Preventing%20Progression%20and%20Complications%20of%20Renal%20Disease

1
(No Transcript)
2
Recent Advances in Management of CRF

• Yousef Boobess, M.D.
• Head, Nephrology Division
• Tawam Hospital

3
What is chronic renal failure ? Definitions

• Azotemia
• Elevated blood urea and creatinine
• Chronic renal failure
• The irreversible, substantial, and usually
  long-standing (gt3 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.

4
STAGES OF Chronic Kidney Disease (CKD)
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 lt 15 ml/min)
5
Epidemiology

• The number of ESRD patients is increasing
  rapidly, with very costly treatment
• Early recognition of renal disease and
  appropriate interventions may decrease
• Human suffering
• Financial costs associated with ESRD

6
Dialysis Sessions in Tawam
7
Incidence Rates of ESRD Therapy
300 250 200 150 100 50
Rate per Million Population
1982 1984 1986
1988 1990 1992
1994 1995 Years
U.S. Renal Data System, (1997)
8
Causes of ESRD in USA
1999 USRDS Report
9
Team Approach Primary Helth Care (PHC)
Physician and Nephrologist in CKD

• PHC Physician
• Early 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

• Nephrologist
• Diagnose and assess patients
• Assist in developing strategic guidance
• Recommend and implement patient care
• Provide role-specific patient education

10
Principles of Management of CKD 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 progression
• Treatment of complications
• Planning for renal replacement therapy

11
Principles of Management of CKD 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 progression
• Treatment of complications
• Planning for renal replacement therapy

12
Recognizing Renal Failure,Clinical Features

• Mild 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

13
Recognizing Renal Failure,Clinical Features

• Mild 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

14
Hyperventilation

• 13 y-o-f, came to ER with hyperventilation
• ER physician examined her ? psychosis ? valium,
  reassured the family DC
• No improvement ? taken to another hospital ?
  Blood Chemistry ABGs
• ? ESRD with very severe metabolic acidosis
  (Bicarbonate 2.7 mmol/l)

15
Recognizing Renal Failure,Investigations

• Urinalysis
• Urine dipstick microscopic exam
• gt Ptu, Htu, pyuria, glycosuria
• Blood chemistry
• s.Creatinine, urea (or BUN)
• Electrolytes (Na, K, CO2, Ca, Ph--)
• GFR
• Estimated or measured
• Ultrasound
• Morphologic evaluation

16
s.Creatinine Concentration

• Normal values
• lt115 umol/L in males (1.3 mg/dL)
• lt90 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

17
High s.Creatinine with Normal 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

18
Normal s.Creatinine with CRF

• Poor production of creatinine
• Severely malnourished patients
• Elderly
• Small children
• Ladies of small size

19
Glomerular Filtration Rate 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

20
Estimation of Creatinine Clearance
Creat. Cl 1.23 x weight x(140-age)/(s.creat)
In Male
In Female
1.03
Cockcroft, Nephron, 1976 16 31-41
21
Determine 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.

22
Principles of Management of CKD 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 progression
• Treatment of complications
• Planning for renal replacement therapy

23
Correcting any Reversible Cause
24
Correction a Reversible CauseSarcoidosis
25
Volume Depletion

• Causes
• Diarrhea, vomiting, iatrogenic (surgery,
  overzealous use of diuretics)
• Renal loss
• Worsening renal arterial stenosis, cholesterol
  emboli
• Volume repletion
• Restores renal function promptly
• Some degree of transient or permanent damage may
  occur

26
Principles of Management of CKD 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 progression
• Treatment of complications
• Planning for renal replacement therapy

27
Slowing the Rate of Progression
The earlier we alter factors that damage the
kidneys, the better
28
Successful Intervention
Therapeutic Intervention

0
.
0
0
7
0
.
0
0
6
0
.
0
0
5
0
.
0
0
4
0
.
0
0
3
0
.
0
0
2
1/s.cretinine
0
.
0
0
1
0
0
5
1
0
1
5
2
0
Months, follow-up
Rashed M., Tawam 125991
29
InterventionRenal Diet

• Protein Restriction
• High calories
• Law potassium
• Law salt
• Law phosphate

30
InterventionControlling BP in CKD

• Target BP
• CKD lt130/85 mm Hg
• If proteinuria lt125/75 mm Hg
• Benefits
• Slows the progression of CKD, especially if
  proteinuria
• Reduces the cardiovascular complications

Zabetakis PM, Nissenson AR. Am J Kid Dis.
200036(suppl)S31-S38.
31
BP Control and GFR Decline

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

32
(No Transcript)
33
Prevalence of LV Disorders at Start of Dialysis
Echocardiograms of 413 incident hemodialysis
patients
Parfrey PS, et al.. Nephrol Dial Transplant.
1996111277-1285
34
Consequences of CKD (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 gt 3 increased risk of LVH.
• ? Systolic BP by 5 mm Hg gt 3 increased risk.
• ? Hemoglobin by 1 g/dl gt 6 increased risk of LVH

