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Acute Gout After Renal Transplantation with Notable Hypouricemia
CLINICAL COMMUNICATION TO THE EDITOR
Acute Gout After Renal Transplantation with Notable Hypouricemia To the Editor: Postoperative gout is a frequent complication following renal transplantation among patients with established gout and hyperuricemia.1 However, in this report we describe a patient who developed a severe post-transplant polyarticular gout exacerbation associated with hypouricemia. This represents a different potential cause of post-renal-
Funding: SPJ is supported by a National Institutes of Health/National Heart, Lung, and Blood Institute T32HL007024 Cardiovascular Epidemiology Training Grant. Conflict of Interest: None. Authorship: All authors had access to the data and a role in writing the manuscript. The observations presented in this case report have not been published previously in whole or part. Requests for reprints should be addressed to Allan C. Gelber, MD, Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Mason F Lord Building, Center Tower, Suite 4100, Baltimore, MD 21224. E-mail address: [email protected]
transplant flaresehypouricemia due to normalized kidney function. A 71-year-old African American woman underwent a living-donor renal transplant for hemodialysis-dependent end-stage renal disease at the Johns Hopkins Hospital. Her renal failure resulted from longstanding hypertension; pretransplant serum creatinine was 3.7 mg/dL. Past medical history included known hyperuricemia and gout, previously treated with daily colchicine for several years. Her operative course was uneventful. Medications posttransplantation included metoprolol, nifedipine, trimethoprim-sulfamethoxazole, prednisone, mycophenolate mofetil, and tacrolimus. However, 13 days after transplantation, she was re-admitted with debilitating pain affecting the left wrist and right great toe. There was no associated fever, chills, nausea, vomiting, dyspnea, diarrhea, abdominal pain, hematuria, or lower extremity edema. Vital signs were normal despite considerable physical discomfort. Her left wrist was warm, swollen, and red. Pain was elicited upon both passive and active motion. Wrist swelling extended distally to the hand, involving the index and middle fingers; these fingers were tender at the proximal
Figure (A) Erosions affecting the ulnar styloid (arrows). (B) Multiple wrist amorphous soft tissue calcifications (arrow), indicating gouty tophi. (C) Prominent soft tissue densities medial to the first metatarsophalangeal joint (arrow).
0002-9343/$ -see front matter Ó 2013 Elsevier Inc. All rights reserved.
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The American Journal of Medicine, Vol 126, No 10, October 2013
and distal interphalangeal joints with palpable tophi in both fingers. Olecranon bursae demonstrated palpable tophi. The left ankle medial malleolus and forefoot were swollen, warm, and tender, with a tophus over the dorsum of the foot. The first metatarsophalangeal joint and medial malleolus of the right lower extremity were similarly inflamed. Left wrist radiographs revealed multiple erosions at the distal ulna, and multiple amorphous soft tissue calcifications, corresponding to palpable tophi (Figure, Panels A, B). Similarly, right foot radiograph revealed tophi adjacent to the first metatarsophalangeal joint (Figure, Panel C). Left wrist arthrocentesis yielded cloudy synovial fluid (with 2103 white blood cells/mm3; 89% neutrophils) positive for monosodium urate crystals; gram stain and culture were negative. Serum uric acid was 3.4 mg/dL and 2.7 mg/dL (with paired confirmatory measurement). Serum creatinine had normalized to 0.9 mg/dL. A gout flare following renal transplantation occurs in one quarter to one half of at-risk patients.1 Hyperuricemia before and after surgery is considered the principal contributor to postoperative flares.2 Our case presents a distinctly different potential explanation accounting for post-renal-transplant flaresehypouricemia due to enhanced kidney function. Acute reductions in uric acid are strongly associated with gout flares.3 There is evidence that uric acid concentrations decrease abruptly following renal transplantation.4 The kidneys are responsible for over 70% of uric acid excretion.5 Rapid improvement in kidney function post transplant may explain the low serum urate concentration observed in our patient.4 Ultimately, our patient was treated with an increased dose of oral prednisone at 60 mg daily for 4 days with
prompt improvement, then tapered to 30 mg daily over the course of 10 days. Colchicine 0.6 mg daily was restarted on the day of admission. Despite these treatments, pain in the affected joints persisted, prompting intra-articular triamcinolone injections to the left wrist, right ankle, and left ankle. Her ability to ambulate was gradually restored along with participation in physical and occupational therapy. Stephen P. Juraschek, BAa,b,c Tracie Kurano, MDc Antony Rosen, MDc Allan C. Gelber, MDa,b,c a Johns Hopkins Bloomberg School of Public Health Welch Center for Prevention, Epidemiology and Clinical Research c Johns Hopkins University School of Medicine Baltimore, MD
b
http://dx.doi.org/10.1016/j.amjmed.2013.04.008
References 1. Stamp L, Ha L, Searle M, O’Donnell J, Frampton C, Chapman P. Gout in renal transplant recipients. Nephrology (Carlton). 2006;11(4): 367-371. 2. Clive DM. Renal transplant-associated hyperuricemia and gout. J Am Soc Nephrol. 2000;11(5):974-979. 3. Yamanaka H, Togashi R, Hakoda M, et al. Optimal range of serum urate concentrations to minimize risk of gouty attacks during anti-hyperuricemic treatment. Adv Exp Med Biol. 1998;431:13-18. 4. Schmidt P, Zazgornik J, Kopsa H. Hypouricemia after renal transplantation [Letter]. N Engl J Med. 1973;289(25):1373. 5. Lipkowitz MS. Regulation of uric acid excretion by the kidney. Curr Rheumatol Rep. 2012;14(2):179-188.
