Involvement of xanthine oxidase activity with oxidative and inflammatory renal damage in silver catfish experimentally infected with Streptococcus agalactiae: Interplay with reactive oxygen species and nitric oxide.

Xanthine oxidase (XO) is a final enzyme of purine metabolism linked with initiation and progression of infectious diseases, since is considered an important source of reactive oxygen species (ROS) and nitric oxide (NO), developing a pro-oxidant and pro-inflammatory profile in some infectious diseases. Thus, the aim of this study was to evaluate the involvement of XO activity in the renal oxidative and inflammatory damage, as well as the interplay with ROS and metabolites of nitric oxide (NOx) levels in silver catfish experimentally infected with Streptococcus agalactiae. Xanthine oxidase activity, and uric acid, ROS and NOx levels increased in renal tissue of infected animals compared to uninfected animals. Moreover, the histopathological analyses revealed the presence of necrosis, generalized edema and nuclear degeneration of renal tubules. Based on these evidences, the upregulation on renal XO activity exerts a pro-oxidant and pro-inflammatory profile in kidney of fish infected with S. agalactiae. The excessive uric acid levels induced the release of oxidative and inflammatory mediators, such as ROS and NOx, that directly contribute to renal oxidative and inflammatory damage. In summary, the upregulation on XO activity may be considered a pathway involved in the renal injury during S. agalactiae infection.

HSP72 is an early biomarker to detect cisplatin and acetaminophen nephrotoxicity.

OBJECTIVE: To evaluate whether the urinary HSP72 levels (uHSP72) are a useful biomarker for early diagnosis of acute kidney injury (AKI) induced by two widely used drugs: cisplatin and acetaminophen. MATERIALS AND METHODS: To analyze the time-course of nephrotoxic injury and uHSP72 levels, male Wistar rats were administered a single high dose of cisplatin (7 mg/kg) or acetaminophen (750 mg/kg) and were assessed at 6, 12, 24, 48, 72, 96 and 120 h. RESULTS: AKI induced by cisplatin was characterized by tubular injury that started at 6 h and was enhanced after 48 h. Plasma creatinine was increased only after 72 h. In contrast, uHSP72 levels were augmented after 6 h and were enhanced after 48 h of cisplatin administration, which was consistent with the tubular injury. In acetaminophen-induced AKI, the tubular lesions were less severe and predominantly characterized by tubular cell detachment. Interestingly, uHSP72 levels were increased after 6 h of acetaminophen injection and remained elevated at the following time points, reflecting the tubular injury, even in the absence of major functional changes. CONCLUSIONS: In two models of renal injury induced by nephrotoxic drugs, we showed that uHSP72 could be used as an early biomarker to detect subtle to severe tubular injury.

Evaluation of urinary N-acetyl-beta-D-glucosaminidase as a marker of early renal damage in patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the clinical usefulness of urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion for the detection of early tubular damage in type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: Thirty six patients with T2DM were divided into two groups based on urinary albumin to creatinine ratio (ACR): normoalbuminuria (ACR <30 mg/g; n=19) and microalbuminuria (ACR =30-300 mg/g; n=17). The following parameters were determined in both groups: urinary NAG and albumin, serum and urine creatinine, fasting plasma glucose and glycated hemoglobin (HbA1c). RESULTS: Urinary NAG levels [Units/g creatinine; median (range)] were significantly increased in microalbuminuria group [17.0 (5.9 - 23.3)] compared to normoalbuminuria group [4.4 (1.5 - 9.2)] (P<0.001). No differences between groups were observed in fasting glucose, HbA1c, serum creatinine levels and estimated glomerular filtration rates (eGFR). Urinary NAG positively correlated with ACR (r=0.628; p<0.0001), while no significant association was observed between NAG and glycemia, HbA1c, serum creatinine and eGFR. CONCLUSIONS: The increase of urinary NAG at the microalbuminuria stage of diabetic nephropathy (DN) suggests that tubular dysfunction is already present in this period. The significant positive association between urinary NAG excretion and ACR indicates the possible clinical application of urinary NAG as a complementary marker for early detection of DN in T2DM.

