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8/17/2019 Diabetic Nephropathy Baru
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DIABETIC NEPHROPATHY
BY
SUPARJO
09310217
University ! "#$#%#y#ti
B#nr '#()*n+
2013,201-
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CASEA 46-years old woman presents to the clinic for the first time, complaining of
decreased urinary output for 5 months with a foamy appearance. She also complain of
swelling in both leg and none bloody, non billious emesis a few times a wee . She was
diagnosed with diabetes !" years ago. And has been ta ing insulin for two years. She does
not chec her sugars at home because she does not li e to stic herself. #hen as ed about her
diet she states that she eats the best she can for what she can afford but often has $ery little
apetitte.
%he patient last saw her physician & months ago. And insulin her only medication. 'n
e(amination, the patients is an obese woman. )er temperature is ** + ,/ C0, her heart⁰ ⁰
!"&beats1min, her blood pressure is !*&1!"5 mm)g, her respiration is !* breaths1min, her
o(ygen saturation is *42 on room air. A head, ears, eyes, nose, throat )EE3%0 e(amination
re$eal periorbital edema. )er s in is hyperpigmented on both lower e(tremities. )er heart is
tachycardi with an S!, S/, S4, gallop ausculatated with no murmur or rub. #hen palpating
the hearts point of ma(imal impuls 0, it is lateral tp the left midcla$icular line. %here are
$esicular breath sound in both lungs throughout. )er nec re$eals no 7ugular $enous
distension and there are no carotid bruits. )er abdomen is non tender, with no bruits or
masses palpated. %he lower e(tremities re$eal piting pretibial edema with a pit reco$ery time
less than 4" second. 8aboratory studies in your office include a urinalysis showing hyaline
casts, 9 proteinuria, and glucose, but negati$e for etones. )er hemoglobin is !",* gr1dl and
her hematocryt is /2 with a mean corpuscullar $olume C:0 of &/, gr1dl.
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- >lood pressure = !*&1!"5 mm)g
- ?espiration = !* breaths1min
- '/ saturation = *42 on room air
- )EE3% = re$eals periorbital edema
- S in = hyperpigmented on both lower e(tremities.
- )eart = tachycardic with S!, S/, S4 gallop auscultated with no murmur or rub
- alpating = lateral to the left midcla$icular line
- 8ung = $esicular breath sounds in both lungs throughout
- 3ec = no 7ugular $enous distension, no carotid bruits
- Abdomen = non tender, non bruits, no masses palpated
- E(tremities lower e(tremities = pitting edema, pit reco$ery time less than 4" seconds.
- @rinalysis = showing hyaline casts, 9 proteinuria, glucose, etones -0.
- )b = !",* g1d8
- )t = /2 with mean corpuscillar $olume C:0 of &/, g1d8
Di#+n se
Diabetic Nephropathy
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I4 De!initi n
;iabetic nephropathy is idney disease or damage that can occur in people
with diabetes . ;iabetic nephropathy ;30 is typically defined by
macroalbuminuria that is, a urinary albumin e(cretion of more than "" mg
in a /4-hour collection or macroalbuminuria and abnormal renal function as
represented by an abnormality in serum creatinine, calculated creatinine
clearance, or glomerular filtration rate B+?0. Clinically, diabetic nephropathy
is characteri ed by a progressi$e increase in proteinuria and decline in B+?,
hypertension, and a high ris of cardio$ascular morbidity and mortality.
;iabetic nephropathy nephropatia diabetica0, also nown as Dimmelstiel
#ilson syndrome, or nodular diabetic glomerulosclerosis and intercapillary
glomerulonephritis, is aprogressi$e idney disease caused
by angiopathy of capillaries in the idney glomeruli . t is characteri ed
by nephrotic syndrome and diffuse glomerulosclerosis. t is due to
longstanding diabetes mellitus , and is a prime indication for dialysis in many
#estern countries. t is classified as a micro$ascular complication of diabetes
II4 E)i&e(i $ +y
%he prognostic $alue of a small amount of albumin in urine for the de$elopment of
idney damage in patients with type ! or / ; was confirmed in the early !*&"Fs.
