Materne Christine, Gerth Jens, Ott Undine, Gröne Hermann-Josef, Wolf Gunter
Klinik für Innere Medizin III, Friedrich-Schiller-Universität Jena, Jena, Germany.
Med Klin (Munich). 2009 Aug;104(8):644-8. doi: 10.1007/s00063-009-1136-1. Epub 2009 Aug 23.
A 56-year-old male patient with terminal renal insufficiency received a living donor kidney transplant from his wife in June 2007. Initial immunosuppression consisted of prednisolone, tacrolimus, and mycophenolate mofetil (MMF). 4 months after transplantation, the serum creatinine increased to 192 micromol/l and urinary analysis revealed the presence of decoy cells. A biopsy showed a focal interstitial nephritis and SV40 antigen was detected in tubular nuclei. Polymerase chain reaction (PCR) in serum and urine showed high titers of BK virus. Tacrolimus was stopped, MMF was reduced, and leflunomide (20 mg/day) was started. The patient was readmitted because the serum creatinine further increased to 262 micromol/l. Leflunomide concentrations were in the target range, but renal biopsy still revealed the presence of BK virus nephropathy. MMF was stopped. Serum creatinine stabilized at 233 micromol/l and PCR for BK virus in serum was negative. In April 2008, a deterioration of renal function occurred (serum creatinine 308 micromol/l) and renal biopsy revealed signs of acute interstitial rejection without the presence of SV40 antigen. A methylprednisolone pulse therapy for 5 days was performed and cyclosporine was added. After a few weeks serum creatinine increased to 444 micromol/l and a new biopsy revealed the reoccurrence of BK virus nephropathy. Since the tubulointerstitial injury was > 80%, no further therapy was performed and soon after dialysis therapy was initiated.
BK virus nephropathy is a still rare, but increasing complication of renal transplantation, presumably mediated by intensive immunosuppression. The disease can induce graft dysfunction and may ultimately lead to graft failure. BK virus nephropathy can trigger acute rejection. Unfortunately, therapy of BK virus nephropathy and acute rejection is just the opposite: BK virus nephropathy requires a reduction of immunosuppression whereas acute rejection calls for intensification. A potential therapeutic approach may be leflunomide, an immunosuppressive substance with antiviral properties, but potential severe side effects. The described case demonstrates the frustrating course of a graft from a living donor despite initial successful therapy with leflunomide and illustrates the problems choosing between intensive and moderate immunosuppression.
一名56岁终末期肾功能不全男性患者于2007年6月接受了来自其妻子的活体供肾移植。初始免疫抑制方案包括泼尼松龙、他克莫司和霉酚酸酯（MMF）。移植后4个月，血清肌酐升至192微摩尔/升，尿液分析发现有诱饵细胞。活检显示局灶性间质性肾炎，在肾小管细胞核中检测到SV40抗原。血清和尿液的聚合酶链反应（PCR）显示BK病毒高滴度。停用他克莫司，减少MMF用量，并开始使用来氟米特（20毫克/天）。患者因血清肌酐进一步升至262微摩尔/升而再次入院。来氟米特浓度在目标范围内，但肾活检仍显示存在BK病毒性肾病。停用MMF。血清肌酐稳定在233微摩尔/升，血清BK病毒PCR检测为阴性。2008年4月，肾功能恶化（血清肌酐308微摩尔/升），肾活检显示有急性间质性排斥反应迹象，但未检测到SV40抗原。进行了为期5天的甲泼尼龙冲击治疗，并加用环孢素。几周后血清肌酐升至444微摩尔/升，再次活检显示BK病毒性肾病复发。由于肾小管间质损伤>80%，未再进行进一步治疗，不久后开始透析治疗。
BK病毒性肾病是肾移植中一种仍然罕见但呈上升趋势的并发症，可能由强化免疫抑制介导。该疾病可导致移植肾功能障碍，并最终可能导致移植失败。BK病毒性肾病可引发急性排斥反应。不幸地是，BK病毒性肾病和急性排斥反应的治疗方法恰恰相反：BK病毒性肾病需要减少免疫抑制，而急性排斥反应则需要强化免疫抑制。一种潜在的治疗方法可能是来氟米特，一种具有抗病毒特性的免疫抑制药物，但可能有严重的副作用。所述病例显示了尽管最初使用来氟米特治疗成功，但活体供肾移植的过程仍令人沮丧，并说明了在强化免疫抑制和适度免疫抑制之间选择的问题。
