Sarcletti M, Petter A, Romani N, Lhotta K, König P, Maier H, Zangerle R
Department of Dermatology and Venereology, University of Innsbruck, Austria.
Clin Nephrol. 2000 Oct;54(4):261-70.
Indinavir therapy is associated with a continuum of crystal-related syndromes, including nephrolithiasis, renal colic, flank pain without recognizable stone formation, dysuria and asymptomatic crystalluria. A frank nephropathy has been recognized recently as part of the spectrum.
A retrospective analysis of 72 HIV-infected individuals receiving indinavir was performed to identify the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals treated with nucleoside analogues alone served as controls.
Mean serum creatinine levels rose from 1.03 +/- 0.16 mg/dl to 1.11 +/- 0.22 mg/dl at week 12 and 1.15 +/- 0.27 mg/dl at week 24 (both, p < 0.01). Thirteen individuals developed serum creatinine levels > or =1.4 mg/dl. Increased serum creatinine levels were found more frequently in women (p < 0.01) and were associated with pyuria and microhematuria (p < 0.01). Frank renal colic and/or nephrolithiasis (seven patients) and urinary pH were not associated with serum creatinine levels > or =1.4 mg/dl. The mean duration of indinavir treatment, until sterile pyuria occurred, were 22 weeks and 32 weeks until the first rise of serum creatinine levels to > or =1.4 mg/dl. Ten patients showed both findings, pyuria preceded the first rise in serum creatinine levels to > or = 1.4 mg/dl (18 vs. 27 weeks, p = 0.02). Renal biopsy, done in three patients, revealed tubulointerstitial disease with crystals in collecting ducts. In 21 patients, among them 11 with pyuria, indinavir was replaced for various reasons and pyuria disappeared in nine. In these patients mean serum creatinine levels decreased from 1.43 mg/dl at withdrawal of indinavir to 1.04 mg/dl three months later (p < 0.01).
Indinavir therapy is associated with a decrease in renal function which is reversible after withdrawal. In addition, indinavir-associated tubulointerstitial disease does no in patients taking indinavir may help to identify patients being at risk for nephrotoxicity.
茚地那韦治疗与一系列晶体相关综合征有关,包括肾结石、肾绞痛、无明显结石形成的胁腹疼痛、排尿困难和无症状性结晶尿。一种明显的肾病最近被确认为该综合征谱的一部分。
对72例接受茚地那韦治疗的HIV感染个体进行回顾性分析,以确定茚地那韦相关肾病和泌尿系统并发症的发生率及危险因素。仅接受核苷类似物治疗的个体作为对照。
血清肌酐平均水平在第12周时从1.03±0.16mg/dl升至1.11±0.22mg/dl,在第24周时升至1.15±0.27mg/dl(均p<0.01)。13例个体的血清肌酐水平≥1.4mg/dl。血清肌酐水平升高在女性中更常见(p<0.01),且与脓尿和镜下血尿相关(p<0.01)。明显的肾绞痛和/或肾结石(7例患者)以及尿液pH值与血清肌酐水平≥1.4mg/dl无关。直到出现无菌性脓尿,茚地那韦治疗的平均持续时间为22周,直到血清肌酐水平首次升至≥1.4mg/dl的平均持续时间为32周。10例患者出现了这两种情况,脓尿先于血清肌酐水平首次升至≥1.4mg/dl(18周对27周,p=0.02)。对3例患者进行了肾活检,结果显示为肾小管间质性疾病,集合管中有晶体。在21例患者中,其中11例有脓尿,因各种原因停用了茚地那韦,9例脓尿消失。在这些患者中,血清肌酐平均水平从停用茚地那韦时的1.43mg/dl降至3个月后的1.04mg/dl(p<0.01)。
茚地那韦治疗与肾功能下降有关,停药后肾功能可逆转。此外,茚地那韦相关的肾小管间质性疾病在服用茚地那韦的患者中可能有助于识别有肾毒性风险的患者。