urine samples were collected on days 0, 15, and 30 and were analyzed for oxalate, citrate, and GGT levels. Urine oxalate level in group B was significantly higher than group C on days 15 and 30. Urinary citrate excretion was significantly higher in group C compared to the other groups on day 15; however, it decreased during the entire experiment in groups B and C. Urinary Gamma Glutamyl Transferase level was increased in hyperoxaluric cats and decreased in the treated group during the experiment. Based on our results, C.dactylon extract could reduce the hyperoxaluria and has beneficial effects on preventing the renal damage in cats. Such findings provide a scientific explanation for applying C.dactylon in prevention and possible treatment of CaOx kidney stones in cats and humans

Citrato y litiasis renal / Citrate and renal stones

El citrato es un potente inhibidor de la cristalización de sales de calcio. La hipocitraturia es una alteración bioquímica frecuente en la formación de cálculos de calcio en adultos y especialmente en niños. El pH ácido (sistémico, tubular e intracelular) es el principal determinante de la excreción de citrato en la orina. Si bien la mayoría de los pacientes con litiasis renal presentan hipocitraturia idiopática, hay un número de causas para esta anormalidad que incluyen acidosis tubular renal distal, hipokalemia, dietas ricas en proteínas de origen animal y/o dietas bajas en álcalis y ciertas drogas, como la acetazolamida, topiramato, IECA y tiazidas. Las modificaciones dietéticas que benefician a estos pacientes incluyen: alta ingesta de líquidos y frutas, especialmente cítricos, restricción de sodio y proteínas, con consumo normal de calcio. El tratamiento con citrato de potasio es efectivo en pacientes con hipocitraturia primaria o secundaria y en aquellos desordenes en la acidificación, que provocan un pH urinario persistentemente ácido. Los efectos adversos son bajos y están referidos al tracto gastrointestinal. Si bien hay diferentes preparaciones de citrato (citrato de potasio, citrato de sodio, citrato de potasio-magnesio) en nuestro país solo está disponible el citrato de potasio en polvo que es muy útil para corregir la hipocitraturia y el pH urinario bajo, y reducir marcadamente la recurrencia de la litiasis renal.

Citrate is a powerful inhibitor of the crystallization of calcium salts. Hypocitraturia is a biochemical common alteration in calcium stone formation in adults and especially in children. The acid pH (systemic, tubular and intracellular) is the main determinant of citrate excretion in the urine. While the etiology of hypocitraturia is idiopathic in most patients with kidney stones, there are a number of causes for this abnormality including distal renal tubular acidosis, hypokalemia, diets rich in animal protein and / or diets low in alkali and certain drugs, such as acetazolamide, topiramate, ACE inhibitors and thiazides. Dietary modifications that benefit these patients include high intake of fluids and fruits, especially citrus, sodium and protein restriction, with normal calcium intake. Treatment with potassium citrate is effective in patients with primary or secondary hypocitraturia and acidification disorders, which cause unduly acidic urine pH persistently. Adverse effects are low and are referred to the gastrointestinal tract. While there are various preparations of citrate (potassium citrate, sodium citrate, potassium citrate, magnesium) in our country is available only potassium citrate powder that is useful to correct both the hypocitraturia and the low urinary pH and reduce markedly the recurrence of kidney stones.

Nephrocalcinosis induced by hyperoxaluria in rats

PURPOSE: To investigate nephrocalcinosis due to hyperoxaluria induced by two different inducing agents in rats. METHODS: Forty Sprague-Dawley male rats were randomly distributed into four groups: Group1 (Clinical control, n = 10); Group 2 (0.5% Ethylene Glycol + Vitamin D3, n = 10); Group 3 (1.25% Ethylene Glycol, n = 10); and Group 4 (5%Hydroxy L-proline, n = 10). Five animals from each group were euthanized after one week of follow-up (M1 Moment) and the remaining, after four weeks (M2 Moment). All animals underwent 24h urine dosages of calcium, oxalate, uric acid, citrate and serum creatinine. Histology and histomorphometric analyses were performed using Image J program in the hematoxylin-eosin stains. Calcium deposits in the renal parenchyma were quantified by PIXE technique (Proton Induced X-Ray Emission). RESULTS: 24h urinary parameters did not show any significant variations after 28 days of experiment except by hyperoxaluria that was significantly higher in Group 3. Histomorphometric analyses showed a significantly higher nephrocalcinosis in Group 2 (p<0.01). The calcium deposits in the renal parenchyma were 10 and 100 times higher in Group 2 in comparison to other groups in the M1 and M2 moments, respectively. CONCLUSION: The Group 2 (vitamin D3+Ethylene Glycol 0.5%) was the best model to induce nephrocalcinosis in rats after 28 days.

