recent advances in management of crf

Recent Advances in Recent Advances in Management of CRFManagement of CRF

Yousef Boobess, M.D.Head, Nephrology Division

Tawam Hospital

What is chronic renal failure ? What is chronic renal failure ? DefinitionsDefinitions

Azotemia: Elevated blood urea and creatinine

Chronic renal failure: The irreversible, substantial, and usually long-

standing (>3 months) loss of renal function.

Uremia: Azotemia with symptoms or signs of renal failure

End-stage renal disease (ESRD): The degree of CRF that without renal replacement

treatment would result in death.

Urinary abnormalities

(GFR 90 ml/min)

Mildly impaired (GFR 60 - 89 ml/min)

Moderate CRF(GFR 30 - 59 ml/min)

Severe CRF (GFR 15 - 29 ml/min)

ESRD(GFR < 15 ml/min)

STAGES OF STAGES OF Chronic Kidney Chronic Kidney Disease (CKD)Disease (CKD)

EpidemiologyEpidemiology

The number of ESRD patients is increasing rapidly, with very costly treatment

Early recognition of renal disease and appropriate interventions may decreaseHuman sufferingFinancial costs associated with ESRD

Dialysis Sessions in Dialysis Sessions in TawamTawam

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Incidence Rates of ESRD Incidence Rates of ESRD TherapyTherapy

U.S. Renal Data System, (1997)U.S. Renal Data System, (1997)

1982 1984 1986 1988 1990 1992 1994 1995

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250

200

150

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Causes of ESRD in USACauses of ESRD in USA40.3

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Team Approach: Team Approach: Primary Helth Care (PHC) Physician and Primary Helth Care (PHC) Physician and

Nephrologist in CKDNephrologist in CKD

PHC PhysicianEarly recognition of renal disease PHC Physicians treat

patients with DM, HTN

Timely referral to a Nephrologist Collaboration with a Nephrologist to provide long term care Patient education

NephrologistDiagnose and assess patients

Assist in developing strategic guidance

Recommend and implement patient care

Provide role-specific patient education

Principles of Management of Principles of Management of CKD PatientsCKD Patients

Early recognition of CKD Estimate the severity of CKD What is the cause of CKD?

Detection and correction of any reversible cause. Avoidance of additional renal injury Institution of interventions to delay progressionTreatment of complications Planning for renal replacement therapy

Recognizing Renal Failure,Recognizing Renal Failure,

Clinical FeaturesClinical FeaturesRecognizing Renal Failure,Recognizing Renal Failure,

Clinical FeaturesClinical FeaturesMild to Moderate renal failure: Usually no symptoms

Severe renal failure: non specific Pale, fatigueability & shortness of breath Hypertension, headaches Polyuria/nocturia Body itch Poor appetite, nausea, vomiting Hyperventilation Swelling of the face and legs

HyperventilationHyperventilation

13 y-o-f, came to ER with hyperventilation ER physician examined her psychosis valium, reassured the family & DCNo improvement taken to another hospital Blood Chemistry & ABGs ESRD with very severe metabolic acidosis (Bicarbonate ~ 2.7 mmol/l)

Recognizing Renal Failure,Recognizing Renal Failure,

InvestigationsInvestigationsRecognizing Renal Failure,Recognizing Renal Failure,

InvestigationsInvestigationsUrinalysis: Urine dipstick & microscopic exam => Ptu, Htu, pyuria, glycosuria

Blood chemistry: s.Creatinine, urea (or BUN) Electrolytes (Na+, K+, CO2, Ca++, Ph--)

GFR: Estimated or measured

Ultrasound Morphologic evaluation

s.Creatinine Concentration s.Creatinine Concentration s.Creatinine Concentration s.Creatinine Concentration

Normal values: <115 umol/L in males (1.3 mg/dL) <90 umol/L in females (1 mg/dL)

Changes in its level are more important: an increase from 55 to 110 umol/L represents a

50% decline in renal function

Limitations

High s.Creatinine with High s.Creatinine with Normal GFRNormal GFR

Spurious elevation: Cephalosporin DKA Alcohol intoxication

Blocking tubular secretion: Cimetidine or trimethoprim

Increased creatinine production: Exogenous: ingestion of large quantities of cooked

meat Endogenous: Muscular disorders, or increases in

muscular mass

Normal s.Creatinine with CRF Normal s.Creatinine with CRF

Poor production of creatinine:Severely malnourished patients ElderlySmall childrenLadies of small size

Glomerular Filtration Rate Glomerular Filtration Rate “GFR” “GFR”

Normal values: In males 120 20 mL/minute In females 115 20 mL/minute.

