Tratamiento con tocilizumab en amiloidosis AA: informe de casos y revisión de la literatura / Tocilizumab treatment in aa amyloidosis: case report and literature review

Introducción: la amiloidosis AA puede ser una complicación de ciertos trastornos inflamatorios crónicos, aunque entre el 21% y 50% puede ser idiopática. No existe un tratamiento específico. El tocilizumab, dirigido contra el receptor de IL-6 y orientado a disminuir la producción de SAA, podría ser eficaz. Métodos: en este estudio informamos datos de 6 pacientes con amiloidosis AA tratados con tocilizumab monoterapia subcutáneo en el período 2011-2018. Los criterios de valoración principales fueron la mejora clínica y bioquímica de los órganos afectados y los parámetros bioquímicos marcadores de inflamación. Resultados: el riñón estaba afectado en todos los pacientes, manifestándose con caída del filtrado glomerular y síndrome nefrótico. La hemorragia digestiva se presentó en un paciente y otro tenía afectación pulmonar en la biopsia. Luego del posterior al tratamiento, todos mejoraron el hematocrito, la albúmina sérica y el índice de masa corporal. El SAA disminuyó en 5 pacientes. Un paciente mejoró su función renal, mientras 4 se mantuvieron estables. Tres pacientes disminuyeron los valores de proteinuria. Conclusión: el tratamiento con tocilizumab podría ser eficaz en el tratamiento de los pacientes con amiloidosis AA. (AU)

Introduction: AA amyloidosis can be a complication of certain chronic inflammatory disorders, although between 21% and 50% can be idiopathic. There is no specific treatment. Tocilizumab, directed against the IL-6 receptor and aimed at decreasing SAA production, could be effective. Methods: in this study, we report data from 6 patients with AA amyloidosis treated with subcutaneous tocilizumab monotherapy between the period 2011-2018. The main endpoints were the clinical and biochemical improvement of the affected organs and the biochemical parameters markers of inflammation. Results: the kidney was affected in all patients, manifesting with a fall in glomerular filtration rate and nephrotic syndrome. Gastrointestinal bleeding occurred in one patient and another had lung involvement on biopsy. After treatment, all improved hematocrit, serum albumin, and body mass index. SAA decreased in 5 patients. One patient improved his kidney function, while 4 remained stable. Three patients decreased proteinuria values. Conclusion: treatment with tocilizumab could be effective in the treatment of patients with AA amyloidosis. (AU)

Switch from agalsidase beta to agalsidase alfa in the enzyme replacement therapy of patients with fabry disease in Latin America

There are currently two available enzyme replacement therapies for Fabry disease and little information regarding efficacy and safety of switching therapies. Between 2009 and 2012 there was a worldwide shortage of agalsidase beta and patients on that enzyme were switched to agalsidase alfa. This retrospective observational study assessed a 2-year period of efficacy and safety in a population of Fabry patients, in Argentina (30 patients) and Venezuela (3 patients), who switched therapies from algasidase beta to agalsidase alfa. Thirty-three patients completed 24-months follow-up after the switch (age 32.4 ± 2.0, range 10.0-55.9 years; male: female 23:10). Measures of renal function such as estimated glomerular filtration rate remained almost unchanged in 31 patients without end stage renal disease over the 2 years after switching and urine protein excretion continued stable. Cardiac functional parameters: left ventricular mass index, interventricular septum, left ventricular posterior wall showed no significant change from baseline in the 33 patients. Quality of life, pain and disease severity scores were mostly unchanged after 24-months and agalsidase alfa was generally well tolerated. Our findings showed there is no significant change in the efficacy measured through the renal or cardiac function, quality of life, pain, disease severity scoring and safety for at least 2 years after switching from agalsidase beta to agalsidase alfa.

