Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey.
Department of Medicine, Koc University School of Medicine, Istanbul, Turkey.
Nephrol Dial Transplant. 2024 Jul 31;39(8):1228-1238. doi: 10.1093/ndt/gfae027.
The global burden of chronic kidney disease (CKD) is high and increasing. Early diagnosis and intervention are key to improve outcomes. Single-nephron glomerular hyperfiltration is an early pathophysiologic manifestation of CKD that may result in absolute glomerular hyperfiltration, i.e. a high glomerular filtration rate (GFR), or be associated with normal or low GFR because of nephron loss (relative glomerular hyperfiltration). Even though compensatory glomerular hyperfiltration may contribute to maintain kidney function after the loss of kidney mass, the associated increased glomerular capillary pressure and glomerular and podocyte size drive podocyte loss, albuminuria and proximal tubular overload, contributing to CKD progression. In this regard, all kidney protective drugs in clinical use so far, from renin-angiotensin system blockers to mineralocorticoid receptor blockers to sodium-glucose co-transporter 2 inhibitors to tolvaptan, induce an early dip in glomerular filtration that is thought to represent reversal of hyperfiltration. As glomerular hyperfiltration may be present early in the course of kidney disease, its recognition may provide an effective intervention window that may predate current criteria based on high albuminuria or loss of GFR. Nevertheless, there is no diagnostic method with high sensitivity and specificity to identify single-nephron glomerular hyperfiltration, except when it leads to obvious absolute glomerular hyperfiltration, as observed in the early stages of diabetic kidney disease when nephron mass is still preserved. We now review the concept of glomerular hyperfiltration as an indicator of CKD risk, including definitions, challenges in diagnosis and evaluation, underlying pathophysiological mechanisms, potential therapeutic approaches and unanswered questions.
全球慢性肾脏病（CKD）负担很高且呈上升趋势。早期诊断和干预是改善结局的关键。单肾单位肾小球高滤过是 CKD 的早期病理生理表现，可能导致绝对肾小球高滤过，即肾小球滤过率（GFR）高，或由于肾单位丢失而与正常或低 GFR 相关（相对肾小球高滤过）。尽管代偿性肾小球高滤过可能有助于在肾单位丢失后维持肾功能，但相关的肾小球毛细血管压力升高和肾小球及足细胞增大导致足细胞丢失、白蛋白尿和近端肾小管超负荷，从而促进 CKD 进展。在这方面，迄今为止，所有临床使用的肾脏保护药物，从肾素-血管紧张素系统阻滞剂到盐皮质激素受体阻滞剂，再到钠-葡萄糖共转运蛋白 2 抑制剂再到托伐普坦，都会导致肾小球滤过率的早期下降，这被认为是高滤过的逆转。由于肾小球高滤过可能在肾脏病早期就存在，因此识别肾小球高滤过可能提供一个有效的干预窗口期，这可能早于目前基于高白蛋白尿或 GFR 丧失的标准。然而，除了在保留肾单位的早期糖尿病肾病阶段观察到的明显绝对肾小球高滤过之外，目前还没有一种具有高灵敏度和特异性的诊断方法来识别单肾单位肾小球高滤过。我们现在回顾肾小球高滤过作为 CKD 风险指标的概念，包括定义、诊断和评估的挑战、潜在的病理生理机制、潜在的治疗方法和未解决的问题。