Creatinine Clearance (24-h urine collection)

Creatinine Clearance in Severe CKD: Overestimate GFR due to the tubular secretion To correct this overestimation:

Take the average of urea and creatinine clearances Or give oral cimetidine 1200 mg, 3h before collection

Estimation of Creatinine Estimation of Creatinine ClearanceClearance

Creat. Cl =1.23 x weight x(140-age)/(s.creat)Creat. Cl =1.23 x weight x(140-age)/(s.creat)

In Male:

In Female

Cockcroft, Nephron, 1976; 16: 31-41

1.03

Determine the cause of CKDDetermine the cause of CKD

A specific diagnosis is needed:To consider specific TRT:

obstructive uropathy, analgesic NP, drug-related IN, RPGN, SLE, vasculitis, accelerated HTN, tuberculosis, myeloma, amyloid, ..

To be aware of potential complications:SLE, DM..

To advise the family:PKD or other familial renal disease.


1. Early recognition of CKDEstimate the severity of CKDWhat is the cause of CKD?

2. Detection and correction of any reversible cause. Avoidance of additional renal injury

3. Institution of interventions to delay progression

4. Treatment of complications 5. Planning for renal replacement therapy

Correcting any Reversible Correcting any Reversible CauseCause

Correction a Reversible CauseCorrection a Reversible Cause“Sarcoidosis”“Sarcoidosis”

0

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Time (days)

Cre

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Corticotherapy

Dialysis Sessions

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500

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Time (days)

Cre

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Corticotherapy

Dialysis Sessions

Volume DepletionVolume Depletion

Causes: Diarrhea, vomiting, iatrogenic (surgery,

overzealous use of diuretics) Renal loss Worsening renal arterial stenosis, cholesterol

emboliVolume repletion Restores renal function promptly Some degree of transient or permanent damage

may occur



1. Early recognition of CKDEstimate the severity of CKDWhat is the cause of CKD?




Slowing the Rate of Slowing the Rate of ProgressionProgression

The earlier we alter factors that damage the kidneys, the better

Successful InterventionSuccessful Intervention

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Therapeutic Intervention

Months, follow-up

Rashed M., Tawam #125991

InterventionInterventionRenal DietRenal Diet

InterventionInterventionRenal DietRenal Diet

Protein Restriction

High calories

Law potassium

Law salt

Law phosphate

Intervention:Intervention:Controlling BP in CKD Controlling BP in CKD

Target BP: CKD: <130/85 mm Hg If proteinuria: <125/75 mm Hg

Benefits Slows the progression of CKD, especially if

proteinuriaReduces the cardiovascular complications

Zabetakis PM, Nissenson AR. Am J Kid Dis. 2000;36(suppl):S31-S38.

BP Control and GFR DeclineBP Control and GFR Decline

•Parving HH et al. Br Med J 1989 Moschio G et al. NEJM 1996• Viberti GC et al. JAMA 1993

Prevalence of LV Disorders at Prevalence of LV Disorders at Start of Dialysis Start of Dialysis

Parfrey PS, et al.. Nephrol Dial Transplant. 1996;11:1277-1285

LV dilation28%

Cincentric LVH41%

Normal16%

Systolic dysfunct.16%

Echocardiograms of 413 incident hemodialysis patients

Consequences of CKD: Consequences of CKD: (LVH) (LVH)

LVH is an independent predictor of cardiac death in dialysis patients.

Hypertension, anemia and diabetics are modifiable predictors of LVH

Increase in LVH risk: For each: Ccr of 25 mL/min => 3% increased risk of LVH. Systolic BP by 5 mm Hg => 3% increased risk. Hemoglobin by 1 g/dl => 6% increased risk of

LVH

Levin A, et al. Am J Kid Dis. 1996;27:347-354.

< 130/8511%

< 140/9027%

> 140/9062%

BP is Poorly Controlled in BP is Poorly Controlled in CKDCKD

Coresh J, et al. Arch Intern Med. 2001;161:1207-1216.

