Department of Nephrology, Queen Elizabeth Medical Centre, Renal Institute of Birmingham, University of Birmingham, Birmingham, UK.
J Clin Pathol. 2010 Oct;63(10):884-7. doi: 10.1136/jcp.2010.079236.
Most cases of dialysis-dependent acute kidney injury due to myeloma cast nephropathy do not recover renal function. Renal biopsy typically shows cast formation, direct tubular injury and interstitial inflammation caused by nephrotoxic monoclonal free light chains (FLC). Established scarring at presentation is rarely severe. There is little data on in situ evolution of renal injury.
To conduct a detailed histological study of four patients with cast nephropathy.
Cast nephropathy was confirmed by renal biopsy. Treatment consisted of chemotherapy and high cut-off dialysis to maximise extracorporeal removal of FLC and reduce renal toxicity. All four patients remained dialysis dependent at 6 weeks, at which time they underwent a further biopsy.
Three patients achieved independence from dialysis. Six-week biopsies showed differential changes in chronic damage from no progression, to accelerated progression of scarring from 10% to 42%, despite a rapid and sustained fall in FLC in all patients. In three patients there was a major reduction in intratubular cast numbers; these patients subsequently recovered renal function. In one patient who continued to have high cast formation at 6 weeks there was no subsequent renal recovery.
Some FLC clones can promote rapid renal scarring. Significant reductions in cast formation on repeat biopsy may identify the potential for late renal recovery. Early diagnosis and treatment may prove crucial in determining renal recovery. Patients who have not recovered renal function after a period of treatment may be usefully reassessed by repeat biopsy for quantitative analysis of chronic damage and cast numbers.
大多数骨髓瘤铸型肾病导致的透析依赖型急性肾损伤病例的肾功能无法恢复。肾活检通常表现为铸型形成、毒性单克隆游离轻链(FLC)引起的直接肾小管损伤和间质炎症。发病时的固有瘢痕很少严重。关于肾损伤的原位演变的数据很少。
对 4 例铸型肾病患者进行详细的组织学研究。
通过肾活检证实铸型肾病。治疗包括化疗和高截止透析,以最大限度地去除 FLC 并减少肾毒性。所有 4 例患者在 6 周时仍依赖透析,此时他们进行了进一步的活检。
3 例患者摆脱了透析依赖。6 周时的活检显示慢性损伤的差异变化,从无进展到瘢痕加速进展(从 10%到 42%),尽管所有患者的 FLC 迅速且持续下降。在 3 例患者中,管腔内铸型数量明显减少;这些患者随后恢复了肾功能。在 1 例 6 周时仍有大量铸型形成的患者中,随后没有出现肾功能恢复。
一些 FLC 克隆可以促进快速的肾瘢痕形成。重复活检时铸型形成的显著减少可能表明潜在的晚期肾功能恢复。早期诊断和治疗可能对确定肾功能恢复至关重要。经过一段时间的治疗后仍未恢复肾功能的患者,可以通过重复活检进行定量分析慢性损伤和铸型数量,以进行有用的重新评估。