Evaluation of urinary N-acetyl-beta-D-glucosaminidase as a marker of early renal damage in patients with type 2 diabetes mellitus / Avaliação da N-acetil-beta-D-glucosaminidase urinária como marcador de dano renal precoce em pacientes com diabetes melito tipo 2

Objective To evaluate the clinical usefulness of urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion for the detection of early tubular damage in type 2 diabetes mellitus (T2DM). Subjects and methods Thirty six patients with T2DM were divided into two groups based on urinary albumin to creatinine ratio (ACR): normoalbuminuria (ACR <30 mg/g; n=19) and microalbuminuria (ACR =30‐300 mg/g; n=17). The following parameters were determined in both groups: urinary NAG and albumin, serum and urine creatinine, fasting plasma glucose and glycated hemoglobin (HbA1c). Results Urinary NAG levels [Units/g creatinine; median (range)] were significantly increased in microalbuminuria group [17.0 (5.9 - 23.3)] compared to normoalbuminuria group [4.4 (1.5 - 9.2)] (P<0.001). No differences between groups were observed in fasting glucose, HbA1c, serum creatinine levels and estimated glomerular filtration rates (eGFR). Urinary NAG positively correlated with ACR (r=0.628; p<0.0001), while no significant association was observed between NAG and glycemia, HbA1c, serum creatinine and eGFR. Conclusions The increase of urinary NAG at the microalbuminuria stage of diabetic nephropathy (DN) suggests that tubular dysfunction is already present in this period. The significant positive association between urinary NAG excretion and ACR indicates the possible clinical application of urinary NAG as a complementary marker for early detection of DN in T2DM. .

Objetivo Avaliar a utilidade clínica da excreção urinária da N-acetil-beta-D-glucosaminidase (NAG) para a detecção de dano tubular precoce no diabetes melito tipo 2 (DM2). Sujeitos e métodos Foram estudados trinta e seis pacientes com DM2 que se dividiram em dois grupos com base na excreção urinária de albumina (EUA): normoalbuminúrico (EUA <30 mg/g de creatinina; n=19) e microalbuminúrico (EUA =30‐300 mg/g de creatinina; n=17). Em ambos os grupos foram determinados os seguintes parâmetros: NAG e albumina urinária, creatinina sérica e urinária, glicemia de jejum e hemoglobina glicada (HbA1c). Resultados Os níveis de NAG urinária [unidades/g de creatinina; mediana (intervalo interquartílico)] foram significativamente maiores no grupo microalbuminúrico [17,0 (5,9 - 23,3)] em comparação com o grupo normoalbuminúrico [4,4 (1,5 - 9,2)] (p<0,001). Não se observaram diferenças significativas entre os dois grupos nos níveis de glicemia de jejum, HbA1c, creatinina sérica e taxa de filtração glomerular estimada (TFGe). A NAG urinária se correlacionou positivamente com o EUA (r=0,628, p<0,0001), não sendo observada associação significativa da NAG com glicemia, HbA1c, creatinina sérica e TFGe. Conclusões O aumento da NAG urinária na fase de microalbuminúria da nefropatia diabética (ND) sugere que a disfunção tubular já está presente nesse período. A associação positiva significativa entre a excreção urinária da NAG e EUA indica a possível aplicação clínica da NAG urinária como marcador complementar para a detecção precoce da ND no DM2. .

Tubular overexpression of gremlin induces renal damage susceptibility in mice.

A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-ß. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1) specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-ß and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage progression. This transgenic mouse model could be used as a new tool for enhancing the knowledge of renal disease progression.

