Long-term prevention of diabetic nephropathy: an audit

Abstract

Aims/hypothesis In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin-angiotensin-aldosterone system (RAAS) with an ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in microalbuminuric type 1 diabetic patients on progression of microalbuminuria and development of DN. Methods All patients with type 1 diabetes and persistent microalbuminuria (30-300 mg/24 h) were identified (n=227) in 1995 at Steno Diabetes Center and followed for 11 years. Development of DN was defined as a UAER of >300 mg/24 h in two of three consecutive urine samples. Results Age and duration of diabetes at baseline (mean±SD) were 46±15 and 28±13 years, respectively. During followup 14 patients emigrated and 58 (26%) died. Over the same period 79% were treated with an ACEI or ARB. There was a mean decline in UAER of 4%/year. Sixty-five patients (29%) progressed to overt DN, corresponding to 3.1%/year. However, 29 of them regressed to normo-or microalbuminuria on intensified antihypertensive treatment. Glycaemic control and blood pressure remained nearly unchanged. Conclusions/interpretation In our outpatient clinic, the implementation of RAAS-blocking treatment in type 1 diabetic patients with microalbuminuria successfully reduced longterm progression to overt DN to a rate similar to those previously reported in randomised, double-blind intervention trials of shorter duration using RAAS blockade.

Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications

“…RAS activation and subsequent up-regulation of angiotensin II (Ang II) causes increased fluid and sodium retention within the kidneys and increased vascular tone, predisposing the patients to endothelial injury and damage in the kidneys, heart and nervous system [2][3][4]. Thus, pharmacological blockade of the RAS with an angiotensin-converting enzyme inhibitor (ACEi) or an Ang II receptor blocker (ARB) serves as the first-line treatment of hypertension in diabetic patients [5]. However, complex feedback regulation loops exist within the RAS that may lead to a paradoxical increase in Ang II and aldosterone levels during ACEi or ARB treatment [6].…”

Antihypertensive Treatment and Resistant Hypertension in Patients With Type 1 Diabetes by Stages of Diabetic Nephropathy

“…16 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) 11 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) ,0.0001 11 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16) ,0.0001 12 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) ,0.0001 12 (7)(8)(9)(10)(11)(12)<...>…”

“…Despitestrong evidence that intensive treatment of elevated BP reduces the risk of cardiovascular disease and microvascular complications, as well as improves the prognosis of patients with diabetic nephropathy (especially with the use of ACE inhibitors [ACEIs] and angiotensin II antagonists [angiotensin receptor blockers, ARBs]) (1,(9)(10)(11), treatment targets and recommendations seem difficult to meet in clinical practice (12)(13)(14)(15). This suggests that the patients might either show poor adherence to the treatment and lifestyle changes or have a suboptimal drug regimen.…”

Diabetes in the young: what are their long term health prospects?

“…Principal among these studies was the Diabetes Control and Complications Trial (DCCT)12 which demonstrated that improving glycaemic control (mean HbA1c 9.1% to 7.4%; adolescent cohort aged 13–18 years 10.1% to 8.2%) reduced the progression of established retinopathy by 54% and the appearance of new retinopathy by 76%. Subsequently, several studies have shown that the progression of microvascular changes to permanent pathological damage can be prevented by aggressive therapy in combination with other medical treatments (antihypertensive therapy for microalbuminuria and associated elevated blood pressure, and statin therapy in young adults with abnormal blood lipid profiles) 13. This approach together with the lifestyle recommendations of no smoking, maintaining exercise and fitness, and weight control have appeared in some reports to dramatically alter the risk of long term microvascular disease complications.…”