Current Management of End-Stage Renal Disease

adapted from talk given by Millie Samaniego, M.D.

 

ESRD STATISTICS

•      No. of Pts on treatment for ESRD  in the US in 1997 (Prevalence) =       361, 031.

•      No. of Pts with newly diagnosed ESRD in the US in 1997 (Incidence) = 79,102.

•      Proj. increase in prevalence/year after 1997 = 5.0%.

•      Proj. increase in incidence/year after 1997 = 3.5%.

•      Average survival time for ESRD patients = 4-5 yrs

 

•      CAUSES OF ESRD

–    Diabetes mellitus

–    Hypertension

–    Glomerulonephritis

–    Interstitial nephritis

–    Hereditary diseases

•    ADPKD

•    Other cystic diseases

•    Alport’s Syndrome

–    Miscellaneous

•      MODALITIES OF TREATMENT

–    Dialysis

•    Hemodialysis (HD)

–   Traditional
–   Home HD

•    Peritoneal dialysis (PD)

–   CAPD/CCPD

–    Transplantation

 

Stages of Chronic Kidney Disease

 

Stage

Description

GFR (mL/min/1.73 m2)

1

Kidney damage with normal or ญGFR

ณ90

2

Kidney damage with mild ฏGFR

60-89

3

Moderate ฏGFR

30-59

4

Severe ฏGFR

15-29

5

Kidney failure

<15 (or dialysis)

 

Definition of Chronic Kidney Disease

 

CRITERIA

1. Kidney damage for ≥3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifest by either:

•Pathological abnormalities

•Markers of kidney damage: blood, urine or imaging tests

 

2. GFR <60 mL/min/1.73m2 for ณ 3 months, with or without kidney damage

 

 

 

Stages of Chronic Kidney Disease

 

GFR  (mL/min/1.73 m2)

with kidney disease

without kidney disease

>=90

1

htn or “normal”

60-89

2

“htn + decr GFR” or “decr GFR”

30-59

3

3

15-29

4

4

<15 (or dialysis)

5

5

 

 

Management of ESRD

 

ER Patient:

Dialysis unit Patient:

ESRD of unknown etiology is diagnosed on presentation:

Hx of ESRD of known or unknown etiology:

Uremic syndrome:

•    Cardiovascular issues:

–   Hypervolemia and hypertension.
–   Pericarditis
–   Left ventricular dysfuntion: systolic Vs diastolic

Complications of ESRD:

•    Cardiovascular issues:

–   Coronary artery disease
–   Peripheral vascular disease
–   Left ventricular dysfunction: systolic Vs diastolic

•    Metabolic issues:

–   Metabolic acidosis
–   Hyperkalemia
–   Bone disease
ป   2ary HPTD
ป   hypocalcemia
ป   hyperphosphatemia

•    Metabolic issues:

–    Metabolic acidosis
–    Hyperkalemia
–   Bone disease
ป   2ary and 3ary HPTD
ป   Adynamic bone disease
ป   b2-microglobulin amyloidosis

•    Hematological issues:

–    Severe anemia with hypoplastic BM  response.
–    Uremic platelet dysfunction and bleeding diathesis

•    Hematological issues:

–   EPO resistance:
ป   Fe++ deficiency
ป   Bone disease
ป   GI blood loss
ป   Co-enzymes deficiency
ป   Use of ACEI
                        -  Hypercoagulability

•    Nutritional issues:

–   Hypoalbuminemia.
–   Hyperkalemia.
–   แแ PO4, โโ Ca++.
–   Na+ and fluid management.

                      Diet: 2g Na+, 2g K+, 60g Prot

 

 

•    Nutritional issues:

–    Hyperkalemia.
–   แแ PO4, โโCa++.
–   Na+ and fluid management

                    Diet: Xg Na+, Xg K+, 1.5g/Kg/d Prot, 35 Kcal/Kg/d

 

 

•    GI issues:

                         Erosive gastritis and esophagitis

•    GI issues:

–    Erosive gastritis and esophagitis
–   AVMs
–   Hepatitis B and C infections
–   Colonic diverticula in ADPKD

•    Neurologic issues:

–   Altered mental status
–    Seizure disorders
–    Severe sensori-motor peripheral neuropathies

•    Neurologic issues:

–   Altered mental status
–    Movement disorders
ป    Restless leg syndrome and sleep disorders
–    Peripheral neuropathy
ป    b2-microglobulin amyloidosis
                        - Autonomic neuropathy

•    Modality of dialysis and access issues:

–   HD  Vs PD
–    HD:
ป   Native fistula Vs PTFE graft
ป   Vascular imaging
–    PD:
                                Placement of PD catheter and Pt training

•    Modality of dialysis and access issues:

–    HD  Vs PD
–    HD:
ป   Loss of vascular access
–    PD:
                                    Membrane failure

 

 

•      Native AV Fistulas

–    Vascular access of choice

•    Longer t1/2 , lower complication rate.

