OTHER COMPLICATIONS OF DIABETES

Diabetic nephropathy

then declines to about 1% per year in patients with type 1 diabetes of 40 years duration or more. Those with diabetes for more
than 35 years who have not yet developed kidney disease are at
low risk of doing so. This pattern suggests that only some patients are susceptible to renal disease in diabetes, and provides
strong evidence that genetic susceptibility combined with the
cumulative effect of hyperglycaemia is necessary. A family history of diabetic kidney disease, or indeed a parental history of
cardiovascular disease or hypertension, increases the risk of
diabetic kidney disease in the individual with type 1 diabetes.
In type 2 diabetes, classical diabetic kidney disease also occurs, but in an older population other kidney diseases, particularly hypertensive ischaemic damage, are more common and
kidney disease in those with type 2 diabetes may have atypical
features.
Classical diabetic kidney disease in type 2 diabetes often occurs
in younger individuals, and may be accompanied by retinopathy
and progression from microalbuminuria to overt proteinuria.
In older individuals with type 2 diabetes, retinopathy and
proteinuria may be absent or minimal. Although other renal
diseases should be considered and excluded, the kidney lesion is
often related to hypertension or glomerular ischaemia and its
treatment is largely the same.
The cumulative risk of nephropathy in type 2 diabetes varies
with ethnic origin, ranging from 25% in those of European origin
to about 50% in other ethnic groups (e.g. Afro-Caribbeans, AsianIndians, Japanese). Those of African, Caribbean or Asian-Indian
origin may develop type 2 diabetes more commonly and at a
younger age.
Type 2 diabetes is more common than type 1, and in some
areas the number of patients with type 2 diabetes requiring renal
replacement therapy (dialysis or transplantation) exceeds that in
type 1. Worsening glycaemic control, higher blood pressure,
smoking and adverse lipid profile are all risk factors for diabetic
nephropathy in both type 1 and type 2 diseases.

Stephen Thomas
Janaka Karalliedde

Abstract
Diabetic nephropathy is a major underlying cause of morbidity and mortality in both type 1 and type 2 diabetes mellitus, giving rise principally
to cardiovascular disease, in particular heart failure, the incidence of
which is about 15-fold greater in patients with diabetic kidney disease.
The all-cause mortality in patients with diabetic nephropathy is nearly
20e40 times higher than in patients without nephropathy. Many patients
with diabetes, in particular type 2 diabetes, and renal impairment die
from cardiovascular disease well before they progress to end-stage
renal disease. Nevertheless, diabetic nephropathy is the most common
cause of end-stage renal disease worldwide. Suboptimal glycaemic control and a higher blood pressure are particularly important risk factors
for the development of diabetic nephropathy. Over a lifetime, diabetic nephropathy occurs in approximately 30e35% of patients with type 1 and
type 2 diabetes. The disease can be detected in most cases many years
before the development of advanced renal failure through the detection
of raised urinary albumin excretion e microalbuminuria. Early detection
allows time for the intensive treatment of glycaemic control, blood pressure and other cardiovascular risk factors, such as lipids, in order to
reduce the morbidity and mortality.

Keywords diabetic nephropathy; end-stage renal failure; glycaemic

control; microalbuminuria

Definition and detection

By convention, diabetic nephropathy is defined as the appearance
of persistent clinical albuminuria (albumin excretion rate (AER)
>300 mg/24 hours) in an individual with diabetes mellitus for
more than 5 years and concomitant retinopathy, in the absence of
urinary tract infection (UTI), other renal diseases or heart failure.
This process is often associated with increasing blood pressure.
After initial stabilization of metabolic control, all patients should
be screened for albuminuria at least once per year. Screening for
diabetic nephropathy is usually performed by measuring the
albumin:creatinine ratio (ACR) in a single early-morning urine
sample. Values of 2.5 mg/mmol or more in men, or 3.5 mg/mmol
or more in women are abnormal. An elevated ACR should be
confirmed before the diagnosis of nephropathy is established.

