SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 7 NUMBER 1 • MARCH 2010
7
The problem of diabetic nephropathy and
practical prevention of its progression
JULIAN WRIGHT, ANAND VARDHAN
Abstract
I
n commonwith all countries in the developedworld,
the United Kingdom is experiencing a dramatic
increase in the incidence of diabetes and chronic
kidney disease. The most common cause of renal
impairment is diabetes. The evolution of diabetic
nephropathy is usually predictable with evidence-
based interventions available at each stage. This review
examines this evidence and gives practical advice on the
management of patients with diabetic nephropathy.
Introduction
DiabetesandCKDhaveseveralcommonentities.Theprevalence
of both conditions is increasing, the economic healthcare
burden of these diseases is increasing, public and healthcare
worker awareness is increasing, both conditions have National
Service Frameworks applicable in the United Kingdom and
they have a commonality of patients. In all renal replacement
therapy patient populations the most common cause of CKD
and indeed end-stage kidney disease is diabetic nephropathy.
In developed countries type 2 diabetes is now overtaking
type 1 diabetes in terms of numbers of incident renal
replacement therapy patients. Inmany countries the incidence
of patientswithdiabeticnephropathy reachingend-stage renal
disease has shown a marked increase over recent decades.
1
Diabetic nephropathy in both type 1 and 2 diabetes
progresses in a relatively predictable manner through
the stages of normoalbuminuria, microalbuminuria and
macroalbuminuria, which often heralds increasing creatinine
as the final manifestation of overt diabetic nephropathy.
Such a classification has a profound effect on mortality risk
with annual death rates of 0.7%, 2.0%, 3.5% and 12.1%
for patients with normoalbuminuria, microalbuminuria,
macroalbuminuria and elevated creatinine respectively, in
patients with type 2 diabetes.
2
Similarly,mortality in type1diabeticpatients canbe linked to
the absence or degree of albuminuria. In a five-year follow-up
study of patients with long standing diabetes, mortality rates
for patients with normoalbuminuria, microalbuminuria,
macroalbuminuria and end-stage renal disease were 11%,
26%, 44% and 71% respectively with two-thirds of deaths
being attributable to cardiovascular disease.
3
Of benefit to the clinician is the growing body of evidence-
based interventions which can be made at each stage of
diabetic nephropathy in order to reduce the risk of progression
of diabetic nephropathy and the cardiovascular morbidity and
mortality inherent to diabetic nephropathy. New treatments
for diabetic nephropathy are in development; sulodexide – a
highly purified mixture of glycosaminoglycans – is an agent
which alters glomerular permeability leading to a reduction
in proteinuria in an independent manner from blood pressure
reduction. One recent pilot study demonstrated a reduction
in urinary albumin excretion with sulodexide.
4
However, to
date the use of sulodexide remains of unproven benefit.
In this article the main lines of trials are explored, along
with practical suggestions regarding treatment of individuals
with this progressive condition.
Normoalbuminuria
Although it would seem self-evident that good glycaemic
control would be ideal in patients with diabetic nephropathy,
it is only in normoalbuminuric patients that large studies
have demonstrated a beneficial effect of intensified
glycaemic control on reduction of patients progressing to
the microalbuminuric phase of diabetic nephropathy. The
Diabetes Control and Complications trial demonstrated
a risk reduction of 35–45% over a nine-year period in the
development of microalbuminuria for type 1 diabetic patients
treated with intensified insulin regimens with a mean HbA
1c
of 7% compared to a conventional treatment group with a
mean HbA
1c
of 9%.
5
Similarly, in patients with type 2 diabetes, the UKPDS
demonstrated a 25–30% reduction in progression from
normoalbuminuria to microalbuminuria over a nine-year
period with an intensified treatment regimen of oral agents
or insulin achieving an HbA
1c
of 7.0% compared to 7.9%
in the conventional treatment group.
6
Further UKPDS data
showed that there was a 2% per annum progression from
normoalbuminuria to microalbuminuria, tight blood pressure
control reduced albuminuria but at six years there were no
differences in plasma creatinines.
7
The UKPDS also demonstrated that increasing systolic
hypertension is associated with an increase in any diabetic
complications, be it vitreous haemorrhage, cataract extraction
or any cardiovascular comorbidity.
2
The 2002 NICE guidelines
suggest a target blood pressure
<
140/80 mmHg which
Correspondence to: Dr Julian Wright
Manchester Institute of Nephrology and Transplantation, Manchester Royal
Infirmary, Oxford Road, Manchester, M13 9WL, UK.
Tel: +44 (0) 2764540
Fax: +44 (0) 2768022
e-mail:
S Afr J Diabetes Vasc Dis
2010;
7
: 7–11
