Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Muenster, 48149 Muenster, Germany.
Department of Cardiology I-Coronary and Peripheral Vascular Disease, Heart Failure Medicine, University Hospital Muenster, 48149 Muenster, Germany.
Int J Mol Sci. 2024 May 15;25(10):5376. doi: 10.3390/ijms25105376.
Urinary dickkopf 3 (uDKK3) is a marker released by kidney tubular epithelial cells that is associated with the progression of chronic kidney disease (CKD) and may cause interstitial fibrosis and tubular atrophy. Recent evidence suggests that uDKK3 can also predict the loss of kidney function in CKD patients and kidney transplant recipients, regardless of their current renal function. We conducted a prospective study on 181 kidney transplant (KTx) recipients who underwent allograft biopsy to determine the cause, analyzing the relationship between uDKK3 levels in urine, histological findings, and future allograft function progression. Additionally, we studied 82 living kidney donors before unilateral nephrectomy (Nx), 1-3 days after surgery, and 1 year post-surgery to observe the effects of rapid kidney function loss. In living donors, the uDKK3/creatinine ratio significantly increased 5.3-fold 1-3 days after Nx. However, it decreased significantly to a median level of 620 pg/mg after one year, despite the absence of underlying primary kidney pathology. The estimated glomerular filtration rate (eGFR) decreased by an average of 29.3% to approximately 66.5 (±13.5) mL/min/1.73 m after one year, with no further decline in the subsequent years. uDKK3 levels increased in line with eGFR loss after Nx, followed by a decrease as the eGFR partially recovered within the following year. However, uDKK3 did not correlate with the eGFR at the single time points in living donors. In KTx recipients, the uDKK3/creatinine ratio was significantly elevated with a median of 1550 pg/mg compared to healthy individuals or donors after Nx. The mean eGFR in the recipient group was 35.5 mL/min/1.73 m. The uDKK3/creatinine ratio was statistically associated with the eGFR at biopsy but was not independently associated with the eGFR one year after biopsy or allograft loss. In conclusion, uDKK3 correlates with recent and future kidney function and kidney allograft survival in the renal transplant cohort. Nevertheless, our findings indicate that the uDKK3/creatinine ratio has no prognostic influence on future renal outcome in living donors and kidney recipients beyond the eGFR, independent of the presence of acute renal graft pathology, as correlations are GFR-dependent.
尿 dickkopf 3(uDKK3) 是一种由肾小管上皮细胞释放的标志物，与慢性肾脏病(CKD)的进展有关，可能导致间质纤维化和肾小管萎缩。最近的证据表明，uDKK3 还可以预测 CKD 患者和肾移植受者的肾功能丧失，而与他们目前的肾功能无关。我们对 181 例接受同种异体肾移植活检以确定病因的肾移植(KTx)受者进行了前瞻性研究，分析了尿中 uDKK3 水平与组织学发现和未来同种异体肾功能进展之间的关系。此外，我们在单侧肾切除术前 1-3 天和术后 1 年观察了 82 例活体供者的变化，以观察肾功能迅速丧失的影响。在活体供者中，uDKK3/肌酐比值在肾切除术后 1-3 天内显著增加了 5.3 倍。然而，尽管没有原发性肾脏病理学基础，其在一年后显著下降至中位数 620pg/mg。估算肾小球滤过率(eGFR)在一年后平均下降 29.3%，降至约 66.5(±13.5)mL/min/1.73m，随后几年无进一步下降。uDKK3 水平随肾切除术后 eGFR 下降而升高，随后在随后的一年中部分恢复时下降。然而，uDKK3 与活体供者的单一时间点的 eGFR 无关。在 KTx 受者中，uDKK3/肌酐比值显著升高，中位数为 1550pg/mg，与健康个体或肾切除术后供者相比。受者组的平均 eGFR 为 35.5mL/min/1.73m。uDKK3/肌酐比值与活检时的 eGFR 有统计学相关性，但与活检后 1 年的 eGFR 或同种异体移植物丢失无关，也不独立相关。总之，uDKK3 在肾移植队列中与近期和未来的肾功能及肾移植移植物存活相关。然而，我们的研究结果表明，uDKK3/肌酐比值对活体供者和肾移植受者的未来肾功能结局没有预后影响，与急性肾移植物病理学的存在无关，因为相关性是基于 GFR 的。
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