Acute Gout After Renal Transplantation with Notable Hypouricemia To the Editor: Postoperative gout is a frequent complication following renal transplantation among patients with established gout and hyperuricemia.1 However, in this report we describe a patient who developed a severe post-transplant polyarticular gout exacerbation associated with hypouricemia. This represents a different potential cause of post-renal-
Funding: SPJ is supported by a National Institutes of Health/National Heart, Lung, and Blood Institute T32HL007024 Cardiovascular Epidemiology Training Grant. Conflict of Interest: None. Authorship: All authors had access to the data and a role in writing the manuscript. The observations presented in this case report have not been published previously in whole or part. Requests for reprints should be addressed to Allan C. Gelber, MD, Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Mason F Lord Building, Center Tower, Suite 4100, Baltimore, MD 21224. E-mail address: [email protected]
transplant flaresehypouricemia due to normalized kidney function. A 71-year-old African American woman underwent a living-donor renal transplant for hemodialysis-dependent end-stage renal disease at the Johns Hopkins Hospital. Her renal failure resulted from longstanding hypertension; pretransplant serum creatinine was 3.7 mg/dL. Past medical history included known hyperuricemia and gout, previously treated with daily colchicine for several years. Her operative course was uneventful. Medications posttransplantation included metoprolol, nifedipine, trimethoprim-sulfamethoxazole, prednisone, mycophenolate mofetil, and tacrolimus. However, 13 days after transplantation, she was re-admitted with debilitating pain affecting the left wrist and right great toe. There was no associated fever, chills, nausea, vomiting, dyspnea, diarrhea, abdominal pain, hematuria, or lower extremity edema. Vital signs were normal despite considerable physical discomfort. Her left wrist was warm, swollen, and red. Pain was elicited upon both passive and active motion. Wrist swelling extended distally to the hand, involving the index and middle fingers; these fingers were tender at the proximal
Figure (A) Erosions affecting the ulnar styloid (arrows). (B) Multiple wrist amorphous soft tissue calcifications (arrow), indicating gouty tophi. (C) Prominent soft tissue densities medial to the first metatarsophalangeal joint (arrow).
0002-9343/$ -see front matter Ó 2013 Elsevier Inc. All rights reserved.
e6
The American Journal of Medicine, Vol 126, No 10, October 2013
and distal interphalangeal joints with palpable tophi in both fingers. Olecranon bursae demonstrated palpable tophi. The left ankle medial malleolus and forefoot were swollen, warm, and tender, with a tophus over the dorsum of the foot. The first metatarsophalangeal joint and medial malleolus of the right lower extremity were similarly inflamed. Left wrist radiographs revealed multiple erosions at the distal ulna, and multiple amorphous soft tissue calcifications, corresponding to palpable tophi (Figure, Panels A, B). Similarly, right foot radiograph revealed tophi adjacent to the first metatarsophalangeal joint (Figure, Panel C). Left wrist arthrocentesis yielded cloudy synovial fluid (with 2103 white blood cells/mm3; 89% neutrophils) positive for monosodium urate crystals; gram stain and culture were negative. Serum uric acid was 3.4 mg/dL and 2.7 mg/dL (with paired confirmatory measurement). Serum creatinine had normalized to 0.9 mg/dL. A gout flare following renal transplantation occurs in one quarter to one half of at-risk patients.1 Hyperuricemia before and after surgery is considered the principal contributor to postoperative flares.2 Our case presents a distinctly different potential explanation accounting for post-renal-transplant flaresehypouricemia due to enhanced kidney function. Acute reductions in uric acid are strongly associated with gout flares.3 There is evidence that uric acid concentrations decrease abruptly following renal transplantation.4 The kidneys are responsible for over 70% of uric acid excretion.5 Rapid improvement in kidney function post transplant may explain the low serum urate concentration observed in our patient.4 Ultimately, our patient was treated with an increased dose of oral prednisone at 60 mg daily for 4 days with
prompt improvement, then tapered to 30 mg daily over the course of 10 days. Colchicine 0.6 mg daily was restarted on the day of admission. Despite these treatments, pain in the affected joints persisted, prompting intra-articular triamcinolone injections to the left wrist, right ankle, and left ankle. Her ability to ambulate was gradually restored along with participation in physical and occupational therapy. Stephen P. Juraschek, BAa,b,c Tracie Kurano, MDc Antony Rosen, MDc Allan C. Gelber, MDa,b,c a Johns Hopkins Bloomberg School of Public Health Welch Center for Prevention, Epidemiology and Clinical Research c Johns Hopkins University School of Medicine Baltimore, MD
b
http://dx.doi.org/10.1016/j.amjmed.2013.04.008
References 1. Stamp L, Ha L, Searle M, O’Donnell J, Frampton C, Chapman P. Gout in renal transplant recipients. Nephrology (Carlton). 2006;11(4): 367-371. 2. Clive DM. Renal transplant-associated hyperuricemia and gout. J Am Soc Nephrol. 2000;11(5):974-979. 3. Yamanaka H, Togashi R, Hakoda M, et al. Optimal range of serum urate concentrations to minimize risk of gouty attacks during anti-hyperuricemic treatment. Adv Exp Med Biol. 1998;431:13-18. 4. Schmidt P, Zazgornik J, Kopsa H. Hypouricemia after renal transplantation [Letter]. N Engl J Med. 1973;289(25):1373. 5. Lipkowitz MS. Regulation of uric acid excretion by the kidney. Curr Rheumatol Rep. 2012;14(2):179-188.