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ACE inhibitors and cough.
Diabetes mellitus and diabetic nephropathy.
One of the more common ACE inhibitor side-effects is dry- cough. Various reports put the incidence of cough at Recent research is now being published, that supports our between 5 and 39%. Not always does this side-effect lead to previous suspicions. It is nearly ten years since data was first discontinuation of the ACE inhibitor, fortunately. On published revealing the benefits of ACE inhibitors and enough occasions, however, therapy is ceased and the improved diabetic control on renal tissue in type I diabetes There is probably some differences in the nephropathy Therapies to either treat the cough, or angiotensin II receptor physiology of both type I and type II diabetes. The histopathology is similar. The clinical picture is similar, except – perhaps – the severity of macrovascular changes in type II The cough seems to be related to a genetic predisposition, diabetes mellitus seen, especially in groups such as in the and a particular genotype is associated with the ACE- Polynesian population. The survival of the type II diabetes induced cough. Short of gene analysis, how to identify these mellitus patients with established diabetic nephropathy is also high-risk people is not yet available. Meanwhile anti-cough remedies such as cromoglycate, baclofen, theophylline, or NSAIDs – even oral iron! - will continue to be used. Type I diabetes mellitus patients with established diabetic nephropathy (more than micro-albuminuria) progress to end- A second option is the application for and approval of an A- stage renal failure in 7 to 10 years, and longer with better control of HbA1c, and BP and use of ACE inhibitors. Angiotensin II receptor blockers.
The question remained over the benefits of ACE inhibitor therapy and diabetes control in type II diabetes mellitus These agents have quickly replaced ACE inhibitors where a patients. It is pleasing to see that evidence supporting the cough side effect has occurred, rather than the additional of management of diabetes mellitus types I and II similarly, for
cough-therapies. The pharmaceutical companies have been both diabetes control and ACE inhibitors is now available. quick to show the renal benefits of ACE inhibition are similarly seen with the A-II receptor blockers – leaving very With the recent evidence of therapies delaying the progression few patients suffering with the ACE inhibitor cough. of established nephropathy in type II diabetes mellitus patients we can hope the two to four year period from diagnosis to But which is better “renally” - ACE or A-II blockade? ESRF will be also prolonged. We do not know if good diabetic control in ESRF patients will benefit their survival and/or reduce the macrovascular W H A T ’ S I N H E R E T H I S T I M E ? complications. Similarly we do not know which group will gain greater benefit attaining good glucose and blood pressure What is new? – Diabetes nephropathy prevention control aggressively - type I or type II diabetes mellitus. Such studies may never be undertaken. We must go with what we have now. Clearly good glucose A-II-receptor blockers replace cough therapies. control by keeping the HbA1c in the optimal range (monitoring HbA1c every three months should be adequate) and blood Added benefit of ACEIs and A-II blockers together pressure control are even more important goals to strive for. ACE and A-II in combination.
Dr David Voss ED
Specialist Physician
Some South Auckland diabetes mellitus type II patients took part
Renal and Internal Medicine
in a multi-centre, multi-national study recently published. The trial studied the A-II receptor blocker irbesartan. Blood pressure Residence
control, mortality and diabetic nephropathy (the time taken for the serum creatinine to double) were some of the end-points. Contact on cellular phone
Mortality reduced in the treated arm. Blood pressure control was similar in the irbesartan and placebo arms of the study. Facsimile
From the renal failure progression aspect, irbesartan was effective in prolonging the time taken for the serum creatinine to double, and hence delaying the time to end-stage renal failure. Secretary
So what? This is further support to the theories, and further evidence that A-II receptor blockers, along with ACE inhibitors are renal friendly. They provide protection to the renal tissue over and above that seen with just improved blood pressure control. Irbestartan lowered the number of patients whose diabetic nephropathy progressed. Qualifications
BSc (Biochemistry, Otago) 1981
Clearly, in impaired renal function, stimulation of the reno- MBChB (Otago) 1984
angiotensin system is not a good thing; and blockade of either the FRACP 1992
receptor or enzymatic pathway is a good thing. MRCP(UK) 1993
Investigation of renovascular disease and In a subsequent analysis of this irbesartan in hypertensive and diabetic patients study, the results equated to: 15 patients
Investigation of proteinuria and haematuria with hypertension and type II diabetes mellitus
Investigation and management of impaired renal for three years
one patient from worsening renal function/end-stage kidney
failure or death
East Auckland Rooms
So where from here for diabetes mellitus patients?
Type I and type II diabetes patients should optimise Patients with microalbuminuria, or established nephropathy (with macroalbuminuria, with or without impaired renal function) should definitely be considered for an ACE or an A-II blocker (nothing new here). South Auckland Rooms
Of interest, some early evidence suggests that we are not using enough ACE inhibition. We should be using much higher doses of ACE inhibition (eg. quinapril 40mg/day) even in the presence of renal dysfunction, and gain further renal protection And of more interest, the combination of a high dose of
an ACE inhibitor with an A-II receptor blocker is more reno-protective than either agent alone.


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