Salvianolic acid A alleviates the renal damage in rats with chronic renal failure

Abstract Purpose: To investigate the protective effects of salvianolic acid A (SAA) on renal damage in rats with chronic renal failure (CRF). Methods: The five-sixth nephrectomy model of CRF was successfully established in group CRF (10 rats) and group CRF+SAA (10 rats). Ten rats were selected as sham-operated group (group S), in which only the capsules of both kidneys were removed. The rats in group CRF+SAA were intragastrically administrated with 10 mg/kg SAA for 8 weeks. The blood urine nitrogen (BUN), urine creatinine (Ucr), creatinine clearance rate (Ccr), and serum uperoxide dismutase (SOD) and malondialdehyde (MDA) were tested. The expressions of transforming growth factor-β1 (TGF-β1), bone morphogenetic protein 7 (BMP-7) and Smad6 protein in renal tissue were determined. Results: After treatment, compared with group CRF, in group CRF+SAA the BUN, Scr, serum MDA and kidney/body weight ratio were decreased, the Ccr and serum SOD were increased, the TGF-β1 protein expression level in renal tissue was decreased, and the BMP-7 and Smad6 protein levels were increased (all P < 0.05). Conclusion: SAA can alleviate the renal damage in CRF rats through anti-oxidant stress, down-regulation of TGF-β1 signaling pathway and up-regulation of BMP-7/Smad6 signaling pathway.

Relato de caso: Insuficiência renal crônica estádio 5 D em paciente com doença renal crônica medicado com varfarina / Case Report: End stage renal disease in a chronic kidney patient on warfarin therapy

Resumo Introdução A terapêutica com varfarina pode provocar hematúria grave e lesão renal aguda pela formação de cilindros eritrocitários oclusivos. Estas alterações são sugestivas de uma doença recentemente conhecida como nefropatia relacionada pela varfarina. Caso Clínico: Apresentamos um doente de 74 anos de idade com doença renal crônica estádio 3 A, que progrediu com declínio na taxa de filtração glomerular (TFG) após o início de terapêutica com varfarina devido a um quadro fibrilação atrial. O diagnóstico foi confirmado pela histologia renal, que demonstrou a presença de oclusão tubular por cilindros eritrocitários, achados consistentes com este diagnóstico. O paciente não recuperou a TFG, tendo iniciado terapêutica substitutiva da função renal. Discussão: O objetivo da descrição deste caso clínico é alertar para a complicação associada a este fármaco e reforçar a necessidade de monitorização cuidada da função renal e dos parâmetros de coagulação em doentes tratados com a varfarina. A patogênese e o prognóstico desta entidade também serão discutidos. .

Abstract Background: Warfarin therapy can provoke severe hematuria and acute kidney injury with the presence of occlusive red blood cell casts. These findings are compatible with a recently described disease entity, warfarin related nephropathy, which adversely affects renal and patient outcome. Case report: We report a 74-year-old man with chronic kidney disease stage 3 A, who developed a decline in glomerular filtration rate (GFR) after the initiation of warfarin therapy due to of atrial fibrillation. The diagnosis could be confirmed by renal histology which showed occlusion of renal tubules by red blood cells and casts consistent with this diagnosis. The patient did not recover the GFR and started renal replacement therapy in June (fourteen months after starting warfarin) 2014. Discussion: The aim of the present report is to alert for this drug recognized complication and reinforce the need of carefully motorization of kidney function and coagulation parameters in patients treated with warfarin. The pathogenesis and outcome of warfarin-related nephropathy is also discussed here. .

Risk factors for contrast-related acute kidney injury according to risk, injury, failure, loss, and end-stage criteria in patients with coronary interventions

