ORIGINAL ARTICLE Immunohistochemical renal expression of aquaporin 2, arginine-vasopressin, vasopressin receptor 2, and renin in saltwater drowning and freshwater drowning Rosario Barranco 1 & Francesco Ventura 1 & Tony Fracasso 2,3 Received: 14 October 2019 /Accepted: 12 March 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract The diagnosis of drowning is considered one of the most difficult in forensic medicine. Due to the paucity of signs, it is a classical diagnosis by exclusion. For this reason, specific immunohistochemical markers would be useful. Far too little has been done to analyze in-depth the differences between SWD and FWD. We focused on the renal immunohistochemical expression of aqua- porin 2, AVP, V2R, and renin in cases of drowning. This study has two purposes: (1) to better understand the differences between saltwater drowning (SWD) and freshwater drowning (FWD), which may indicate different pathophysiology and (2) to eventually identify markers useful for the diagnosis of drowning. We retrospectively investigated 10 cases of SWD gathered from the Institute of Legal Medicine in Genoa (Italy), and 10 cases of FWD from the University Center of Legal Medicine in Geneva (Switzerland). As a control group, we investigated 10 cases of death by gunshot to the head. A strong expression of AQP2 and AVP was significantly (p <0.05) more evident in cases of SWD than in FWD and control cases. Regarding the V2R, no statistically significant differences were found between the studied groups. The renin tubular expression was particularly intense (p < 0.05) both in SWD and in FWD compared controls. According to our results, AQP2 and AVP represent potential useful markers for the differential diagnosis between SWD and other causes of death, including FWD. Renin may be a useful marker in the diagnosis of drowning but it does not allow for differentiation between FWD and SWD. Keywords Drowning . Saltwater, freshwater, aquaporin 2 . Arginine-vasopressin . Vasopressin receptor 2 . Renin . Forensic histopathology, immunohistochemistry Introduction The medicolegal evaluation of cases of death in water repre- sents a particularly complex task for the forensic pathologist and requires thorough investigations. A corpse found in water does not necessarily imply that death occurred by drowning. At present, the diagnosis of drowning is based on the integra- tion of an autopsy, histological, and toxicological results. The findings in classic drowning, generally described in the liter- ature [1–7], consist of the presence of foam in the airways, subpleural petechiae (also known as Paltauf ’s spots), pleural effusion, presence of water in the stomach, and acute pulmo- nary emphysema. Some of these findings, however, are only suggestive and not specific and do not result in any definitive evidence of drowning [1]: drowning is still considered a diag- nosis by exclusion. To make things more complex, the drown- ing medium plays an important role in both the pathophysiol- ogy and the pathology of drowning [8]. According to the literature [3, 5], the pathophysiology of drowning in SWD is different compared to FWD due to respective osmotic proper- ties. From a pathological point of view, only a few macroscop- ic and histological differences between the two forms of drowning have been reported [2–6]. Generally, aqueous em- physema in FWD and pulmonary edema in SWD were report- ed [9]. We recently observed that [8] the alveolar distention in FWD is significantly higher than in SWD and controls. Immunohistochemical investigation in drowning often * Rosario Barranco rosario.barranco@libero.it 1 Department of Legal and Forensic Medicine, University of Genova, via De’ Toni 12, 16132 Genoa, Italy 2 Centre universitaire romand de Médecine Légale, Rue Michel-Servet 1, 1206, Geneva, Chemin de la Vulliette 4, 1000 Lausanne, Switzerland 3 Centre Universitaire Romand de Médecine Légale, Chemin de la Vulliette 4, 1000 Lausanne, Switzerland International Journal of Legal Medicine https://doi.org/10.1007/s00414-020-02274-4