%his stage of idney damage was called the microalbuminuria stage or initial
nephropathy. Appro(imately /"- "2 of the patients de$elop microalbuminuria after
!5 years of disease duration and less than half de$elop real nephropathy. %he
European ;iabetes E@?'; A>0 rospecti$e Complications Study Broup and !&-
year ;anish study showed that the o$erall occurrence of microalbuminuria in patients
with type ! and / ; is !/.62 after . years0 and 2, respecti$ely. According to
http://www.nlm.nih.gov/medlineplus/ency/article/001214.htmhttp://en.wikipedia.org/wiki/Kidney_diseasehttp://en.wikipedia.org/wiki/Kidney_diseasehttp://en.wikipedia.org/wiki/Angiopathyhttp://en.wikipedia.org/wiki/Angiopathyhttp://en.wikipedia.org/wiki/Capillaryhttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Glomerulushttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Diabetes_mellitushttp://en.wikipedia.org/wiki/Dialysishttp://en.wikipedia.org/wiki/Dialysishttp://en.wikipedia.org/wiki/Dialysishttp://en.wikipedia.org/w/index.php?title=Microvascular&action=edit&redlink=1http://en.wikipedia.org/wiki/Kidney_diseasehttp://en.wikipedia.org/wiki/Angiopathyhttp://en.wikipedia.org/wiki/Capillaryhttp://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Glomerulushttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Diabetes_mellitushttp://en.wikipedia.org/wiki/Dialysishttp://en.wikipedia.org/w/index.php?title=Microvascular&action=edit&redlink=1http://www.nlm.nih.gov/medlineplus/ency/article/001214.htm
8/17/2019 Diabetic Nephropathy Baru
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the @nited Dingdom rospecti$e ;iabetes Study @D ;S0, the annual incidence of
microalbuminuria in patients with type / ; in Breat >ritain is /2 and the
pre$alence is /52 ten years after the diagnosis. roteinuria de$elops in
appro(imately !5-4"2 patients with type ! ; , usually after !5-/" years of ;
duration. n patients with type / ; , the pre$alence $aries between 52 and /"2 on
a$erage. ;iabetic nephropathy is more freGuent in African Americans, Asian
Americans, and 3ati$e Americans. n Caucasians, the progressi$e idney disease is
more freGuent in patients with type ! than type / ; , although its o$erall pre$alence
in the diabetic population is higher in patients with type / ; because this type of
; is more pre$alent. %he occurrence of diabetic nephropathy in ima ndians is
$ery interesting, indeed. According to a study published in !**", around 5"2 of ima
ndians with type / ; de$eloped nephropathy after /" years of the disease, and
!52 of them were already in the terminal stage of idney failure. n the @nited
States, the occurrence of diabetic nephropathy in patients beginning idney
replacement therapy doubled in the !**!-/""! period. +ortunately, the trend has been
decreasing, most li ely due to the better pre$ention and earlier diagnosis and
treatment of ; .
III4 Eti $ +y
Each idney is made of hundreds of thousands of small units called nephrons.
%hese structures filter your blood and help remo$e waste from your body.
n people with diabetes, the nephrons thic en and slowly become scarred o$er
time.
• %he idneys begin to lea and protein albumin0 passes into the urine.
•
%his damage can happen years before any symptoms begin.
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• %he e(act cause is un nown. )owe$er, idney damage is more li ely if
there is poor control of diabetes and high blood pressure.
n some cases, your family history may also play a role. 3ot e$eryone with
diabetes de$elops this idney problem. eople with diabetes who smo e, and
those with type ! diabetes that started before age /" ha$e a higher ris for
idney problems.
I54 Sy()t (
'ften, there are no symptoms as the idney damage starts and slowly gets
worse. Didney damage can begin 5 to !" years before symptoms start.
eople who ha$e more se$ere and long-term chronic0 idney disease may
ha$e symptoms such as=
• +atigue most of the time
• Beneral ill feeling
• )eadache
• 3ausea and $omiting
• oor appetite
• Swelling of the legs
http://www.nlm.nih.gov/medlineplus/ency/article/003089.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003024.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003117.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003104.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003089.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003024.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003117.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003104.htm
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54 P#t )%ysi $ +y
%he ey pathophysiologic e$ent in diabetic nephropathy is basement
membrane damage. #ith renal damage, there is progressi$e thic ening of the
basement membrane, pathologic change in mesangial and $ascular cells,
formation of ABEs, accumulation of polyols $ia the aldose reductase pathway,
and acti$ation of protein inase C. assage of macromolecules through the
basement membrane may also acti$ate inflammatory pathways that contribute
to the damage secondarily.
%he renal hemodynamic abnormality is similar in type ! and type / diabetes.
