Pathophysiology of acute renal failure
Abteilung für Nieren und Hochdruckkrankheiten, Medizinische Klinik und Poliklinik, Universitätsklinikum Essen, Germany. Journal of nephrology
(Impact Factor: 1.45).
01/1999; 12 Suppl 2:S142-51.
Acute renal failure (ARF) is a common renal disease affecting up to 5% of all hospitalized patients, with a higher prevalence of 10-30% in patients in critical care units (1-3). Despite advances in the management of critically ill patients and technological advances in renal replacement therapy, the high mortality of patients with ARF has not changed over the last decades and remains above 50% (4-6). Moreover, as a consequence of more advanced medical therapy and more complicated surgical interventions in older and multimorbid patients, the number of patients with ARF is increasing (1, 4, 5). Moreover, ARF itself increases the risk to develop additional complications that can be deleterious. Recently, an independent association between ARF and mortality has been shown in patients following administration of radiocontrast media in an intensive care unit and in patients following cardiac surgery (6, 7). Following radiocontrast media the mortality of patients with ARF was increased five fold and following cardiac surgery sixteen-fold as compared to patients with the same underlying disease without ARF. The pathophysiology of ischemic ARF is reviewed with the emphasis on the following mechanisms: Increased fractional excretion of sodium, Activation of tubuloglomerular feedback, Cytoskeletal disruption, Tubular obstruction, Vascular mechanisms. The following mediators will also be discussed: Calcium, Cysteine proteases, Nitric oxide, Adhesion receptors and integrins.
Available from: Houshang Najafi
- "Most importantly, curcumin has been used for the treatment of rheumatoid arthritis (Deodhar et al., 1980), postoperative inflammation (Satoskar et al., 1986), idiopathic orbital inflammation (Lal et al., 2000), Alzheimer's disease, multiple myeloma (Hatcher et al., 2008), pancreatic and colon cancer (Lao et al., 2006; Kanai, 2014), and chronic renal failure (Trujillo et al., 2013). The most important damages caused by renal I/R are vascular endothelium and tubular epithelium damages that result in the development of oxidative stress and interstitial inflammation (Thadhani et al., 1996; Kribben et al., 1999; Clarkson et al., 2008). Therefore, this study aimed to investigate the therapeutic effects of curcumin on functional disturbances and oxidative stress caused by I/R in the rat model. "
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ABSTRACT: Objectives: Curcumin has anti-inflammatory and antioxidative
properties. The objective of this study was to investigate the
therapeutic effects of curcumin on functional disturbances, oxidative
stress, and leukocyte infiltration induced by renal
Materials and Methods: Animals were randomly divided into 9
groups. The groups with 24-h reperfusion consisted of sham-24h,
I/R-24h, and three I/R groups treated with curcumin at 10, 20, or 30
mg kg-1, i.p. after the ischemic period. The 72-h reperfusion groups
also included Sham-72h, I/R-72h, I/R treated with curcumin at
single dose of 20 mg kg-1, i.p., and I/R group which received three
doses of curcumin at 20 mg kg-1, i.p., consecutively. Renal
functional injury was assessed by measuring serum creatinine and
urea-nitrogen concentrations. Oxidative stress was evaluated by
assessment tissue malondialdehyde (MDA) and the ferric
reducing/antioxidant power (FRAP) levels. Moreover, renal tissue
leukocyte infiltration was measured by histopathology examination.
Results: Ischemia/reperfusion resulted in a significant increase in
serum concentration of creatinine, urea-nitrogen, tissue MDA level,
and leukocytes infiltration as well as reduced FRAP level.
Treatment with curcumin in 24-h reperfusion groups could only lead
to a significant change in the levels of MDA and FRAP. However,
in 72-h reperfusion groups, curcumin was able to correct all
functional disturbances, oxidative stress, and leukocytes infiltration
with more effectiveness in groups that received three doses of
Conclusion: The administration of curcumin during 72-h
reperfusion following 30 minutes of ischemia can decrease renal
oxidative stress and leukocytes infiltration as well as improve
kidney function. However, during first 24-h reperfusion, curcumin
only decreased oxidative stress.