–    Order of preference for placement:            

•    Wrist (radio-cephalic)

•    Elbow (brachio-cephalic)

•    Transposed brachial-basilic

–    Long maturation times (1-4mos)

–    Lower infection rate

•    Access of choice in HIV or

                IV drug users

•      PTFE AV grafts

–    2nd choice

•    Shorter t1/2 , higher complication rate.

–    Site of placement:

•    Depends on Pt’s anatomy

–    Easier to repair and to cannulate

–    Larger cannulation area

–    Short maturation time (3-6wk)

–    Higher infection rate

                 Contraindicated in IV drug users

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


•     Bone disease in ESRD:

                                Renal Osteodystrophy

–  Osteitis Fibrosa Cystica (2ary or 3ary HPTH).

–  Osteomalacia.

–  Adynamic bone disease.

–  b2-microglobulin amyloidosis.

 

 

SPECIAL ISSUES IN ESRD

•      Bone disease management:

–   Osteitis Fibrosa Cystica (2ary HPTH):

•   Clinical features:

–   Hypocalcemia and hyperphosphatemia
–   Elevated Alk phos with normal GGT/LFTs
–   Bone lytic lesions:
ป   Skull series, long bones, hands/wrists, spine and bony chest films.
–   Bone/joint pains; ectopic calcifications; pruritus.
–   iPTH levels (>200 pg/ml).

 

•   Target levels:

– Calcium levels:          9.5-10.5 mg/dl
– PO4 levels:                 4.5-5.5 mg/dl
–   Ca x P product:         75 mg2/dl2
– iPTH levels:                2-4 times nl levels (~200 pg/ml)

 

•   Medical management:

–   Pathophysiology-guided
ป   Replacement of Vitamin D3 (calcitriol) levels
ป   Phosphate binding
ป   Correction of metabolic acidosis
ป   Avoidance of aluminum toxicity
ป   Avoidance of high Ca x P product

•   Surgical management:

–   Failure of medical therapy = iPTH levels >=1000 pg/ml

 

•   Medical management:

–   Vitamin D3 (calcitriol) supplementation:
ป   Oral preparations Vs IV preparations
    Pts with iPTH levels > 1000 pg//ml
    Pts with severe hyperphosphatemia on Rocaltrol
ป   Pulse calcitriol therapy:
    2 - 4 mg twice a week (4-8 tablets per Tx).
    An excellent choice in Pts on CAPD.
–   Avoid if iPO4 level is > 7 mg/dl ่ แ Ca x P product

 

–   Calcium supplementation:
ป   Dialysate Ca++ 3.25-3.50 mEq/L (all ionized)
ป   Low Ca++ dialysate (2.0-2.5 mEq/L) can be used in the event of hypercalcemia.
–   Calcium preparations: Ca++ acetate VS Ca++ carbonate
ป   1250 mg of Ca++ carbonate: 500 mg of elemental Ca++
ป   667 mg of Ca++ acetate:   167 mg of elemental Ca++

 

–   Phosphate removal
ป   Hemodialysis removes กึ 1,000 mg/Tx of PO4
ป   CAPD removes กึ 300 mg/day of PO4
–   Phosphate binding: Ca++ acetate VS Ca++ carbonate
ป   1250 mg of Ca++ carbonate: 500 mg of elemental Ca++
ป   667 mg of Ca++ acetate:   167 mg of elemental Ca++

 

–   Correction of acidemia:
    ้ 1,25 (OH)2D3 levels and ๊ osteocalcin ่            osteoblast                                                                                                 function
ป   Sodium bicarbonate VS Sodium citrate:
    Pre-HD or stabilized serum NaHCO3  กร 22 mEq/L.ถ
    Dosing:              NaHCO3 of 2-4 g/day PO
ป   Sodium citrate has the same short-term effects on acid-base homeostasis in normal subjects as NaHCO3.
      Less  well tolerated than NaHCO3.
    Increases absorption of trivalent cations: Al+++ and Fe+++.