Clinical course
Diabetic nephropathy is a multi-stage condition that takes several
years to become clinically overt (Figure 1). At the onset of diabetes, there are usually changes in renal function, such as
glomerular hyperfiltration, increased renal blood flow and hypertrophy of the kidney. Most of these changes can be reversed at
an early stage by good glycaemic control, but in many patients
they persist and may be important in the later development of
clinical nephropathy.
Microalbuminuria
In the past, the definition of diabetic nephropathy was dictated
by the lower limit of detection of available urinary albumin assays. Development of more sensitive assays enabled detection of
previously undetectable sub-clinical increases in urinary albumin
excretion, which were termed microalbuminuria. This is the
first indication of diabetic nephropathy, and is defined as a
persistent increase (in at least two of three consecutive, urine
specimens) in AER to 20e200 mg/minute (30e300 mg/day). It
may be detected 1 year after the onset of diabetes in postpubertal patients with type 1 disease, and at diagnosis in type
2. There is significant structural glomerular disease even at this
early phase, and the glomerular filtration rate (GFR) starts to

Epidemiology
In type 1 diabetes, the most common cause of kidney damage is
classical diabetic nephropathy. Kidney disease is relatively rare
in the first 5e10 years, but the incidence increases rapidly over
the next 10 years, to a peak of about 3% per year after 15 years. It

Stephen Thomas MRCP is Consultant Physician at Guys and St Thomas

Foundation Trust, London, UK. Competing interests: none declared.
Janaka Karalliedde MRCP is Consultant Physician at Guys and St
Thomas Foundation Trust, London, UK. Competing interests: none
declared.

MEDICINE 43:1

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OTHER COMPLICATIONS OF DIABETES

Diabetic nephropathy is associated with

cardiovascular mortality in type 2 diabetes

Natural history of diabetic nephropathy

Glomerular filtration rate

Normal albumin excretion

1.4%

2.0%
Serum creatinine
Microalbuminuria

End-stage renal failure

Proteinuria 200 g/minute
Microalbuminuria 20 < 200 g/minute

2.8%
Death
Overt proteinuria

10

3.0%

15

20

4.6%

2.3%

Duration of diabetes (years)

Elevated plasma creatinine
or renal replacement therapy

Figure 1

decline during the phase of microalbuminuria, though it may

remain within the normal range until the AER approaches 200
mg/minute (300 mg/day). In healthy adults the normal AER
ranges between 1.5 and 20 mg/minute with a median value
around 6.5 mg/minute. ACR correlates closely with AER and the
relative constancy of urine creatinine excretion corrects to an
extent for variability of urine albumin.1
Long-term studies in type 1 diabetes have demonstrated that
microalbuminuria is associated with a 20-fold risk of progression
to overt renal disease compared with normoalbuminuria.1e3
Without intervention, microalbuminuria progresses to clinical
albuminuria over approximately 10e15 years. In studies that
followed patients from the late 1960s to early 1980s, approximately 80% of patients with type 1 diabetes and microalbuminuria developed persistent clinical albuminuria. However,
more recent studies suggest that the natural history has become
more variable: in around 20% microalbuminuria progresses towards clinical albuminuria over 5e9 years, whereas in 50% it
remains in the microalbuminuric range, and in approximately
30% of patients AER reverts back towards the normal range (<30
mg/minute).1 This change most likely reflects advances and improvements in medical care with ever more stringent glycaemic,
lipid and blood pressure control as well as the widespread use in
recent years of agents such as ACE inhibitors and angiotensin II
receptor blockers (ARB). Microalbuminuria is also strongly predictive of death from cardiovascular disease, particularly in older
patients with type 2 diabetes (Figure 2). Furthermore, in those
with type 1 diabetes who develop microalbuminuria after a very
long duration of disease, it is a more consistent predictor of
cardiovascular than of progressive renal disease.
Microalbuminuria is also associated with retinopathy, peripheral vascular disease and neuropathy.
In type 1 diabetes, blood pressure increases in patients with
microalbuminuria (Figure 3), and lipid abnormalities, including
increased low-density lipoprotein cholesterol (LDL-C), total triglycerides and apolipoprotein B, and reduced high-density lipoprotein (subclass 2) cholesterol, develop. These progressive
abnormalities are seen in both type 1 and type 2 diabetes, though

MEDICINE 43:1

19.2%

Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR. Development
and progression of nephropathy in type 2 diabetes: the United Kingdom
Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003;63:22532.
PubMed PMID: 12472787. Epub 2002/12/11. eng.

