Product Information
Clinic Support
Client Information
Technical Information

Persistent Albuminuria Precedes Onset of Overt Proteinuria in Male Dogs with X-Linked Hereditary Nephropathy

» View Only (Acrobat PDF)

SUMMARY:

• Persistent microalbuminuria was observed prior to onset of overt proteinuria (urine protein to creatinine ratio >1.0). Conclusions: persistent microalbuminuria "is a reliable indicator of incipient nephropathy" and testing for microalbuminuria "could be an effective method for early detection of other progressive renal diseases."

Testing for excess urine albumin content holds promise as a method for early detection of dogs with progressive renal disease. Dogs with progressive nephropathies, particularly those involving damage to the glomerular filtration barrier, might be identified by finding excessive albuminuria even before they develop overt proteinuria. To test this theory, we examined the temporal relationship between development of albuminuria and the onset of overt proteinuria in male dogs with X-linked hereditary nephropathy (XLHN).

Male dogs with XLHN have a rapidly progressive glomerular disease caused by a genetic defect in type IV collagen, which is a glomerular basement membrane (GBM)component. Early in life, renal structure and function are normal, but GBM lesions begin to develop by 2 months of age. Onset of overt proteinuria occurs between 3 and 6 months of age, and progression to end-stage renal failure happens by the time the dogs are 6 to 18 months old. For this study, we evaluated serial urine samples obtained from 36 males with XLHN and 10 normal male littermates while they were 2 to 7 months (8 to 30 weeks) of age.

Voided urine was collected every 2 weeks from all dogs, and weekly from some dogs, for analyses including protein:creatinine ratio (UPC) determination. Aliquots of urine were stored at -80° C and subsequently assayed for albumin concentration using a canine-specific competitive binding ELISA method. Urine albumin (UAlb) concentrations (mg/dl) were expressed as values normalized to 1.010 urine specific gravity, as well as in a ratio to urine creatinine (UCr) concentration. A total of 421 urine samples were analyzed.

Among 92 samples from 10 normal dogs (3-12; median, 10 samples/dog), only 4 samples from 3 dogs had UAlb values >1 mg/dl, and no dog had 2 consecutive samples containing excessive albumin. In affected dogs, onset of persistent proteinuria (UPC >2 then and thereafter) occurred at 14 to 30 (median, 20) weeks of age. In these dogs, onset of persistent albuminuria (UAlb >1mg/dl then and thereafter) occurred at 8 to 23 (median, 15) weeks of age.

Equivalent results were obtained when albuminuria was alternatively defined as UAlb/UCr >30 mg/gm. Thus, persistent albuminuria was observed for 0 to 16 (median, 4) weeks before onset of overt proteinuria. Only one dog failed to demonstrate albuminuria on at least one occasion before onset of proteinuria, but his urine was not tested weekly.

We conclude that persistent albuminuria is a reliable indicator of incipient nephropathy in dogs with XLHN, a rapidly progressive glomerular disease. These results support the concept that screening for albuminuria could be an effective method for early detection of other progressive renal diseases involving glomerular damage in dogs.

Reproduced with permission of the Journal of Veterinary Internal Medicine.