Although a series of risk factors for contrast-induced nephropathy are known, data on significance of some of the risk factors such as age, sex, hypercholesterolemia, hyperuricemia, and dose of contrast medium are inconsistent. Our aim was to identify risk factors for contrast-related acute kidney injury [AKI]. In this prospective study, 290 consecutive patients with a serum creatinine level lower than 3 mg/dL undergoing percutaneous angiography were analyzed. Contrast-related AKI was evaluated using the risk, injury, failure, loss, and end-stage [RIFLE] criteria, and its correlation with clinical and laboratory data of the patients was analyzed. Contrast-related AKI was found in 15.5% of the patients, with a maximum RIFLE category [risk in 13.8%, injury in 1.4%, and failure in 0.3%]. Serum creatinine level, contrast volume, safe contrast volume factor, diabetes mellitus, and dehydration were significantly associated with contrast-related AKI. Age, sex, and serum uric acid level did not differ significantly between those with and without contrast-related AKI. Multiple logistic regression analysis disclosed diabetes mellitus to be the strongest predictor for being at risk of contrast-related AKI [odds ratio, 5.1; 95% confidence interval, 1.9 to 11.0; P=.001], followed by hypercholesterolemia [odds ratio, 4.6; 95% confidence interval, 1.1 to 8.3; P=.03], and an estimated glomerular filtration rate lower than 90 mL/min/1.73 m[2] [odds ratio, 3.0; 95% confidence interval, 1.8 to 5.7; P=.003]. Our results indicate that diabetes mellitus, hypercholesterolemia, and underlying chronic kidney disease are the major factors of contrast-related AKI

Persistent hypertension and progressive renal injury induced by salt overload after short term nitric oxide inhibition

INTRODUCTION: Administration of the NO inhibitor Nwð-nitro-L-arginine methyl ester (NAME) and a high-salt diet (HS) promotes severe albuminuria and renal injury, which regresses upon discontinuation of treatments. OBJECTIVE: We investigated whether these changes reappear after reinstitution of HS, and whether they are prevented by treatment with the antilymphocyte agent mycophenolate mofetil (MMF) or the AT-1 receptor blocker losartan (L). Adult male Munich-Wistar rats received NAME and HS. A control Group (C) received only HS. After 20 days, rats receiving HS and NAME exhibited severe hypertension and albuminuria. After a 30-day recovery period, hypertension was attenuated and albuminuria had virtually disappeared. MATERIAL AND METHODS: Rats were then distributed among the following groups: HS, receiving HS; NS, receiving a normal salt (NS) diet; HS-MMF, receiving HS and MMF; HS-LOS, receiving HS and L; HS-HDZ, receiving HS and hydralazine (HDZ). Sixty days later, NS rats showed only slight albuminuria and renal damage or inflammation. In contrast, HS rats developed severe hypertension, marked glomerulosclerosis with interstitial expansion and renal infiltration by macrophages and angiotensin II-positive cells. The group treated with losartan had lowered blood pressure and a lack of albuminuria or renal injury. MMF provided similar protection without altering blood pressure, suggesting a nonhemodynamic effect, a hypothesis reinforced by the finding that HDZ lowered blood pressure without preventing renal injury. RESULTS: These results indicate that treatment with HS and NAME predisposes to the development of hypertension and renal injury upon salt overload, characterizing a new model of chronic nephropathy. CONCLUSION: The response to MMF or L, but not HDZ, suggests a key role for inflammatory rather than hemodynamic factors.

INTRODUÇÃO: A administração de Nômega-nitro-L-arginina metiléster (NAME), um inibidor da produção de NO, com dieta rica em sal (HS) promove albuminúria e dano renal graves, reversíveis ao interromperem-se os tratamentos. OBJETIVO: Investigamos se tais alterações recrudescem ao reinstituir-se a HS e se são prevenidas pelo micofenolato mofetil (MMF), um agente antilinfócito, ou losartan, um bloqueador do receptor AT-1. MATERIAL E MÉTODOS: Ratos Münich-Wistar machos adultos receberam NAME e HS. Um grupo controle (C) recebeu apenas HS. Após 20 dias, os ratos que receberam HS e NAME exibiam hipertensão e albuminúria graves. Após recuperação de 30 dias, a hipertensão atenuou-se e a albuminúria praticamente desapareceu. Formaram-se então os grupos: HS, recebendo HS; NS, recebendo dieta normal em sal (NS); HS-MMF, recebendo HS e MMF; HS-LOS, recebendo HS e losartan; HS-HDZ, recebendo HS e hidralazina. Após sessenta dias os ratos NS tinham albuminúria e dano/inflamação renal apenas discretos. Já os ratos HS desenvolveram hipertensão e glomerulosclerose acentuadas, expansão intersticial e infiltração renal por macrófagos e células positivas para angiotensina II. Losartan baixou a pressão arterial e preveniu albuminúria e lesão renal. MMF proporcionou proteção semelhante sem alteração pressórica, sugerindo a ação de mecanismos não hemodinâmicos, hipótese reforçada pelo achado de que a HDZ baixou a pressão arterial sem prevenir a nefropatia. RESULTADOS: Esses resultados indicam que o tratamento com HS e NAME predispõe ao desenvolvimento de hipertensão e lesão renal induzidos por excesso de sal, caracterizando um novo modelo de nefropatia crônica. CONCLUSÃO: A resposta ao MMF ou losartan, mas não à hidralazina, sugere o predomínio de fatores inflamatórios.

