The incidence of renal cell carcinoma (RCC) is concurrently rising with increased prevalence of end-stage renal disease (ESRD) world-wide. Treatment for RCC is limited and usually involves nephron-sparing partial nephrectomy, requiring clamping of the renal pedicles and resulting in warm renal ischemia and reperfusion injury (IRI) upon restoration of blood flow. Prolonged warm IRI injures residual renal tissue and can lead to premature dialysis, increasing the number of patients placed on renal transplant waiting lists. We have recently demonstrated that hydrogen sulphide (H2S), a novel endogenous gaseous molecule, is protective against prolonged cold and short-term warm renal IRI. In the current study, we examined whether exogenous H2S has long-term protective effects against warm renal IRI.
Uni-nephrectomized Lewis rats underwent 1 hour of warm ischemia and 2 hours of reperfusion during intraperitoneal treatment with phosphate buffered saline (PBS; IRI group) (n=6) or PBS supplemented with 150 ΜM NaHS (H2S group) (n=6), and were compared with sham-operated rats (n=4). Serum creatinine (Cr), aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels were analyzed at post-operative days 3 and 7 to assess graft function and systemic inflammation. Animals were sacrificed at day 7 and kidneys were obtained for RT-PCR analysis.
H2S treatment improved long-term graft function as serum Cr at day 7 was significantly decreased in the H2S group compared to IRI animals (p<0.05), though Cr levels in both treatment groups decreased with time. AST and ALT levels were initially elevated in both treatment groups, but subsided to baseline levels at day 3 and remained at baseline at day 7. There were no significant differences in the expression of inflammatory and apoptotic markers TLR4, CCR5, IL8, TNFΑ, IFNΓ, IL2, ICAM1, BCL2, ERK1, ERK2, BID and KIM1.
H2S treatment improved long-term renal function and decreased inflammation associated with warm IRI, and may offer a novel therapeutic approach to preventing injury associated with warm IRI incurred during renal surgery. These actions may reduce rates of acute tubular necrosis in ESRD patients following renal surgery, preserving renal function and lessening the subsequent burden on renal transplant waiting lists.
To cite this abstract in AMA style:Zhu J, Lobb I, Liu W, Garcia B, Lan Z, Sener A. Exogenous Hydrogen Sulphide Mitigates Long-Term Renal Dysfunction Associated with Warm Renal Ischemia-Reperfusion Injury [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/exogenous-hydrogen-sulphide-mitigates-long-term-renal-dysfunction-associated-with-warm-renal-ischemia-reperfusion-injury/. Accessed July 5, 2020.
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