Clinical Case: Transplant and Dialysis

Question 1

Dialysis Needs:

Answer 1

1. semiperm membrane
2. anticoag
3. access
4. know what to remove and how much

Question 2

Besides the kidney, what is a natural membrane?

Answer 2

Peritoneum (paracentesis to remove fluid from abdo)

Question 3

For dialysis, could use; take advantage of

Answer 3

hollow tubes made of cellulose acetate, with dialysate on the outside (cellulose acetate is a semipermeable membrane);
countercurrent flow such that a concentration gradient is always maintained

Question 4

Drug dosing is based onc

Answer 4

creatinine clearance

Question 5

The MDRD (GFR) and Cockgroft-Gault formula are only useful if; also, what do you have to account for?

Answer 5

you have stable renal function (if you clamp off the renal arteries, your GFR will not be what the formula says, it will be ZERO);
BSA!!!

Question 6

Possible derangements in kidney function?

Answer 6

1. Water balance
2. Electrolyte balance (Na, K, P, protein)
3. Hormonal disruption (EPO, whose production declines with declining renal function; PTH upreg by low Ca or high P, downreg by 1,25 vit D: give 1,25 Vit D or analogues, or Cinalcalcet; vit D normally upregulated by increased PTH)

Question 7

Uremia:

Answer 7

1. loss of appetite (particularly to protein)
2. Nausea
3. Metallic taste
4. Serositis (pericarditis)
5. Mental status change

Question 8

Deciding to supplement a drug depends on

Answer 8

1. Size
2. Volume of distribution (drugs NOT IN BLOOD won’t get cleared)
3. Protein binding (not cleared)
4. Time on dialysis (have to give someone e.g. more PO4);
   think about MIDDLE MOLECULES

Question 9

Diet as a drug:

Answer 9

1. Fluid restriction
2. Na restriction (increased Na intake leads to increased fluid intake because of more thirst)
3. K restriction (GI tract becomes a major excretor)
4. PO4 restriction (Phosphate binders like Lanthanide, or resins)
5. Protein (ENCOURAGE increased intake)

Question 10

Why are kidney transplants so low anatomically?

Answer 10

BLOOD SUPPLY

Question 11

Immunosuppresion: induction agents

Answer 11

1. Abs: Pan T-cell (ATGAM or polyclonal horse, ALG/thymoglobulin or polyclonal rabbit, OKT3 is murine monoclonal that targets the CD3 TCR signaling complex)
2. Abs: Targeted T cells (Anti-IL-2 receptor like dacluzimab which is humanized murine mono, and basiliximab which is chimeric murine monoclonal; misc is alemtuzimab which is humanized anti-CD52 or nuclear warfare)
3. Methylprednisilone

Question 12

Adverse effects of the induction agents?

Answer 12

1. OKT3, ATGAM: cytokine release syndrome (shake and bake), lymphopenia
2. ALG: lymphopenia is prolonged and less cytokine release syndrome than above
3. Anti-IL2 receptor: rare hypersens reactions

Question 13

Immunosuppression agents: maintenance:

Answer 13

1. Calcineurin inhibitors: block IL-2 production (cyclosporin and tacrolimus with high levels early and tapered over next two months)
2. Steroids: methylpredinisilone and prednisone (high dose early, taper over first few mos)
3. Antimetabolites: inhibit de novo purine synthesis (azathioprine metabolized into 6-mercaptopurine; mycophenolate mofetil and mycophenolic acid)
4. mTOR inhibitors (sirolimus that blocks cell cycle progression from G1 to S phase; also everolimus)
5. Belatacept: fusion of IgG1 FC and EC domain of CTLA-4, blocking co-stim of T cells by preventing CD28-CD80/86 interaction

Question 14

Anti-rejection drugs:

Answer 14

1. Cell-mediated rejection (pulse steroids like methylpred, and thymoglobulin)
2. Antibody-mediated rejection (rituxumab as chimeric ab to CD-20; plasmapheresis and IVIG)

Question 15

Steroid complications:

Answer 15

1. Weight gain
2. glucose intolerance/diabetes
3. Hyperlipidemia/tension
4. Osteoporosis
5. Avascular necrosis
6. Cataracts

Question 16

Calcinurin inhibitors complications:

Answer 16

1. NEPHROTOXIC
2. Gingival hyperplasia
3. Hypertrichosis: too much hair in women with cyclosporine
4. Hyperlipidemia
5. Tremor
6. Neuropathy
7. Hyperuricemia/gout
8. glucose intolerance/diabetes (Tacro)
9. HUS
10. significant drug interactions (if metabolized through CYP3A4)

Question 17

Azathioprine and mycophenolate complications:

Answer 17

1. leukopenia/myelosuppression
2. hepatotoxicity
3. pancreatic toxicity
4. interaction with allopurinol (if you get gout on this drug, don’t go on gout);
5. GI intolerance
6. leukopenia/myelosuppression

HALPern and GILlian are good friends

Question 18

Sirolimus med complications:

Answer 18

1. Hyperlipidemia
2. Impaired wound healing (NOT FOR LUNG TRANSPLANTS)
3. Interstitial pneumonitis

HIP