Blood Pressure ControlBlood Pressure Control

Several classes of drugs are available

Some can slow the decline of GFR:First-line treatment:

ACE inhibitors & angiotensin receptor blockers There's still a great reluctance by PHC physicians to

use them for fear that they will damage the kidneys rather than preserve function.

Diuretics in combination with ACE inhibitors.

JNC VI. Arch Intern Med. 1997;157:2413-2446.

Reno-protective Effect of Reno-protective Effect of ACEisACEis

ACEis (independent of their antihypertensive action):

Decrease proteinuria Delay the progression of renal disease

Mechanisms: Dilatation of EA =>reducing intra-glomerular

pressure Restoration of glomerular perm-selectivity in

proteinuric NPs ? Effect on the GH like of AII

Adverse Effects of ACEisAdverse Effects of ACEis

Acute worsening of renal function if bilateral renal artery stenosis or if decreased

effective circulating volume advices:

monitor renal function after initiation of ACEi in high risk patients: renal scan with captopril test adjust the dose according to the renal function

Hyperkalemia same considerations apply

Glycemic Control in DiabeticsGlycemic Control in Diabetics

Tight control of blood glucose: HbA1C <7%Delay the onset of microalbuminuriaDecrease or stabilize protein excretion in

patients who already had microalbuminuria

ACE inhibitors, and ARBs: Delay the progression of kidney

dysfunction.

Zabetakis PM, Nissenson AR. Am J Kid Dis. 2000;36(suppl):S31-S38.The Diabetes Control and Complications Trial, long-term Sweden study, Japanese study

RENAAL Primary Components

ESRD

Months

% w

ith

ev

ent

0 12 24 36 480

10

20

30

p=0.002Risk Reduction: 28%

P

L

ESRD or Death

P (+ CT)L (+ CT)

Months

% w

ith

ev

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0 12 24 36 480

10

20

30

40

50

751 714 625 375 69762 715 610 347 42

P

L


Doubling of Serum Creatinine

Months

% w

ith

ev

ent


751 692 583 329 52762 689 554 295 36P (+ CT)

L (+ CT)

0 12 24 36 480

10

20

30

P

L

P (+ CT)L (+ CT) 751 714 625 375 69

762 715 610 347 42

Brenner BM et al New Engl J Med 2001;345(12):861-869.

HyperlipidemiaHyperlipidemiaHyperlipidemiaHyperlipidemia

In CRF: Mainly hypertriglyceridemia

=> Increases glomerulosclerosis by: Increasing mesangial proliferation and

matrix productionAltering glomerular hemodynamics Increasing local inflammation

Smoking CessationSmoking Cessation

All patients with renal disease should be encouraged to quit smokingDM is 3 to 4 times more common in

smokers than in nonsmokersSmoking increases the relative risk for

progression of CRF in nondiabetics

Former smokers have an intermediate risk


1. Early recognition of CKDEstimate the severity of CKD What is the cause of CKD?

2. Detection and correction of any reversible causes. Avoidance of additional renal injury



Fluid and electrolyte disorders Fluid and electrolyte disorders

Sodium and WaterSodium and WaterMost often: Impaired Na excretion => Edema, HTN, CHF TRT:

Moderate Na+ restriction Loop diuretics

In some patients: Salt wasting => volume depletion => worsening of

CRF TRT:

Na+ replacement

Fluid and Electrolyte DisordersFluid and Electrolyte Disorders

Potassium BalancePotassium BalanceFluid and Electrolyte DisordersFluid and Electrolyte Disorders

Potassium BalancePotassium BalanceHyperkalemia Develops in advanced CRF Can occur earlier in patients with:

Tubulointerstitial disease Diabetic NP and hyporeninemic hypoaldosteronism Drugs: as ACEis, A2 antagonist, b- blockers, NSAIDs,

K+ sparing diuretics, trimethoprim, salt substitutes.. TRT:

Dietary K+ restriction, loop diuretics, K+ exchange resins..