Actualmente hay disponibles dos terapias de reemplazo enzimático en enfermedad de Fabry y existe poca información sobre la eficacia y seguridad del cambio de una a la otra. Entre 2009 y 2012 hubo falta a nivel mundial de agalsidasa beta y los pacientes tratados hasta entonces con esa enzima iniciaron tratamiento con agalsidasa alfa. El presente estudio retrospectivo, observacional evaluó la eficacia y seguridad a 2 años en pacientes con enfermedad de Fabry en Argentina (30 pacientes) y Venezuela (3 pacientes), que cambiaron su tratamiento de agalsidasa beta a agalsidasa alfa. Treinta y tres pacientes completaron 24 meses de seguimiento post-cambio (edad 32.4 ± 2.0; rango 10.0-55.9; hombre: mujer 23:10). La función renal, medida con la tasa de filtrado glomerular, se mantuvo sin cambios en 31 pacientes sin enfermedad renal terminal durante 2 años post-cambio. La secreción de proteína en orina continuó estable. Los parámetros de función cardíaca -índice de masa ventricular izquierda, septum interventricular, espesor de la pared posterior ventricular- no mostraron cambios significativos post-cambio de terapia en los 33 pacientes. La calidad de vida, el dolor y la gravedad de la enfermedad se mantuvieron mayormente estables luego de 24 meses, y la agalsidasa alfa fue generalmente bien tolerada. Nuestros resultados muestran que no hay cambios significativos en la eficacia medida por la función renal y cardíaca, en la seguridad y en los valores de la calidad de vida, el dolor o la gravedad de la enfermedad durante al menos 2 años luego del cambio de agalsidasa beta a agalsidasa alfa.

Acute kidney injury in HIV-infected children: comparison of patients according to the use of highly active antiretroviral therapy / Lesão renal aguda em crianças com HIV: estudo comparativo entre pacientes com e sem terapia antirretroviral altamente ativa

Abstract Objective: To assess clinical and laboratory data, and acute kidney injury (AKI) in HIV-infected children using and not using highly active antiretroviral therapy (HAART) prior to admission. Methods: A retrospective study was conducted with HIV-infected pediatric patients (<16 years). Children who were using and not using HAART prior to admission were compared. Results: Sixty-three patients were included. Mean age was 5.3 ± 4.27 years; 55.6% were females. AKI was observed in 33 (52.3%) children. Patients on HAART presented lower levels of potassium (3.9 ± 0.8 vs. 4.5 ± 0.7 mEq/L, p = 0.019) and bicarbonate (19.1 ± 4.9 vs. 23.5 ± 2.2 mEq/L, p = 0.013) and had a higher estimated glomerular filtration rate (102.2 ± 36.7 vs. 77.0 ± 32.8 mL/min/1.73 m2, p = 0.011) than those not on HAART. In the multivariate analysis, the use of HAART prior to the admission was a protective factor for AKI (p = 0.036; OR = 0.30; 95% CI = 0.097-0.926). Conclusion: AKI is a common complication of pediatric HIV infection. Use of HAART prior to the admission preserved glomerular filtration and was a protective factor for AKI, but increased medication side effects, such as hypokalemia and renal metabolic acidosis.

Resumo Objetivo: Avaliar dados clínicos e laboratoriais, bem como ocorrência de lesão renal aguda (LRA), em crianças HIV positivas com e sem uso de terapia antirretroviral altamente ativa (TARV) antes da admissão. Métodos: Estudo retrospectivo em pacientes pediátricos HIV positivos (< 16 anos). Foram comparadas as crianças que estavam em uso com aquelas sem uso de TARV prévia à internação. Resultados: Foram incluídos 63 pacientes, com média de 5,3 ± 4,27 anos, 55,6% do sexo feminino. LRA foi encontrada em 33 casos (52,3%). Os pacientes que usavam TARV apresentaram menores níveis de potássio (3,9 ± 0,8 vs. 4,5 ± 0,7 mEq/L, p = 0,019) e bicarbonato (19,1 ± 4,9 vs. 23,5 ± 2,2 mEq/L, p = 0,013), bem como maior taxa de filtração glomerular estimada (102,2 ± 36,7 vs. 77,0 ± 32,8 mL/min/1,73m2, p = 0,011), do que o pacientes sem TARV prévia. Na análise multivariada o uso de TARV prévia à internação foi fator protetor contra LRA (p = 0,036; RC = 0,30; IC de 95% = 0,097-0,926). Conclusão: A LRA é uma complicação comum da infecção pediátrica pelo HIV. O uso de TARV antes da internação foi associado a melhor taxa de filtração glomerular e foi fator de proteção contra LRA, porém desencadeou efeitos colaterais como hipocalemia e acidose metabólica.