Efeitos do timol sobre os parâmetros urinários envolvidos na formação de cálculos / Effects of thymol on urinary parameters related to lithogenesis

INTRODUÇÃO: Em estudo anterior, demonstramos que a acidificação ou alcalinização de amostras de urina no momento de entrega do material ao laboratório em comparação a amostras coletadas com conservantes não alterou os resultados urinários de parâmetros relacionados à investigação metabólica de litíase renal como o oxalato (OxU), cálcio (CaU), magnésio (MgU), ácido úrico (AcUrU) e creatinina (CreatU), com exceção do citrato (CitU), cujo valor foi discretamente menor. OBJETIVO: Avaliar se a adição de timol, por meio de sua ação antibacteriana, é capaz de prevenir a redução do CitU em amostras acidificadas 24 horas após a coleta, em relação às pré-acidificadas, sem interferir na determinação dos outros parâmetros urinários. MÉTODOS: 40 voluntários sadios coletaram uma amostra isolada de urina que foi dividida em quatro alíquotas de 10 ml contendo timol (1 g/l). Na primeira, o conservante ácido (HCl 6 N, 20 ml/l) foi adicionado imediatamente após a coleta e na segunda, somente após 24 horas. Além do CitU, nessas amostras também foram determinados OxU, CaU e MgU. Na terceira e quarta alíquotas, um conservante alcalino (NaHCO3, 5g/l) foi adicionado imediatamente ou 24 horas após a coleta para determinação do AcUrU. RESULTADOS: Na presença de timol, não se observou variação significante do CitU entre as urinas pré ou pós-acidificadas (577 ± 490 mg/l vs. 575 ± 501 mg/l). Os valores dos demais parâmetros também não sofreram alteração. CONCLUSÃO: A adição prévia de timol às amostras de urina permite que todos os parâmetros urinários litogênicos possam ser determinados numa mesma amostra, reduzindo o custo e o desconforto de múltiplas coletas de urina de 24 horas.

INTRODUCTION: In a previous study, we demonstrated that acidification or alkalinization of urine samples upon delivery of the material to the laboratory in comparison with samples with preservatives did not alter the results of urinary parameters related to the metabolic investigation into renal lithiasis such as oxalate (OxU), calcium (CaU), magnesium (MgU), uric acid (AcUrU) and creatinine (CreatU), with the exception of citrate (CitU), whose value was slightly lower. OBJECTIVE: To evaluate if the addition of thymol, through its antibacterial effect, is able to prevent the reduction of CitU observed in samples acidified 24 hs after collection in comparison with pre-acidified ones without interfering in the determination of other urinary parameters. METHODS: Forty (40) healthy volunteers collected a single spot urine sample, which was divided into four aliquots of 10 ml containing thymol (1 g/l). In the first sample, the acid preservative (HCl6N, 20 ml/l) was added immediately after collection and in the second, only after 24hs. OxU, CaU, CitU and MgU were determined. In the third and fourth aliquots, an alkali preservative (NaHCO3,5 g/l) was added immediately or 24 hs after collection for AcUrU determination. RESULTS: In the presence of thymol, there was no significant variation in CitU values between pre-or post-acidified samples (577±490 mg/l vs. 575±501 mg/l). The values of other parameters also remained unchanged. CONCLUSION: The prior addition of thymol to urine samples allows the determination of all lithogenic urinary parameters in the same sample, reducing the cost and inconvenience of multiple 24-hour urine collections.

Study of calcium regulating hormones in calcium stone formers

The present study demonstrated that calcium stone formers possesses significant decrease in 1.25 [OH]2 Vit D; 24, 25 [OH]2 Vit D and Vit. D binding protein as compared to control. This finding is accompanied with high activity of alkaline phosphatase due to bone fraction elevation, and serum hypocalcaemia as well as hypophosphataemia. The interesting finding was the inactivation of superoxide dismutase [SOD] couple with hypercalciuria, and elevation of urine citric acid content

Changes in urinary compositions among children after consuming prepared oral doses of aloe (Aloe vera Linn).