NSAIDs and kidney.

NSAIDs are commonly used drugs. Even with the advent of selective COX-2 inhibitors, nephrotoxicity still remains a concern. The adverse effects of NSAIDs are mediated via inhibition of prostaglandin synthesis from arachidonic acid by non-specific blocking of the enzyme cyclooxygenase leading to vasoconstriction and reversible mild renal impairment in volume contracted states. When unopposed, this may lead to acute tubular necrosis and acute renal failure. NSAIDs also produce interstitial nephritis with or without nephrotic syndrome secondary to minimal change disease. Although this presents as acute renal failure, it can progress in some cases to chronic renal failure. Papillary necrosis has been incriminated in the development of chronic renal failure secondary to NSAIDs. In patients on long term NSAIDs without acute or chronic renal failure, subclinical renal dysfunction such as reduced creatinine clearance and impaired urine concentrating ability has been shown to be present. Although this sub-clinical dysfunction is reversible on withdrawal of NSAIDs, some reports have suggested a persistent residual dysfunction. Even with a wide range of NSAIDs at our disposal, a renal safe NSAID is yet to be discovered.

Renoprotective effect of high periprocedural doses of oral N-acetylcysteine in patients scheduled to undergo a same-day angiography

BACKGROUND: Few studies that have assessed the effect of abbreviated oral N-acetylcysteine (NAC) regimens in radiocontrast-induced nephropathy (RCIN) yield mixed results. OBJECTIVE: To evaluate the renoprotective effect of high periprocedural oral doses (HPOD) of NAC in patients with chronic renal impairment undergoing a same-day angiography. METHODS: Sixty one patients with renal impaired function scheduled to undergo a same-day angiography were randomly assigned to NAC 1200 mg orally 3 hours before and 3 after the procedure, or a placebo. All patients received 0.9% saline intravenous. RCIN was defined as an increase in SCC > 0.5 mg/dl 48 hours after the procedure. RESULTS: The mean baseline SCC for all patients was 1.44 +/- 0.42 mg/dl. A significant difference in SCC change at 48 hours after the angiography was found (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P = 0.04). RCIN occurred in 1 (3%) patient of NAC group and in 2 (7.1%) patients of placebo group (P = 0.59). Adverse effects were similar in both groups. CONCLUSIONS: In patients with mild renal impairment patients undergoing angiographic procedures, HPOD of NAC were more effective than placebo in preventing SCC change 48 hours. A non significant benefit in RCIN incidence was found.

Los escasos estudios que han evaluados los efectos de regimenes abreviados de Nacetilcisteína (NAC) oral en la nefropatía por contraste (NC) han encontrado resultados contrapuestos. OBJETIVO: Evaluar el efecto renoprotector de altas dosis orales periprocedimiento (ADOP) de NAC en pacientes con insuficiencia renal con angiografía programada el mismo día. MATERIAL y METODOS: Sesenta y un pacientes con insuficiencia renal y angiografía programada para el mismo día fueron asignados aleatoriamente a 1200 mg de NAC 3 horas previas y 3 horas posteriores al cateterismo o un placebo. Todos los pacientes recibieron hidratación endovenosa con solución salina al 0.9%. La NC se definió como el aumento en la creatinina sérica (CS) > 0.5 mg/dl a las 48 horas del procedimiento. RESULTADOS: La CS media en todos los pacientes fue 1.44: t 0.42 mg/dl. Se encontró una diferencia significativa entre ambos grupos en el cambio de CS a las 48 horas de la angiografía (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P=0.04). La NC se presentó en 1 (3%) paciente del grupo NAC y en 2 (7.1 %) pacientes del grupo placebo (P=0.59). Los efectos adversos fueron similares en ambos grupos. CONCLUSION: En pacientes con insuficiencia renal leve sometidos a angiografía en el mismo día, las ADOP de NAC fueron más efectivas que el placebo en la prevención del cambio de CS a las 48 horas del procedimiento. Se encontró un beneficio no significativo en la incidencia de NC.

