Percutaneous Kidney Biopsy: “The Needle and the Damage Done”?
2011; Elsevier BV; Volume: 57; Issue: 6 Linguagem: Inglês
10.1053/j.ajkd.2011.02.375
ISSN1523-6838
Autores Tópico(s)Chronic Kidney Disease and Diabetes
ResumoRelated Article, p. 850 Related Article, p. 850 In 1954, Kark and Muehrcke1Kark R.M. Muehrcke R.C. Biopsy of kidney in prone position.Lancet. 1954; 266: 1047-1049Abstract PubMed Scopus (114) Google Scholar established the technique of percutaneous kidney biopsy in the prone position to be effective and safe, reporting a series of 50 patients undergoing the procedure, giving a diagnostic yield of 96% without a single patient developing a major complication. This report from my institution, published more than 20 years before I was born, forever changed the practice of nephrology. During the ensuing 57 years, percutaneous kidney biopsy has remained invaluable as it aids in the diagnosis, prognosis, and treatment of a variety of glomerular and tubulointerstitial diseases. It also has continued to be a safe procedure, with loss of life extremely rare and major complications, mostly related to bleeding, occurring in only 1%-6% of procedures.2Korbet S.M. Percutaneous renal biopsy.Semin Nephrol. 2002; 22: 254-267Abstract Full Text PDF PubMed Scopus (148) Google Scholar Major complications of biopsy are those that require an intervention, such as blood transfusion or procedure to achieve hemostasis. Minor complications are those attributed to the biopsy, but no intervention is necessary, such as gross hematuria or symptomatic perinephric hematoma. Although there is no definitive way to determine whether a given individual will develop a complication, previous studies have noted bleeding diatheses, uncontrolled hypertension, anemia, advanced age, female sex, and increased serum creatinine level to be among the reported risk factors.3Whittier W.L. Korbet S.M. Timing of complications in percutaneous renal biopsy.J Am Soc Nephrol. 2004; 15: 142-147Crossref PubMed Scopus (326) Google Scholar, 4Nass K. O'Neill W.C. Bedside renal biopsy: ultrasound guidance by the nephrologist.Am J Kidney Dis. 1999; 34: 955-959Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 5Manno C. Strippoli G.F. Arnesano L. et al.Predictors of bleeding complications in percutaneous ultrasound-guided renal biopsy.Kidney Int. 2004; 66: 1570-1577Crossref PubMed Scopus (240) Google Scholar, 6Shidham G.B. Siddiqi N. Beres J.A. et al.Clinical risk factors associated with bleeding after native kidney biopsy.Nephrology (Carlton). 2005; 10: 305-310Crossref PubMed Scopus (96) Google Scholar Although the procedure itself generally is considered safe based on observational studies, it is not completely free of risk; therefore, there is room for improvement. Unfortunately, there is a paucity of randomized controlled trials testing interventions to improve the safety of kidney biopsies. In this regard, Manno et al,7Manno C. Bonifati C. Domenica Torres D. Campobasso N. Paolo Schena F. Desmopressin acetate in percutaneous ultrasound-guided kidney biopsy: a randomized controlled trial.Am J Kidney Dis. 2011; 57: 850-855Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar in this issue of American Journal of Kidney Diseases, hypothesized that administering desmopressin acetate (also referred to as 1-desamino-8-d-arginine vasopressin [DDAVP]) to patients undergoing real-time ultrasound-guided percutaneous kidney biopsy may improve the safety of the procedure by enhancing hemostasis and decreasing bleeding complications. To test this hypothesis, 162 patients were randomly assigned in a blinded manner to receive either desmopressin or placebo before undergoing percutaneous kidney biopsy. Patients were monitored for bleeding complications, which included decrease in hemoglobin concentration, need for blood transfusion, and development (and size) of perinephric hematoma, as assessed in all patients using routine screening ultrasound. The patients studied would be classified as low risk for bleeding complications because they all had blood pressure <140/90 mm Hg, bleeding time and coagulation profile values in the reference range, and serum creatinine value <1.5 mg/dL or estimated glomerular filtration rates ≥60 mL/min/1.73 m2. All patients tolerated the procedure well as there was no significant decrease in hemoglobin