Role of the kidneys in acid-base regulation and ammonia excretion in freshwater and seawater fish: implications for nephrocalcinosis

Abstract

Maintaining normal pH levels in the body fluids is essential for homeostasis and represents one of the most tightly regulated physiological processes among vertebrates. Fish are generally ammoniotelic and inhabit diverse aquatic environments that present many respiratory, acidifying, alkalinizing, ionic and osmotic stressors to which they are able to adapt. They have evolved flexible strategies for the regulation of acid-base equivalents (H+, NH4+, OH− and HCO3−), ammonia and phosphate to cope with these stressors. The gills are the main regulatory organ, while the kidneys play an important, often overlooked accessory role in acid-base regulation. Here we outline the kidneys role in regulation of acid-base equivalents and two of the key ‘urinary buffers’, ammonia and phosphate, by integrating known aspects of renal physiology with recent advances in the molecular and cellular physiology of membrane transport systems in the teleost kidneys. The renal transporters (NHE3, NBC1, AE1, SLC26A6) and enzymes (V-type H+ATPase, CAc, CA IV, ammoniagenic enzymes) involved in H+ secretion, bicarbonate reabsorption, and the net excretion of acidic and basic equivalents, ammonia, and inorganic phosphate are addressed. The role of sodium-phosphate cotransporter (Slc34a2b) and rhesus (Rh) glycoproteins (ammonia channels) in conjunction with apical V-type H+ ATPase and NHE3 exchangers in these processes are also explored. Nephrocalcinosis is an inflammation-like disorder due to the precipitation of calcareous material in the kidneys, and is listed as one of the most prevalent pathologies in land-based production of salmonids in recirculating aquaculture systems. The causative links underlying the pathogenesis and etiology of nephrocalcinosis in teleosts is speculative at best, but acid-base perturbation is probably a central pathophysiological cause. Relevant risk factors associated with nephrocalcinosis are hypercapnia and hyperoxia in the culture water. These raise internal CO2 levels in the fish, triggering complex branchial and renal acid-base compensations which may promote formation of kidney stones. However, increased salt loads through the rearing water and the feed may increase the prevalence of nephrocalcinosis. An increased understanding of the kidneys role in acid-base and ion regulation and how this relates to renal diseases such as nephrocalcinosis will have applied relevance for the biologist and aquaculturist alike.

Mechanisms and physiological relevance of acid-base exchange in functional units of the kidney

“…The epithelial collecting system also implements NH 3 /NH 4 + transport regulated by a complex process that involves at least two Rhesus glycoproteins: RhB (SLC42A2) and RhC (SLC42A3) ( Harris et al, 2023 ; Takvam et al, 2023 ). Rhbg expressed in IC-α and non-α, non-β intercalated cells, principal cells in the basolateral plasma membrane.…”

New wine in old bottles: Modification of the Na+/K+‐ATPase enzyme activity assay and its application in salmonid aquaculture

“…58,59 Recycling water permits reduced consumption of intake water per produced biomass, constant high temperature, use of continuous light and increased salinity which has resulted in increased proportion of average smolt size, from 50 to 80 g in 2008 to approximately 250 g in 2022 with several companies producing smolts up to 500-600 g in 2023. 24 Despite RAS facilities provide greater control with rearing conditions, the industry experience increased incidents of production disorder such as mineral precipitation in the kidneys, [60][61][62] haemorrhagic smolt syndrome, 63,64 compromised cardiovascular physiology, 65 multifactorial gill disease 66,67 and other issues related to growth, health and general performance. 68 These disorders may partly be a consequence of rapid changes in technology (from FTS to RAS) and/or smolt protocols (photoperiod, temperature and salinity) where the physiological requirements of the salmon are challenged.…”

“…One may also consider applying molecular markers, measuring Nka-α-subunits in both intestine and kidneys, similar to that used in gills. We are currently in the process of testing expression profiles at the mRNA and protein level for relevant transporters in the kidneys 38,51,60 and intestine 35,50 to further increase the available repertoire of tools to evaluate smoltification. We want to highlight the importance of adopting the optimized protocol both in the aquaculture sector and in other research institutes.…”