Nephrotoxicity during tenofovir treatment: a three-year follow-up study in a Brazilian reference clinic

Abstract In this study, 275 patients in use of tenofovir were retrospectively followed-up for three years to evaluate risk factors involved in impaired renal function. Analysis of variance (ANOVA) and Tukey's test were used to verify any differences in creatinine levels and estimated clearance at 0, 6, 12, 24 and 36 months, adjusting for the co-variables sex, skin color, age >50 years, arterial hypertension, diabetes and the use of the ritonavir-boosted protease inhibitors (PI/r) lopinavir/r or atazanavir/r. The software package STATISTICA 10® was used for statistical analysis. The patients’ mean age was 43.2 ± 10.7 years. Systemic arterial hypertension (SAH) and diabetes were found in 20.4% and 8.7% of the patients, respectively. Overall, 96.7% were on tenofovir associated with lamivudine (TDF + 3TC), 39.3% on lopinavir/r, 29.8% on efavirenz, and 17.6% on atazanavir/r. There was a statistically significant difference in estimated creatinine clearance at 24 months, when the co-variables male (F = 3.95; p = 0.048), SAH (F = 6.964; p = 0.009), and age over 50 years (F = 45.81; p < 0.001) were taken into consideration. Analysis of the co-variable use of atazanavir/r showed a tendency toward an increased risk over time (F = 2.437; p = 0.063); however, no significant time interaction was seen. At 36-month, a statistically significant difference was found for age over 50 years, (F = 32.02; p < 0.05) and there was a significant time-by-sex interaction (F = 3.117; p = 0.0149). TDF was discontinued in 12 patients, one because of a femoral neck fracture (0.7%) and 11 due to nephrotoxicity (4%). Of these latter cases, 9/11 patients were also using protease inhibitors. These data strongly alert that tenofovir use should be individualized with careful attention to renal function especially in male patients, over 50 years, with SAH, and probably those on ATV/r.

Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population.

Comparison of the Effects of Telbivudine and Entecavir Treatment on Estimated Glomerular Filtration Rate in Patients with Chronic Hepatitis B

BACKGROUND/AIMS: The aim of this study was to evaluate the estimated glomerular filtration rate (eGFR) during telbivudine (LdT) versus entecavir (ETV) treatment in chronic hepatitis B (CHB) patients with underlying comorbidities such as diabetes mellitus (DM), hypertension, and cirrhosis. METHODS: From 2010 to 2012, 116 CHB patients treated with LdT and 578 treated with ETV were compared in this real-practice cohort. The mean changes in eGFR (Modification of Diet in Renal Disease [MDRD] formula) from baseline to months 6, 12, and 18 were analyzed using a linear mixed model. RESULTS: In LdT-treated patients, the mean eGFR increased by 7.6% at month 18 compared with the eGFR at baseline (MDRD formula in mL/min/1.73 m2). However, in ETV-treated patients, the mean eGFR decreased by 4.1% at month 18 compared with the eGFR at baseline. In the LdT-treated patients with DM, hypertension, cirrhosis or low eGFR <90 mL/min/1.73 m2, the mean eGFR showed a steady improvement, whereas the mean eGFR was reduced in the same subgroups of ETV-treated patients. CONCLUSIONS: The eGFR gradually increased over time during LdT treatment, especially in patients with mild abnormal eGFR at baseline, and in those with DM, hypertension, and cirrhosis, whereas a reduction in eGFR was seen with ETV treatment.