Levin A, et al. Am J Kid Dis. 199627347-354.
35
BP is Poorly Controlled in CKD
Coresh J, et al. Arch Intern Med.
20011611207-1216.
36
Blood 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. 19971572413-2446.
37
(No Transcript)
38
Reno-protective Effect of ACEis

• ACEis (independent of their antihypertensive
  action)
• Decrease proteinuria
• Delay the progression of renal disease
• Mechanisms
• Dilatation of EA gtreducing intra-glomerular
  pressure
• Restoration of glomerular perm-selectivity in
  proteinuric NPs
• ? Effect on the GH like of AII

39
Adverse 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

40
Glycemic Control in Diabetics

• Tight control of blood glucose HbA1C lt7
• Delay the onset of microalbuminuria
• Decrease 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.
200036(suppl)S31-S38. The Diabetes Control and
Complications Trial, long-term Sweden study,
Japanese study
41
RENAAL Primary Components
ESRD
Risk Reduction 28
P
p0.002
with event
L
Doubling of Serum Creatinine
Risk Reduction 25
p0.006
Months
P ( CT)
762
715
610
347
42
L ( CT)
751
714
625
375
69
with event
ESRD or Death
Risk Reduction 20
p0.010
P
with event
L
Months
762
689
554
295
P ( CT)
36
L ( CT)
751
692
583
329
52
Brenner BM et al New Engl J Med
2001345(12)861-869.
Months
P ( CT)
762
715
610
347
42
L ( CT)
751
714
625
375
69
42
Hyperlipidemia

• In CRF
• Mainly hypertriglyceridemia
• gt Increases glomerulosclerosis by
• Increasing mesangial proliferation and matrix
  production
• Altering glomerular hemodynamics
• Increasing local inflammation

43
Smoking Cessation

• All patients with renal disease should be
  encouraged to quit smoking
• DM is 3 to 4 times more common in smokers than in
  nonsmokers
• Smoking increases the relative risk for
  progression of CRF in nondiabetics
• Former smokers have an intermediate risk

44
Principles of Management of CKD Patients

• Early recognition of CKD
• Estimate the severity of CKD
• What is the cause of CKD?
• Detection and correction of any reversible
  causes. Avoidance of additional renal injury
• Institution of interventions to delay progression
• Treatment of complications
• Planning for renal replacement therapy

45
Fluid and electrolyte disorders Sodium and Water

• Most often
• Impaired Na excretion gt Edema, HTN, CHF
• TRT
• Moderate Na restriction
• Loop diuretics
• In some patients
• Salt wasting gt volume depletion gt worsening of
  CRF
• TRT
• Na replacement

46
Fluid and Electrolyte DisordersPotassium Balance

• Hyperkalemia
• 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..

47
Fluid and Electrolyte DisordersAcid-Base
Disorders

• Metabolic acidosis
• Occurs relatively early
• Treatment
• Decrease protein intake
• Alkali supplementation if bicarbonate lt 17mEq/L
• Na bicarbonate or Na citrate, 1 mEq/kg/day
• This will prevent
• Excessive bone loss
• Muscle breakdown
• Tubulointerstitial inflammation

48
Hypocalcemia Hyperphosphatemia

• Hypocalcemia
• Deficiency in Vit.D, Hyperphosphatemia
• Hyperphosphatemia
• Early in renal failure Ph-- clearance gt
  Ph-- gt PTH gt Ph-- clearance
• Frank hyperphosphatemia occur if GFR lt 30 mL/min
• Management
• Dietary phosphate restriction
• Phosphate binders Ca carbonate, Renalgel,..
• Vit D Rocaltrol, One Alpha,..

49
Anemia

• Present when GFR lt 30-35 mL/min
• Causes
• 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.
200138955-962.
50
Independent Risk of a Fall in Mean Hb of 1 g/dL
in Dialysis 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. 19962853-61.
51
Cardio - Renal - Anemia Syndrome
Vicious Circle of Destruction
CKD
CHF
Anemia
52
Cardio - Renal - Anemia Syndrome

• 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
• gt To save the heart and the kidney, treat the
  anemia

53
Treatment 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

54
Principles of Management of CRF Patients

• Early recognition of CRF
• Estimate the severity of CKD
• What is the cause of CRF?
• Detection and correction of any reversible cause.
  Avoidance of additional renal injury
• Institution of interventions to delay progression
• Treatment of complications
• Planning for renal replacement therapy

55
Planning for Renal Replacement 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 gt need for A-V fistula (4-6 months)
• Tx work-up

56
TRADITIONAL DIALYSIS START
57
Timely Dialysis Start
58
EARLY DIALYSIS START

• Early dialysis start (CrCl gt 10 ml/min) vs late
  dialysis start (CrCl lt 4 ml/min)
• gt higher 12 yr survival (85 vs 51)
• Bonomini et al Kidney Int 17S57 1985
• gt improved quality of life at 6 months post
  initiation of RRT
• Korevaar et al AJKD Jan 2002

59
Conclusion, 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

60
Conclusion, 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 lt 16-17 mEq/L
• Phosphate binders, Vit D
• EPO, Iron