Novel renoprotection methods by local and remote conditioning

Implication for health policy/practice/research/medical education: The possibility to create resistance against ischemic injury through ‘organ conditioning’ is an area of increasing interest. The remote ischemic conditioning may have an immense effect on the renal patients and in clinical practice in the near future. Remote ischemic per-conditioning is perhaps the most promising protective strategy among the adaptive surgical techniques. By far, no integral treatment is available to improve outcomes in patients encountering renal ischemia-reperfusion injury (IRI), when blood supply to the kidney is interrupted and then restored. IRI occurs in a broad spectrum of clinical settings, including surgery, trauma or sepsis that leads to the functional disturbances of the kidneys. During transplantation, IRI is a risk factor for delayed graft function, which prolongs hospitalization and increases the cost. However, in recent years, ischemic conditioning methods have been discussed as powerful protective techniques to reduce the extent of renal IRI. These novel approaches have shown promising results in animals and research are underway to examine their exact effect in human in the clinical scenarios

Postconditioning is protective in renal reperfusion injury only in male rats. A gender difference study

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Involvement of neuronal pathways in the protective effects of hindlimb perconditioning during renal ischemia

Remote ischemic perconditioning (RPEC) is a therapeutic intervention that has been demonstrated to reduce renal ischemia/reperfusion (I/R) injury. However, the underlying renal protective mechanism remains unclear. The present study hypothesized that RPEC may utilize neural pathways to transfer the protective signal from the perconditioned hindlimb to the kidney. Following a right nephrectomy, rats were randomly allocated into five groups (n=6). The sham group underwent the surgical protocol only. In all other groups, the left renal pedicle was clamped for 45 min and reperfused for 24 h. The I/R control group then underwent 45 min ischemia and 24 h reperfusion (I/R) with no more intervention but the I/R‑NR control group underwent the ischemia and reperfusion followed by left femoral nerve (FN) and sciatic nerve (SN) resection. The RPEC group underwent ischemia and reperfusion followed by four cycles of 5 min occlusions of the left femoral artery and 5 min reperfusion. Finally, the RPEC‑NR group underwent ischemia and reperfusion followed by left FN and SN resection. Following 24 h, renal functional indices, plasma blood urea nitrogen (BUN) and creatinine (Cr) levels, urinary N‑acetyl‑β‑glucosaminidase (NAG) release and histopathological changes were assessed. Compared with the sham group, ischemia and reperfusion in the sham and I/R control groups resulted in renal dysfunction, indicated by significantly increased levels of BUN and Cr. This was accompanied by increased urinary NAG activity and morphological damage observed in control groups. In the RPEC group, renal histology and function were significantly improved compared with the control groups. However, FN and SN resection eliminated the protection of the kidney, which was induced by RPEC. In conclusion, remote hindlimb ischemic perconditioning reduced renal I/R injury in the rat kidney in a manner that potentially involves a neural pathway

Protective effects of hydrogen sulfide on chronic kidney disease by reducing oxidative stress, inflammation and apoptosis

The current study aimed to examine the renoprotective effects of long-term treatment with sodium hydrosulfide (NaHS), a prominent hydrogen sulfide donor, in 5/6 nephrectomy animal model. Twenty-four rats were randomly divided into 3 groups including sham-operated group (Sham), 5/6-nephrectomized group (5/6 Nx), and NaHStreated group (5/6Nx+NaHS). NaHS (30 micromol/l) was added twice daily into the drinking water and renal failure was induced by 5/6 nephrectomy. Twelve weeks after surgical procedure, blood pressure, creatinine clearance (CCr), urine concentration of neutrophil gelatinase associated lipocalin (NGAL) and tissue concentration of malondialdehyde (MDA), superoxide dismutase (SOD), as well as renal morphological changes, apoptosis (cleaved caspase-3) and inflammation (p-NF-κB) were measured. Five-sixth nephrectomy induced severe renal damage as indicated by renal dysfunction, hypertension and significant histopathological injury which were associated with increased NGAL and MDA levels, oxidant/antioxidant imbalance, decreased SOD activity and CCr and also overexpression of p-NF-κB and cleaved caspase-3 proteins. Instead, NaHS treatment attenuated renal dysfunction through reduction of NGAL concentration, hypertension, CCr, oxidant/antioxidant imbalance, inflammation and apoptosis. These findings suggest that long term NaHS treatment can be useful in preventing the progression of CKD by improving oxidant/antioxidant balance and reducing inflammation and apoptosis in the kidney