Effect of renin-angiotensin-system blockers on contrast-medium-induced acute kidney injury after coronary angiography

BACKGROUND/AIMS: With the increasing incidence of cardiovascular disease, angiocardiography using contrast-enhancing media has become an essential diagnostic and therapeutic tool, despite the risk of contrast-medium-induced acute kidney injury (CIAKI). CIAKI may be exacerbated by renin-angiotensin-system (RAS) blockers, which are also used in a variety of cardiovascular disorders. This study evaluated the effects of RAS blockade on CIAKI after coronary angiography. METHODS: Patients who underwent coronary angiography in our hospital between May 2009 and July 2011 were reviewed. Serum creatinine levels before and after coronary angiography were recorded. CIAKI was diagnosed according to an increase in serum creatinine > 0.5 mg/dL or 25% above baseline. RESULTS: A total of 1,472 subjects were included in this study. Patients taking RAS blockers were older, had a higher baseline creatinine level, lower estimated glomerular filtration rate (eGFR), and had received a greater volume of contrast medium. After propensity score matching, no difference was observed between the RAS (+) and RAS (.) groups. Multiple logistic regression identified RAS blockade, age, severe heart failure, contrast volume used, hemoglobin level, and eGFR as predictors of CIAKI. Multiple logistic regression after propensity matching showed that RAS blockade was associated with CIAKI (odds ratio, 1.552; p = 0.026). CONCLUSIONS: This study showed that the incidence of CIAKI was increased in patients treated with RAS blockers.

Alkali Therapy Attenuates the Progression of Kidney Injury via Na/H Exchanger Inhibition in 5/6 Nephrectomized Rats

Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO3-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO3 group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO3 group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney.

Tc-99m diethylenetriamine pentaacetic acid [DTPA]: is it reliable for assessment of methotrexate-induced cumulative effect on renal filtration in rheumatoid arthritis patients?

Methotrexate [MTX] is commonly employed as the initial DMARD used for treatment of Rheumatoid arthritis [RA]. We aimed to contribute to the safety profile of MTX by assessing its cumulative effect on renal filtration. Fifty two RA adult females with normal base-line serum creatinine and GFR at the initial diagnosis of the disease were included. Group-1 [G1] included 30 patients [mean age 40.4 +/- 4.4 years] on MTX and NSAIDS, while 22 RA patients [mean age 38.5 +/- 8.2 years] who received NSAIDs only served as the control group [G2]. Renal function was assessed by GFR-measurement using Technetium diethylenetriamine-pentaacetic acid [Tc-99 m-DTPA] at the point of the study time corresponding to disease duration. 21/30 [70%] in G1 showed reduced GFR compared to 6/22 [27.3%] in G2 [P0.007] with 3.3 +/- 0.5% annual reduction of GFR. Reduced GFR in G1 showed significant negative correlation with age [r = -0.396, P = 0.005], MTX-cumulative dose [r = -0.263, P = 0.049], MTX-intake duration [r = -0.293, P = 0.031] and NSAID-intake duration [r = -0.344, P = 0.014]. Low dose MTX has a slow cumulative effect on renal filtration manifested by GFR reduction over time that could be monitored by Tc-99 m DTPA

Stepwise Treatment Using Corticosteroids Alone and in Combination with Cyclosporine in Korean Patients with Idiopathic Membranous Nephropathy

PURPOSE: We undertook an observational study to investigate the effects of immunosuppressive treatment on proteinuria and renal function in 179 Korean idiopathic membranous nephropathy patients with nephrotic syndrome. MATERIALS AND METHODS: The primary outcome was regarded as the first appearance of remission and the secondary outcomes as a decline in estimated glomerular filtration rate (eGFR) >50% or initiation of dialysis, and all-cause mortality. Seventy-two (40.2%) and 50 (27.9%) patients were treated with corticosteroids alone (C) and corticosteroids plus cyclosporine (C+C), respectively, whereas 57 (31.8%) did not receive immunosuppressants (NTx). Cyclosporine was added if there was no reduction in proteinuria of >50% from baseline by corticosteroids alone within 3 months. RESULTS: There were no differences in baseline renal function and the amount of proteinuria among the three groups. Overall, complete remission (CR) was achieved in 88 (72.1%) patients by immunosuppressants. In a multivariate analysis adjusted for covariates associated with adverse renal outcome, the probability of reaching CR was significantly higher in the C [hazard ratio (HR), 4.09; p<0.001] and C+C groups (HR, 2.57; p=0.003) than in the NTx group. Kaplan-Meier analysis revealed that 5-year CR rates of C, C+C, and NTx groups were 88.5%, 86.2%, and 56.7% (p<0.001). Ten-year event-free rates for the secondary endpoints in these three groups were 91.7%, 79.9%, and 57.2% (p=0.01). CONCLUSION: Immunosuppressive treatment was effective in inducing remission and preserving renal function in these patients. Therefore, stepwise treatment using corticosteroids alone and in combination with cyclosporine is warranted in these patients.