An early physiologic abnormality is glomerular hyperfiltration associated with
intraglomerular hypertension. %his is accompanied by the onset of
microalbuminuria, the first practical e$idence of renal in$ol$ement in
diabetes. %his is a critical time in the e$olution of diabetic renal disease, since
the greatest impact of treatment is to intercept this point in the otherwise
ine(orable downward path of renal function.
A clinically asymptomatic period of decline follows, with progression of
microalbuminuria " "" mg albumin per day0 to macroalbuminuria H ""
mg albumin per day0. 'nce o$ert nephropathy macroalbuminuria0 has
de$eloped, renal function falls at a significant but $ariable rate decline in
B+? of //" ml1min1year0. %he rate of decline depends on type of diabetes,
genetic predisposition, glycemic control, and, $ery importantly, blood
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pressure. )ypertension is the single most important cause of progression and
point of successful inter$ention in diabetic nephropathy. 8ater stages may also
be accompanied by clinically significant albuminuria, edema, and nephrotic
syndrome. E$entually, the characteristic clinical picture of renal failure
de$elops.
athogenesis of diabetic nephropathy is $ery complicated and results from the
interaction of hemodynamic and metabolic factors.
6$ (er*$#r %y)er !i$tr#ti n4 ncreased intraglomerular pressure and hyper
filtration as early changes in the de$elopment of diabetic nephropathy were
described by Stadler and Schmidt in !*5*. n the !* "Is, ogensen
emphasi ed that as many as 4"2 newly found ; cases had increased
glomerular filtration. Although the mechanism of de$elopment of hyper
filtration is not completely understood, se$eral factors ha$e been found to play
a role in its de$elopment.
H r( nes4 %he role of hormones was e(perimentally demonstrated in the
study by Serri et al, who showed that the infusion of somatostatin analogues
octreotide0 partly led to the decrease in hyperfiltration and idney si e. n
their study, glycemic regulation, plasma glucagon, and growth hormone le$els
remained unchanged, but the concentration of insulin-li e growth factor-!
B+-!0 decreased. athogenetic role of B+-! has not been completely
elucidated, but it is nown that e(ogenous administration of his hormone in
non-; patients leads to afferent arteriolar dilation and B+? increase, which
are the changes also obser$ed in initial diabetic nephropathy. %he identical
hemodynamic changes, along with the increase in idney si e, occur in
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connecti$e tissue growth factor C%B+0. n non-diabetic mice, the infusion of
early products of glycation up to the concentration seen in diabetic mice
increases the idneys blood flow, B+?, and intraglomerular pressure, which
are characteristic of untreated ; .
Hyperglycemia
%he e$idence from in $itro studies shows that hyperglycemia has a direct
effect on mesangial cell proliferation, matri( e(pansion, and glycosylation of
glomerular proteins.
He)#r#n#se E )ressi n4 %he regulation of heparanase e(pression plays an
important role in the pathogenesis of diabetic nephropathy. %he reduction in
heparin sulfate on the surface of endothelial cell changes the negati$e charge
of glycocaly( and conseGuently increases albumin permeability of the
glomerular filtration membrane.
Re# tive O y+en S)e ies4 ncreasing e$idence shows the importance of
reacti$e o(ygen species ?'S0 in the pathogenesis of diabetic nephropathy.
Although the ?'S production may be influenced by numerous mechanisms,
the most important role in their production is played by supero(ide produced
by glycolysis and o(idati$e phosphorylation in the mitochondria. ?'S acti$ate
all important pathogenetic mechanisms, such as increased production of
ABEs, increased glucose entry into the polyol pathway, and DC acti$ation.
n addition, ?'S directly damage endothelial glycocaly(, which leads to
albuminuria without the concurrent damage to the B> itself.
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Pr renin4 ncreased serum prorenin plays a role in the de$elopment of
diabetic nephropathy in children and adolescents. rorenin binds to a specific
tissue receptor, leading to the acti$ation of the signal pathway of mitogen-
acti$ating protein inases A D0, which potentiate the de$elopment of
idney damage. @sing an e(perimental model of diabetic nephropathy,
chihara et al. indicated a possible role of prorenin in the de$elopment of
diabetic nephropathy. n their study, a prolonged prorenin receptor bloc ade
cancelled the acti$ation of A D, which pre$ented the de$elopment of
diabetic nephropathy despite the increased acti$ity of angiotensine .