Figure 2

in the latter they often occur on a background of pre-existing

hypertension and dyslipidaemia. Microalbuminuria is also associated with generalized endothelial dysfunction in both type 1
and type 2 diabetes.
Persistent albuminuria
An increase in AER to a persistent value of more than 200 mg/
minute (>300 mg/day) marks the onset of clinically defined overt
diabetic nephropathy and is a harbinger of renal failure and cardiovascular complications in both types of diabetes. Blood pressure rises progressively in this phase in both type 1 and type 2
diabetes.
Over time, the protein loss may increase to more than 3e4 g/
day and occasionally lead to nephrotic syndrome with hypoalbuminaemia, hypercholesterolaemia and peripheral oedema.
As proteinuria rises, the urine protein:creatinine ratio (PCR) is
measured in preference to the ACR as the proteinuria becomes
less selective. The heavier the proteinuria, particularly if this
exceeds 2e3 g/day, the more rapid is the loss of GFR. Lipid
disturbances and atherosclerotic complications are prominent in
this phase. In those patients who develop persistent clinical
albuminuria, GFR gradually declines in a linear fashion; the rate
of decline (average 4.5 ml/minute/year) is variable and depends
on how well promoters of progression, such as hypertension and
degree of albuminuria, are controlled, and on individual
response to treatment. Although the rate fall in GFR varies from
patient to patient, it remains relatively constant for each individual patient. Since the advent of early and intensive treatment
of hypertension, the time from the onset of clinical albuminuria
to death has virtually trebled from 7 to 21 years.1

21

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OTHER COMPLICATIONS OF DIABETES

 eGFR often greater than 90 ml/minute and always greater

than 60 ml/minute.

HbA and mean arterial pressure are raised in

microalbuminuria in type 1 diabetes

Screening tests (Figure 4)

All patients with diabetes over the age of 12 years should have
their ACR, blood pressure and eGFR measured at least once per
year.4 Measurement of ACR in a mid-stream, first-morning urine
sample is a reliable screening method. Alternatively, semiquantitative dipstick tests (developed to determine albumin
concentration in the microalbuminuria range) may be used as
first-line screening.
It should be remembered that heavy exercise, UTI, acute
illness or cardiac failure can increase ACR/AER transiently.

Albumin excretion rate

(g/minute)

60
50
40
30
20
10

Mean arterial pressure

(mmHg)

0
120

Confirmation
If ACR is raised, the test should be repeated. If confirmed in
two of three urine samples tested within 6e12 weeks, this
establishes the presence of microalbuminuria. The implied
kidney disease can be staged using eGFR (>90 ml/minute is
stage 1; 60e90 ml/minute is stage 2). If the eGFR already
confirms stage 3 kidney disease (eGFR <60 ml/minute), the
presence of microalbuminuria or proteinuria has prognostic
significance, indicating a higher risk of renal progression and
cardiovascular disease.
Progression of the albuminuria should be checked, usually by
repeated measurements of ACR or, as the proteinuria rises and
becomes less selective, PCR in an early-morning urine sample.
Occasionally, at higher levels of proteinuria, timed collections are
performed as the greater the degree of albuminuria the higher is
the renal and cardiovascular risk.
In these patients, regular and more frequent check-ups should
be undertaken to assess blood pressure, glycaemic control,
serum lipids, and serum creatinine or eGFR.

110

100

90

80
13

HbA (%)

12
11
10
9
8
0

12

24

36

48

60

72

84

96

Months
Progressors

Non-progressors

Screening for renal complications in diabetes

Predictors of the development of microalbuminuria in patients with Type 1

diabetes mellitus: a seven-year prospective study. The Microalbuminuria
Collaborative Study Group. Diabet Med. 1999;16:91825. PubMed
PMID: 10588521.

Annual dipstick urinalysis

Annual albumin:creatinine ratio
Annual eGFR

Figure 3

Positive
dipstick
protein

Diabetic retinopathy
Diabetic retinopathy usually accompanies persistent proteinuria,
and its absence should alert health professionals to the possibility
of a non-diabetic cause of the proteinuria. It should be remembered
that proteinuria may have a non-diabetic cause. The absence of
other microvascular complications, the presence of nephrotic
syndrome and unusually fast progression are features that should
raise suspicion of non-diabetic kidney disease.

Positive dipstick
protein confirmed
x 2 (proteinuria)

eGFR <45 ml/minute

or fall in eGFR
>5 ml/minute/year
Refer/discuss with
diabetes/renal clinic

Confirm x 2 within
36 months
(microalbuminuria)

Start renin angiotensin system inhibitor

Screen for microvascular and macrovascular disease
Refer to diabetes clinic as appropriate

Diagnosis
Normal values are:
 urinary albumin concentration less than 20 mg/litre
 ACR less than 2.5 mg/mmol in men, less than 3.5 mg/
mmol in women
 AER less than 20 mg/minute (<30 mg/day)

MEDICINE 43:1

Albumin:creatinine
ratio
>2.5 mg/mol men
>3.5 mg/mol women

eGFR, estimated glomerular filtration rate.