Hidratação com bicarbonato de sódio não previne a nefropatia de contraste: ensaio clínico multicêntrico / Hydration with sodium bicarbonate does not prevent contrast nephropathy: a multicenter clinical trial

FUNDAMENTO: A exposição ao meio de contraste radiográfico pode causar comprometimento agudo da função renal. Há evidências limitadas e conflitantes de que a hidratação com bicarbonato de sódio previne a Nefropatia Induzida por Contraste (NIC) em pacientes submetidos a cateterismo cardíaco. OBJETIVO: O presente estudo teve como objetivo determinar se o bicarbonato de sódio é superior à hidratação com soro fisiológico para evitar a nefropatia em pacientes de risco submetidos a cateterismo cardíaco. MÉTODOS: Trezentos e um pacientes submetidos a intervenção coronariana percutânea ou angiografia coronariana com creatinina sérica > 1,2 mg/dL ou Taxa de Filtração Glomerular (TFG) < 50 mL/min, foram randomizados para receber hidratação com bicarbonato de sódio a partir de 1 hora antes do procedimento, e 6 horas após o procedimento, ou hidratação com solução salina a 0,9%. A NIC foi definida como um aumento de 0,5 mg/dL na creatinina em 48h. RESULTADOS: Dezoito pacientes (5,9%) desenvolveram nefropatia induzida por contraste: 9 pacientes no grupo do bicarbonato (6,1%) e 9 pacientes no grupo da solução salina (6,0%), p = 0,97. A variação na creatinina sérica foi semelhante em ambos os grupos, 0,01 ± 0,26 mg/dL no grupo do bicarbonato, e 0,01 ± 0,35 mg/dL no grupo da solução salina, p = 0,9. Não foi observada diferença estatística entre a alteração na taxa de filtração glomerular (0,89 ± 9 mL/ min vs. 2,29 ± 10 mL/min, p = 0,2, grupo do bicarbonato e grupo da solução salina, respectivamente). CONCLUSÃO: A hidratação com bicarbonato de sódio não foi superior ao soro fisiológico na prevenção a nefropatia induzida pelo contraste, em pacientes de risco submetidos a cateterismo cardíaco.

BACKGROUND: Radiographic contrast media exposition can cause acute renal function impairment. There is limited and conflicting evidence that hydration with sodium bicarbonate prevents contrast-induced nephropathy (CIN) in patients undergoing cardiac catheterization. OBJECTIVE: The present study was aimed at determining whether sodium bicarbonate is superior to hydration with saline to prevent nephropathy in patients at risk undergoing cardiac catheterization. METHODS: Three hundred and one patients undergoing coronary angiography or percutaneous coronary intervention with serum creatinine > 1.2mg/dL or glomerular filtration rate (GFR) < 50ml/min were randomized to receive hydration with sodium bicarbonate starting 1 hour before the procedure and 6 hours after the procedure, or hydration with 0.9% saline. CIN was defined as an increase of 0.5mg/dL in creatinine in 48h RESULTS: Eighteen patients (5.9%) developed contrast induced nephropathy: 9 patients in the bicarbonate group (6.1%) and 9 patients in the saline group (6.0%), p = 0.97. The change in serum creatinine was similar in both groups, 0.01 ± 0.26 mg/dL in the bicarbonate group and 0.01 ± 0.35 mg/dL in the saline group, p = 0.9. No statistical difference was observed between the change in glomerular filtration rate (0.89 ± 9 ml/min vs. 2.29 ± 10 ml/min, p = 0.2 bicarbonate group and saline group, respectively). CONCLUSION: Hydration with sodium bicarbonate was not superior to saline to prevent contrast media induced nephropathy in patients at risk undergoing cardiac catheterization.