Cyt 8ines #n& 6r /t% # t rs4 )yperglycemia stimulates increased
e(pression of different growth factors and acti$ation of cyto ines, which
o$erall contributes to further idney damage. n the idney biopsy samples
from patients with type / ; , a significant increase in platelet deri$ed growth
factor ;B+0 e(pression was found. oreo$er, the site of e(pression of this
factor is ad7acent to the areas of interstitial fibrosis, which is important in the
pathogenesis of fibrosis in idney in7ury. )yperglycemia also increases the
glomerular e(pression of %B+-betaJ matri( proteins are specifically stimulated
by this growth factor. +urthermore, the e(pression of bone morphogenic
protein > - 0 in ; is decreased, and the e(pression of profibrinogenic
%B+-beta is increased.
Ne)%rine E )ressi n4 3ephrine is a transmembrane protein, the main
structural element in slit diaphragm and as such, it is important for the
maintenance of filtration membrane integrity. ore recent studies ha$e shown
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the association between the decreased e(pression of nephrine and albuminuria
progression in the model of human diabetic nephropathy.
5I4 Ris8 # t r
%here are se$eral ris factors for the de$elopment of diabetic nephropathy.
%hey can be di$ided into those that cannot be altered genetic factors, age, and
race0 and those that can and must be changed hyperglycemia, hypertension,
dyslipidemia, and B+?0
6eneti Pre&is) siti n4 Benetic predisposition substantially determines the
occurrence and se$erity of diabetic nephropathy. %he li eliness of diabetic
nephropathy is higher in siblings and children of parents with diabetic
nephropathy, independently of the type of ; . %here is a !42 probability for
a child of the parents without proteinuria to de$elop clinical proteinuria, / 2
probabilities in cases where one of the parents has proteinuria, and 462
probability in case that both parents ha$e proteinuria. %his increased ris
cannot be e(plained by the duration of ; , increased blood pressure or
gycemic regulation. )owe$er, genetic predisposition for e(cessi$e salt inta e
and arterial hypertension could play a role. Although li eliness of
chromosomes , , !&, and /" to be associated with diabetic nephropathy is
relati$ely high, we still cannot confirm the role of particular predisposing
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genetic determinants due to inconsistent results of the studies of genetic
factors important in the de$elopment of this disease.
R# e4 %he incidence of diabetic nephropathy is increased in African American,
e(ican American, and Asian ndian ethnic groups. 'ccurrence and se$erity
of the disease are higher in >lac s - to 6-fold in comparison with
Caucasians0, American e(icans, and especially in ima ndians in the 3orth
#est part of the @nited States. %his obser$ation in genetically incongruent
populations suggests that socioeconomic factors, such as nutrition and poor
control of glycemia, blood pressure, and body weight, play the ey role.
A+e4 n patients with type / ; , age and duration of ; increase the ris for
albuminuria. n the population study of !5&6 ima ndians with type / ; ,
sub7ects diagnosed with ; before age /" had a higher ris of de$eloping
terminal idney failure /5 $s. 5 patients in !""" incident patients0. According
to S$ensson et al. the ris of terminal idney failure in patients with type !
; was low if the disease was diagnosed by the age of 5.
In re#se& B$ & Press*re4 %here is a high pre$alence rate of hypertension in
patients with type ! ; 4"20 and type / ; "20, e$en before
albuminuria can be found. E$idence from se$eral large clinical studies
@D ;S, A;:A3CE0 indicates a causal relationship between the increased
arterial pressure and diabetic nephropathy. oreo$er, at least three factors
ha$e been shown to contribute to the de$elopment of increased arterial
pressure in this metabolic disorder including hyperinsulinemia, e(cessi$e
e(tracellular fluid $olume, and increased arterial rigidity. )yperinsulinemia
contributes to the de$elopment of increased arterial pressure $ia insulin
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resistance in type / ; or $ia administration of insulin per se. ?anderee et al.
study in &" patients with type / ; who started treatment with e(ogenous
insulin showed an increase in their blood pressure from ! /1&! mm )g to
!4*1&* mm )g K5&L. %his hypertensi$e response, although not reported in all
clinical studies, is most li ely mediated by weight gain combined with pro-
hypertensi$e effect of insulin. )yperinsulinemia could be the lin between
o$erweight and increased blood pressure in patients with or without ; , since
it increases sympathetic acti$ity and retention of sodium in the idneys.
