Case study: Discovering early kidney disease with SDMA

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Lovely blonde woman nuzzling her golden retriever

Dr. Andrea Kirsch shows us how to put the IDEXX SDMA test into clinical practice. Serendipitous discovery of increased SDMA in her patient Scarlet, a 6-year-old, spayed female golden retriever, led to a diagnosis of chronic kidney disease and development of a plan for investigation, monitoring and management.

Chief complaint

Scarlet is a 6-year-old, spayed female golden retriever living in northern California who was presented by her veterinary-student owner for being just a little off for several weeks. She was slightly less energetic and not playing quite as long with her canine housemate.

History

Scarlet had no history of anorexia, vomiting or diarrhea, coughing or sneezing, and no noted changes in appetite, thirst or urination. She was not overtly lame, and she was still jumping readily into the car and climbing stairs.

Scarlet was current on vaccinations, including for leptospirosis, and was receiving monthly heartworm prophylaxis. She received diphenhydramine occasionally for treatment of presumed allergic conjunctivitis. For several years, her main diet was a premium limited-ingredient dry food* with some canned food added.

Scarlet had no major medical history since acquired as a puppy, but she did have two urinary tract infections prior to November 2013. Both times, she was symptomatic with an active urine sediment. No culture was performed to confirm infection, but her signs responded to short courses of antimicrobials. Follow-up urinalyses were normal at the conclusion of treatment, and there had been no recurrence of signs in more than one year.

Clinical presentation

Scarlet was overall a bright dog, with a normal physical examination, aside from nonpainful crepitus in the right shoulder. Her other joints were palpably normal and demonstrated normal range of motion. Her weight was stable with an ideal body condition score (BCS) of 4/9.1


Laboratory results

A minimum database that included symmetric dimethylarginine (SDMA) was submitted to IDEXX Reference Laboratories. The complete blood count (CBC) was largely normal aside from mild lymphopenia, which was considered insignificant. Biochemical abnormalities were limited to an increased SDMA of 17 µg/dL (reference interval, 0‒14 µg/dL) and a moderate increase in cholesterol. It was noted that both the BUN and creatinine were in the upper end of the reference interval. Urine specific gravity (USG) on a urine specimen acquired by cystocentesis was 1.026. The rest of the urinalysis was essentially unremarkable with a pH of 7.0 and a few red blood cells and epithelial cells. Results of thyroid screening tests were borderline, with low normal total T4 and free T4. Her resting cortisol was normal.

Assessment

Scarlet’s owner and Dr. Kirsch discussed the equivocal thyroid testing. They agreed that Scarlet’s clinical signs of reduced energy and slightly increased cholesterol could support a diagnosis of hypothyroidism, but that her stable weight, unchanging hair coat, and normal red blood cell parameters did not. They decided on a therapeutic trial with L-thyroxine and a glucosamine/chondroitin sulfate joint supplement. Dr. Kirsch was also concerned that the SDMA result above 14 µg/dL indicated meaningful kidney disease.

The IDEXX SDMA test is a new test to help evaluate kidney function. SDMA typically increases when there is on average a 40% decrease in kidney function. This occurs earlier than creatinine, which doesn’t increase until there is up to 75% loss of kidney function.2,3 Scarlet’s high SDMA result, along with her high-normal creatinine and BUN, was consistent with her likely having early kidney disease. Although not isosthenuric, her USG of 1.026 was consistent with some loss of urine concentrating ability and could be expected with a modest reduction in kidney function.

Dr. Kirsch discussed Scarlet’s case with Dr. Clements, an IDEXX internal medicine consultant. They reviewed the recommendations for investigating, managing, and monitoring a dog when early kidney disease is diagnosed. Scarlet was well-hydrated and eating normally and her urine sediment was inactive. They decided to first repeat blood work in a couple of weeks to determine if the SDMA was persistently increased and to reevaluate other kidney parameters before proceeding with additional diagnostics to investigate for an underlying cause of her kidney disease. They reviewed her medication and environmental history for any possible toxins, but none were identified.

Follow up visit

Scarlet presented for recheck visit 18 days later. The owner reported that Scarlet’s energy level had improved. Otherwise, the owner noted no changes in Scarlet’s health. A minimum database, which included CBC, chemistry profile with the IDEXX SDMA test, urinalysis, and post-pill T4 testing, was performed. The CBC was normal. The SDMA was persistently increased and the creatinine was now also just above normal with a normal BUN. The urinalysis was largely unchanged. Total T4 was now in the low therapeutic range.