Infecção por leptospiras em ovinos e caracterização da resposta inflamatória renal / Leptospirosis infection in sheep and characterization of the renal inflammatory response

As Leptospiroses são zoonoses graves de distribuição mundial que afetam o homem e outros animais. A infecção em animais, geralmente, é inaparente, ou os sintomas quando presentes são similares a outras infecções. Neste estudo foram colhidos soros de 119 ovinos e seus respectivos rins durante abate em feiras livres no município de Teresina-Piauí. Pela técnica de soroaglutinação microscópica (SAM) obtiveram-se 34 amostras sorológicas positivas para um ou mais sorovares de Leptospira spp., com taxa de ocorrência de 28,6 por cento de anticorpos anti-leptospiras, sendo 23 casos de infecção para um único sorovar e 11 com coaglutinações para dois ou mais sorovares. Dentre os sorovares patogênicos, o de maior ocorrência foi o Autumnalis (29,4 por cento). A análise histopatológica de 36 fragmentos de rins revelou alterações túbulo intersticiais em 33 (91,7 por cento) animais soro-reagentes. Lesões tubulares foram observadas em 20 (55,5 por cento) animais soro-reagentes. A presença de leptospiras, pela técnica de Warthin Starry, foi observada em 8 (22,20 por cento) amostras positivas. Pela técnica de imunoperixidase, de 20 casos analisados, foi verificada a presença de leptospira em 12 (60 por cento) de 20 amostras positivas. Nos animais soro-reagentes, o infiltrado inflamatório foi significantemente mais evidente na região córtico-medular e cortical do que na região medular (p=0,000), mas não houve diferença entre animais soro-reagentes e soro não-reagentes. Cilindros hialinos nos túbulos proximais estavam presentes em quantidade significantemente maior nos animais soro-reagentes comparados aos não-reagentes (p=0,0001). Em glomérulos, foi observada lesão discreta. Os resultados deste estudo mostram que ovinos soro-reagentes para leptospiras apresentam lesões renais túbulo intersticiais, com presença de leptospiras nos túbulos, o que confere a esses animais a condição de disseminadores da infecção.(AU)

Lepitospirosis is a serious worldwide distribution disease which affects man and other animals. The infection is generally asymptomatic in animals. In cases whose symptoms are present, symptoms are similar to other infections. In the present study serum samples from 119 sheep and their kidneys were collected during their slaughter in outdoor markets in the city of Teresina, Piauí, Brazil. The Microscopic Agglutination Test (MAT) obtained 34 positive serological samples for one or more Leptospira spp. serovar with occurrence rate of 28.6 percent of leptospiral antibodies. There were 23 cases of infection for a single serovar, and 11 cases with coagglutination for two or more serovars. Autumnalis had the highest occurrence (29.4 percent) among the pathogenic serovars. The histopathological analysis of 36 kidney fragments revealed tubulo-interstitial alterations in 33 (91.7 percent) positive animals. Tubular lesions were observed in 20 (55.5 percent) positive animals. The Warthin Starry staning revealed the presence of Leptospira in 8 (22.20 percent) of the 36 positive samples. The immunoperoxidase staining revealed the presence of Leptospira in 12 (60 percent) of 20 positive samples. The inflammatory infiltrate in the positive animals was significantly more evident in the cortical-medullar and cortical regions than in the medullar region (p=0.000), however, there was no difference between positive and negative animals. The presence of hyaline casts in the proximal tubules was significantly higher in positive animals compared to the negative ones (p=0.0001). Discrete lesion was observed in glomeruli. In conclusion, the results from this study showed that sheep which are positive for Leptospira present tubulo-intersticial renal lesions with the presence of Leptospira in the tubules, conferring to these animals the condition of asymptomatic carriers.(AU)

Histologic alterations of rat kidneys perfused with a Euro-Collins diltiazem solution / Alterações histológicas ocorridas em rins de ratos perfundidos com solução de Euro-Collins associada à diltiazem

PURPOSE: Analyse the histologic changes of rat kidneys perfused with isotonic saline solution (ISS), Euro-Collins solution (ECS) and Euro-Collins solution with diltiazem (ECSD). METHODS: Thirty-six Wistar rats were used divided equally, as follow: group A (ISS), group B (ECS) and group C (ECSD). Through a catheter placed into the abdominal aorta, a renal perfusion was performed using a solution according to the group to which the animal belonged. After the complete perfusion, bilateral nephrectomy was performed and the organs were preserved under hypothermia for five distinct periods of time. Glomerulus and tubule were evaluated through optical microscopy. RESULTS: Renal perfusion with ECS and ECSD proved effectiveness in the preservation of the organs up to 36 hours and an increase in the percentage of injured glomeruli was noticed only in the period of 48 hours. CONCLUSIONS: The results showed that exists an association between the tubular injury and the glomeruli lesion degree; kidneys with a higher degree of tubular damage were related to severe glomerular lesion. Also, the addition of a calcium channel blocker, diltiazem, to the ECS for the renal perfusion does not decrease the percentage of glomerular lesion.(AU)