Sodium and water retention are induced by insulin itself, while the increased
filtration of glucose is induced by hyperglycemia. %he e(cess filtered glucose
is reabsorbed as long as there is a moderate hyperglycemia0 in the pro(imal
tubule $ia sodium-glucose co-transport, which concurrently leads to the
increase in sodium reabsorption. Sodium reabsorption increases blood
pressure, which may be pre$ented and regulated by salt-free diet. atients with
; ha$e increased arterial stiffness, which de$elops due to the increased
glycation of proteins and conseGuent de$elopment of arteriosclerosis.
;ecreased arterial elasticity in patients with glucose intolerance or ;
contributes to the increased systolic pressure as an independent mortality ris
factor.
6$ (er*$#r i$tr#ti n R#te4 ncreased B+? at diagnosis is a ris factor for
the de$elopment of diabetic nephropathy. n appro(imately half of the patients
with type ! ; lasting up to fi$e years, B+? $alue is appro(imately /5-5"2
abo$e normal range. %hese patients ha$e a higher ris of de$eloping diabetic
nephropathy. ;ynamics of structural and hemodynamic changes is influenced
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by increased intraglomerular pressure, with the resulting glomerular
hyperfiltration and hypertrophy and damage to the endothelial wall. Strict
glycemic control, limited protein inta e, and blood pressure control may slow
down the progress of renal disease in type ! ; . %he situation with type /
; is somewhat different. ore than 452 of patients with type / ; at
diagnosis ha$e B+? that is two standard de$iations higher than that in their
age-matched no-; or o$erweight controls K6 L. Branted, the hyper filtration
rate !! -! m81min on a$erage0 is lower than that in type ! ; . atients
with type / ; are older and, therefore, ha$e greater li elihood of de$eloping
atherosclerotic $ascular changes that influence B+? and glomerular si e. %he
role of intraglomerular hypertension in the pathogenesis of diabetic
nephropathy e(plains why systemic hypertension is such an important ris
factor for the de$elopment of this idney disease. Studies on animal models
showed that ; is associated with damage of renal autoregulation. As a
result, increased blood pressure does not induce the e(pected $asoconstriction
in the afferent arteriole, which would reduce the influence of systemic
hypertension on intraglomerular pressure.
6$y e(i Re+*$#ti n4 ;iabetic nephropathy often de$elops in patients with
poor glycemic control. %he degree of glycemic control is an important
predictor of terminal idney failure. n Drolews i et alIs study, the pre$alence
of terminal idney failure was 62 in patients with the worst glycemic control
in comparison with *2 in the group with well-controlled glycaemia. t is
generally accepted that the degree of glycemic control is a $ery important ris
factor for the de$elopment diabetic nephropathy.
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Over/ei+%t4 )igh body mass inde( > 0 increases the ris of de$elopment
of chronic idney disease in patients with ; . +urthermore, adeGuate diet and
reduction in body weight decrease proteinuria and impro$e idney function in
these patients. %he role of o$erweight as a ris factor for diabetic nephropathy
independent of ; and glycemic control0 has not been clearly confirmed.
S( 8in+4 Although recent studies ha$e shown the association between
smo ing and progression of diabetic nephropathy, a large prospecti$e study by
)o$ind et al. did not confirm the association between smo ing and decreased
B+? rate in patients with ; with or without ACE therapy.
Or#$ C ntr# e)ti n4 Ahmed et al. showed the association between the use of
oral contracepti$es and de$elopment of diabetic nephropathy. Each of the
abo$e-described factors increases the ris of diabetic nephropathy, but none is
predicti$e enough for the de$elopment of diabetic nephropathy in an
indi$idual patient.
5II4 Investi+#ti n
Monitoring of renal function
B+? is the best parameter of o$erall idney function and should be measured
or estimated in micro- and macroalbuminuric diabetic patients. n
microalbuminuric patients, B+? may remain stable, but a subset of patients
has shown a rapid decline in B+? le$els. n type ! macroalbuminuric patients,
B+? declines about !./ ml M min N! M monthN! without therapeutic inter$entions.
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n patients with type / diabetes, B+? decline is more $ariable. 'ne study
reported a mean decline of ∼".5 ml M minN! M monthN!, although in some
patients B+? may remain stable for long periods. atients with a more rapid
B+? decline usually ha$e more ad$anced diabetic glomerulopathy and worse
metabolic control.
atients should be referred to a nephrologist for e$aluation and comanagement
when B+? reaches " ml M min N! M !. mN/ , since there is e$idence that
nephrologist care may impro$e morbidity and mortality when patients enter
renal replacement therapy.
