Association between vitamin D metabolites, vitamin D binding protein, and proteinuria in dogs

Abstract

Background: Proteinuria has been associated with progression of renal disease and increased morbidity and mortality in dogs and people. In people, proteinuria also has been associated with hypovitaminosis D. Little is known about the relationship between vitamin D metabolism and proteinuria in dogs. Objectives: To further elucidate vitamin D status in dogs with protein-losing nephropathy (PLN) and minimal to no azotemia. We hypothesized that vitamin D metabolites would be lower in dogs with PLN compared to healthy dogs. Animals: Twenty-three client-owned adult dogs with PLN and 10 healthy control dogs. Methods: Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25 [OH] 2 D), 24,25-dihydroxyvitamin D (24,25[OH] 2 D), serum vitamin D binding protein (VDBP), and urine 25(OH)D concentrations were measured. Results: Compared to healthy dogs, dogs with PLN had lower concentrations of all vitamin D metabolites (P < .01). Correlations (rho; 95% confidence interval [CI]) in dogs with PLN are reported. Serum 25(OH)D and 24,25(OH) 2 D concentrations were positively correlated with albumin (r = 0.47; 0.07-0.74), and 24,25(OH) 2 D was negatively correlated with urine protein-to-creatinine ratio (UPC; r = −0.54; −0.78 to −0.16). Urine 25(OH)D-to-creatinine ratio was negatively correlated with serum albumin concentration (r = −0.77; −0.91 to −0.50) and positively correlated with UPC (r = 0.79; 0.53-0.91). Serum VDBP concentration was positively correlated with serum albumin concentration (r = 0.53; 0.05-0.81). Conclusions and Clinical Importance: Dogs with PLN have decreased serum concentrations of vitamin D metabolites. Urine 25(OH)D-to-creatinine ratio and UPC are correlated in PLN dogs. Future studies are needed to assess additional management strategies for dogs with PLN.

Serum 25‐hydroxyvitamin D concentrations in dogs with coccidioidomycosis and variables associated with extent of clinically evident disease

“…To specifically address laboratory differences would require a separate prospective study testing the same serum at multiple laboratories to identify a systematic difference which could be accounted for statistically. Immune complex glomerulonephritis is a reported complication in dogs with coccidioidomycosis and decreased serum vitamin D is a sequela of protein losing nephropathies in dogs 61,62 . Our study did not account for the potential influence of proteinuria on serum 25(OH)D concentrations.…”

Vitamin D metabolism and disorders in dogs and cats

“…Vitamin D homeostasis disorders may increase the risk of other renal disorders, with a recent study suggesting that altered vitamin D catabolism may predispose some dogs to the development of calcium oxalate uroliths (Groth et al 2019). In dogs with non-azotaemic protein-losing nephropathy (PLN), a significant positive correlation between serum albumin and concentrations of both 25(OH)D and 24,25(OH) 2 D was observed (Miller et al 2020). Additionally, dogs with PLN had significantly lower serum 25(OH)D, 1,25(OH) 2 D and 24,25(OH) 2 D concentrations compared with the control population (Miller et al 2020).…”

“…In dogs with non-azotaemic protein-losing nephropathy (PLN), a significant positive correlation between serum albumin and concentrations of both 25(OH)D and 24,25(OH) 2 D was observed (Miller et al 2020). Additionally, dogs with PLN had significantly lower serum 25(OH)D, 1,25(OH) 2 D and 24,25(OH) 2 D concentrations compared with the control population (Miller et al 2020).…”

Calcium and phosphate homeostasis in dogs with newly diagnosed naturally occurring hypercortisolism

“…The mechanism of action by which glucocorticoid excess influences vitamin D metabolism in humans is not completely understood; however, it has been proposed that cortisol directly upregulates 24‐hydroxylase expression, leading to the increased inactivation of 25‐(OH)D and calcitriol 33,34 . Circulating concentrations of 25‐(OH)D and calcitriol are decreased in proteinuric non‐azotemic dogs in which hypercortisolism was excluded 35 . Urine loss of vitamin D‐binding proteins‐complexed and albumin‐complexed vitamin D metabolites has been suggested as part of a multifactorial explanation, and it could play a role also in hypercortisolemic dogs.…”

“…33,34 Circulating concentrations of 25-(OH)D and calcitriol are decreased in proteinuric non-azotemic dogs in which hypercortisolism was excluded. 35 The circulating concentration of FGF-23 had never been evaluated before either in dogs or in humans with hypercortisolism. The major determinant of FGF-23 secretion is the circulating concentration of phosphate, with hyperphosphatemia leading to an increase in plasma FGF-23 concentration.…”