Diabetic nephropathyDiabetic nephropathy

Diabetic nephropathy- Diabetic nephropathy- definitiondefinition

Chronic microangiopathy type complication Chronic microangiopathy type complication of DM characterized by:of DM characterized by:

1.1. proteinuriaproteinuria

2.2. hypertension hypertension

3.3. pprogressive loss of GFR leading to ESRDrogressive loss of GFR leading to ESRD

MicroalbuminuriaMicroalbuminuria

1.1. albumin excretion in urine albumin excretion in urine 30 – 300 mg/d or 20 – 200 ug/min30 – 300 mg/d or 20 – 200 ug/min

2. If temporary, but >80 mg/d it means 2. If temporary, but >80 mg/d it means in in 95% progression to continuous 95% progression to continuous microalbuminuriamicroalbuminuria

3. If continuous - it means threatening 3. If continuous - it means threatening nephropathy. Not treated increases 20 – nephropathy. Not treated increases 20 – 40% a year. After 5 years becomes 40% a year. After 5 years becomes macroalbuminuriamacroalbuminuria = evident diabetic = evident diabetic nephropathy nephropathy

MacroalbuminuriaMacroalbuminuria

1.1. Albumin excretion in urine >300 mg/d Albumin excretion in urine >300 mg/d

2. It 2. It mamay lead to development of nephrotic y lead to development of nephrotic syndrome (proteinuria, syndrome (proteinuria, hypoalbuminaemia, hyperlipidaemia, hypoalbuminaemia, hyperlipidaemia, edema)edema)

3. ESRD appears usually after 5 years 3. ESRD appears usually after 5 years

TimTimee course of DN according to course of DN according to type of DM (Mogensen scale)type of DM (Mogensen scale)

IDDMIDDM NIDDM NIDDMI stadium (0-2 yrs) hyperfiltration (100%) I stadium (0-2 yrs) hyperfiltration (100%)

(unnoticeable)(unnoticeable)II stadium (2-5yrs) silent DN II stadium (2-5yrs) silent DN (1 (100%)00%)

(100%)(100%)III stadium (>5 yrs) threatening DN (30%)III stadium (>5 yrs) threatening DN (30%) (30%) (30%)IVIV stadium (>15 stadium (>15 yrs yrs) ) evident DNevident DN (25%)(25%)

(25%)(25%)V stadium (>15V stadium (>15 yrs yrs) ) ESRDESRD (20%) (20%) (20%)(20%)

Factors contributing to development of Factors contributing to development of DNDN

1.1. Long-lasting hyperglycemiaLong-lasting hyperglycemia

2.2. Family predispositionFamily predisposition

3.3. HTHT

4.4. High-protein dietHigh-protein diet

5.5. Cigarette smokingCigarette smoking

6.6. hyperlipidaemiahyperlipidaemia

BP in children of DM BP in children of DM patientspatientswithout DN without DN with DNwith DN

SBPSBP 117 117 ++13 13 mmHgmmHg125 125 ++17 17 mmHgmmHg

Strojek i wsp.Strojek i wsp.

Mutual coincidence of DM and HTMutual coincidence of DM and HT

Age [yrs] % with HT

< 20 15%

20 - 40 33%

40 - 60 52%

> 60 70%

Age [yrs] % with HT

< 20 15%

20 - 40 33%

40 - 60 52%

> 60 70%

DM patients with HTDM patients with HT

Age of DM patients = % of patients with HT Age of DM patients = % of patients with HT

BP, DM control and loss of GFR BP, DM control and loss of GFR [ml/min/r][ml/min/r]

MABP MABP [mm [mm Hg]Hg]

