Herbal Medicines for Acute Kidney Injury: Evidence, Gaps and Frontiers

Abstract

Acute kidney injury (AKI) is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI, promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to chronic kidney disease (CKD). Altogether, 16 herbal formulae and a few extracts derived from individual herbs were reported to prevent or mitigate AKI in animal models induced by renal ischemia/reperfusion, cisplastin, gentamicin, glycerol, adenine, sepsis or physical exhaustion. Four formulae and six individual herbs were reported to accelerate recovery and/ or to prevent CKD in established AKI animal models. Intrarectal herbal medicines, with or without simultaneous oral administration, were reported in six clinical trials and in an animal model to increase extrarenal clearance of uremic toxins. Additional 13 clinical trials reported oral or intravenous herbal interventions in AKI of different etiologies. Despite recurring problems, notably poor compliance with good practice guidelines for clinical trials and for authentication, naming and quality control of herbal materials, accumulating experimental data on the preventive effects of herbal medicines in AKI look encouraging and urge for better, definitive trials to guide clinical practice. Herbal enemas promoting extrarenal clearance of uremic toxins seem cost-effective, but better clinical evidence is certainly needed before any affirmative recommendation be made for AKI patients without access to dialysis. New frontiers, however, lie in those herbal remedies that promote repair/ regeneration and prevent chronicity after AKI. Recent experimental data suggest that this may be possible. Abbreviations: AKI: acute kidney injury; AKIN: Acute Kidney Injury Network; αSMA: α smooth muscle actin; ARF: acute renal failure; ATN: acute tubular necrosis; BUN: blood urea nitrogen; CAT: catalase; CKD: chronic kidney disease; CXCL12: chemokine C-X-C motif ligand 12; CXCR4: chemokine C-X-C motif receptor 4; CLP: cecal ligation and puncture; Cu-Zn-SOD: copper-zinc superoxide dismutase; ECM: extracellular matrix; eGFR: estimated glomerular filtration rate; EMT: epithelial-to-mesenchymal transition; ESWL: extracorporeal shock wave lithotripsy; FSP: fibroblast-specific protein 1; GSH: glutathione; GSH-Px: glutathione peroxidase; HMP: herbal medicinal product; HO-1: heme oxygenase 1; ICAM-1: intercellular adhesion molecule-1; ICU: intensive care unit; IFN-γ: interferonγ; IL: interleukin; iNOS: inducible nitric oxide synthase; i.p.: intraperitoneally or intraperitoneal; I/R: ischemia/reperfusion; i.v.: intravenous or intravenously; JNK: c-Jun N-terminal kinase; KDIGO: Kidney Disease Improving Global Outcomes; KIM-1: kidney injury molecule 1; LPS: lipopolysaccharides; MCP-1: monocyte chemotactic protein 1; MDA: malondialdehyde; MMP9: matrix metalloproteinase 9; Mn-SOD: manganese superoxide dismutase; NF-κB: nuclear factor κB; NGAL: neutrophil gelatinase-associated lipocalin; NO: nitric oxide; PCI: percutaneous coronary intervention; PCNA: proliferating cell nuclear antigen; p.o.: per os (oral administration); pRIFLE: modified RIFLE guideline for pediatric use; RCT: randomized controlled clinical trial; ROS/RNS: reactive oxygen/nitrogen species; RIFLE: Risk, Injury, Failure, Loss, and End-stage renal disease; RPTECs: renal proximal tubular epithelial cells; Scr: serum creatinine; TCM: traditional Chinese medicine; TGF-β: transforming growth factor β; TIMP1: tissue inhibitor of metalloproteinase 1; TNF-α: tumor necrosis factor-α; UUO: unilateral ureteral obstruction.