OBJETIVO: Analisar as alterações histológicas nos rins de ratos perfundidos com solução salina isotônica (ISS), solução Euro-Collins (ECS) e solução Euro-Collins com diltiazem (ECSD). MÉTODOS: Foram divididos, de forma igual, 36 ratos Wistar, como se segue: grupo A (ISS), grupo B (ECS), grupo C (ECSD). Através de um cateter localizado na aorta abdominal, foi realizada a perfusão renal com a solução de acordo com o grupo ao qual o animal pertencia. Após a perfusão total, realizou-se nefrectomia bilateral com a preservação dos órgãos sob hipotermia por cinco períodos distintos de tempo. Glomérulos e túbulos foram avaliados por microscopia óptica. RESULTADOS: Tanto a perfusão renal com ECS quanto a com ECSD provaram sua efetividade na preservação dos órgãos em até 36 horas e aumento da porcentagem de glomérulos injuriados foi notada apenas no período de 48 horas. CONCLUSÕES: Os resultados mostraram haver uma correlação entre a injúria tubular e o grau de lesão glomerular; rins com um maior grau de dano tubular foram relacionados com lesão glomerular severa. Além disso, a adição de um bloqueador de canal de cálcio, diltiazem, à ECS para a perfusão renal não diminui a porcentagem de lesão glomerular.(AU)

Predicción de sobrevida del injerto a corto y largo plazo mediante el uso de índices gamagráficos en receptores de trasplante renal / Prediction of short and long term graft survival by 99mTc-MAG3 scintigraphy after renal transplantation

Background: 99Tcm-MAG3 is a non-invasive method for the evaluation of renal transplants, giving information about allograft function and short- and long-term allograft survival. However, few studies have validated this observation. Objetive: To determine the predictive power of different scintigraphic parameters on graft survival at 6 -12 months after renal transplantation. Methods: Between 1996-2007, receptors with varying degrees of kidney dysfunction were studied with 99mTc-MAG3 scintigraphy within 14 days after transplantation. Tubular injury score (TISS) ranging I-VI according to severity and renal extraction index (R20/3) were calculated. Survival analysis and Cox regression were used for analysis. Results: Three-hundred and four renograms were performed in 146 allografts (143 receptors, mean age 38.9 +/- 17 years, 81.5 percent from cadaveric donor). Mean follow-up time was 44 months. There was graft loss (GL) in 32 percent renal trasplants. According to severity range, graft survival at 6 and 12 months was: TISS I-II 85.23 percent and 81.17 percent; TISS III-IV 82.43 percent and 80.56 percent, and TISS V-VI 32 percent and 2.,43 percent respectively. TISS score of V-VI score was an independent predictor for GL (HR = 6.3 CI 95 percent 2.9–13; p<0.0001). R20/3 index was not a good predictor of GL. Conclusions: TISS score was an independent predictor of short- and long-term allograft survival using 99mTc-MAG3 scintigraphy performed early after kidney transplantation in patients with suspected patients renal dysfunction. TISS V-VI had a greater discriminatory power. R20/3 index individually did not present a good prognostic performance.

Role of p21 and oxidative stress on renal tubular resistance after acute ischaemic injury.