levels or need for blood transfusion in any patient. In addition, patients given desmopressin or placebo tolerated the intervention well without side effects. However, patients who received desmopressin had significantly fewer hematomas on the screening ultrasound compared with the group of patients receiving placebo. In addition, the size of the hematoma, if present, was on average smaller in the intervention group. Although there was no decrease in hemoglobin level or need for transfusion and the hematomas were clinically asymptomatic, patients who developed a hematoma on the screening ultrasound stayed in the hospital an average of nearly 5 days if they received desmopressin and nearly 6 days if they received placebo. The investigators recommended desmopressin be given to all patients before percutaneous kidney biopsy because it: (1) was tolerated well, (2) decreased bleeding complications, and (3) was cost saving due to the length of hospital stay. On the surface, this is a compelling conclusion. However, all 3 reasons for the basis of their recommendation, when examined closely, are controversial. The first rationale is that desmopressin was tolerated well, and in this study of 80 low-risk patients receiving the drug, there were no documented side effects (eg, arterial or venous thrombosis, hyponatremia, tachycardia, and flushing). Desmopressin has a long history of being used to decrease the template bleeding time in patients with uremia in an effort to improve hemostasis.8Mannucci P.M. Remuzzi G. Pusineri F. et al.Deamino-8-d-arginine vasopressin shortens the bleeding time in uremia.N Engl J Med. 1983; 308: 8-12Crossref PubMed Scopus (454) Google Scholar It also has been used in high-risk patients undergoing kidney biopsy,9Mattix H. Singh A.K. Is the bleeding time predictive of bleeding prior to a percutaneous renal biopsy?.Curr Opin Nephrol Hypertens. 1999; 8: 715-718Crossref PubMed Scopus (34) Google Scholar, 10Stratta P. Canavese C. Marengo M. et al.Risk management of renal biopsy: 1387 cases over 30 years in a single centre.Eur J Clin Invest. 2007; 37: 954-963Crossref PubMed Scopus (100) Google Scholar, 11Waldo B. Korbet S.M. Freimanis M.G. Lewis E.J. The value of post-biopsy ultrasound in predicting complications after percutaneous renal biopsy of native kidneys.Nephrol Dial Transplant. 2009; 24: 2433-2439Crossref PubMed Scopus (92) Google Scholar, 12Whittier W.L. Korbet S.M. Renal biopsy: update.Curr Opin Nephrol Hypertens. 2004; 13: 661-665Crossref PubMed Scopus (99) Google Scholar such as those with decreased glomerular filtration rate or increased bleeding time. In the 1980s and 1990s, because of the improved hemostasis in uremic patients and its successful use in patients with other bleeding disorders (eg, von Willebrand disease and hemophilia),13Mannucci P.M. Ruggeri Z.M. Pareti F.I. Capitanio A. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands' diseases.Lancet. 1977; 1: 869-872Abstract PubMed Scopus (488) Google Scholar desmopressin was administered empirically to patients without uremia or bleeding disorders undergoing major cardiac surgery with high bleeding risk. An early investigation showed promising results for the hemostatic capabilities of the agent, showing decreased blood loss and transfusion requirements in patients who received desmopressin and, notably, no side effects from the drug.14Salzman E.W. Weinstein M.J. Weintraub R.M. et al.Treatment with desmopressin acetate to reduce blood loss after cardiac surgery A double-blind randomized trial.N Engl J Med. 1986; 314: 1402-1406Crossref PubMed Scopus (391) Google Scholar Shortly thereafter, as there is no way to titrate to the desired hemostatic effect, reports of thrombosis associated with desmopressin became evident.15Mannucci P.M. Lusher J.M. Desmopressin and thrombosis.Lancet. 1989; 2: 675-676Abstract PubMed Scopus (82) Google Scholar, 16McLeod B.C. Myocardial infarction in a blood donor after administration of desmopressin.Lancet. 1990; 336: 1137-1138Abstract PubMed Scopus (32) Google Scholar, 17Byrnes J.J. Larcada A. Moake J.L. Thrombosis following desmopressin for uremic bleeding.Am J Hematol. 