Dear Editor,
Under common practice, diabetic nephropathy (DN) is reflected by microalbuminuria, serum creatinine greater than 1 mg/dL, or glomerulonephropathy.Citation1 The preceding diagnostic marker such as serum creatinine determination or microalbuminuria recognizes a rather late stage (chronic kidney disease (CKD) stage 3) DN indicating an insensitive marker.Citation2 In addition, the histopathologic finding of the kidney is generally an unavailable information. Such practice leads to the recognition of DN as well as the initiation of treatment at a rather late stage. The general consensus has been that the treatment of this DN at late stage fails to restore renal function and simply slows the renal disease progression.Citation3 To explain the therapeutic resistance to vasodilator, we have recently studied on vascular homeostasis in late stage DN which reveals a defective angiogenesis, namely vascular endothelial growth factor (VEGF)receptor 1 and angiopoietin 1, leading to an impaired nitric oxide production,Citation4 which explains such therapeutic resistance. In addition, the antiangiogenic factors, namely angiopoietin 2 and VEGF receptor 2, are abnormally elevated leading to the progression of renal microvascular disease, which is supported by the progressive decline in renal perfusion commonly documented in late stage DN. In this essence, the progression of late stage DN is due to the inability to correct the state of renal ischemia, which is the crucial mechanism of renal disease progression.
This would raise a crucial issue as to whether a treatment to restore renal function in DN possible? In this regard, we as well as others have attended the early stage DN patients who have generally been left unattended without an appropriate therapeutic treatment. These patients are underrecognized by the conventionally available diagnostic marker and allowed to spontaneously progress until the serum creatinine becomes abnormally elevated or microalbuminuria presents. In fact, this early stage DN associated with normal serum creatinine value and normoalbuminuria can be recognized by (1) a depleted creatinine clearance; (2) an abnormally elevated fractional excretion of magnesium (FE Mg; normal 1.6 ± 0.6%) indicating the presence of tubulointerstitial fibrosis, since FE Mg has previously been demonstrated to correlate with the magnitude of tubulointerstitial fibrosisCitation5,6; and (3) a reduction in peritubular capillary flow or renal plasma flow indicating renal microvascular disease or ischemia.Citation7 Recent study on vascular homeostasis in early stage DN during normoalbuminuria and CKD stages 1–2 has supported this new conceptual view. The vascular homeostasis is adequately functional in early stage DN, which implies that the production of nitric oxide by the endothelial cell in the renal microcirculation would likely be sufficient to respond to vasodilator treatment.Citation8 In fact, the pilot study of vasodilator treatment (angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB)combination) implemented at the early stage DN during normoalbuminuria shows an enhancement in renal plasma flow and peritubular capillary flow following the vasodilator treatment. This would correct the renal ischemia and thus, increase the creatinine clearance.Citation8,9 This evidence-based information has confirmed that DN is a restorative disease if the vasodilator treatment is implemented at the early stage of DN. Therefore, this new strategy would minimize the number of end-stage renal diseases in the long-term outcome.
Declaration of interest: The authors received financial support from Thailand Research Fund, National Research Council Fund of Thailand, Bhumirajanagarindra Kidney Institute, and The Royal Society of Thailand. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Narisa Futrakul
Renal Microvascular Research Group,
Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand
E-mail: [email protected]
Prasit Futrakul
Bhumirajanagarindra Kidney Institute, Phyathai Road,
Bangkok, Thailand
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- Futrakul N, Futrakul P. Diabetic nephropathy: Current concept of therapeutic strategy toward self-sufficiency. Nephrol Therap. 2011, doi:10.4172/2161-0959.S2-002.
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