BACKGROUND: Subsequent ischaemic episodes may induce renal resistance. P21 is a cell cycle inhibitor that may be induced by oxygen-free radicals and may have a protective effect in ischaemic acute kidney injury (AKI). This study aimed at evaluating the role of oxidative stress and p21 on tubular resistance in a model of acquired resistance after renal ischaemia and in isolated renal tubules. METHODS: Wistar rats were divided into: Group 1--sham; Group 2--sham operated and after 2 days submitted to 45-min ischaemia; and Group 3--45-min ischaemia followed after 2 days by a second 45-min ischaemia. Plasma urea was evaluated on Days 0, 2 and 4. Serum creatinine, creatinine clearance and oxidants (thiobarbituric acid-reactive substances) were determined 48 h after the second procedure (Day 4). Histology, immunohistochemistry for lymphocytes (CD3), macrophages (ED1), proliferation (PCNA) and apoptosis (TUNEL) were also evaluated. Rat proximal tubules (PTs) were isolated by collagenase digestion and Percoll gradient from control rats and rats previously subjected to 35 min of ischaemia. PTs were submitted to 15-min hypoxia followed by 45-min reoxygenation. Cell injury was assessed by lactate dehydrogenase release and hydroperoxide production (xylenol orange). RESULTS: Ischaemia induced AKI in Group 2 and 3 rats. Subsequent ischaemia did not aggravate renal injury, demonstrating renal resistance (Group 3). Renal function recovery was similar in Group 2 and 3. Plasma and urine oxidants were similar among in Group 2 and 3. Histology disclosed acute tubular necrosis in Group 2 and 3. Lymphocyte infiltrates were similar among all groups whereas macrophages infiltrate was greater in Group 3. Cell proliferation was greater in Group 2 compared with Group 3. Apoptosis was similar in groups 2 and 3. The p21 expression was increased only in Group 3 whereas it was similar in groups 1 and 2. PTs from the ischaemia group were sensitive to hypoxia but resistant to reoxygenation injury which was followed by lower hydroperoxide production compared to control PT. CONCLUSION: Renal resistance induced by ischaemia was associated with cell mechanism mediators involving oxidative stress and increased p21 expression.

Correlación entre el daño tubulointersticial y vascular en la nefritis lúpica con algunas variables clínicas / Correlation between the tubulointerstitial and vascular damage in lupus nephritis with some clinical variables

Las lesiones tubulointersticiales (TI) y vasculares (VS) son frecuentes en la nefritis lúpica (NL) a pesar de no ser consideradas en la clasificación de la OMS de 1995. Se revisaron 339 biopsias renales para correlacionar ciertas variables clínicas con las lesiones del TI y los vasos y saber la frecuencia con la que se producen. Se determinó la frecuencia del daño TI 101/29,8 por ciento y VS 65/19,2 por ciento. Se tuvo en cuenta además la incidencia de las lesiones TI en los distintos tipos de glomerulonefritis lúpica: 0 en la tipo I; 7/9,8 por ciento en la II; 8/15,7 por ciento en la III; 65/50 por ciento en la IV; 2/6,3 por ciento en la V y 16/100 por ciento en la VI. Quedó evidenciado que el daño TI y VS fue expresión de severidad clínica, pues se acompañó de mayor frecuencia de hipertensión 83/82 por ciento y 64/97 por ciento, que cuando no existieron estas lesiones 128/58 por ciento, mayor tiempo medio de evolución de la enfermedad: 3,4; 2,8 y 1,89 años y cifras de creatinina plasmática 189,1; 172,1 y 134,5 mmol/L para el daño TI, VS y la ausencia de estos, respectivamente. La proteinuria fue mayor en presencia de lesión TI, 3,4 g/L y menor en los pacientes con daño VS, 1,89, lo contrario a la incidencia de hematuria, 65/100 por ciento VS y 48/47,5 por ciento TI. En los pacientes sin lesión en estas estructuras los resultados fueron: 2,02 g/L para la proteinuria y 143/61 por ciento para la hematuria(AU)

Correlación entre el daño tubulointersticial y vascular en la nefritis lúpica con algunas variables clínicas / Correlation between the tubulointerstitial and vascular damage in lupus nephritis with some clinical variables