Figure 4

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OTHER COMPLICATIONS OF DIABETES

Management

anti-proteinuric than other classes of agents. Overall, these

agents reduce renal and cardiovascular risks, as well as disease
progression. The evidence base is different in type 1 and type 2
diabetes but the benefits appear similar in both.
First-line treatment in those with microalbuminuria or diabetic nephropathy in both type 1 and type 2 diabetes is usually an
angiotensin converting-enzyme (ACE) inhibitor, though some
authorities favour an angiotensin-receptor blocker (ARB) in
those with type 2 diabetes in view of the greater evidence base.
Combination of diuretic or a calcium channel blocker with ACE
inhibitor or ARB is often required to achieve blood pressure
control. Recent evidence has shown that a combination of an
ACE inhibitor and an ARB leads to a higher incidence of hyperkalaemia and acute kidney injury than respective monotherapies
with no additional beneficial effect upon progression of renal
disease or CVD.8 After starting an ACE inhibitor or an ARB,
serum creatinine and potassium should be closely monitored (in
the first 2e3 weeks), especially in patients with peripheral
vascular disease, because of the possible co-existence of renal
artery stenosis, which may result in a significant rise in serum
creatinine more than 30% from baseline. Hyperkalaemia may be
a particular concern in those with hyporeninaemic pseudohypoaldosteronism e type IV renal tubular acidosis e especially in
those with type 1 diabetes.
More than one anti-hypertensive agent is likely to be required.
In type 2 diabetes with microalbuminuria, there is evidence that
the combination of a low-dose thiazide with a renineangiotensin
system inhibitor may be beneficial.9,10

Glycaemic control
Good glycaemic control can prevent diabetic nephropathy in
both type 1 and type 2 diabetes and there is evidence that, once
microalbuminuria has developed, good glycaemic control slows
the progression of the kidney lesion.
In type 1 diabetes, improved blood glucose control and
intensified insulin treatment reduce histological worsening of
glomerulopathy in those with microalbuminuria, and worse
glycaemic control is associated with a faster decline in GFR.
There are no conclusive data on the effects of good glycaemic
control on the progression of established kidney disease in type 2
diabetes, but this should also be achieved and maintained.
Once renal function is impaired, renally excreted sulphonylureas, such as glibenclamide, glipizide and glimepiride, must
not be used.
Guidelines for metformin vary. In advanced renal failure
metformin carries the risk of potentially life-threatening lactic
acidosis. Nowadays, this happens mostly in the context of acute
kidney injury in a patient with chronic kidney disease. The risk/
benefit ratio of using the drug should be considered carefully in
all those with an eGFR less than 45 ml/minute, particularly if
they have a previous history of acute kidney injury5 Having
assessed the risk, metformin may be continued provided eGFR
does not fall below 30 ml/minute. It is important to consider
temporary discontinuation of the drug in patients with symptoms, such as nausea and diarrhoea or vomiting, which can lead
to dehydration and an increased risk of acute kidney injury.
Glitazones, inhibitors of renal sodium glucose co-transporter2 (SGLT-2) and injectable incretin therapy are not currently
licensed for use if eGFR is below 30e45 ml/minute. There have
been sporadic reports of an acute kidney injury with injectable
incretins.6 Gliptins that are renally excreted require dose reduction when GFR falls below 60 ml/minute. Insulin clearance
through the kidney starts to fall when eGFR is less than 30 ml/
minute (stage 4 kidney disease), and the risk of hypoglycaemia
increases progressively. This may be compounded by reduced
appetite and worsening nutritional status.