 

–   Avoidance of high Ca x P product
ป   Renagelฎ:           Polymer phosphate binder.
    Pts on Al containing binder due to hypercalcemia on Ca++-containing binder.
    Pts who develop hypercalcemia on calcitriol.
    Pts on large amounts of Ca++-containing binder (>4 per meal)
    ? Pts with adynamic bone disease?
    ? Pts with known CAD?

 

–   Dosing: Renagelฎ (sevelamer; caps=465 or 800 mg)           
ป   Starting dose:
                2 to 4 caps three times a day with meals
ป   Dose adjustment:
                Every 2 weeks:
                dosage increment by one capsule/meal as
                needed to achieve a PO4 level = 2.5-5.5 mg/dl
               
–  Renagelฎ (sevelamer; caps=465 or 800 mg):        
ป   Dosing:
ป   Mean starting dose:         3.4g/day
ป   Maintenance dose:           4.9g/day (at the end of 8 wks)

•    Compared to PhosLoฎ, Renagelฎ is as effective in lowering PO4 concentrations with a much lower incidence of hypercalcemia.

•    In addition, treatment with Renagelฎ results in lower Ca x P product and lower serum LDL cholesterol (binding of bile acids). 

 

Biochemical Parameters

 

 

 

 

 

 

 

 

 

 

 

 

 


Chertow, GM et al: Kidney International 62 (1):245-52

 

 

SPECIAL ISSUES IN ESRD

•      Anemia:

–   Pathogenesis:

•    Decreased renal mass and low EPO production:

–   Inadequate dialysis.

•    Abnormal iron metabolism:

–   Abnormal Fe++ metabolism.
–    Impaired utilization/mobilization of Fe++.

•    Occult and chronic blood loss.

•    Bone disease: Osteitis fibrosa and Al+++ toxicity.

•    Special problems:

–   Carnitine deficiency.
–   Ascorbate deficiency.
–   Coexistent diseases:  Multiple myeloma.
–   Malnutrition.

 

•    Evaluation of Iron Kinetics:

–   Ferritin levels and transferrin saturation

•    Erythropoietin administration

•    IV Iron Vs PO Iron

•    Evaluation of Bone Marrow response

–   Reticulocyte count

•    Erythropoietin resistance:

–   Occult GI blood loss                     ่           Guiac test x 3
–   Abnormal hemoglobins                ่           Electrophoresis
–   Vit B12 or folate deficiency           ่           Blood/RBC levels

•   Clinical Practice Guidelines (DOQI):

–  Hct of 33-36% (Hb 11-12 g/dl)   
–  Ferritin >= 100 ng/ml
–  TSAT >= 20%            
–  Preferred use of parenteral Iron over PO Iron for repletion and maintenance.

 

Evaluation of Iron Stores

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

EPO RESISTANCE

 

–   Administration of Erythropoietin:

•    The preferred route of administration is SQ (regardless modality of dialysis).

•    Preparation of choice: multi-dose Epo with benzyl alcohol.

•    Dosing:              80-120 U/Kg/wk (divided in 3 doses).

•    Monitoring:       Every 1-2 wks, initially.

                Every 2-4 wks once the Hct is stable.

•    IV administration of Epo requires a dose increase of 50% (120-180 U/Kg/wk in 3 doses).

•      CORONARY ARTERY DISEASE:

–    Cardiovascular mortality in the general and in ESRD populations – significant difference

–    Screening recommendations in the ESRD population:

•    Routine screening for inducible ischemia is not recommended in ESRD patients without clinical manifestations of CAD.

•    Presurgical screening recommendations for non-cardiac surgery for patients with ESRD : as in general population.

•    Pharmacological stress testing (dobutamine or Persantineฎ) is the test of choice in asymptomatic ESRD patients.

–   Baseline EKG:

•   Loss of sensitivity and specificity due to LVH, electrolyte derangement.

–   Cardiac enzymes in the diagnosis of injury:

•   Total Creatine Kinase (CK) levels

–   Baseline total CK values may be elevated in up to 30%

          of Pts on HD (MM isoenzyme).

ป   AA >>Caucasians; M>>F

•   The utility of CK-MB is not compromised.