Renal Dysplasia in Soft Coated Wheaten Terriers
Published in Benchmarks, Fall 1995.
Renal dysplasia (RD) was described in related SCWT dogs in the 1980's in Europe. The diagnosis of RD has since been made in young SCWT dogs in North America. RD is also thought to be familial in the Cocker, Chow, Doberman, Lhasa Apso, Miniature Schnauzer, Shih Tzu, and Standard Poodle breeds. How does RD differ from protein-losing nephropathy (PLN) and can we screen for it?
DEFINITION: Renal dysplasia is a congenital or neonatal disease which causes maldevelopment of the kidneys in utero or early in life (the puppy's kidneys need to complete their development in the first 3 weeks of life). When the kidneys fail to mature, there is decreased renal reserve and the dog is predisposed to progressive renal failure early in life. Renal failure is manifested by
- inability to conserve water (thus the low urine specific gravity), and
- inability to excrete toxic metabolic wastes (e.g., creatinine, BUN) from the bloodstream.
Renal dysplasia is congenital and may be genetically determined. But environmental factors (e.g., poor husbandry, neonatal illness, toxins) may also cause maldevelopment of the kidneys. Confusion arises because the changes of RD seen by kidney biopsy look the same whether the cause was genetic or environmental. Since most affected dogs are without a history of neonatal illness, since they are genetically related, and since RD is diagnosed in the SCWT with much higher frequency than expected, we strongly suspect RD in the SCWT is an inherited trait. Furthermore, it appears to be autosomal (not sex-linked), and recessive. The exact mode of inheritance is not worked out.
More confusion arises because of gradations of severity of the kidney maldevelopment. Some pups may be showing their RD at age 2-6 months, while others seem normal, even until 18-24 months. Owners may not realize early signs (drinking a lot).
COMPARISONS WITH PLN
- Age of Onset: RD causes renal failure and death earlier in life than does PLN. Most dogs with RD die before 2 years of age. Most dogs with PLN show their illness at age 5-7 years.
- Urine Specific Gravity (USG): Most dogs with RD cannot concentrate their urine well, even early-on before the blood test values are abnormal. The USG is often low. Because they lose more water in their urine, these dogs need to drink more than normal dogs, lest they become dehydrated. Dogs with PLN may not necessarily have trouble concentrating their urine until they are in end-stage renal failure.
- Proteinuria (Uprot): Most dogs with RD do not lose a lot of protein in the urine and the serum albumin stays normal. Dogs with PLN lose large quantities of protein in the urine (they have a high urine protein/creatinine ratio) and the serum albumin drops.
- Blood Tests: Although both RD and PLN dogs eventually have high serum creatinine and BUN, RD dogs don't have the low serum albumin and high serum cholesterol which are typical of PLN cases.
- Kidney Size: Dogs with RD may show small kidneys on radiographs or ultrasound, even before the blood test values are abnormal. Dogs with PLN may have normal-sized kidneys until the later stages of disease.
- Biopsy: Dogs with RD have different changes seen under the microscope, compared with PLN changes. In RD in the renal cortex there are microscopic cystic lesions with decreased numbers of glomeruli, many immature (fetal) glomeruli and cystic glomerular atrophy seen. There are segmental interstitial and periglomerular fibrosis. In the renal medulla, there are tubular changes including atrophy, dilatation, basement membrane mineralization, interstitial fibrosis, and adenomatous proliferation of the collecting duct epithelium. Dogs with PLN have kidney biopsies which show glomerular changes such as membranoproliferative glomerulonephritis and/or glomerulosclerosis. They do not show many fetal glomeruli.
- Effusions and Thromboembolism: Since dogs with RD are not losing lots of small molecular weight proteins in the urine, they are not predisposed to effusions (e.g. ascites, edema) nor the hypercoagulation which might predispose to thromboembolism (clots) in the lung, heart, brain, portal vein, or distal aorta (saddle).
- Signs of Renal Failure: Dogs with RD and dogs with PLN may show the same signs of renal failure. Distinguishing between the RD and PLN may require further tests (see above). Signs of renal failure include vomiting, decreased appetite, polydipsia, polyuria, weight loss (or failure to grow), and anemia. Also, there are other causes for renal failure (e.g., urinary tract infection, neoplasia, stones, toxins) and these may need to be ruled out by history, physical examination, complete urinalysis, urine culture, abdominal radiographs, abdominal ultrasound, or kidney biopsy.
CAN WE SCREEN FOR RD?
- USG: If one pup seems more thirsty than the rest, and if the USG of that pup is consistently lower when compared with its littermates, that pup should be watched carefully and may deserve further testing. The USG of dogs with RD is usually low. But can we screen all pups at 6-8 weeks of age by this method? Probably not, since the concentrating ability of normal puppies is not mature until 12 weeks of age. Even at 12 weeks, normal pups may make dilute urine. Dilute urine may be due to pups drinking more water because they have RD or because they are thirsty for some other reason. USG by itself cannot be used to screen for RD. Also, dogs with mild RD may be able to concentrate urine until their renal reserve has dropped to less than 33%. Should we do water deprivation tests? I don't advise it since dehydrating a dog with renal disease is dangerous.
- Kidney Size (Radiographs): Since RD kidneys are often smaller than normal, radiographs or ultrasound may be helpful to screen for decreased renal reserve. Radiographs are probably better than ultrasound to assess size since formulas have been developed for normal kidney size in relation to the dog's own second lumbar vertebra in a ventrodorsal view. However, it may be difficult to visualize the kidneys radiographically because of overlying food/stool and lack of contrasting fat around the kidneys. Excretory urograms (IVP) can be done to help visualize the kidneys, but are technically difficult. Abdominal ultrasound may be helpful but it is expensive.
- Blood Tests: Blood tests (serum creatinine, BUN) may stay normal until less than 25% renal function exists. So abnormal blood tests are a relatively late sign of renal dysplasia. BUN is influenced by how much protein is in the diet, so BUN alone is not a good screening test.
- Renal Function Tests: Clearance tests can help determine what % renal reserve exists before the routine blood tests become abnormal. A substance which is cleared by the kidney is given intravenously (or exists in the bloodstream) and carefully timed collections of urine samples are done. The tests are technically difficult to do in small pups. Clearance of radioisotopes and nuclear imaging do not require urine collection but are expensive and availability is limited.
- Biopsy: Kidney biopsy is the most definitive way of diagnosing renal dysplasia. However, it is invasive, expensive, and not risk-free. Certainly if a dog dies, a necropsy should be done, including kidney biopsy.
As you can see, there are no easy screening tests for RD. Pieces of the puzzle for diagnosis of RD include urine tests (USG, urinalysis, urine protein/creatinine ratio), blood tests (creatinine, BUN, total protein, albumin, cholesterol), radiographs and/or ultrasound, and if necessary, biopsy. Careful interpretation of a combination of these tests, perhaps compared over time, is our best bet. At this time, there is no easy/inexpensive way to determine, before pups are given new homes, what exactly is their current renal reserve.
Although the breeding of affected to affected SCWT in Group 1 and 2 producing primarily affected SCWT is consistent with an autosomal recessive mode of inheritance, the development of PLE and PLN in the SCWT x Beagle outcross suggests an autosomal dominant trait. The risk for SCWT to develop PLE and PLN is clearly inherited, however, further breeding and clinical follow up is needed to reach a definitive conclusion.