Proteinuria and lipoprotein lipase activity in Miniature Schnauzer dogs with and without hypertriglyceridemia

Abstract

Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature shnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77–0.83, P < 0.001). Proteinuria (UPC ≥ 0.5) was present in 60% of dogs with HTG and absent from all dogs without HTG (P < 0.001). Proteinuric dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (P < 0.001); HL activity did not differ. Proteinuria occurs with HTG in Miniature schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required.

Clinical Consequences of Hypertriglyceridemia‐Associated Proteinuria in Miniature Schnauzers

“…In people, glomerular lipid thrombi are a hallmark of lipoprotein glomerulopathy, and the disease can progress to nephrotic syndrome if hyperlipidemia is not controlled . However, we found no evidence of nephrotic syndrome in 8 dogs with HTGP, and a previous study similarly reported normal albumin concentrations in 18 dogs with HTGP . Therefore, dogs with HTG, proteinuria, and hypoalbuminemia should not be assumed to have HTGP and should be evaluated for alternative causes of proteinuria.…”

“…Dogs were included if they were >7 years of age; this cutoff was selected because the manifestations of HTG and proteinuria are age‐dependent . Dogs were not considered for enrollment if they had a history of previously diagnosed diabetes mellitus, hyperadrenocorticism, or hypothyroidism; dogs also were screened for these conditions during the study (see Procedures below).…”

“…Blood was collected from the jugular vein for CBC and serum biochemistry, along with measurement of serum triglyceride, ATIII, cTnI, and total thyroxine (T4) concentrations. Hypertriglyceridemia was defined based on 12‐ to 18‐hour fasting blood concentrations ≥100 mg/dL, with severity classified as mild (100–400 mg/dL), moderate (401–800 mg/dL), or severe (>800 mg/dL) . The upper end of the laboratory reference range was 85 mg/dL.…”

“…Specific values recorded included UPC and serum triglyceride, BUN, creatinine, and albumin concentrations. Because only 2 dogs with HTGP enrolled in the primary study had follow‐up data, we also acquired follow‐up data on 6 Miniature Schnauzers with HTGP that had participated in a previous study …”

Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs

“…25 A recent study documented a strong association between hypertriglyceridemia and proteinuria in Miniature Schnauzers, but the temporal relationship between the 2 abnormalities could be not be determined. 5 …”