Análisis crítico de un artículo: La suspensión de inhibidores de la bomba de protones induciría síntomas de reflujo / Critically appraised article

Background & Aims: Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). IfRAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. Methods: A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom. Results: There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPIgroup at week 10 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .023), week 11 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .009), and week 12 (1.3 ± 1.2 vs 1.0 ± 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported >1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPIgroup was 13 of 59 (22%) at week 10,13 of59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). Conclusions: PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury

Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA) on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 çg/mL); CsA (100 µg/mL); sirolimus (50 and 250 çg/mL) + CsA (100 µg/mL); control; vehicle (20 percent ethanol). For in vivo studies, 3-week-old Wistar rats (150-250 g) were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I) in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po), I + CsA (3 mg·kg-1·day-1, sc), I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR) at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min) but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min) despite the reduction in renal blood flow (3.9 ± 0.5 mL/min). Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.

Nephrotoxicity of CDDP assessed estimating glomerular filtration rate with 99mTc-DTPA plasma sample method

To assess early nephrotoxicity of CDDP [Cis-diamminedichloroplatinum] manifested by a decline in the glomerular filtration rate [GFR] estimated by plasma two sample clearance method [PSC 2] after 99mTc.DTPA injection. Descriptive study. Department of Nuclear Medicine, Karachi Institute of Radiotherapy and Nuclear Medicine, Karachi, from September 2004 to January 2005. The renal function was assessed on 36 patients suffering from different types of cancer and receiving CDDP in doses of >/= 50 mg/m[2] before and after in each of six CDDP cycles. The GFR was determined by PSC 2 method after 99mTc-DTPA injection]. A paired sample t-test was used for comparison of the mean value with significance at p < 0.01. There were [28 males and 8 females; age range being 16-68 years]. The average decline in GFR baseline to the end of sixth cycles was 43.86 ml/min/1.73m[2] [p=0.000] as estimated by PSC 2 method. There was a significant fall of average 9.36 ml/min/1.73m[2] [p <0.01] in GFR as observed in each cycle of CDDP estimated by the PSC 2 method. In the initial four cycles, CDDP produced a major nephrotoxic effect of average 10.27 ml/min/1.73m[2] [p <0.01] fall in GFR. This then gradually declined to a plateau of an average decline in GFR of 7.76 and 7.31 ml/min/1.73m[2] [p=0.000] after the 5[th] and 6[th] cycle respectively. CDDP produced an early nephrotoxicity which was manifested by a significant decline in GFR in each cycle. Tc-99m PSC 2 method for GFR estimation should be used periodically for the early detection of nephrotoxicity induced by CDDP

Steviol effect, a glycoside of Stevia rebaudiana, on glucose clearances in rats / O efeito do esteviol, um glicosídeo da Stevia rebaudiana, no clearance da glicose em ratos

Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previously suggested as the preferential action of steviol on the Na+-glucose renal tubular transport system. Steviol was obtained by enzymatic hydrolysis of stevioside with pectinase. Thirty normal male Wistar rats weighing 345 g were used. After a control period, steviol was infused iv at three doses (0.5, 1.0 and 3.0 mg.kg-1/h), according to classical clearance techniques. During all the experiments no significant changes in inulin clearance (Cin) and p-aminohipuric acid clearance (C PAH) were observed. Administration of steviol resulted in a statistically significant increase in the fractional sodium excretion (FeNa+), fractional potassium excretion (FeK+), urinary flow as percent of glomerular filtration rate (V/GFR) and glucose clearance (C G) when compared to controls, but these effects were absent with the dose of 0.5 mg.kg-1/h. The steviol clearance (C S) was higher than the Cin and lower than the C PAH at all the doses employed in this study. The data suggest that steviol is secreted by renal tubular epithelium, causing diuresis, natriuresis, kaliuresis and a fall in renal tubular reabsorption of glucose.

