CASE 1.CASE 1.

MrsMrs C.P. 17 years old .C.P. 17 years old .PMH PMH pyelonephritispyelonephritis resulting in ESRF.resulting in ESRF.Been Been dialyseddialysed at the moment .at the moment .Because her Because her unabilityunability to cope with to cope with transport requirements may not be transport requirements may not be accepted in program .accepted in program .

CASE 2.CASE 2.

MrsMrs MM.MM.52 years old 52 years old Jehovah witness Jehovah witness Dialysis requiring . Has given consent Dialysis requiring . Has given consent for it.for it.May not be taken in programs May not be taken in programs because has refuse blood because has refuse blood transfusion.transfusion.

CASE 3.CASE 3.

MrMr AN 43 years old AN 43 years old PMH smoker. Asthmatic . COAD .PMH smoker. Asthmatic . COAD .In CRF after over dose of NSAID.In CRF after over dose of NSAID.Not dialysis requiring as yet ,but Not dialysis requiring as yet ,but progressing to ESRF.progressing to ESRF.Will not be taken for renal transplant Will not be taken for renal transplant due his advance COAD.due his advance COAD.

CASE 4.CASE 4.MrsMrs P.N P.N 25 years old .25 years old .HIV positive .HIV positive .ARF after a septic abortion.ARF after a septic abortion.DialysedDialysed for 2 /52 then discharge with for 2 /52 then discharge with nomalnomal U & E .U & E .Presented again early CRF 6/12 later.Presented again early CRF 6/12 later.Biopsy HIVAS .Biopsy HIVAS .NOT accepted in CRP because her NOT accepted in CRP because her inmuneinmunestatus.status.

CASE 5.CASE 5.

MrsMrs HA , 62 years olds.HA , 62 years olds.NIDDN , HPT , IHD , Ischemic CMO.NIDDN , HPT , IHD , Ischemic CMO.Renal function deterioration for last Renal function deterioration for last 4/12.4/12.Family willing to donate a kidney.Family willing to donate a kidney.Because of her age an CMO has not Because of her age an CMO has not being accept in chronic renal being accept in chronic renal program(CRPprogram(CRP). ).

20 millions people are living with CRF 20 millions people are living with CRF in USA .in USA .By 2010 2 millions will require some By 2010 2 millions will require some form of renal replacement to survive form of renal replacement to survive ..Chronic renal replacement program Chronic renal replacement program in South Africa will not change the in South Africa will not change the current requirement in the near current requirement in the near future.future.

CRFPCRFPWill go on a restrict diet .Will go on a restrict diet .Will take 6 different med per day.Will take 6 different med per day.Will make 8 extra hospital visit per years .Will make 8 extra hospital visit per years .

To delay the initiation of dialysis for a few To delay the initiation of dialysis for a few weeks.weeks.

Slowing progression of CRF by 30% will Slowing progression of CRF by 30% will result in 60 billion saving in US health result in 60 billion saving in US health system .system .

STRATEGIES TO RETARD STRATEGIES TO RETARD PROGRESION OF CRF.PROGRESION OF CRF.

CRF occur by a common pathway CRF occur by a common pathway with angiotensin 2 playing a central with angiotensin 2 playing a central role in the process .role in the process .RenoprotectionRenoprotection can be achieved can be achieved irrespective of etiology of nephron irrespective of etiology of nephron losslossRenoprotectionRenoprotection is complementary to is complementary to the treatment of original cause .the treatment of original cause .

Mechanism of progression of CRF.Mechanism of progression of CRF.

GFR decline to below normal value.GFR decline to below normal value.

Even in absence of original diseases Even in absence of original diseases activity ,there is progressive loss of activity ,there is progressive loss of function function

Resulting in proteinuira HPT and Resulting in proteinuira HPT and progressive decline in GFRprogressive decline in GFR

CONTINUINING,CONTINUINING,Acquired loss of nephrons/dec renal massAcquired loss of nephrons/dec renal mass

Remaining nephrons undergo structural and Remaining nephrons undergo structural and functional changes to increase single nephron functional changes to increase single nephron GFR.GFR.

Glomerular capillary HPT which is mantained by Glomerular capillary HPT which is mantained by angiotensin depending angiotensin depending mechanismomechanismo..

It will lead to more glomerular sclerosis and It will lead to more glomerular sclerosis and nephron death.nephron death.

STRATEGY 1.STRATEGY 1.Renin angiotensin inhibitor as renoprotective Renin angiotensin inhibitor as renoprotective agents.agents.

ACE inhibitor ACE inhibitor angiotensin angiotensin receptor blocker.receptor blocker.

Reducing the production Inhibiting the type 1Reducing the production Inhibiting the type 1of angiotensin 2 angiotensin2 of angiotensin 2 angiotensin2

receptrecept

ACE Inhibitor.ACE Inhibitor.

Reduction of 48% in doubling of creatinin.Reduction of 48% in doubling of creatinin.Reduction of 50% in the risk of death Reduction of 50% in the risk of death transplant and dialysis.transplant and dialysis.Reduce micro Reduce micro albuminuiraalbuminuira..Increase chances of regression to normal Increase chances of regression to normal albuminuriaalbuminuria..No benefit for primary prevention .No benefit for primary prevention .All above effect seen in non diabetic pt too All above effect seen in non diabetic pt too

ANGIOTENSIN RECEPTOR ANGIOTENSIN RECEPTOR BLOCKERBLOCKER

Less side effects than ACEI.Less side effects than ACEI.Reduce microalbuminuira and Reduce microalbuminuira and proteinuria in type 2 diabetic proteinuria in type 2 diabetic patients.patients.Effect in non diabetic patient type 1 Effect in non diabetic patient type 1 DM is still under investigation .DM is still under investigation .