Additional diagnostics

Scarlet’s owner consented to a urine culture, infectious disease testing, and abdominal ultrasound to try to identify an underlying cause of kidney disease. A urine protein:creatinine ratio (UPC) and blood pressure were performed to substage the chronic kidney disease (CKD) in accordance with the International Renal Interest Society (IRIS) staging system for CKD.

Results of urine culture and susceptibility, Leptospira spp. RealPCR™ Test on blood and urine, and Leptospira spp. Antibody by ELISA were negative. The UPC was normal at 0. The average systolic blood pressure was normal at 140 mm Hg.

Abdominal sonography performed by a radiologist identified substantial renal abnormalities with asymmetry. The left kidney was somewhat rounded and mildly irregular. The left renal pelvis was distorted, mildly to minimally dilated, with an echogenic and shadowing signal. The right kidney was mildly enlarged with a normal anatomic definition. Left renal changes were assessed as consistent with previous pyelonephritis, with no evidence of significant renal fibrosis. Right renal changes were most compatible with hypertrophy.

Discussion

This case highlights the clinical utility of SDMA as a biomarker of early renal disease. The laboratory findings of high-normal BUN and creatinine and inappropriately concentrated urine would have been considered insignificant in this clinically healthy patient had it not been for the increased SDMA. It is important to note that the clinician would have missed a valuable opportunity for early intervention.

We suggest you outline a three-step IMM plan for your kidney disease patients and communicate it clearly to their caretakers:

  1. Investigate for causes of kidney disease and substage the kidney disease based on proteinuria and blood pressure.
  2. Manage for the stage of kidney disease and concurrent health concerns, with appropriate treatments.
  3. Monitor regularly for changes in IRIS stage and health status, and reassess regularly, as needed.
Investigate

This patient had sonographic evidence of kidney disease, possibly associated with previous chronic pyelonephritis and historical lower urinary signs, but the urine culture was negative. Occult pyelonephritis was considered, but pyelocentesis to culture the renal pelvis was not advised since the pelvis was not markedly dilated. The incidence of aerobic culture-negative pyelonephritis has not been well characterized in dogs, but it can occur in chronic cases where bacteria may shed intermittently or in patients with a prior history of antimicrobial use or uncommonly with anaerobic bacteria infections. In the absence of fever, flank pain, leukocytosis, an active urine sediment, progressive azotemia, or general illness, active pyelonephritis was considered unlikely, but empiric antibiotic treatment with marbofloxacin, 4.6 mg/kg orally once daily for 6 weeks, was elected. A fluoroquinolone was chosen for safety and efficacy against Gram-negative bacteria, the most common cause of urinary tract infection (UTI), and for excellent penetration into the renal pelvis, as well as for the convenience of dosing once daily.

Using International Renal Interest Society (IRIS) guidelines, we assessed the renal architectural changes, insufficiently concentrated urine (USG <1.030), and stable creatinine greater than 1.4 as consistent with stage 2 chronic kidney disease. Scarlet was scored as IRIS CKD Stage 2, substaging as nonproteinuric, with arterial blood pressure indicating minimal risk of target-organ damage (IRIS CKD Stage 2-NP-AP0).4 We anticipated that documenting an increased SDMA will help identify this patient group more readily during routine preventive care testing.

Manage

Strategies for managing Scarlet’s kidney disease were based on general goals since most evidence-based recommendations focus on dogs with stage 3 or 4 CKD. Early diagnosis of stage 1 or 2 CKD raised some challenging questions about what management is appropriate to recommend.

Basic management principles for patients with all stages of renal disease are:5

  • Provide adequate and appropriate nutrition.
  • Correct imbalances in fluids, electrolytes, or acid base status.
  • Attend to the clinical signs of CKD.
  • Provide treatment to slow progression of CKD.

Other rational suggestions are to:

  • Discontinue or minimize use of potentially nephrotoxic drugs.6
  • Attend to all urinary and extraurinary diseases, particularly if they influence hydration status, or potentiate hypertension or proteinuria.6
  • Use extra care with any anesthesia to guard systemic blood pressure and renal blood supply.

Dietary therapy is often a key component for management of CKD in dogs. Renal therapeutic diets are protein-restricted, phosphorus-restricted, nonacidifying and often supplemented with antioxidants and omega-3 fatty acids. According to the IRIS treatment guidelines, it is appropriate to start a renal therapeutic diet in dogs with IRIS Stage 2 CKD while the dog’s appetite is still good. One of the primary goals of feeding a renal diet is to maintain a low-normal serum phosphorus above 2.7 mg/dL and below 4.6 mg/dL.4 While Scarlet’s current dry food* has been appropriate for healthy adult maintenance, the average dietary phosphorus of 402 mg/100 kcal reported by the manufacturer7 is not optimal for a patient with kidney disease, providing approximately 3–8 times more phosphorus than most commercial canine renal therapeutic diets. Consequently, it was recommended to transition Scarlet onto a renal therapeutic diet.