Different dose-dependent effects of hydrogen sulfide on ischemia-reperfusion induced acute kidney injury in rats

Background: Renal ischemia reperfusion (RIR) injury is a common clinical syndrome that affects renal function and significantly increases morbidity and mortality. Hydrogen sulfide (H2S) is an endogenously gaseous mediator that exhibits many cytoprotective effects. Recently, studies have shown that H2S have opposite effects in different doses. Therefore, in the current study we investigated the effects of H2S at different doses on renal function after induced renal ischemia reperfusion injury model. Methods: The present study is an experimental study in animals and was conducted in Tehran University of Medical Sciences in April 2014. Male Wistar rats were assigned to five main groups (n= 6): 1) Sham, 2) Ischemia reperfusion (IR), 3) Administration of 50 &micro;mol/kg Sodium hydrosulfide (NaHS)+IR, 4) Administration of 75 &micro;mol/kg NaHS+IR and 5) Administration of 125 &micro;mol/kg NaHS+IR. Sham group underwent laparotomy without cross-clamping of renal pedicles. Renal ischemia (IR) was induced in rats by both renal arteries occlusion for 55 min followed by reperfusion. Rats in the NaHS groups received intraperitoneal injections of 50, 75, or 125 &micro;mol/kg of NaHS 10 minutes before the onset of ischemia and immediately after the onset of reperfusion. After reperfusion, plasma was collected for functional evaluation. Results: Compared to the sham, IR animals demonstrated a significant rise in plasma creatinine and BUN levels. Rats in the low-dose NaHS treated groups (H50, H75) had improved renal function by significantly decrease of creatinine and BUN levels. However, treatment with a high-dose of NaHS increased the levels of plasma creatinine and BUN levels as compared with these indices in the IR group. Conclusion: Our study demonstrates that different doses of Sodium hydrosulfide (NaHS) can play diverse role in renal ischemia reperfusion injury. However, NaHS in the low-doses could protect the kidney from the RIR injury, in a higher dose NaHS exaggerated the renal function by increases plasma creatinine and BUN. Therefore, determining of the therapeutic doses of NaHS may be important in the protection of kidney from the RIR injury

Renal tissue pro-inflammatory gene expression is reduced by erythropoietin in rats subjected to hemorrhagic shock

Background: Hemorrhagic shock (HS) is a condition produced by considerable loss of intravascular volume, which may eventually lead to organ damage and death. Objectives: In the present study, the potential implication of the kidney tissue tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were evaluated in the protective effects of erythropoietin (EPO) during HS. Materials and Methods: Male Wistar rats were randomized into three experimental groups; Sham, HS (hemorrhagic shock and resuscitation), and EPO (erythropoietin). HS was induced by 50% blood volume hemorrhage over 30 minutes. After 2 hours, resuscitation was performed within 30 minutes. In the EPO group, EPO (300 IU/kg, i.v.) was administered 10 minutes before HS induction. Urine was collected to determine urinary N-acetyl-β-D-glucosaminidase (NAG) activity level. The kidney cytokines (TNF-α, IL-6 and IL-10) mRNA expressions were measured by real-time polymerase chain reaction (PCR). Results: HS rats showed significant increase in urinary NAG activity compared to the sham group. EPO significantly attenuated the rises in urinary NAG activity compared to the HS group. In the HS animals, renal TNF-α and IL-6 mRNA expressions increased whereas no difference was observed in IL-10 mRNA expression between the HS and sham groups. EPO was able to decrease renal TNF-α and IL-6 production and increase IL-10 mRNA expression. Conclusions: In this study, we demonstrated that EPO attenuates kidney damage in rats subjected to HS. The beneficial effects of EPO may be at least partly mediated by modifications in the inflammatory cascade