The Role of Renal Biopsy in Dogs with Proteinuric Kidney Disease--What Are We Learning?
David J. Polzin, DVM, PhD, DACVIM
University of Minnesota, St. Paul, MN, USA
Chronic renal disease is reportedly among the most common causes of mortality in dogs and cats. Yet the origin of the underlying renal disease is not established in most patients. Failure to understand the cause of renal disease has lead to generic recommendations for therapy that are largely symptomatic and supportive in nature, rather than directed at a specific renal disorder.
It has been generally believed for years, that inability to identify the causes(s) of renal disease in dogs and cats is, at least in part, a function of our limited ability to detect early renal disease. Once renal disease has progressed to renal insufficiency or failure, it becomes difficult, if not impossible, to identify the inciting disease process using current techniques. Unfortunately, renal biopsies are often performed in patients that have relatively advanced disease. The inability to translate lesions observed in such patients to effective therapy should is not surprising.
Other factors limiting our use of renal biopsies include the lack of: 1) a generally recognized classification scheme for renal biopsies based on light, immunofluorescent and electron microscopic evaluation, and 2) randomized, controlled clinical trials linking biopsy findings to therapeutic outcomes in canine and feline patients.
In human nephrology, renal biopsies are obtained to help establish the diagnosis, suggest prognosis, or to direct therapy. It is in the area of glomerular disease that renal biopsy has found its greatest utility. Glomerular injury produces a multiplicity of clinical signs and symptoms. In humans, specific glomerular diseases tend to produce characteristic syndromes of renal dysfunction; however, multiple different diseases can produce the same syndrome. Renal biopsy findings are often required for definitive diagnosis of the glomerular disease responsible for the syndrome in each patient.
Specific pathogenic categories are often of great importance in directing therapy and predicting prognosis.1 For example, it is known that a patient with post streptococcal glomerulonephritis with 50% crescents has a much better prognosis for renal recovery than does a patient with anti-glomerular basement membrane glomerulonephritis or antineutrophil cytoplasmic autoantibodies (ANCA) glomerulonephritis with 25% crescents. Key point: the type and severity of light microscopic morphologic categories alone is inadequate for diagnosis, prognosis or therapy. In addition to light microscopy, electron microscopy and immunopathology are essential for adequate categorization of disease. The ultrastructural pattern detected by electron microscopy is essential for appropriate classification of renal lesions. Immunohistology establishes the presence or absence of immunoglobulins and complement and permits the distribution, pattern, and composition of immunoglobulins.
Although biopsy findings are qualitative and subject to interobserver variation, the World Health Organization has established a classification scheme for glomerulonephritis. These guidelines assist in patient management and in interpreting clinical studies from different centers on effectiveness of treatments and prognoses.
Application of renal biopsy in humans is not without controversy. Several studies have examined the influence of renal biopsy on patient management. In a retrospective study designed to establish whether biopsy findings altered therapy, it was reported that that while a diagnosis was established by biopsy in 77% of patients, therapy was modified in only 19%.2 In this study, therapy was altered primarily for patients with proteinuria. Another retrospective study determined that of 30 patients with severe lupus nephritis, knowledge of the biopsy results failed to improve predictive accuracy scores of estimates of future serum creatinine values, proteinuria, renal death, or long-term immunosuppressive therapy.3 In contrast, several other more recent studies have suggested that in patients with diverse renal diseases, biopsy findings influenced physicians judgment on diagnosis, prognosis, and treatment from 42% to over 50% of the time.4-7
Probably the most common indications for renal biopsy in dogs and cats include investigation of proteinuric renal diseases, renomegaly (or renal mass), familial renal disease, and acute renal failure. However, clinical benefits of renal biopsy for these patients remains to be established. Presumably, identification of treatable disease or evidence of reversible disease in acute renal failure translates to improved patient care. There appears to be a clear benefit in confirming familial renal disease for genetic counseling.
Although generally safe, there are some relative contraindications for renal biopsy.8 These include coagulopathy, severe anemia, solitary kidney, uncontrolled systemic hypertension, pyonephrosis, renal abscess, Hydronephrosis, and bilateral reduction in kidney size. Potential complications to renal biopsy may include hemorrhage, infection, arteriovenous fistula, renal obstruction (with blood clots), and inadequate biopsy sample. Adequate patient evaluation and experience with renal biopsy reduce these risks.
The utility of renal biopsies in dogs and cats with proteinuric renal diseases seems clear. Many different diseases and pathophysiologic mechanisms can lead to the nephrotic syndrome, nephritic syndrome and acute renal failure. These various diseases and pathophysiologic mechanisms may have vastly different prognostic and therapeutic implications. The renal biopsy is a key diagnostic tool in differentiating these various conditions. For example, while it is commonly assumed that proteinuric renal diseases indicated immune mediated injury of the kidneys, this is not always the case. It would clearly be inappropriate to intervene with various forms of immunosuppressive therapy. Recognition of several forms of congenital glomerulopathies in recent years were only possible because of properly performed and analyzed renal biopsies.
The clinical value of renal biopsies remains to be fully established in dogs and cats. It is essential for veterinary nephrologists to develop a standardized classification scheme for renal biopsies, and to apply this system to randomized controlled clinical trials to establish the value of various interventions in managing renal disorders. Epidemiological studies are needed linking biopsy findings to clinical outcomes.
Performing the Renal Biopsy
In most instances (and all instances of proteinuric kidney disease), the goal of renal biopsy is to obtain samples of the renal cortex. The least invasive method is percutaneous renal biopsy obtained using ultrasound guidance. This technique should be performed by an individual familiar with the technique and its complications. Handling of the biopsy samples is critical in obtaining a satisfactory sample for analysis. An excellent reference (available on line) is: Walker PD, et al: Practice guidelines for the renal biopsy. Modern Pathology 17: 1555-1563, 2004. Submission to a full-service diagnostic renal pathology center is essential to obtain adequate evaluation of the biopsy. Currently, only the Veterinary Renal Pathology Services at Texas A&M University and Utrecht University (in the Netherlands) provide this service.
1. Jenette JC, Falk RJ. Glomerular clinicopathologic concepts. In: Greenberg A. ed. Primer on Kidney Diseases ed 3. San Diego: The National Kidney Foundation, 2001.
2. Paone DB, Meyer LE. The effect of biopsy on therapy in renal disease. Arch Intern Med 1981:1039-1041.
3. Whiting-O'Keefe Q, Riccardi PJ, Henke JE, et al. Recognition of information in renal biopsies of patients with lupus nephritis. Ann Intern Med 1982: 723-727.
4. Cohen AH, Nast CC, Adler SG, et al. The clinical usefulness of kidney biopsies in the diagnosis and management of renal disease. Kidney Int 1985;135.
5. Turner MW, Hutchinson TA, Barré PE, et al. A prospective study on the impact of the renal biopsy in clinical management. Clin Nephrol 1986217-221.
6. Shah RP, Vathsala A, Chiang GS, et al. The impact of percutaneous renal biopsies on clinical management. Ann Acad Med Singapore 1993;908-911.
7. Richards NT, Darby S, Howie AJ, et al. Knowledge of renal histology alters patient management in over 40% of cases. Nephrol Dial Transplant 1994;1255-1259.
8. Osborne CA, Bartges JB, Polzin DJ, et al. Percutaneous needle biopsy of the kidney. Vet Clin North Amer Small Anim Pract 1996;1461-1504.