Urine dipstick analysis
%his is a $ery cheap, Guic and easy way to detect o$ert proteinuria and
therefore should be performed at e$ery annual re$iew. n addition, if pro$ides
information on whether there is li ely to be any urinary tract infection
important to e(clude as a cause of proteinuria0 and haematuria. )aematuria is
not a normal feature of diabetic nephropathy and its presence should alert the
physician to the possibility of an alternati$e diagnosis.
Urinary albumin: creatinine ratio
%he ablumin=creatinine ratio AC?0 is a way of detecting proteinuria before it
becomes apparent on dipstic testing. t is performed on a spot urine sample
and therefore dispenses with the necessity to perform a /4 hr urine collection.
:alues of less than three are normal and greater than three, especially if
persistent, indicate early nephropathy so long as other potential causes such
as urinary tract infection ha$e been e(cluded0.
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Renal ultrasound scan
Assessing renal si e and ruling out obstruction or other structural lesions are
important steps in ma ing a diagnosis of diabetic nephropathy.
What other investigations should be arranged?
!. @rinalysis to screen for haematuria and if haematuria is present in the
absence of infection0 then urinary microscopy should be performed to loo for
other features of acti$e sediment such as casts. f these are present, they
indicate a glomerular lesion such as glomerulonephritis.
/. Consideration should be gi$en to reGuesting other blood tests such as
protein strip, immunoglobulins, complement le$els, C? , ES?, calcium and
auto-antibodies if there are clinical indications to do these.
5III4 Tre#t(ent
Se$!: #re4
mportant treatments for idney disease are tight control of blood glucose and
blood pressure. >lood pressure has a dramatic effect on the rate at which the
disease progresses. E$en a mild rise in blood pressure can Guic ly ma e
idney disease worsen. +our ways to lower your blood pressure are losing
weight, eating less salt, a$oiding alcohol and tobacco, and getting regular
e(ercise.
Dr*+s
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#hen these methods fail, certain medicines may be able to lower blood
pressure. %here are se$eral inds of blood pressure drugs, howe$er, not all are
eGually good for people with diabetes. Some raise blood sugar le$els or mas
some of the symptoms of low blood sugar. ;octors usually prefer people with
diabetes to ta e blood pressure drugs called ACE inhibitors.
ACE inhibitors are recommended for most people with diabetes, high blood
pressure and idney disease. ?ecent studies suggest that ACE inhibitors,
which include captopril and enalapril, slow idney disease in addition to
lowering blood pressure. n fact, these drugs are helpful e$en in people who
do not ha$e high blood pressure.
Diet
Another treatment some doctors use with macroalbuminuria is a low-protein
diet. rotein seems to increase how hard the idneys must wor . A low-protein
diet can decrease protein loss in the urine and increase protein le$els in the
blood. 3e$er start a low-protein diet without tal ing to your health care team.
Stri t 6$y e(i C ntr $ 4 %he effect of strict glycemic control depends on the
; stage in which it was started and conseGuent normali ation of glucose
metabolism. ntensified insulin therapy has the following effects on the
idney=
a. t partly decreases glomerular hypertrophy and hyperfiltration in fasting
state and after protein-rich meal0, both of which are important ris factors for
permanent glomerular damage.
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b. t postpones the de$elopment of albuminuria K& L. ntensified insulin
therapy that eeps glucose $alues within normal ranges decreases the
de$elopment or progress of diabetic nephropathy.
c. t stabili es or decreases the elimination of proteins in patients with
pronounced proteinuria. %his effect is not apparent in patients who are not
relati$ely normogycemic during two years. +urthermore, re-established
normoglycemia after combined idney and pancreas transplantation in patients
with type ! ; has pre$enti$e effects on recurrence of nephropathy in idney
transplant.
d. t slows down the progress of idney disease in case of already de$eloped
proteinuria confirmed by semiGuantitati$e method test strip0.
e. t reduces mesangial cell number and mesangial matri(.
f. n some patients, the thic ness of glomerular and tubular basement
membranes and mesangial cell number become normal and glomerular
nodules disappear.
g. %he progress of tubular atrophy is slowed down.