Serum lipids
From the onset of microalbuminuria, cholesterol and triglycerides may be elevated in both type 1 and type 2 diabetes.
Statin therapy should be considered for all patients with diabetic
nephropathy.
Dietary restriction, weight reduction and improved metabolic
control should be considered in all cases. In type 2 diabetes,
statin therapy should be used to reduce total cholesterol to less
than 4.0 mmol/litre and the LDL-C to less than 2.0 mmol/litre in
the patient with diabetic nephropathy, and it seems reasonable to
extrapolate this to type 1 diabetes with microalbuminuria/overt
nephropathy, given its association with premature cardiovascular disease.
Smoking is associated with the development and progression
of diabetic nephropathy and with cardiovascular disease, and
should be discouraged in all patients.
Protein restriction is controversial, but has been shown to
have a beneficial effect in type 1 diabetes with overt nephropathy. Reduction in animal protein intake to 0.6e0.7 g/kg/day
should be considered. Replacement of animal by vegetable protein sources may also be considered, because vegetable protein
seems to be less damaging to the kidney. An expert nutritionist
should supervise all such treatment, and care should be taken to
minimize any potentially detrimental effects. No prospective data
are available for type 2 diabetes.

Blood pressure
Raised blood pressure has particularly damaging consequences
for the kidney, heart and retina. Current recommendations suggest that blood pressure should be lowered to 130/80 mmHg or
less in those with microalbuminuria or overt diabetic nephropathy (although in younger patients, especially those with type 1
diabetes, sustained readings <125/80 mmHg are desirable to
reduce proteinuria further).4,5,7 Non-pharmacological interventions such as dietary and lifestyle changes (e.g. restriction
of salt and alcohol intake, weight reduction, increased exercise)
are important, though most patients require anti-hypertensive
agents (often more than one) to achieve target blood pressures.
Tighter blood pressure control in the elderly or those with evidence of heart disease may be associated with increased risk, and
lowering systolic blood pressure below 120 mmHg in these individuals affords no extra benefit.
First-line treatment is usually with an inhibitor of the renin
eangiotensin system. These agents are effective blood pressurelowering agents in those with diabetic nephropathy and are more

MEDICINE 43:1

Associated complications
Microvascular and macrovascular complications may progress
rapidly in patients with clinical albuminuria. Retinopathy, neuropathy and atherosclerotic complications should be monitored more

23

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OTHER COMPLICATIONS OF DIABETES

3 Karalliedde J, Viberti G. Proteinuria in diabetes: bystander or pathway

to cardiorenal disease? J Am Soc Nephrol 2010; 21: 2020e7. PubMed
PMID: ISI:000285533300006. English.
4 American Diabetes A. Executive summary: standards of medical care
in diabetese2014. Diabetes Care 2014; 37(suppl 1): S5e13. PubMed
PMID: 24357214.
5 Home P, Mant J, Diaz J, Turner C. Management of type 2 diabetes:
summary of updated NICE guidance. Br Med J 2008; 336: 1306e8.
PubMed PMID: 18535074. Pubmed Central PMCID: 2413390. Epub
2008/06/07. eng.
6 Filippatos TD, Elisaf MS. Effects of glucagon-like peptide-1
receptor agonists on renal function. World J Diabetes 2013; 4:
190e201. PubMed PMID: 24147203. Pubmed Central PMCID:
3797884.
7 Executive summary: standards of medical care in diabetese2010.
Diabetes Care 2010; 33(suppl 1): S4e10. PubMed PMID:
20042774. Pubmed Central PMCID: 2797389. Epub 2010/01/29.
eng.
8 Messerli FH. The sudden demise of dual renin-angiotensin system
blockade or the soft science of the surrogate end point. J Am Coll
Cardiol 2009; 53: 468e70. PubMed PMID: 19195602. Epub
2009/02/07. eng.
9 Mogensen CE, Viberti G, Halimi S, et al. Effect of low-dose
perindopril/indapamide on albuminuria in diabetes: preterax
in albuminuria regression: PREMIER. Hypertension 2003; 41:
1063e71. PubMed PMID: 12654706.
10 Karalliedde J, Viberti G. Evidence for renoprotection by blockade of
the renin-angiotensin-aldosterone system in hypertension and diabetes. J Hum Hypertens 2006; 20: 239e53. PubMed PMID:
16452996. Epub 2006/02/03. eng.
11 [CG182] Ng. Chronic kidney disease: early identification and management of chronic kidney disease in adults in primary and secondary care: NICE. 2014. Available from: http://www.nice.org.uk/
guidance/CG182/chapter/1-Recommendations#referral-criteria.