Nefropatía terminal en pacientes de un hospital de referencia en El Salvador / End-stage renal disease among patients in a referral hospital in El Salvador

Objetivos. El Salvador es un país con alta mortalidad por nefropatía terminal (NT). El objetivo de este estudio consistió en conocer las características epidemiológicas de una serie de nuevos casos de NT atendidos en un hospital de referencia de este país. Métodos. Se realizó un estudio transversal de todos los nuevos casos que iniciaron diálisis crónica entre noviembre de 1999 y marzo de 2000. Mediante una entrevista personal se obtuvieron datos sobre aspectos clínicos, demográficos, laborales y ambientales. Resultados. Durante los 5 meses que duró el estudio se observaron 205 nuevos casos de NT. Entre los 202 entrevistados, se diferenciaron claramente dos grupos: uno de 67 pacientes (33 por ciento) con factores de riesgo conocidos de NT, similares a los de países desarrollados (fundamentalmente, diabetes mellitus, hipertensión arterial y consumo crónico de antiinflamatorios no esteroideos), y otro de 135 pacientes (67 por ciento) con características peculiares, en los que no se pudo detectar ningún factor asociado. La mayoría de estos últimos pacientes eran hombres, agricultores, habitantes de zonas costeras o adyacentes a ríos, que años atrás habían estado expuestos, sin protección, a insecticidas o plaguicidas agrícolas por razones laborales. Conclusiones. Se ha identificado un importante grupo de pacientes con NT que aparentemente carecen de una causa para su enfermedad y que presentan características peculiares que permiten sospechar una relación con la exposición laboral a insecticidas o plaguicidas. Son necesarios nuevos estudios para confirmar esta hipótesis

A case of living-related kidney transplantation in Bartter's syndrome

Bartter's syndrome is a renal tubular disorder characterized by hypokalemia, metabolic alkalosis, increased urinary excretion of potassium and prostaglandins, a relative vascular resistance to the pressor effects of exogenous angiotensin II, and hyperplasia of the juxtaglomerular apparatus. In most patients, the glomerular filtration rate is normal and chronic renal failure does not develop. We report here on a case of living-related kidney transplantation in Bartter's syndrome, in which a non-steroidal anti-inflammatory drug is suspected to be the cause of the end-stage renal disease.

Histologic and histochemical studies on the bone marrow, spleen and liver in experimentally-induced chronic renal failure in the rat

Albino rat has been used as an animal model for adenine induced chronic renal failure. Animals were fed a diet containing 0.75% adenine in a dose of 250-350 mg/kg body weight/day for one month. Histologic and histochemical changes of bone marrow, spleen and liver were investigated. Bone marrow smear showed a hypocellularity in the from of a marked decrease of different stages of development of RBCs, leucocytes and megakaryocytes. This was associated with a marked increase in acid phosphatase enzyme activity and a decrease in succinic dehydrogenase enzyme activity. Numerous mast cells were also observed. With the spleen, lymphocytic depletion was observed in the periarteriolar lymphatic sheath, the rest of lymphatic follicle and the red pulp. Macrophage number was apparantely increased in the red pulp. Haemosiderin granules showed a marked increase in the red pulp. Like with the bone marrow, an increase in activity of acid phosphatase enzyme and a decrease in succinic dehydrogenase enzyme activity were noticed in the red pulp. In the liver, hepatocyte vacuolation and increased number of von Kupffer cells were noticed. An increase in acid phosphatase enzyme activity and a decrease in succinic dehydrogenase enzyme activity were observed. There was a patchy depletion of glycogen granules