OBJECTIVES: 1) To investigate the amount of citrate and tartrate in aloe gel, and in the urine of healthy normal children, before and after consuming fresh aloe gel. 2) To evaluate the changes in the chemical composition of urine among subjects after taking aloe gel. 3) To determine the value of consuming aloe gel for prevention of renal stone formation. DESIGN: Experimental study. MATERIAL AND METHOD: Thirteen healthy boys between 9 and 13 years of age were enrolled (with informed permission) in the clinical trial. Subjects ingested 100 g of fresh prepared aloe gel twice a day for seven consecutive days. The 24-hour urine was collected one day prior to taking the gel (Day 0), Days 2 and 5 of consumption, and Day 8 (one day after completion). The authors determined the urine volume, osmolality, potassium, sodium, phosphate, calcium, magnesium, uric acid, citrate, tartrate, oxalate, Permissible Increment in Calcium (PI Ca), Permissible Increment in Oxalate (PI Ox), Concentration Product Ratio of Calcium Phosphate (CPR CaPO4) and the citrate per creatinine ratio. RESULTS: The citrate and tartrate concentration in 100 g of fresh aloe gel was 96.3 and 158.9 mg, respectively. The 24-hr urine volume and urinary citrate excretion were significantly increased (p < 0.05). The PI Ca and the PI Ox were also significantly increased (p < 0.05). The other measurements were unremarkable. CONCLUSION: One hundred grams of fresh Aloe vera gel contains 96.3 milligrams of citrate and 158.9 milligrams of tartrate and were in the mid-range among Thai fruits. Changes in chemical compositions of urine after aloe gel consumption shows potential for preventing kidney stone formation among children.

Effect of aloe (Aloe vera Linn.) on healthy adult volunteers: changes in urinary composition.

OBJECTIVE: 1. To investigate the amount of citrate and tartrate in aloe gel, and in the urine of healthy normal volunteers, before and after consuming fresh aloe gel. 2. To evaluate the changes in the chemical composition of urine among subjects after taking aloe gel. 3. To determine the value of consuming aloe gel for prevention of renal stone formation. DESIGNS: Experimental study; before and after experiment with no control group MATERIAL AND METHOD: Thirty one healthy male medical students between 18 and 23 years of age were enrolled (with informed consent) in the clinical trial. Subjects ingested 100 g of fresh aloe gel twice a day for seven consecutive days. The 24-hr urine was collected one day prior to taking the gel (Day 0), Days 2 and 5 of consumption, and Day 8 (one day after completion). The authors determined the urine volume, osmolality, potassium, sodium, phosphate, calcium, magnesium, uric acid, citrate, tartrate, oxalate, Permissible Increment in calcium (PI in calcium), Permissible Increment in oxalate (PI in oxalate), Concentration product ratio of calcium phosphate (CPR of CaPO4) and the citrate per creatinine ratio. RESULTS: The citrate and tartrate concentration in 100 g of fresh aloe gel was 96.3 and 158.9 mg, respectively. The urinary excretion of oxalate was significantly decreased (p < 0.05). The PI in calcium was significantly increased (p < 0.05), while the citrate excretion and PI in oxalate were consistently, albeit non-significantly, increased. The mean CPR values of CaPO4 were decreased non-significantly. The other measurements were unremarkable. CONCLUSION: Fresh Aloe vera gel (100 g) contains 96.3 mg of citrate and 158.9 mg of tartrate. This is mid-range for Thai fruits. Changes in chemical compositions of urine after aloe consumption shows its potential for preventing kidney stone formation among adults.

Stone composition, metabolic profile and the presence of the gut-inhabiting bacterium oxalobacter formigenes as risk factors for renal stone formation

To examine stone composition, metabolic evaluation and colonization of Oxalobacter formigenes as risk factors for renal stone formation. Subjects and Eighty patients with renal stones and 70 healthy controls were enrolled in the study. Of the 80 patients, 48 were first-time stone formers [FSF] and 32 were 'recurrent' stone formers [RSF], recurrent indicating 2 or more episodes of stone formation. Stone analysis by X-ray crystallography, 24-hour urine metabolic profile and detection of O. formigenes-specific DNA by PCR were performed for each patient. Detection of O. formigenes was also performed on 45 and urinary metabolic profile on an additional 25 controls. Calcium oxalate monohydrate was the major component of stones, hyperoxaluria and hypocitraturia were the most common urinary abnormalities in the 80 patients, 46% of RSF patients had hypercalciuria. Urinary abnormalities were far less frequent in the controls, with the exception of hypocitraturia [40%]. Of the urinary metabolites, only calcium levels were significantly different [p < 0.05] between FSF [6.50 +/- 4.08 mmol/24 h] and RSF [8.21 +/- 5.26 mmol/24 h] patients. Colonization of O. formigenes was higher in controls [62.2%] than in FSF [33.3%] or RSF [28%] patients, it was least in patients with more than 4 episodes [7%] of stone formation. The findings indicate that lack of colonization of O. formigenes may be an important risk factor for recurrence of stone formation [calcium oxalate monohydrate]

Urinary citrate excretion in idiopathic nephrolithiasis.