1988; 28: 63-65Crossref PubMed Scopus (97) Google Scholar Subsequently, meta-analyses have shown that in nonuremic patients receiving desmopressin undergoing major cardiac surgery, there was no benefit to the clinically relevant end point of decreasing transfusion requirements.18Cattaneo M. Harris A.S. Stromberg U. Mannucci P.M. The effect of desmopressin on reducing blood loss in cardiac surgery—a meta-analysis of double-blind, placebo-controlled trials.Thromb Haemost. 1995; 74: 1064-1070PubMed Google Scholar, 19Laupacis A. Fergusson D. Drugs to minimize perioperative blood loss in cardiac surgery: meta-analyses using perioperative blood transfusion as the outcome The International Study of Peri-operative Transfusion (ISPOT) Investigators.Anesth Analg. 1997; 85: 1258-1267PubMed Google Scholar, 20Levi M. Cromheecke M.E. de J.E. et al.Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints.Lancet. 1999; 354: 1940-1947Abstract Full Text Full Text PDF PubMed Scopus (451) Google Scholar, 21Carless P.A. Henry D.A. Moxey A.J. et al.Desmopressin for minimising perioperative allogeneic blood transfusion.Cochrane Database Syst Rev. 2004; 1 (CD001884)PubMed Google Scholar Furthermore, in a meta-analysis by Levi et al,20Levi M. Cromheecke M.E. de J.E. et al.Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints.Lancet. 1999; 354: 1940-1947Abstract Full Text Full Text PDF PubMed Scopus (451) Google Scholar desmopressin was associated with a 2.4-fold increased risk of postoperative myocardial infarction. Therefore, routine use of prophylactic desmopressin currently is not recommended in patients undergoing major cardiac surgery. The present study by Manno et al,7Manno C. Bonifati C. Domenica Torres D. Campobasso N. Paolo Schena F. Desmopressin acetate in percutaneous ultrasound-guided kidney biopsy: a randomized controlled trial.Am J Kidney Dis. 2011; 57: 850-855Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar in which 80 low-risk patients received desmopressin, was powered to detect a side effect of only the procedure (bleeding), not a side effect of the drug (thrombosis). In addition, patients with nephrotic syndrome (33% in the present study) already may be in a state of hypercoagulability predisposing to thrombosis. To adequately determine the safety of desmopressin for this population of patients, a much larger sample size would be required, as was the lesson learned from the cardiac surgery population. The investigators' next reason for recommending desmopressin to all patients undergoing percutaneous kidney biopsy was that the drug decreased bleeding complications. In this low-risk population of patients, perinephric hematomas were smaller and less frequent in the intervention group. However, all hematomas were clinically silent (no difference in pain between groups, no gross hematuria, and no change in blood pressure). There also were no major complications in either group because there were no differences in change in hemoglobin values and no need for medical intervention or blood transfusion. The question then is what is the clinical significance of a silent perinephric hematoma? Introducing a needle into an organ with a large vascular supply theoretically would produce a hematoma. This is the rule rather than the exception because perinephric hematomas are found in up to 86% of patients after percutaneous kidney biopsy when screened using ultrasonography22Ishikawa E. Nomura S. Hamaguchi T. et al.Ultrasonography as a predictor of overt bleeding after renal biopsy.Clin Exp Nephrol. 2009; 13: 325-331Crossref PubMed Scopus (48) Google Scholar and up to 91% when screened using computed tomography.2Korbet S.M. Percutaneous renal biopsy.Semin Nephrol. 2002; 22: 254-267Abstract Full Text PDF PubMed Scopus (148) Google Scholar, 23Ralls P.W. Barakos J.A. Kaptein E.M. et al.Renal biopsy-related hemorrhage: frequency and comparison of CT and sonography.J Comput Assist Tomogr. 1987; 11: 1031-1034Crossref PubMed Scopus (104) Google Scholar The overwhelming majority of these are clinically asymptomatic. More importantly, the presence of hematoma found on a screening ultrasound has not been predictive of clinically significant major complications when evaluated retrospectively22Ishikawa E. Nomura S. Hamaguchi T. et al.Ultrasonography as a predictor of overt bleeding after renal biopsy.Clin Exp Nephrol. 2009; 13: 325-331Crossref PubMed Scopus (48) Google Scholar or prospectively.11Waldo B. Korbet S.M. Freimanis M.G. Lewis E.J. The value of post-biopsy ultrasound in predicting complications after percutaneous renal biopsy of native kidneys.Nephrol Dial Transplant. 