Monitor

The doctors have suggested regular monitoring using the physical examination and minimum database of CBC, renal panel with the IDEXX SDMA test and electrolytes, urinalysis, blood pressure, and UPC ratio at least four times a year to evaluate for progression of kidney disease. Restaging will direct future treatment options and dietary considerations. Repeating a urine culture and susceptibility periodically may also be reasonable, or an abdominal ultrasound, especially if there is decompensation or rapid progression.

On her 3-month recheck, Scarlet continued to act well. Her owner felt that the dog’s activity level was near normal and that her hair coat was more luxuriant, likely because of her euthryoid state. Scarlet’s IRIS stage for CKD was stable at stage 2 and her serum phosphorus was still low-normal, with no significant changes in kidney values after antibiotic treatment. Her doctors were still confident that SDMA’s contribution to early discovery of her chronic kidney disease will give her the best chance to share the spotlight when her owner graduates from veterinary school in a couple of years.

Visit the SDMA Resources Page.

Verifying abnormal kidney function with a persistent increase in SDMA gave us the confidence to perform a comprehensive kidney workup.

Andrea Kirsch, DVM

Andrea Kirsch, DVM, and Celeste Clements, DVM, DACVIM

Dr. Kirsch received her DVM from the University of California at Davis School of Veterinary Medicine in 1988 and, since then, has been practicing small-animal medicine and surgery in Northern California. In 2006, she opened Natomas Veterinary Hospital, a small-animal veterinary hospital in Sacramento. Dr. Kirsch enjoys treating exotic animals and has a special interest in diagnostic ultrasound.

Dr. Clements graduated from the University of Florida College of Veterinary Medicine in 1989, and then did a 1-year internship at the Animal Medical Center in New York City. After 2 years of general practice, she entered into a clinical residency in small-animal internal medicine at Texas A&M University, which concluded with her board certification in 1995. She practiced for 5 years in referral centers in Maryland and Texas, and was employed by a veterinary pharmacy. She joined IDEXX as a consultant in 2007. Her professional interests include gastroenterology, immunology and infectious disease.

 
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References
  1. Laflamme DP. Development and validation of a body condition score system for dogs. Canine Pract. 1997;22:10–15.
  2. Yerramilli M, Yerramilli M, Obare E, Jewell DE, Hall JA. Symmetric dimethylarginine (SDMA) increases earlier than serum creatinine in dogs with chronic kidney disease (CKD). [ACVIM Abstract NU-42]. J Vet Intern Med. 2014;28(3):1084–1085.
    http://onlinelibrary.wiley.com/doi/10.1111/jvim.12361/abstract. Accessed June 8, 2015.
  3. Hall JA, Yerramilli M, Obare E, Yerramilli M, Jewell DE. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease. J Vet Intern Med. 2014;28(6):1676–1683.
  4. IRIS Guidelines. International Renal Interest Society website. www.iris-kidney.com/guidelines. Accessed June16, 2015.
  5. Polzin DJ, Osborne CA, Ross S. Evidence-based management of CKD. In: Bonagura JD, Twedt DC, eds. Kirk’s Current Veterinary Therapy XIV. 14th ed. St Louis, MO: Saunders; 2009:872–879.
  6. Elliot J, Watson ADJ. Chronic kidney disease: International Renal Interest Society staging and management. In: Bonagura JD, Twedt DC, eds. Kirk’s Current Veterinary Therapy XV. 15th ed. St Louis, MO: Saunders; 2014:857–863.
  7. Dick Van Patten's Natural Balance L.I.D. Limited Ingredient Diets Lamb Meal & Brown Rice Formula ingredient listing/guaranteed analysis. Dick Van Patten's Natural Balance Pet Foods website.
    www.naturalbalanceinc.com/product.aspx?ProductId=15&product=L.I.D.+Limited+Ingredient+Diets%c2%ae+Lamb+Meal+%26+Brown+Rice+Dry+Dog+Formula. Accessed June 17, 2015.
Footnotes

*Dick Van Patten’s Natural Balance® L.I.D. Limited Ingredient Diets® Lamb Meal & Brown Rice Formula, Dick Van Patten's Natural Balance Pet Foods, Inc., Burbank, California.
†Dasuquin®, Nutramax Laboratories Veterinary Services, Inc., Lancaster, South Carolina.