We investigated the pathobiological course of uranyl nitrate (UN) induced polyuric acute tubular necrosis (ATN) in male Sprague Dawley rats. UN (5mg/kg 15mg/kg and 3Omg/kg) in 5% NaHCO3 induced weight loss, polydipsia, and polyuria 24 hrs after injection when compared to the controls which were treated with 5% NaHCO3 only. Twenty four hours following the injection of UN, serum creatinine and blood urea nitrogen levels had increased. These changes continued for at least 72 hours, although the concentration of uranium had decreased. Light microscopic studies conducted 24 hours after injection, revealed partial degeneration and necrosis of the proximal tubules and many casts m the distal convoluted tubules. These changes progressed for 72 hours. Despite this tubular damage, the glomeruli were relatively intact. 5 days after injection, the epithelial cells lining the proximal tubules displayed regenerative activities; these findings were more prominent after 10 days. Through electron microscopic examination, we observed the destruction of mitochondria in the proximal tubular cells, a possible cause of polyuria. Ten days post injection regenerative activities in the proximal tubular cells showed that the maturation of intracellular organelles followed the proliferation of the premature cells.
Animal ; Kidney Failure, Acute/chemically induced* ; Kidney Function Tests ; Kidney Tubular Necrosis, Acute/chemically induced* ; Male ; Rats ; Rats, Inbred Strains ; Uranium/pharmacology* ; Uranyl Nitrate/pharmacology*

Aristolochic Acids ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Kidney Tubular Necrosis, Acute ; chemically induced ; prevention & control

Drug-induced nephrotoxicity is very common in both new drug development and clinic practice. Various drugs can induce kidney injuries, including tubulointerstitial, glomerular and renal vascular disease. To investigate the mechanism of drug induced nephrotoxicity is important for risk reduction of new drug development, reasonable drug usage, early discovery and effective prevention/treatment of adverse effects in clinics.
Acute Kidney Injury ; chemically induced ; Animals ; Anti-Infective Agents ; adverse effects ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; Antineoplastic Agents ; adverse effects ; Humans ; Immunosuppressive Agents ; adverse effects ; Kidney Diseases ; chemically induced ; Kidney Tubular Necrosis, Acute ; chemically induced ; Nephritis, Interstitial ; chemically induced ; Renal Insufficiency ; chemically induced

Aristolochic Acids ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Infant, Newborn ; Kidney Diseases ; chemically induced ; Kidney Tubular Necrosis, Acute ; chemically induced ; Magnoliopsida ; adverse effects ; Male ; Retrospective Studies

OBJECTIVETo summarize the clinical characteristics and prognosis of newborn aristolochic acid nephropathy induced by akebia.

METHODRetrospective analysis of clinical manifestations, therapy and prognosis was made upon data of 3 newborn infants with renal function lesion induced by akebia.

RESULTThree infants who were fed with Chinese herbal medicines containing akebia trifoliate suffered from acute renal failure, renal glomerular and tubular injury, with symptoms of vomiting, diarrhea, and oliguria. Laboratory tests manifested hyperpotassemia, hyponatremia, elevation of serum creatinine and urea nitrogen, and metabolic acidosis. Renal glomerular lesion was mild, presented with proteinuria and increased serum β(2) microglobin. Renal dysfunction was manifested with alkaline urine, glucosuria, positiveness of urine glucose, ketone and aminoaciduria, and increased urine β(2) microglobin excretion. After symptomatic treatment for 3 to 4 weeks, the renal function of these infants recovered. Proteinuria, aminoaciduria and glucosuria turned negative within 5 to 8 months, 3 months to 1 year, and 9 months to 3 years, respectively. Urine pH decreased to 7.0 after 5.0 - 5.5 years. All cases took citric acid mixtures for 5.5 to 6 years. A 12-years follow-up demonstrated that serum creatinine of 3 cases were within normal range during the first 11 years of life, however recent follow-up showed increased serum creatinine of case 1 and case 2, except for serum creatinine of case 3 remained normal. The estimated glomerular filtration rate (eGFR) of all the 3 cases decreased. Among which, eGFR of case 1 and case 2 were lower than 90 [ml/(min·1.73 m(2))], and decreased 1.1 [ml/(min·1.73 m(2))] and 0.6 [ml/(min·1.73 m(2))] per year during recent six years, respectively. No obvious decrease of eGFR was observed in case 3. Blood gas analysis and urine routine were normal, yet blood and urine β(2) microglobin excretion were still high. Urinary N-acetyl-β-D-glucosaminidase increased again after having returned to normal.