often and any abnormalities treated promptly. Anaemia is common

in diabetic nephropathy and may occur at an earlier stage than in
other kidney diseases, particularly in type 1 diabetes, and in women.
Nephrological referral
Current guidelines suggest joint treatment by diabetes and renal
specialists in patients whose eGFR is lower than 30 ml/minute,
where the rate of progression is unduly fast (sustained decrease
in GFR of 25% or more, and a change in GFR category or sustained decrease in GFR of 15 ml/minute/1.73 m2 or more within
12 month) and where atypical kidney disease is suspected.11
Referral to a joint clinic may be necessary earlier for management of anaemia.
Late referral
Late referral (within 6 months of the need for renal replacement
therapy) is associated with higher mortality.
Stage 5 kidney disease e end-stage renal failure
The mode of therapy (dialysis or transplantation) in end-stage
renal failure depends on clinical judgement, and on local facilities and resources. Good glycaemic control is important for patients wellbeing before and during renal replacement therapy
and is associated with lower mortality.
In specialized centres, combined kidney and pancreas transplantation may be considered, mostly for type 1 diabetes.
In stage 5 kidney disease, interpretation of HbA1c, and
particularly fructosamine, may be less reliable, undermining
their use as indices for monitoring diabetes control. HbA1c is
probably preferable, but should be interpreted with caution as
reduced red cell life span may lead to lower values, especially in
those undergoing haemodialysis.
The outcome of renal replacement therapy remains poorer in
patients with diabetic chronic renal failure than in those with
non-diabetic disease. Furthermore, the associated vascular,
neuropathic and infective complications increase the socioeconomic costs of renal replacement therapy in diabetes.

FURTHER READING
Fineberg D, Jandeleit-Dahm KA, Cooper ME. Diabetic nephropathy:
diagnosis and treatment. Nat Rev Endocrinol 2013; 9: 713e23.
Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type
2 diabetes. N Engl J Med 2003; 348: 383e93.
Heart Outcomes Prevention Evaluation (HOPE) Study Investigators.
Effects of ramipril on cardiovascular and microvascular outcomes in
people with diabetes mellitus: results of the HOPE study and
MICROHOPE substudy. Lancet 2000; 355: 253e9.
Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensinconverting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993; 329: 1456e62.
Wolf G, Ritz E. Diabetic nephropathy in type 2 diabetes
prevention and patient management. J Am Soc Nephrol 2003; 14:
1396e405.
Bilous R. Microvascular disease: what does the UKPDS tell us about
diabetic nephropathy? Diabet Med 2008; 25(suppl 2): 25e9.
Microalbuminuria Collaborative Study Group. Predictors of the development of microalbuminuria in patients with type 1 diabetes mellitus: a
seven-year prospective study. Diabet Med 1999; 16: 918.
Practice Guideline for Diabetes and CKD: 2012 update http://www.kidney.
org/professionals/KDOQI/guidelines_diabetesUp/diabetes-ckd-update2012.pdf.

Pregnancy and proteinuria

Development of microalbuminuria or macroalbuminuria during
pregnancy in a woman with diabetes should alert the physician
to the risk of pre-eclampsia. Pregnancy is no longer contraindicated in women with diabetic proteinuria, but proteinuria
may increase during pregnancy and the risk of eclampsia is
increased. Pre-pregnancy counselling and planning is vital. The
risk of further loss of kidney function appears to be greatest in
those whose eGFR is less than 50 ml/minute at conception or in
whom proteinuria is present. Specialist renal pre-pregnancy
counselling may be advisable.
A

REFERENCES
1 Karalliedde J, Vibert GC. In: Davies MAS, ed. Diabetic nephropathy.
2nd edn. Oxford: Oxford University Press, August 2011.
2 Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H.
Microalbuminuria as a predictor of clinical nephropathy in insulindependent diabetes mellitus. Lancet 1982; 1: 1430e2. PubMed
PMID: 6123720.

MEDICINE 43:1

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2014 Elsevier Ltd. All rights reserved.

OTHER COMPLICATIONS OF DIABETES

Practice points
C

Diabetic nephropathy is associated with much higher cardiovascular risk

Diabetic nephropathy is characterized by abnormal urinary protein excretion with rising blood pressure and other microvascular
complications usually retinopathy

MEDICINE 43:1

C
C

25

Worsening glycaemic control, rising blood pressure, smoking,

higher low-density lipoprotein cholesterol and triglycerides and
family history of kidney/cardiovascular disease all increase the risk
of diabetic nephropathy
Different ethnic groups have different risks
Oral hypoglycaemic agents, especially metformin, should be used
with particular care in stage 3 kidney disease or worse

2014 Elsevier Ltd. All rights reserved.