Stevia rebaudiana, uma planta da América do Sul usada como adoçante natural, parece exercer efeitos benéficos para a saúde humana, incluindo ação anti-hipertensiva e anti-hiperglicêmica. No presente trabalho objetivamos avaliar a excreção renal do esteviol, uma aglicona extraída das folhas de S. rebaudiana, e elucidar a participação deste composto na excreção renal de glicose em ratos, o qual foi sugerido agir no sistema de transporte tubular renal Na+-glicose. O esteviol foi obtido por hidrólise enzimática com pectinase. Foram usados 30 ratos Wistar machos e pesando 345 g. Após um período controle, o esteviol foi infundido iv em três doses (0,5, 1,0 e 3,0 mg.kg-1/h) de acordo com técnicas clássicas de clearance. Durante os experimentos não houve alterações significantes no clearance da inulina (Cin) e do ácido-aminohipúrico (C PAH). A administração de esteviol resultou em um aumento estatisticamente significante na excreção fracional de sódio (FeNa+) e potássio (FeK+ ), no fluxo urinário como porcentagem da taxa de filtração glomerular (V/GFR) e do clearance de glicose (C G) quando comparados aos animais controles, embora estes efeitos estivessem ausentes na dose de 0,5 mg.kg-1/h. O clearance de esteviol (C S) foi maior que o Cin e menor que o C PAH em todas as doses usadas nos experimentos. Os dados sugerem a secreção de esteviol pelo epitélio tubular renal, causando diurese, natriurese, caliurese e uma redução na reabsorção tubular renal de excreção de glicose.

[ study of halothane anesthesia on the dog's kidney: histopathological and biochemical findings]

Inhalant anaesthetics are used widely for producing general anaesthesia in animals and humans.Approximately 20% of halothane uptake is metabolised via oxidative and reductive pathways during and following halothane anaesthesia in humans. Fifteen clinically healthy dogs were assigned in three groups [group 1, 2and 3] randomly. All dogs were anesthetized with halothane three times that was repeated 48 hours after the first anesthesia in all groups. Dogs in group one, two and three anesthetized for one, three and five hours respectively. All anesthesia were repeated every 48 hours as totally three anesthesia [D1, D2, and D3] were performed in each group. Jugular blood samples were obtained in 0 [before anesthesia], 1, 3, 5 and 24 hours after induction of anesthesia for measurement of BUN and Creatinin concentration. 72 hours after anesthesia, animals were euthanized and kidneys were removed for histopathological evaluation. No significant differences were observed in serum BUN and Creatinin concentration in group 1 in different sampling times compared with time 0 during study. In group 2 and 3 serum BUN and Creatinin were increased 3,5 and 24 hours compared to group 1 in third anesthesia [D3][P<0.05].In group 3 serum BUN and Creatinin were increased 1 hours after anesthesia compared to group 1 and group 2 in third anesthesia [D3] [P<0.05]. Microscopic findings revealed that there were not any pathological changes in group 1. However, kidneys of animals in group 2 and 3 were affected with acute tubular necrosis [ATN], medullary congestion and glomerular atrophy. Basement membrane of tubules with ATN appeared normal and necrotic cells were sloughed into the tubular lumens. The significant difference of BUN and Creatinin among the experiment groups revealed that long duration halothane anesthesia might be resulted in renal damage, decreased glomerular filtration rate and increased BUN and Creatinin

Determination of renal function in long-term heart transplant patients by measurement of urinary retinol-binding protein levels

Significant improvements have been noted in heart transplantation with the advent of cyclosporine. However, cyclosporine use is associated with significant side effects, such as chronic renal failure. We were interested in evaluating the incidence of long-term renal dysfunction in heart transplant recipients. Fifty-three heart transplant recipients were enrolled in the study. Forty-three patients completed the entire evaluation and follow-up. Glomerular (serum creatinine, creatinine clearance measured, and creatinine clearance calculated) and tubular functions (urinary retinol-binding protein, uRBP) were re-analyzed after 18 months. At the enrollment time, the prevalence of renal failure ranged from 37.7 to 54 percent according to criteria used to define it (serum creatinine > or = 1.5 mg/dL and creatinine clearance <60 mL/min). Mean serum creatinine was 1.61 ± 1.31 mg/dL (range 0.7 to 9.8 mg/dL) and calculated and measured creatinine clearances were 67.7 ± 25.9 and 61.18 ± 25.04 mL min-1 (1.73 m²)-1, respectively. Sixteen of the 43 patients who completed the follow-up (37.2 percent) had tubular dysfunction detected by increased levels of uRBP (median 1.06, 0.412-6.396 mg/dL). Eleven of the 16 patients (68.7 percent) with elevated uRBP had poorer renal function after 18 months of follow-up, compared with only eight of the 27 patients (29.6 percent) with normal uRBP (RR = 3.47, P = 0.0095). Interestingly, cyclosporine trough levels were not different between patients with or without tubular and glomerular dysfunction. Renal function impairment is common after heart transplantation. Tubular dysfunction, assessed by uRBP, correlates with a worsening of glomerular filtration and can be a useful tool for early detection of renal dysfunction.