Stri t B$ & Press*re C ntr $4 Strict blood pressure control is important in
the pre$ention of progress of diabetic nephropathy and other complications in
patients with type / ; . %he optimum lower range of systolic blood pressure
is not clearly defined. According to the @D ;S study, a reduction in systolic
blood pressure by !" mm )g decreases the ris of de$elopment of diabetic
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complications by !/2J the ris is the lowest where systolic blood pressur
$alues are below !/" mm )g. %he rbesartan ;iabetic 3ephropathy %rial
showed that decreasing systolic blood pressure to the lower limit $alue of !/"
mm )g reduces the ris of cardio$ascular mortality and heart failure but not
of myocardial infarction0 and the ris of double increase in serum creatinine or
progress to terminal idney failure. According to the current Buidelines on
Arterial )ypertension %reatment, the target blood pressure in patients with
; should be O! "1&" mm )g. Antihypertensi$e therapy may be started e$en
when blood pressure $alues are in the upper normal range. nhibition of
?enin-Angiotensin-Aldosterone System Angiotensin is the most effecti$e
factor of renin-angiotensin-aldosterone system ?AAS0, resulting from a range
of proteolytic reactions that begin with the con$ersion of angiotensinogen to
angiotensin through the catalytic action of renin +igure 0. ?AAS is directly
associated with blood pressure regulation, body fluid $olume, and $ascular
response to in7ury and inflammation. nappropriate acti$ation of this system
increases the blood pressure and has anti-inflammatory, prothrombotic, and
proatherogenic effects, which in the long run lead to irre$ersible damage of
target organs. Although aldosterone, renin, and end-products of angiotensin
degradation are also in$ol$ed in this process, ma7ority of the ?AAS effects on
target organs are mediated by angiotensin , which is present in the
bloodstream and tissues. Angiotensin , which is produced in the heart, brain,
and idneys through alternati$e pathways by inase and endopeptidase
acti$ity, is more effecti$e than angiotensin produced in the bloodstream.
Angiotensin binds to A%! i A%/ receptors. A%! receptor acti$ation is
responsible for $asoconstriction, release of aldosterone, $ascular remodeling,
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o(idati$e stress, and has anti-inflammatory, proatherogenic, and prothrombotic
effects. %he acti$ation of A%/ receptors leads not only to $asodilatation,
growth inhibition, and antiatherogenic effects, but also to heart
hypertrophy and poorer re$asculari ation after the obstruction of coronary or
peripheral artery.
I;4 C ()$i #ti n
• hypoglycemia due to decreased renal clearance of insulin0
• rapidly progressing chronic idney failure
• end-stage idney disease
• hyper alemia
• se$ere hypertension
• complications of hemodialysis
• complications of idney transplant
• coe(istence of other diabetes complications
• peritonitis if peritoneal dialysis used0
• increased infections
;4 Pr +n sis
http://en.wikipedia.org/wiki/Hypoglycemiahttp://en.wikipedia.org/wiki/Clearance_(medicine)http://en.wikipedia.org/wiki/Clearance_(medicine)http://en.wikipedia.org/wiki/Kidney_failurehttp://en.wikipedia.org/wiki/End-stage_kidney_diseasehttp://en.wikipedia.org/wiki/Hyperkalemiahttp://en.wikipedia.org/wiki/Hypertensionhttp://en.wikipedia.org/wiki/Hemodialysishttp://en.wikipedia.org/wiki/Kidney_transplanthttp://en.wikipedia.org/wiki/Diabeteshttp://en.wikipedia.org/wiki/Peritonitishttp://en.wikipedia.org/wiki/Infectionshttp://en.wikipedia.org/wiki/Hypoglycemiahttp://en.wikipedia.org/wiki/Clearance_(medicine)http://en.wikipedia.org/wiki/Kidney_failurehttp://en.wikipedia.org/wiki/End-stage_kidney_diseasehttp://en.wikipedia.org/wiki/Hyperkalemiahttp://en.wikipedia.org/wiki/Hypertensionhttp://en.wikipedia.org/wiki/Hemodialysishttp://en.wikipedia.org/wiki/Kidney_transplanthttp://en.wikipedia.org/wiki/Diabeteshttp://en.wikipedia.org/wiki/Peritonitishttp://en.wikipedia.org/wiki/Infections
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;iabetic nephropathy continues to get gradually worse. Complications of
chronic idney failure are more li ely to occur earlier, and progress more
rapidly, when it is caused by diabetes than other causes. E$en after initiation
of dialysis or after transplantation, people with diabetes tend to do worse than
those without diabetes.