Vascular disease in early stage of diabetic nephropathy

• Cardio-Ankle Vascular Index, diabetic nephropathy, macrovascular disease, renal function, renal microvascular disease

Dear Sir,

Vascular disease comprising renal microvascular disease and macrovascular disease has been recognized in diabetic nephropathy.1,2 The crucial issue remains to be addressed is when it develops during the course of diabetes mellitus. With respect to the renal microvascular disease, its recognition has been well reflected by either histopathologic study of the renal microvessels, or intrarenal hemodynamic study determined by a double isotope techniques namely ¹³¹I-labeled orthoiodohippuric acid to reflect the renal plasma flow, and ^99mtechnitium-labeled diethylene triamine pentaacetic acid to reflect glomerular filtration rate.3 The intrarenal hemodynamic study in 30 patients associated with early diabetic nephropathy during the stage of normoalbuminuria reveals a significant alteration characterized by reductions in renal plasma flow, peritubular capillary flow as well as an abnormally elevated level of renal arteriolar resistances. It has also been noted that such intrarenal hemodynamic alteration is documented even in the presence of normotension indicating dissociation between systemic and renal microvascular circulations (Table 1). The above findings imply that renal microvascular disease has developed during the early course of diabetic nephropathy. The cause-and-effect relationship between renal microvascular disease and the magnitude of renal functional and structural impairments has been appreciated and thus, signifies the essential role of renal microvascular disease relevant to therapeutic and preventive strategy of the renal disease.4,5

Table 1. Demonstrated renal function, renal hemodynamics and macrovascular disease index in early diabetic nephropathy.

	Healthy subject	p Value	Early diabetic nephropathy
I. Renal Function
Serum creatinine mg/dL	0.8 + 0.1	NS	1 + 0.2
Mean arterial pressure mmHg	79 + 5	0.001	90 + 11
Creatinine clearance   mL/min/1.73 m^2	117 + 13	<0.001	88 + 14
FE Mg %	2 + 0.2	<0.05	4.3 + 1
Microalbumin/creatinine ratio	<30 µg/mg	NS	7 + 6
II. Microvascular Index
Renal plasma flow   mL/min/1.73 m^2	585 + 30	<0.01	395 + 41
Glomerular filtration rate   mL/min/1.73 m^2	116 + 14	<0.01	86 + 16
Peritubular capillary flow   mL/min/1.73 m^2	479 + 26	<0.001	322 + 33
Afferent arteriolar resistance (RA)   dyne·s·cm^−5	2332 + 108	<0.05	5057 + 861
Efferent arteriolar resistance (RE)   dyne·s·cm^−5	3012 + 130	<0.05	4997 + 483
III. Macrovascular Index:
Cardio-Ankle Vascular Index (CAVI)
Arterial stiffness	7.2 + 1	<0.001	9.3 + 1.2
Estimated age of artery	39 + 15		66 + 11
	p < 0.05		p < 0.05
Actual age of patients (years)	41 + 14		63 + 11

With respect to the macrovascular disease in diabetes mellitus, it is a general consensus that the recognition of macrovascular disease is usually precipitated by the onset of major organ damage such as myocardial infarction or cerebrovascular incident. In this regard, many people view that macrovascular disease is associated with late stage diabetes. Surprisingly, the study on macrovascular disease by Cardio-Ankle Vascular Index (CAVI) method in this study revealed that there was an increase in arterial stiffness as well as an advanced estimated age of artery observed in early stage of diabetic patients (normoalbuminuria) as compared to the healthy subjects (Table 1). The presence of both macrovascular disease and renal microvascular disease in normoalbuminuric diabetic nephropathy implies that these two forms of vascular disease develop during the early course of diabetes mellitus. The documentation of an impaired renal function prior to the onset of other major organ damage indicates that the renal microvascular disease has the more advanced impact on renal disease than the macrovascular disease has on other major organs in diabetes mellitus.

Declaration of conflict of interest.

There is no conflict of interest.

Acknowledgments

This study is supported by Bumirajanagarindra Kidney Institute, The Royal Institute of Thailand and Thailand Research Fund.