Cisplatin, nephrotoxicity

G. Ciarimboli, T. Ludwig, D. Lang, H. Pavenstadt, H. Koepsell, H. J. Piechota, J. Haier, U. Jaehde, J. Zisowsky, and E. Schlatter. Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol 167 1477-1484... 

Zhang, J.-G., Lindup, E. (1994) Cisplatin Nephrotoxicity Decreases in Mitochondrial Protein Sulphydryl Concentration and Calcium Uptake by Mitochondria from Rat Renal Cells, Biochem. 

Kelsen DP, Alcock N, Young CW. Cisplatin nephrotoxicity. Correlation with plasma platinum concentrations. Am J Clin Oncol 1985 8(l) 77-80. 

Safirstem R, Wiston J. Cisplatin nephrotoxicity. J UOEH 1987 9(Suppl) 216-22. 

Stewart DJ, Dulberg CS, Mikhael NZ, Redmond MD, Montpetit VA, Goel R. Association of cisplatin nephrotoxicity with patient characteristics and cisplatin... 

Jacobs C, Kaubisch S, Flalsey J, Lum BL, Gosland M, Coleman CN, Sikic Bl.The use of probenecid as a chemoprotector against cisplatin nephrotoxicity. Cancer 1991 67 1518-1524. 

Mayer RD, Lee KE, and Cockett AT. Improved use of buthionine sulfoximine to prevent cisplatin nephrotoxicity in rats. Journal ofCancer Research and Clinical Oncology 115 418-422,1989. 

Mishra J, Mori K, Ma Q, et al. Neutrophil gelatinase-associated lipocalin a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 2004 24 307-315. 

Yang C, Kaushal V, Flaun RS, Seth R,Shah SV, Kaushal GP. Transcriptional activation ofcaspase-6and-7 genes by cisplatin-induced p53 and its functional significance in cisplatin nephrotoxicity. Cell Death and Dfferentiation, 2008 15 530-544. 

Lau AEI Apoptosis induced by cisplatin nephrotoxic injury. Kidney Int 56 1295-1298,1999... 

Hanigan MH and Devarajan P. Cisplatin nephrotoxicity molecular mechanisms. CancerTher 1 47-61,2003. 

As mannitol and furosenude reduce the concentration of platinum in the urine, it has been suggested that these agents may attenuate cisplatin nephrotoxicity [40, 41]. However, neither platinum content in the plasma or kidney nor the degree of cellular necrosis it produces is modified by these diuretics [41]. Platinum is not reabsorbed to an important degree after its intra tubular microinjection and, therefore, platinum content in the cell should not be dependent on its luminal concentration [13]. 

While several experimental reports have suggested that diuretics [mannitol and furosemide] decrease cisplatin nephrotoxicity [36, 41] others have shown that they may aggravate it [43]. Further, in humans, there is no convincing evidence than diuretics may attenuate cisplatin nephrotoxicity as shown in a randomized study by Alsarraf et al. [44] hydration + cisplatin was compared to hydration + mannitol + cisplatin. 

The use of hypertonic saline was first introduced in the clinic by Schilsky et al. [19] who concluded than when 3% saline was used as a vehicle for cisplatin, no renal toxicity was observed as measured by serum creatinine and creatinine clearance in patients treated with a high dose of cisplatin. However, when Cr-EDTA was used as a measure of glomerular filtration rate, a significant decrease in the latter was observed despite the use of 3% saline [12,13]. Thus the interest of hypertonic saline in the prevention of high dose cisplatin nephrotoxicity will have to be further delineated... 

An impressive list of compounds has been used to decrease cisplatin nephrotoxicity [ANF, glycine, diethyldithiocarbamate, calcium channel blockers, cimetidine, sodium thiosulphate, glutathione, other sulfidryl compounds,. ..]. Among them only sodium thiosulphate has received a significant clinical application and has been reported to reduce the renal toxicity of cisplatin administered locally by either the intra-arterial, intra-peritoneal or intrathoracic routes [50, 51]. However, controversies still exists as to the effect of sodium thiosulphate on cisplatin antitumor activity. Thus sodium thiosulphate may be most useful in combination with intraperitoneal cisplatin where it confers renal protection without altering local effects of cisplatin [51]. 

The vulnerability of the kidney to cisplatin is almost certainly linked to its primary role in the excretion of the drug. The P3 segment of the proximal tubule is particularly vulnerable to it. The cause of renal cell death induced by cisplatin is unknown, but mounting evidence points to its genotoxic effect. In cisplatin nephrotoxicity, as in other forms of nephrotoxic renal damage, reduced renal blood flow and diminished renal conservation of water are common physiologic derangements. 

Brock PR, Koliouska DE, BarattTM, Yeomans E, Pritchard J. Partial reversibility of cisplatin nephrotoxicity in children. J Pediatric 1991,118 531-4. 

Citkovic E, Hayes DM,Golbey RB, Krakoff IH.Cisplatin-nephrotoxicity diethyldithiocarbomate,WR2721 orjust water. J Clin Oncol... 

Safirstein R, Winston J, Moel D, Dikman S, Guttenplan J. Cisplatin nephrotoxicity insights into mechanism. Int J Andrology 1987 10 325-46. 

Safirstein R, Zelent AZ, Gordon R. CIsplatIn-nephrotoxIcIty new Insights Into mechanisms. In Hacker MP, Lazo JS, Tritton TR, editors. Organ directed toxicitles of anticancer drugs. Boston Martinus NIjhof, 1988 172-89. 

Ramesh G, Reeves WB TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity, J Clin Invest 2002,110 835-842... 

Thompson KL, Afshari CA, Amin RP, Bertram TA, Car B, Cunningham M, Kind Cl, Kramer JA, Lawton M, Mirsky M, Naciff JM, Oreffo V, Pine PS, Sistare FD. Identification of platform-independent gene expression markers of cisplatin nephrotoxicity. Environ Health Perspect 2004 112(4) 488-94. 

Deegan PM, Nolan C, Ryan MP, Basinger MA, Jones MM, Hande KR. The role of the renin-angiotensin system in cisplatin nephrotoxicity. Renal Failure 1995 17 665-74. 

Pabla N et al (2009) The copper transporter Ctrl contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity. Am J Physiol Renal Physiol 296(3) F505-F511... 

Sener G, Satiroglu H, Kabasakal L, et al. The protective effect of melatonin on cisplatin nephrotoxicity. Eundam CUn Pharmacol 2000 14 553- 78. 

Vermeulen NP, Baldew GS, Los G, et al. 1993. Reduction of cisplatin nephrotoxicity by sodium selenite. Lack of interaction at the pharmacokinetic level of both compounds. Drug Metab Dispos Biol Fate Chem 21(l) 30-36. 

Lieberthal W, Koh JS, Levine JS Necrosis and apoptosis in acute renal failure. Semin Nephrol 18 505-518,1998 Lieberthal W Biology of acute renal failure Therapeutic implications. Kidney Int 52 1102-1115, 1997 Lau AH Apoptosis induced by cisplatin nephrotoxic injury. Kidney Int 56 1295-1298, 1999... 

Conclusions regarding the renoprotective action of mannitol and furosemide to decrease experimentally induced cisplatin nephrotoxicity are conflicting [36,41, 43]. However, in humans, a randomized study hy Alsarraf et al. [44] comparing hydration + cisplatin to hydration + mannitol + cisplatin concluded that mannitol did not attenuate cisplatin nephrotoxidly. 

---