CONCLUSIONNewborn aristolochic acid nephropathy induced by akebia might induce acute renal failure and renal tubules injury. Renal function could recover after symptomatic treatment in short-term. Nevertheless, glomerular filtration rate presents a slow descending tendency and renal tubules lesion lasted for many years, which requires a long-term follow-up.

Aristolochic Acids ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Infant, Newborn ; Kidney Diseases ; chemically induced ; Kidney Tubular Necrosis, Acute ; chemically induced ; Magnoliopsida ; adverse effects ; Male ; Retrospective Studies

AIMTo investigate the effect of sodium ferulate (SF) on glycerol-induced renal injury.

METHODSGlycerol solution 50% was injected intramuscularly to establish a model of acute tubular necrosis in mice. SF was administered intraperitoneally at the dose of 100-200 mg.kg-1 at the beginning of establishing the model and its effect was observed by monitoring renal function, antioxidative functions and renal pathologic histology.

RESULTSAt 6 and 72 h after glycerol injection, SF treatment (100-200 mg.kg-1) showed significant and dose-dependent antagonistic actions on the increment of blood urea nitrogen (BUN), creatinine (Cr), and N-acetyl-beta-glucosaminidase (NAG) induced by glycerol. The increase of renal malondialdehyde (MDA) content and the decrease of glutathione content, glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), catalase (Cat) and superoxide dismutase (SOD) activities resulting from glycerol injection were remarkably inversed by SF at the dose of 200 mg.kg-1. Meanwhile, improvement of the renal histology was observed as well.

CONCLUSIONSF showed beneficial effect on glycerol-induced acute tubular necrosis due to its antioxidative action.

Animals ; Antioxidants ; pharmacology ; Blood Urea Nitrogen ; Coumaric Acids ; pharmacology ; Creatinine ; blood ; Glutathione Peroxidase ; metabolism ; Glycerol ; Kidney ; metabolism ; pathology ; Kidney Function Tests ; Kidney Tubular Necrosis, Acute ; chemically induced ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Mice ; Superoxide Dismutase ; metabolism

OBJECTIVETo explore the possible cell biological mechanisms of the difference in prognosis between the acute tubular necrosis (ATN) induced by Manchurian Dutchmanspipe (MD-ATN) and that by antibiotics (A-ATN), by means of comparing their renal tubular mesenchymal cell phenotype characteristics and extra-cellular stroma secretion.

METHODSThe expression of proliferative cell nuclear antigen (PCNA), epithelial cell growth factor (EGF), alpha-smooth muscle actin (alpha-SMA), fibronectin (FN), collagen type III and IV, transforming growth factor beta 1 (TGF beta 1) and connective tissue growth factor in renal biopsy samples of patients with MD-ATN (4 patients) and A-ATN(5 patients) were compared with immunohistochemical SP method. The analysis of above-mentioned parameters on repairing of injury and development of fibrosis was stressed for the obvious difference in clinical prognosis between the two groups.

RESULTS(1) The PCNA positive rate of renal tubular epithelial cell (RTEC) and EGF expression in the MD-ATN group were significantly lower than those in the A-ATN group respectively (P < 0.01); (2) Renal tubular mesenchymal alpha-SMA level increased in both groups with no significant difference; (3) TGF beta 1 positive cell infiltration and obvious CTGF expression revealed in renal mesenchyma of both groups with insignificant difference; (4) FN, collagen III and IV levels were significantly higher in the MD-ATN group than that in the A-ATN group (P < 0.05).

CONCLUSION(1) As compared with A-ATN group, the RTEC auto-repairing ability was lower in the DM-ATN group, lower expression of EGF might be one of the mechanisms of its poor repair; (2) High expression of alpha-SMA, TGF beta 1 and CTGF presented in all patients with ATN, but extra-cellular stromal deposit appeared only in the renal stroma of patients with MD-ATN, suggesting that its chronical trend might be related with the reducing of extra-cellular stromal degradation factor and/or endogenous anti-fibrosis factor.

Adult ; Aminoglycosides ; Anti-Bacterial Agents ; adverse effects ; Aristolochia ; chemistry ; Aristolochic Acids ; adverse effects ; Biopsy, Needle ; Drugs, Chinese Herbal ; adverse effects ; Female ; Fibronectins ; biosynthesis ; Fibrosis ; Humans ; Kidney ; pathology ; Kidney Tubular Necrosis, Acute ; chemically induced ; pathology ; Male ; Middle Aged ; Prognosis ; Proliferating Cell Nuclear Antigen ; biosynthesis