To clarify the difference in nephrotoxicity between cisplatin and carboplatin, the pharmacokinetics of platinum, renal function and nuclear DNA synthesis in renal cortical and outer medullary cells were studied in rats which had received cisplatin or carboplatin. Male Sprague-Dawley rats were given either cisplatin or carboplatin intravenously at an equi-toxic dose (LD10 or LD50) and were killed at various times within 7 days after the injection. Cisplatin bound to plasma proteins more avidly than carboplatin. Much more platinum was detectable in the renal nuclei after cisplatin injection than after carboplatin injection. BUN and serum creatinine levels in the rats treated with 8.5 mg/kg of cisplatin were significantly higher than in those treated with 100 mg/kg of carboplatin. Cisplatin markedly suppressed the renal nuclear DNA synthesis both in vivo and in vitro, when compared with carboplatin. It is concluded that the differences in nephrotoxicity between cisplatin and carboplatin are related to their different inhibitory effects on nuclear DNA synthesis in the renal cells.
To evaluate the effects of repeated administration of cisplatin on kidney platinum (Pt) accumulation and renal function, Pt content in the kidney was determined in 31 autopsy cases and changes in creatinine clearance (Co) were retrospectively assessed in 26 of 31 autopsy cases. There was no significant correlation between the cumulative dose of cisplatin and Pt content in the kidney. However, the kidney Pt level was correlated with the dose of cisplatin injected within a 7-month period prior to the patient’s death. We suggest that the dose of cisplatin injected during a relatively short period before a patient’s death affects Pt content in the kidney. Neither the total dose of cisplatin nor the Pt content in the kidney was significantly correlated with the decrease in Co-following chemotherapy with cisplatin.
An L-shaped kidney is a type of crossed fused renal ectopia and consists of two moieties which were originally two kidneys. It is an uncommon condition and cases of malignant tumors in such anomalies are exceedingly rare. A case of an L-shaped kidney with renal cell carcinoma is herein reported, in which a separation of both moieties was done in situ in order to perform a tumor resection. A literature review of this topic is also reported and the findings are discussed.
To examine the renal damage caused by shock waves, urinary excretion of enzymes and beta 2-microglobulin were determined before and after ESWL. Urine samples were obtained from 35 patients with renal stone and 26 patients with ureteric stone treated with ESWL. Urinary lactate dehydrogenase (LDH) levels significantly increased on day 0, just after ESWL, in both groups. In the ureteric stone group the kidneys received less shock waves than in the renal stone group. Increased urinary lactate dehydrogenase was considered to have derived from erythrocytes in urine. Elevated urinary N-acetyl-beta-D-glucosaminidase (NAG) levels were also observed on day 0 after ESWL in both groups, due to unknown reasons. Indirect effect of ESWL through the sympathetic nervous system or humoral factors may contribute to increases in the urinary excretion of NAG. No significant increase was found in urinary gamma-glutamyl-transpeptidase (GGTP) levels for 5 days after ESWL. Urinary beta 2-microglobulin (BMG) levels increased on day 0 in the renal stone group alone. In our present study, the clinical significance of urinary enzymes and BMG was not well evaluated, because urinary excretion of these indicators following ESWL were transient and mild.
To investigate the protective action of methylprednisolone against cisplatin nephrotoxicity, the effect of in vivo pretreatment with methylprednisolone on the cisplatin-induced reduction in p-aminohippurate (PAH) accumulation and gluconeogenesis was examined using renal cortical slices prepared from Sprague-Dawley rats. The PAH accumulation in the kidney slices prepared from methylprednisolone-pretreated rats was significantly reduced following in vitro incubation with 2 mM cisplatin, to a degree equal to that observed in the slices prepared from untreated rats. However, the inhibitory effect of cisplatin on gluconeogenesis in the renal cortical slices obtained from methylprednisolone-pretreated rats was significantly smaller than that seen in the slices from untreated rats. Our present studies suggest that in vivo pretreatment with methylprednisolone may contribute to its protective effect against cisplatin nephrotoxicity through the process of gluconeogenesis in renal epithelial cells.
To examine the effects of calcium blockers on nephrotoxicity caused by cisplatin, the renal function and renal accumulation of Pt in Sprague-Dawley rats given 6.5 mg/kg i.v. cisplatin simultaneously with several doses of verapamil or nicardipine were evaluated. BUN, serum creatinine and kidney Pt concentrations in rats given more than 5.0 mg/kg of verapamil were significantly higher than those of the control animals injected with 6.5 mg/kg i.v. cisplatin alone, and the increase of each value was dependent upon the dose of verapamil. BUN, creatinine and kidney Pt in rats injected with more than 0.5 mg/kg i.p. nicardipine were also significantly higher than those of the controls. Calcium blockers enhanced the renal accumulation of Pt and the nephrotoxicity of cisplatin.
A clinical statistical survey was performed on 355 patients with asymptomatic microscopic haematuria. Urologic lesions were detected in 19.4% of the patients. Urologic lesions requiring surgical treatment were found in only two patients with bladder carcinoma and with renal calculus. With the exception of glomerulonephritis, the proportion of those over 40 years who had urologic lesions was higher. It is suggested that an initial evaluation based on excretory urography, cystoscopy and ultrasonography is more important for patients over 40 years.
To clarify the difference in nephrotoxicity between cisplatin and carboplatin, ultrastructural alterations and DNA synthesis of renal cell nuclei were studied in Sprague-Dawley rats which had received intravenously either cisplatin or carboplatin at an equitoxic dose. Twelve hours after cisplatin injection, nucleolar segregation accompanied by aggregated nuclear heterochromatin was observed in the third segment of the proximal tubules. Seventy-two hours after cisplatin injection, nuclear damage was more widespread while regenerative cells were also observed. Nuclear damage was not observed in the carboplatin-treated rats. Nuclear DNA synthesis of renal cells was suppressed at 8, 12 and 24 h and was accelerated at 72 h after cisplatin injection. Carboplatin did not suppress nuclear DNA synthesis at any time. The results indicate that cisplatin, but not carboplatin, can affect the renal cell nuclei. Cisplatin-induced nephrotoxicity is related to its effects on renal cell nuclei.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.