2009; 24: 2433-2439Crossref PubMed Scopus (92) Google Scholar If routine imaging had not been used for screening in this study, complication rates in both groups would be similar and miniscule. Therefore, the clinical relevance of a higher proportion of silent perinephric hematomas in a group of patients who did not receive desmopressin is questionable. The final rationale for using desmopressin was cost savings due to a shortened hospital length of stay (mean hospital stay was nearly 5 days for the desmopressin group vs 6 days for the placebo group). A recent survey of 72 medical centers in France shows an average length of observation for all patients after native biopsy to be 24.8 ± 6.9 hours.24Bollee G. Martinez F. Moulin B. et al.Renal biopsy practice in France: results of a nationwide study.Nephrol Dial Transplant. 2010; 25: 3579-3585Crossref PubMed Scopus (27) Google Scholar Other studies show a similar length of observation,3Whittier W.L. Korbet S.M. Timing of complications in percutaneous renal biopsy.J Am Soc Nephrol. 2004; 15: 142-147Crossref PubMed Scopus (326) Google Scholar whereas some advocate even less.25Fraser I.R. Fairley K.F. Renal biopsy as an outpatient procedure.Am J Kidney Dis. 1995; 25: 876-878Abstract Full Text PDF PubMed Scopus (62) Google Scholar, 26Jones B. Puvaneswary M. Nanra R. Trevillian P. Carney S. Gillies A. Reduced duration of bed rest after percutaneous renal biopsy.Clin Nephrol. 1991; 35: 44-45PubMed Google Scholar, 27Murphy B.F. MacIsaac A. Percutaneous renal biopsy as a day-patient procedure.Am J Kidney Dis. 1989; 14: 77PubMed Scopus (21) Google Scholar, 28Simckes A.M. Blowey D.L. Gyves K.M. Alon U.S. Success and safety of same-day kidney biopsy in children and adolescents.Pediatr Nephrol. 2000; 14: 946-952Crossref PubMed Scopus (53) Google Scholar Obviously, for patients who develop a clinically relevant complication, the appropriate length of stay would be based on the time it takes to diagnose and treat this complication. Unfortunately, the investigators do not provide details about why the patients required what many would consider a prolonged hospitalization. It also is not clear why patients who received placebo required on average an extra day because they were clinically similar except for the presence of a silent hematoma. For a patient who develops an asymptomatic perinephric hematoma without a decrease in hemoglobin level, unless there is a medical reason unrelated to the biopsy, the expected length of hospitalization would be approximately 1 day and at most 48 hours. On that basis, the purported cost savings in clinical practice is uncertain. Is the prophylactic use of desmopressin the answer to prevent “the needle and the damage done29Young N. The Needle and the Damage Done.Harvest Album. Reprise Records, Burbank, CA1972Google Scholar”? All nephrologists want is what is safest for their patients, and the idea of giving them an inexpensive harmless medication that decreases the risk of bleeding after kidney biopsy is extremely attractive. The investigators conclude that desmopressin is just that agent. Their results suggest there may be a role for prebiopsy administration of this drug because there was an effect on perinephric hematomas. However, the lack of clinical relevance of a silent hematoma plus the uncertain risk and cost associated with the use of desmopressin limit the applicability in this population. At this time, although there may be a role in patients at high risk of bleeding (which deserves study in itself), administering desmopressin off-label to all patients undergoing percutaneous kidney biopsy is premature and possibly hazardous. Financial Disclosure: The author declares that he has no relevant financial interests. Desmopressin Acetate in Percutaneous Ultrasound-Guided Kidney Biopsy: A Randomized Controlled TrialAmerican Journal of Kidney DiseasesVol. 57Issue 6PreviewBleeding complications occur in one-third of percutaneous kidney biopsies and increase costs of the hospital stay. The aim of the study was to evaluate the effect of prebiopsy administration of desmopressin acetate versus placebo in the incidence of postbiopsy bleeding complications. Full-Text PDF
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