Las lesiones tubulointersticiales (TI) y vasculares (VS) son frecuentes en la nefritis lúpica (NL) a pesar de no ser consideradas en la clasificación de la OMS de 1995. Se revisaron 339 biopsias renales para correlacionar ciertas variables clínicas con las lesiones del TI y los vasos y saber la frecuencia con la que se producen. Se determinó la frecuencia del daño TI 101/29,8 por ciento y VS 65/19,2 por ciento. Se tuvo en cuenta además la incidencia de las lesiones TI en los distintos tipos de glomerulonefritis lúpica: 0 en la tipo I; 7/9,8 por ciento en la II; 8/15,7 por ciento en la III; 65/50 por ciento en la IV; 2/6,3 por ciento en la V y 16/100 por ciento en la VI. Quedó evidenciado que el daño TI y VS fue expresión de severidad clínica, pues se acompañó de mayor frecuencia de hipertensión 83/82 por ciento y 64/97 por ciento, que cuando no existieron estas lesiones 128/58 por ciento, mayor tiempo medio de evolución de la enfermedad: 3,4; 2,8 y 1,89 años y cifras de creatinina plasmática 189,1; 172,1 y 134,5 mmol/L para el daño TI, VS y la ausencia de estos, respectivamente. La proteinuria fue mayor en presencia de lesión TI, 3,4 g/L y menor en los pacientes con daño VS, 1,89, lo contrario a la incidencia de hematuria, 65/100 por ciento VS y 48/47,5 por ciento TI. En los pacientes sin lesión en estas estructuras los resultados fueron: 2,02 g/L para la proteinuria y 143/61 por ciento para la hematuria

Daño tubulointersticial en la nefropatía por ácido úrico y su prevención con citrato de potasio / Tubulointerstitial damage in the nephropathy by uric acid and its prevention with potassium citrate

La pérdida progresiva de la función renal ocurre en un gran número de enfermedades que afectan glomérulos, túbulos, intersticio o vasos. Los mecanismos involucrados en el daño renal progresivo, fundamentalmente la fibrosis, han sido investigados por varios autores y existen evidencias que indican que la injuria tubulo insterticial (TI) primaria o secundaria se correlaciona mejor que las alteraciones glomerulares con la disminución de la función renal. Los estados hiperuricémicos incluyendo la gota, están asociados con dos variedades de enfermedad renal, la litiasis úrica, y la denominada nefropatía úrica (NU). La forma aguda de ésta es una causa de fallo renal agudo y está vinculada a la sobreproducción y elevada excreción de ácido úrico en pacientes con linfomas, leucemias, enfermedades mieloproliferativas como la policitemia Vera, especialmente luego de recibir quimioterapia o radiaciones. La NU crónica se caracteriza por depósitos de uratos intratubulares e intersticiales acompañados de una respuesta inflamatoria y con el transcurso del tiempo, fibrosis intersticial. Actualmente se conoce la presencia en la orina de substancias de bajo peso molecular (citrato, pirofosfato, magnesio y ácido hipúrico), que poseen la capacidad de inhibir el crecimiento y la agregación de diferentes tipos de cristales... (TRUNCADO)(AU)

Daño tubulointersticial en la nefropatía por ácido úrico y su prevención con citrato de potasio / Tubulointerstitial damage in the nephropathy by uric acid and its prevention with potassium citrate

La pérdida progresiva de la función renal ocurre en un gran número de enfermedades que afectan glomérulos, túbulos, intersticio o vasos. Los mecanismos involucrados en el daño renal progresivo, fundamentalmente la fibrosis, han sido investigados por varios autores y existen evidencias que indican que la injuria tubulo insterticial (TI) primaria o secundaria se correlaciona mejor que las alteraciones glomerulares con la disminución de la función renal. Los estados hiperuricémicos incluyendo la gota, están asociados con dos variedades de enfermedad renal, la litiasis úrica, y la denominada nefropatía úrica (NU). La forma aguda de ésta es una causa de fallo renal agudo y está vinculada a la sobreproducción y elevada excreción de ácido úrico en pacientes con linfomas, leucemias, enfermedades mieloproliferativas como la policitemia Vera, especialmente luego de recibir quimioterapia o radiaciones. La NU crónica se caracteriza por depósitos de uratos intratubulares e intersticiales acompañados de una respuesta inflamatoria y con el transcurso del tiempo, fibrosis intersticial. Actualmente se conoce la presencia en la orina de substancias de bajo peso molecular (citrato, pirofosfato, magnesio y ácido hipúrico), que poseen la capacidad de inhibir el crecimiento y la agregación de diferentes tipos de cristales... (TRUNCADO)