Diabetic Nephropathy Baru

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


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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.

Documents

Diabetic Nephropathy Baru