COMBINED ACE AND ARB.COMBINED ACE AND ARB.

COOPERATE TRIAL.COOPERATE TRIAL.ARB ARB ----losartanlosartan ––89 pts.89 pts.----20 develop ESRF.20 develop ESRF.

ACE ACE ----TrandoloprilTrandolopril-- 86pt86pt----23developESRF.23developESRF.

CombinationCombination-------------- 88pt88pt–– 10pt develop ESRF10pt develop ESRF

PRACTICAL POINTSPRACTICAL POINTS

Danger of hypercalemia and initial Danger of hypercalemia and initial raise of creatinin.raise of creatinin.

How to prevent this?How to prevent this?

Avoid fluids depletion .Avoid fluids depletion .Stop NSAID .Stop NSAID .Rule out bilateral RAS.Rule out bilateral RAS.Start at low doses.Start at low doses.Stop K supplements, K sparing Stop K supplements, K sparing diuretics.diuretics.Low K diet.Low K diet.

When to stop?.When to stop?.

If elevation is more than 30% the If elevation is more than 30% the base line creatinin.base line creatinin.

Stop if K is more than 5.6 mmol/l.Stop if K is more than 5.6 mmol/l.

Stop if pts has severe hypotension.Stop if pts has severe hypotension.If after 5 days elevation of creat is If after 5 days elevation of creat is less than 30% is safe to continuous less than 30% is safe to continuous the drug.the drug.

STRATEGY 2.TREATMENT OF STRATEGY 2.TREATMENT OF HPT.HPT.

Proteinuria less than 1g / day target BP Proteinuria less than 1g / day target BP 130/80.130/80.

Proteinuria more than 1g /d target BP Proteinuria more than 1g /d target BP 125/75.125/75.

ACEI and ARB should be part of ACEI and ARB should be part of treatmenttreatment

STRATEGY 3.TREATMENT OF STRATEGY 3.TREATMENT OF DYSLIPIDEMIA.DYSLIPIDEMIA.

LDL play a role in worsening and LDL play a role in worsening and even initiation of CRF.even initiation of CRF.The decline of GFR slow down with The decline of GFR slow down with use of use of statinsstatins..StatinsStatins decrease proteinuria.decrease proteinuria.Recommended in CRF because the Recommended in CRF because the effect in Atherosclerotic vascular effect in Atherosclerotic vascular disease .disease .

STRATEGY 4.SMOKING STRATEGY 4.SMOKING CESSATION.CESSATION.

Nicotine increase microalbuminuiraNicotine increase microalbuminuiraAdvance microalbuminuria to Advance microalbuminuria to proteinuria.proteinuria.Decrease renoprotective effect of Decrease renoprotective effect of ACE and ARB.ACE and ARB.Increase HPT.Increase HPT.Increase angiotensin 2 production.Increase angiotensin 2 production.

STRATEGY 5.DIETARY STRATEGY 5.DIETARY PROTEIN RESTRICTION.PROTEIN RESTRICTION.

There is a beneficial effect of dietary There is a beneficial effect of dietary protein restriction on CRF initiation protein restriction on CRF initiation and progression . and progression . 0,6 to 0,8 gram / kg /day is 0,6 to 0,8 gram / kg /day is recommendedrecommendedMal nutrition and poor compliance Mal nutrition and poor compliance should be prevented.should be prevented.

STRATEGY 6.CORRECTION OF STRATEGY 6.CORRECTION OF OBESITY.OBESITY.

Obesity produce glomerular hyper Obesity produce glomerular hyper filtration.filtration.

Produce glomerular afferente Produce glomerular afferente arteriole dilatation .arteriole dilatation .

41% weight loss is associated with 41% weight loss is associated with 31.2 % reduction in proteinuria.31.2 % reduction in proteinuria.

STRATEGY 7.STRATEGY 7. Correction of Correction of anemia.anemia.

Anemia will produce hypoxia or renal Anemia will produce hypoxia or renal tubule.tubule.Hypoxia produce fast decline of GFR.Hypoxia produce fast decline of GFR.Patient treated with erythropoyetin Patient treated with erythropoyetin will respond better to other will respond better to other strategies to slow down CRF.strategies to slow down CRF.HbHb of 12g/l or more is associated of 12g/l or more is associated with decrease mortality and with decrease mortality and morbidity in CRF.morbidity in CRF.

summary.summary.Intervention Intervention

--ACE / ARBACE / ARB

Antihypertensive.Antihypertensive.

Goal Goal --Proteinuira < 0.5 g/ Proteinuira < 0.5 g/

L.L.--GFR decline GFR decline

0.2ml/min/y0.2ml/min/y

BP <130/80 if BP <130/80 if protprot<1g/d<1g/d

BP<125/75 if prot BP<125/75 if prot >1g/d>1g/d

CONTINUATIONCONTINUATION

Protein restriction Protein restriction

Tight glycemic Tight glycemic control.control.

Cholesterol Cholesterol lowering.lowering.

ErythropoErythropo therapy.therapy.

0.6 to 0.8 0.6 to 0.8 g/kg/dg/kg/d..

HbHb A < 6.5 %.A < 6.5 %.

LDL <100ng/dl.LDL <100ng/dl.

HbHb > 12g/l> 12g/l

CONTINUATIONCONTINUATION

Salt restriction.Salt restriction.

Smoking cessation Smoking cessation

Other approach Other approach

33–– 5g g/d .5g g/d .

Abstinence .Abstinence .

Avoid nephrotoxic Avoid nephrotoxic drug. Reduce drug. Reduce phosphate . Anti phosphate . Anti platelets therapy.platelets therapy.