Fluid and Electrolyte DisordersFluid and Electrolyte Disorders

Acid-Base DisordersAcid-Base DisordersFluid and Electrolyte DisordersFluid and Electrolyte Disorders

Acid-Base DisordersAcid-Base Disorders

Metabolic acidosis: Occurs relatively early

Treatment: Decrease protein intake Alkali supplementation if bicarbonate < 17mEq/L

Na bicarbonate or Na citrate, 1 mEq/kg/day This will prevent:

Excessive bone loss Muscle breakdown Tubulointerstitial inflammation

Hypocalcemia & Hypocalcemia & HyperphosphatemiaHyperphosphatemia

Hypocalcemia & Hypocalcemia & HyperphosphatemiaHyperphosphatemia

Hypocalcemia Deficiency in Vit.D, Hyperphosphatemia

Hyperphosphatemia Early in renal failure: Ph-- clearance => Ph-- =>

PTH => Ph-- clearance Frank hyperphosphatemia occur if GFR < 30 mL/min

Management: Dietary phosphate restriction Phosphate binders: Ca carbonate, Renalgel,.. Vit D: Rocaltrol, One Alpha,..

AnemiaAnemiaAnemiaAnemia

Present when GFR < 30-35 mL/minCauses: Reduced EPO production Others: iron deficiency, rapid destruction of RBC,..

Anemia is an independent risk factor for death in CHF Studies of Left Ventricular Dysfunction (SOLVD)

7000 patients 1% lower Hct was associated with 1% higher risk of

mortality

Al Ahmad. et al. J Am Coll Cardiol. 2001;38:955-962.

Independent Risk of a Fall in Independent Risk of a Fall in Mean Hb of 1 g/dL in Dialysis Mean Hb of 1 g/dL in Dialysis

Patients Patients Odds ratio P

LV Dilation 1.42 0.02

De novo cardiac failure

1.28 0.02

Recurrent cardiac failure

1.20 0.05

IHD NA

Death 1.14 0.02

Foley PS, et al. Am J Kidney Dis. 1996;28:53-61.

Cardio - Renal - Anemia Cardio - Renal - Anemia Syndrome Syndrome

CKDCKD

CHFCHF AnemiaAnemia

Vicious Circle of DestructionVicious Circle of Destruction

Cardio - Renal - Anemia Cardio - Renal - Anemia SyndromeSyndrome

CHF is a common and crucial contributor to the progression of CKD. (new concept)

Treatment of anemia in patients with CHF may improve both the cardiac and the renal function

=> To save the heart and the kidney, treat the anemia

Treatment of AnemiaTreatment of Anemia

Target Hgb 11 to 12 g/dL

Epoetin: Dose: 50 U/kg/inj, iv or sc 1-3 times/week

IV Iron Sucrose: Target:

Serum ferritin: 100 - 500 ng/mL Transferrin saturation: 20 – 50%.

Dose: 100 mg/session X 10, then reevaluate

Principles of Management of Principles of Management of CRF PatientsCRF Patients

1. Early recognition of CRF Estimate the severity of CKD What is the cause of CRF?




Planning for Renal Replacement Planning for Renal Replacement Therapy Therapy

Planning for Renal Replacement Planning for Renal Replacement Therapy Therapy

Options of RRT should be discussed: Difference modalities of dialysis

HD, PD

Transplantation Possibility of preemptive Tx

Outcomes are optimal when RRT is initiated in a planned manner HD => need for A-V fistula (4-6 months) Tx: work-up

TRADITIONAL DIALYSIS TRADITIONAL DIALYSIS STARTSTART

Timely Dialysis StartTimely Dialysis Start

EARLY DIALYSIS STARTEARLY DIALYSIS START

Early dialysis start (CrCl > 10 ml/min) vs late dialysis start (CrCl < 4 ml/min):=> higher 12 yr survival (85% vs 51%)

[Bonomini et al Kidney Int 17:S57 1985]

=> improved quality of life at 6 months post initiation of RRT

[Korevaar et al AJKD Jan 2002]

Conclusion, 1Conclusion, 1

Early recognition of renal disease

Early referral to Nephrologist

Detect and correct any reversible cause

Avoid any additional renal injury

Use ACE inhibitors whenever it is indicated

Lipid-lowering drugs

Conclusion, 2Conclusion, 2Conclusion, 2Conclusion, 2

Avoid: Nephrotoxic drugs:

NSAIDs, aminoglycosides, radiocontrast

In moderate to severe CRF: Diuretic therapy: often necessary Dietary potassium restriction Potassium exchange resins if hyperkalemia Alkali supplementation: if CO2 < 16-17 mEq/L Phosphate binders, Vit D EPO, Iron

recent advances in management of crf

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