Interference of enalaprilat on glomerular permeability to macromolecules (IGG) in acute unilateral ureteral obstruction in rats

INTRODUCTION: Unilateral ureteral obstruction breaks out events that cause the transitory increase of glomerular permeability to macromolecules, both in the obstructed kidney and in the contralateral kidney, suggesting the presence of some factor, with a systemic action, liberated as a response to the obstruction. We know that the rennin-angiotensin system is activated by acute ureteral obstruction. We have developed an experiment to assess the role of angiotensin II on the glomerular permeability to IgG due to acute ureteral obstruction, using enalaprilat, an angiotensin enzyme conversion inhibitor, to block the effects of the activation of the rennin-angiotensin system. MATERIALS AND METHODS: We have used 45 adult Wistar female rats, distributed into 3 main groups: a control group with 5 animals and 2 experiment groups each one with 10 animals submitted to unilateral ureteral obstruction and nephrectomy at 60 and 120 minutes. Each experiment group had its simulation correspondent (sham). We have studied both kidneys through the direct immunofluorescence method. RESULTS: We have found positive permeation in animals without enalaprilat in both kidneys and negative permeation in those in which the drug was used. CONCLUSION: We have concluded that enalaprilat interferes in this alteration of permeability, suggesting that angiotensin II is involved in the loss of selectivity of the glomerular membrane.

Evaluation of safety of Tobramycin and Piperacillin combination on rabbit kidney

Tobramycin, an aminoglycoside, and piperacillin, an antipseudomonal penicillin, are widely used to treat Gram -ve infections. Their concurrent use is recommended because of their synergistic action and prevention of resistant strains against monotherapy. This experimental work was aimed to study the effects and interaction of these important drugs on rabbit kidney. Male rabbits were administered tobramycin, piperacillin, and tobramycin plus piperacillin for 21 days [n = 6 in each group]. Blood and urine samples were collected on day O, 11, and 21. Blood was analyzed for BUN, serum creatinine, serum potassium, and serum sodium while urine was analyzed for urine volume, creatinine, albumin and specific gravity. Renal creatinine clearance was calculated. Results showed some change in renal function with use of tobramycin but piperacillin neither changed the renal function nor did augment the toxic effect of tobramycin so it was concluded that combination of both drugs in safe

Effects of dietary lipids on renal function of aged rats

Normal aging is accompanied by renal functional and morphological deterioration and dietetic manipulation has been used to delay this age-related decline. We examined the effects of chronic administration of diets containing 5 percent lipid-enriched diet (LD, w/w) on renal function of rats at different ages. Three types of LD were tested: canola oil, fish oil and butter. Mean systemic tail-cuff blood pressure and glycemia remained within the normal range whatever the age and the diet of the animals. Proteinuria began to rise from the 8th month in the groups ingesting LD, while in the control group it increased significantly (above 10 mg/24 h) only after the 10th month. With age, a significant and progressive decline in glomerular filtration rate (GFR) and renal plasma flow was observed in the LD groups but after 6 months of lipid supplementation, the decline in these parameters was more marked in the butter and fish oil groups. By the 18th month, the lowest GFR level was observed in the group ingesting the butter diet (2.93 + or - 0.22 vs 5.01 + or - 0.21 ml min-1 kg-1 in control, P<0.05). Net acid excretion, evaluated in 9- and 18-month-old rats, was stimulated in the fish oil group when compared both to control and to the other two LD groups. These results suggest that even low levels of LD in a chronic nutritional regimen can modify the age-related changes in renal function and that the impact of different types of lipid-supplemented diets on renal function depends on the kind of lipid present in the diet