The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.

/pdf/diabetic-kidney-disease-33198zm7m0.pdf

Diabetic kidney disease

Systemic considerations in the management of diabetic retinopathy.

The clinical picture of diabetic control, studied in four settings.

Studies of the microcirculation in diabetes in the last fifteen years have concentrated heavily on anatomic and biochemical abnormalities of the capillary basement membrane Greater insights into basement membrane changes have eclipsed the previous picture of widespread progressive deterioration of the entire microcirculation The history, variety of organ involvement, pattern of circulatory decline, and associated anatomic, physiologic, and biochemical findings are re-examined so that recently described potential mechanisms for the development of diabetic microangiopathy may be understood in a broader perspective The possible contributions of seven categories of diabetic changes to damage of the microcirculation are outlined The categories are: (1) altered basement membrane, (2) altered cellular function, (3) cell metabolic changes, (4) altered blood flow properties, (5) distrubed hemostasis, (6) altered oxygen transport, and (7) altered hormone production The variety of clinical manifestations in long-standing diabetes related to microangiopathy appears to be due to a combination of a widely variable over-all rate of progression and a differing ability of body tissues and organs to accommodate to the sequential circulatory changes The slow rate of deterioration in most diabetics suggests that several abnormalities must interact to produce the observed progression A clear understanding of the interactions responsible for diabetic microangiopathy is becoming more important as new options in the management of diabetes become available

Deterioration of the Microcirculation in Diabetes

To evaluate the effects of therapy on the vascular complications of adult diabetes, the University Group Diabetes Program (UGDP) carried out a prospective double-blind study in 12 centers ...

Sulfonylureas: Effects in Vivo and in Vitro

the observation of patients in whom diabetes exists for a period of 20 or more years, certain vascular or degenerative complications appear frequently. Today, attention is concentrated on the specific effects upon the venules and capillaries as well as arterioles, especially in the retinae and in the glomeruli of the kidneys. A common chemical pathology may be discovered to explain these lesions as well as the frequency of atherosclerosis. In patients whose diabetes began early in life, a triad is being recognized with increasing frequency ; namely, the sequence in the same patient of neuropathy, retinopathy, and nephropathy. The series of 25 such cases described by Root and Kenney * has been increased to 155 in the present report.

Sequence of Neuropathy, Retinopathy, and Nephropathy in One Hundred Fifty-Five Patients

DURING the observation of patients in whom diabetes exists for a period of 20 or more years, certain vascular or degenerative complications appear frequently. Today, attention is concentrated on the specific effects upon the venules and capillaries as well as arterioles, especially in the retinae and in the glomeruli of the kidneys. A common chemical pathology may be discovered to explain these lesions as well as the frequency of atherosclerosis. In patients whose diabetes began early in life, a triad is being recognized with increasing frequency; namely, the sequence in the same patient of neuropathy, retinopathy, and nephropathy. The series of 25 such cases described by Root and Kenney * has been increased to 155 in the present report. DEFINITION The term "triopathy" has been applied to diabetic patients who usually have shown, first, clinical evidence of neuropathy; then, diabetic retinitis, and, finally, the nephropathy of diabetes. In this series, the

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Triopathy of diabetes; sequence of neuropathy, retinopathy, and nephropathy in one hundred fifty-five patients.

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Sequence of Neuropathy, Retinopathy, and Nephropathy in One Hundred Fifty-Five Patients

Triopathy of diabetes; sequence of neuropathy, retinopathy, and nephropathy in one hundred fifty-five patients.