**1. Introduction**

The recent massive hike of kidney disease on the global rankings of disease burden signals public health crisis [1]. Kidney disease (nephropathy) is a product of multiple factors that inflict damage to nephron, renal parenchyma, and subsequent renal failure, if diagnosis and treatment are delayed [2]. Amongst various risk factors such as diabetes, hypertension, hyperuricemia, and infections, drug-induced nephrotoxicity is considered one of the significant contributors to both acute and chronic kidney disease [3]. This is attributable to increased exposure of the general population to a large number of prescribed and over-the-counter drugs as well as a variety of other ingested foodstu ff and environmental intoxicants [4]. Hyperuricemia, a condition characterized by abnormally elevated uric acid levels in the blood, is considered an independent risk factor of kidney disease [5,6]. The underlying kidney damaging e ffects of uric acid are associated with tubular toxicity, vasoconstriction, oxidative stress, and inflammation [6,7].

Though nephropathy is harmful, with early diagnosis it is treatable to prevent end-stage renal failure. Depending on the underlying cause and stage of the injury, there are various drugs currently in clinical use against hyperuricemia and nephropathy. These drugs include captopril, allopurinol, and some diuretics (loop and thiazide). Despite efficacy of these drugs, they are also associated with some adverse reactions such as hypersensitivity syndrome, acute interstitial nephritis, and electrolyte imbalances [8,9]. The discovery of new nephroprotective drugs with improved safety profile and tolerance are encouraged. Since tissue damages are commonly prone to oxidative stress and excessive inflammatory response [10], new therapeutic drugs with strong antioxidant and anti-inflammatory activities would be preferred.

There is substantial evidence on potential role of various medicinal plants, as crude extracts or pure isolated compounds [2,11–13], in protecting the kidney from various insults thus, maintaining its integrity and functions. Even though methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), a lanosteryl triterpene from *Protorhus longifolia* (Bernh) Engl., has displayed significant various bioactivities such as antihyperlipidemic [14], antihyperglycemic [15], and cardioprotective [16] effects, its nephroprotective potential has not been reported. However, the triterpenes from this plant have previously exhibited lack of cytotoxic effects on human embryonic kidney cell lines [17]. To continue exploring potential significant bioactivities of this plant-derived bioactive compound, the current study investigated its antihyperuricemic and nephroprotective potential in adenine-gentamicin induced hyperuricemic and nephrotoxicity rat model. Adenine and gentamicin induced kidney damage is characterized by increased renal tubular cell death and increased blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA). All these parameters are commonly observed in human clinical subjects of nephropathy.
