Lyme nephritis is a well-described sequella of infection by the rickettsial organism Borelia burgdorferi through the deer tick vector (genus Ixodes). Pathogenesis of this syndrome is not clearly understood. Actual organisms have not been identified histologically in affected renal tissue, so the deposition of immune complexes appears to be the cause of the resulting glomerular disease and subsequent protein-losing nephropathy. Renal tissue injury is responsible for the symptoms associated with the illness, including uremia, hyperphosphatemia, hypertension, hypoalbuminemia and weight loss. In general, the prognosis for dogs with Lyme nephritis is poor, with high mortality rates associated with renal failure that has traditionally been treated supportively with IV fluids, phosphate binders, feeding tubes, antibiotic therapy and ACE inhibitors to address the proteinuria and hypertension. The recently improved availability of adipose-derived stem cell therapy by MediVet America Inc. for inflammatory processes other than cartilage damage and tendon/ligament injuries has expanded the treatment options for many illnesses that have previously been difficult or impossible to treat by traditional means. Harvesting the adipose tissue and subjecting it to a rigorous separation, purification and concentration process results in a collection of adult stem cells that are activated and stimulated by combining with platelet-rich plasma and exposure to a multi-wavelength LED light source. When injected intravenously, stem cells are carried throughout the body and collect in areas of inflammation and cell damage. Although the kidneys constitute less than 1 percent of total body mass, they receive 20-25 percent of total cardiac output. This component of the first-pass effect prevents large numbers of stem cells from reaching other parts of the body. When the kidneys are the target organs, however, peripheral intravenous injection becomes an ideal delivery system via renal perfusion. Millie Millie, a 3-year-old Yorkie-poo, presented to the Animal Emergency and Pet Care Clinic of the High Country in Boone, N.C., in December 2011 for a routine ovariohysterectomy procedure. Her pre-anesthetic blood profile and urinalysis revealed a mild azotemia with normal specific gravity (BUN 35, creatinine 2.5, USG 1.035 with 1+ protein) although she was asymptomatic at the time. Her surgery was performed without complication and her blood work was rechecked a week later, at which time her BUN and Cr levels had increased to 45 and 2.7, respectively. Renal ultrasound revealed kidneys of normal size, with the left kidney appearing architecturally normal and the right kidney showing a hyperechoic and slightly thin cortical layer. Urinalysis revealed a specific gravity of 1.036 with 1+ bilirubin, 3+ blood, 4+ protein with WBCs and RBCs present. Urine culture revealed no growth and a urine protein:creatinine ratio of 7.8 was determined. Blood pressure measurement revealed a systolic reading of 175mmHg. Diagnostics suggested that Millie’s ability to concentrate urine indicated some renal tubular function but the presence of proteinuria suggested an ongoing glomerulonephritis with possible etiologies including Lyme disease and leptospirosis. Quantitative antibody titers for Lyme (ELISA) were 392 U/ml with levels >30 U/ml being considered clinically significant. Treatment was initiated for presumed Lyme nephritis and included enalapril, famotidine, doxycycline and sucralfate. Progression Within several days, the dog became clinically ill and presented with weight loss, dehydration, inappetance, lethargy and vomiting with both melena and hematemesis. Repeated blood work revealed a creatinine level of 3.5, dropping albumin level of 2.0 and a systolic blood pressure of 185mmHg. A guarded to poor prognosis was given to the owner based on her clinical deterioration and symptoms associated with ongoing renal failure. Millie was hospitalized at this time for supportive care and aggressive intravenous fluid and antibiotic therapy. She stabilized initially but during her seven-day hospitalization it became clear that traditional supportive care for renal failure was not going to be a long-term solution. Extensive discussions with MediVet Inc. support staff and the owners resulted in determining that adult stem cell therapy could be beneficial in slowing the deterioration of Millie’s failing kidneys and potentially extending her lifespan. Not being an ideal candidate to undergo general anesthesia at this point, Millie was monitored closely and carefully prepped for the brief procedure necessary to collect omental adipose tissue. She tolerated this procedure well and recovered uneventfully. The three-hour processing procedure was completed at the in-house laboratory and Millie was treated with an intravenous injection of concentrated stem cells resuspended in sterile saline later that same day. The remaining stem cell sample was shipped to a central storage facility where the sample was quantified and the percent of cell viability was determined. Individual vials of stem cells were stored at liquid nitrogen temperatures for future use. The effect of infused stem cells is not immediate and the expected delay from administration to clinical response is not clear and can vary greatly. Millie continued to experience lethargy and inappetance in the days following the procedure, so a feeding tube was placed to facilitate feedings and medication administration. The ACE inhibitor was changed to benazepril and a phosphate binder was added to her treatment regimen. A second intravenous stem cell treatment (from frozen banked storage) was administered on Day 8 and a third and final treatment was given on Day 14. During the initial three to four weeks after the initial treatment, her clinical condition gradually continued to improve as her creatinine level decreased to 3.0 and her body weight continued to increase. By eight weeks post-initial treatment, Millie had mostly clinically returned to normal. Her appetite was good, her body weight had continued to increase and her activity level had returned to normal. Her creatinine level stabilized between 2.0 and 2.7 and she has continued to improve since that time. There is no question that the dog benefited greatly from the wide range of aggressive and intensive therapeutic and supportive care that she received during her convalescence. However, most cases of acute renal failure—especially Lyme nephritis—carry a poor prognosis for recovery even with this level of care due to the poor regenerative capacity of renal tissue. The introduction of stem cell regenerative therapy as a viable treatment modality for this type of inflammatory renal disease should be further investigated. The goal for Millie was to slow the progression of her disease and extend her functional lifespan as much as realistically possible. Not only has this been accomplished, but her degree of improvement and the extent of her recovery has far surpassed expectations. While it is impossible to conclude that the stem cell treatment alone resulted in Millie’s recovery, it is the unanimous opinion of her doctors that had we continued with traditional supportive care alone, Millie would not be with us today. Dr. Linzey is a graduate of North Carolina State University and established his clinic in 2005. This Education Series article was underwritten by MediVet America of Nicolasville, Ky. <HOME> 7/27/2012 5:58 PM