9191 9898 102102 105105 112112

HbA1c HbA1c <9%<9%

1,41,4 1,51,5 3,63,6 4,44,4 6,06,0

HbA1c HbA1c >9%>9%

3,33,3 3,53,5 4,64,6 6,16,1 7,57,5

Treatment of DNTreatment of DN

1.1. Proper treatment of DMProper treatment of DM

2.2. Proper treatment of HTProper treatment of HT

3.3. Quit smoking habitQuit smoking habit

4.4. Control of protein content in dietControl of protein content in diet

5.5. Early treatment of anaemiaEarly treatment of anaemia

6.6. Early kidney replacement therapyEarly kidney replacement therapy

Proper treatment of DMProper treatment of DM

1.1. „„Almost normal” glycaemia:Almost normal” glycaemia:

fasting fasting 60 – 140 mg/dl60 – 140 mg/dl

2 h after meal 2 h after meal <200 mg/dl <200 mg/dl

2.2. Proper body massProper body mass

3.3. Correction of hyperlipidaemiaCorrection of hyperlipidaemia

Proper treatment of BPProper treatment of BP

1.1. Lowest tolerable BPLowest tolerable BP

2.2. Treatement with ACE-I & AT-IITreatement with ACE-I & AT-II

Nutrition state (albuminaemia) and the risk of death

Albuminemia [g/dl] Relative risk

> 4,0 0,81

3,6 – 4,0 1,00

3,1 – 3,5 1,18

2,6 – 3,0 1,23

<2,5 1,82

Albuminemia [g/dl] Relative risk

> 4,0 0,81

3,6 – 4,0 1,00

3,1 – 3,5 1,18

2,6 – 3,0 1,23

<2,5 1,82

HakimHakim 19941994

Early treatment of anaemia with epoEarly treatment of anaemia with epo

Anaemia… when?Anaemia… when?

glomerulonephritis DNglomerulonephritis DN

GFRGFR <25-30 ml/min<25-30 ml/min <35-40 <35-40 ml/minml/min

creatininecreatinine >3-4 mg/dl>3-4 mg/dl >2-3 mg/dl>2-3 mg/dl

Attention:Attention:ACE-I may contribute to anaemia! ACE-I may contribute to anaemia!

Early start of renal replacement Early start of renal replacement therapytherapy

1.1. creatinine >3,5 – 4 mg/dl – a-v fistula!creatinine >3,5 – 4 mg/dl – a-v fistula!2.2. creatinine >4,5 – 5 mg/dl (GFR <20 creatinine >4,5 – 5 mg/dl (GFR <20

ml/min):ml/min): - consider KTx- consider KTx(<45 yrs & IDDM)(<45 yrs & IDDM)- consider KTx and pancreas Tx- consider KTx and pancreas Tx(>45 yrs & NIDDM)(>45 yrs & NIDDM)- start RRT- start RRT

HD therapy in DM patientsHD therapy in DM patients

Pro:Pro: Contra:Contra:High efficiacyHigh efficiacy CVS damageCVS damageFrequent control Frequent control problems with a-v problems with a-v fistulafistulaNo protein lossNo protein loss HypotoniaHypotonia

frequent frequent hypoglycaemiahypoglycaemia

frequent hyperkalaemiafrequent hyperkalaemia

CADO treatment in DM patientsCADO treatment in DM patients

Pro:Pro: Contra:Contra:

CVS neutralCVS neutral risk of infectionrisk of infection

No a-vNo a-v protein lossprotein loss

Good control of kalaemiaGood control of kalaemia herniashernias

Good control of glycaemiaGood control of glycaemia helper requiredhelper required

Glycaemia regulation in DM Glycaemia regulation in DM patients with ESRDpatients with ESRD

1.1. Gluconeogenesis decreased by 30 – 40%Gluconeogenesis decreased by 30 – 40%2.2. Insulin requirement decreased 3-4xInsulin requirement decreased 3-4x

3.3. Decreased metabolism of some oral drugs Decreased metabolism of some oral drugs (eg. metformin)(eg. metformin)

4.4. DuringDuring HD glu HD glucose is cose is „„hemodialysedhemodialysed”” and and lostlost

All the above may lead to hypoglycaemiaAll the above may lead to hypoglycaemia!!

DM patient on HD therapy- what DM patient on HD therapy- what should be the treatment?should be the treatment?

1.1. InsulinInsulin – 2-3x lower doses! – 2-3x lower doses!

2.2. Oral drugsOral drugs – short acting, metabolized in liver – short acting, metabolized in liver eg: eg:

- glipizyd (Glipizyd, Minidiab, Glibenese GITS)- glipizyd (Glipizyd, Minidiab, Glibenese GITS)- gliclazyd (Diaprel, Diabezyd)- gliclazyd (Diaprel, Diabezyd)- glikwidon (Glurenorm)- glikwidon (Glurenorm)