Avicenna Journal of Phytomedicine 11/2015; 5(6):576-586.
- "Acute kidney injury (AKI) is a common clinical syndrome that is induced by kidney ischemia. Renal ischemia and reperfusion (I/R) injury also is one of the common complications in clinical surgeries such as renal transplantation. "
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ABSTRACT: Acute kidney injury (AKI) has been recognized as one of the most complex clinical complications in modern medicine, and ischemia/reperfusion (I/R) injury is well-known as a main reason of AKI. In addition, AKI leads to important systemic consequences such as acute lung injury. This study was designed to investigate the role of erythropoietin (EPO) on kidney function makers and tissue damage; and lung endothelial permeability and lung water content (LWC) in bilateral renal I/R injury model in rats.
Male Wistar rats were randomly divided into three groups of sham, I/R, and I/R treated with EPO (I/R + EPO) groups. The I/R and I/R + EPO groups were subjected to bilateral renal I/R injury; however, only the I/R + EPO group received EPO (500 IU/kg, i.p.) 2 h before ischemia surgery, and the same dose was continued once a day for 3 days after ischemia. The sham group underwent a surgical procedure without ischemia process.
The blood urea nitrogen (BUN) and serum creatinine (Cr) levels, kidney tissue damage score (KTDS), and kidney weight (KW) per 100 g body weight significantly increased in I/R group (P < 0.05). EPO administration decreased levels of BUN and Cr significantly (P < 0.05), and KTDS and KW insignificantly (P = 0.1). No significant differences in kidney and serum levels of malondialdehyde, and lung vascular permeability and LWC were observed between the groups. The serum and kidney levels of nitrite were not significantly different between I/R and sham groups; however, administration of EPO increased the renal level of nitrite (P < 0.05).
EPO protected the kidney against I/R injury; however, it may not protect the lung tissue from the damage induced by renal I/R injury in rats.
International journal of preventive medicine 06/2013; 4(6):648-55.
Available from: jpet.aspetjournals.org
- "The decreased amount of dead cells after an apoptotic stimulus (H 2 O 2 ) to bone marrow cells derived from P-gp-deficient mice indicates that these cells are less sensitive to apoptosis (Huls et al., 2007). The amount of apoptotic cells is a major determinant for the extent of renal damage after acute kidney injury, causing obstruction of the tubular lumen leading to a decrease in renal function (Kribben et al., 1999). It is evident that more research is needed to define the role of P-gp and Bcrp in renal protection. "
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ABSTRACT: ATP binding cassette (ABC) transporters are ATP-dependent membrane proteins predominantly expressed in excretory organs, such as the liver, intestine, blood-brain barrier, blood-testes barrier, placenta, and kidney. Here, they play an important role in the absorption, distribution, and excretion of drugs, xenobiotics, and endogenous compounds. In addition, the ABC transporters, P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2), are highly expressed in a population of primitive stem cells: the side population (SP). SP cells were originally discovered in bone marrow by their capacity to exclude rhodamine 123 and Hoechst dye 33342; however, extensive research also revealed their presence in other nonhematopoietic tissues. The expression levels of BCRP and P-gp are tightly controlled and may determine the differentiation of SP cells toward other more specialized cell types. Although their exact function in these cells is still not clear, they may protect the cells by pumping out toxicants and harmful products of oxidative stress. Transplantation studies in animals revealed that bone marrow-derived SP cells contribute to organ repopulation and tissue repair after damage, e.g., in liver and heart. The role of SP cells in regeneration of damaged kidney segments is not yet clarified. This review focuses on the role of ABC transporters in tissue defense and regeneration, with specific attention to P-gp and BCRP in organ regeneration and repair.
Journal of Pharmacology and Experimental Therapeutics 10/2008; 328(1):3-9. DOI:10.1124/jpet.107.132225 · 3.97 Impact Factor
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