OBJECTIVE: To determine urinary citrate excretion in children with nephrolithiasis and normal controls. DESIGN: Prospective. SETTING: Tertiary care center in New Delhi. METHODS: This study was done on 50 children, below the age of 12 years, with idiopathic urinary calculi and 150 age and weight matched controls. The children were divided into 3 groups: Group 1 (1-4 years), Group 2 (5-8 years) and Group 3 (9-12 years). Urinary citrate was estimated in a 24-hour urine sample using colorimetric method. The stones removed from these children were also analysed. RESULTS: There was a preponderance of urinary stones in males; the highest incidence being in Group 1. Excretion of citrate in 24-hour urine sample was significantly lower in patients compared to controls, for males in all age groups and for females in Group 3. However, there was no statistically significant difference in the urinary citrate value between males and females in a given age group for either controls or patients. The urinary citrate excretion increased with age in patients and controls, but the levels in patients were lower. Depending upon the constituents, four types of stones were identified, calcium phosphate, calcium oxalate, uric acid and magnesium ammonium phosphate. Nine stones had at least more than one major constituent. Hypocitraturia was detected in 43 percent cases. The incidence was 76 percent for calcium phosphate, 87 percent for calcium oxalate, 40 percent for uric acid stones and 50 percent for magnesium ammonium phosphate. CONCLUSION: This study shows that low urinary citrate is associated with urinary stones in children, especially in endemic areas, in the absence of obvious etiological factors. Urinary citrate excretion should be determined in all children with nephrolithiasis.

Hypocitraturia in metabolically active calcium nephrolithiasis

Hypocitraturia is presumed to contribute to calcium stone formation. In this study, 52 patients with active calcium urolithiasis have been subjected to infrared spectrophotometric urolith analysis an collection of a 24-hour urinary sample for measurement of citrate, pH, calcium phosphorus, magnesium uric acid and oxalate. A venous blood sample was also taken for the measurement of calcium, potassium, uric acid, sodium phosphorus, carbon dioxide and creatinine levels. 93.3% of these patients had definite hypocitraturia, either as an isolated anomaly in 11.5% of patients or in association with hyperoxaluria and hyperuricosuria. When hypocitraturia was diagnosed more than half of the patients suffered from the severe form. Hypocitraturia in Egyptian metabolically active stone formers exceeds any known universal levels

Study of urinary acidification in patients with idiopathic hypocitraturia

Hypocitraturia (HCit) is one of the most remarkable features of renal tubular acidosis, but an acidification defect is not seen in the majority of hypocitraturic patients, whose disease is denoted idiopathic hypocitraturia. In order to assess the integrity of urinary acidification mechanisms in hypocitraturic idiopathic calcium stone formers, we studied two groups of patients, hypocitraturic (HCit, N = 21, 39.5 + or - 11.5 years, 11 females and 10 males) and normocitraturic (NCit, N = 23, 40.2 + or - 11.7 years, 16 females and 7 males) subjects, during a short ammonium chloride loading test lasting 8 h. During the baseline period HCit patients showed significantly higher levels of titratable acid (TA). After the administration of ammonium chloride, mean urinary pH (3rd to 8th hour) and TA and ammonium excretion did not differ significantly between groups. Conversely, during the first hour mean urinary pH was lower and TA and ammonium excretion was higher in HCit. The enhanced TA excretion by HCit during the baseline period and during the first hour suggests that the phosphate buffer mechanism is activated. The earlier response in ammonium excretion by HCit further supports other evidence that acidification mechanisms react promptly. The present results suggest that in the course of lithiasic disease, hypocitraturia coexists with subtle changes in the excretion of hydrogen ions in basal situations

Avaliaçäo da excreçäo urinária de cálcio, sódio, ácido úrico e citrato durante a semana e no fim de semana / Evaluation of urinary calcium, sodium, uric acid and citrate excretion during the week and in the week-end

A análise de urina de 24 horas é utilizada na investigaçäo ambulatorial de pacientes com nefrolitíase para detectar alteraçöes metabólicas envolvidas em sua patogênese. Avaliamos a influência da ingestäo calórico-protéica em 15 indivíduos normais em dois períodos durante a semana e no fim de semana, para identificar possíveis diferenças na excreçäo de solutos urinários. Os resultados mostraram näo haver diferença significativa entre a ingestäo calórico-protéica durante a semana e no fim de semana. Também näo houve diferença significativa em relaçäo a calciúria, uricosúria, citratúria e demais parâmetros nos dois períodos estudados. Concluímos que a coleta de urina de 24 horas para avaliaçäo metabólica de nefrolitíase poderá ser realizada tanto durante a semana quanto no fim de semana