lab role on renal replacement therapy

1. Laboratory Role in Renal
Replacement Therapy
PRESENTER: DR. JYOTI SHARMA
MODERATOR: DR. PURVI PUROHIT

2. Roadmap
• Normal function of kidneys
• What is renal replacement therapy
• When it is required --- AKI, CKD, via dialysis/ transplant
• What are the guidelines for AKI (in terms of role of lab)
• What are the guidelines for critical care renal replacement therapy (in terms of role of
lab)
• What are the guidelines for CKD patients for renal replacement therapy (in terms of role
of lab)
• Role of lab in renal transplant in terms of KFT, electrolytes and immunosuppression
drugs monitoring
• Any new markers identified for renal replacement therapy monitoring in lab their
significance and their advantages disadvantages over traditional markers.
• Take home message

3. OVERVIEW OF KIDNEY FUNCTIONS
• Excretion of wastes and other foreign substances. (Ammonia and urea
Bilirubin Creatinine ,Uric acid)
• Regulation of blood ionic composition and blood pH. (Removing excess acid
(hydrogen ion) or bases (bicarbonate)
• Production of hormones.(Erythropoietin,Clacitriol)
• Regulation of blood pressure. ( RAAS system)
• Regulation of blood volume.
• Maintenance of blood osmolarity.

4. ACUTE KIDNEY INJURY(AKI)
• The International Acute Dialysis Quality Initiative(ADQI) defines AKI as an
abrupt decrease in kidney function, but is not limited to oliguria nor anuria.
• severe form requires of RRT

5. GUIDELINES FOR AKI ASSESMENT

6. CAUSES OF ACUTE KIDNEY INJURY

7. Indications of Dialysis in AKI
• Uremia
• Hyperkalemia
• Hyponatremia
• Fluid overload
• Metabolic Acidosis
• Hypercatabolic state

8. CHRONIC KIDNEY DISEASE( CKD)
• defined as abnormalities of kidney
structure or function, present for at least
three months, with implications for health.
(KDIGO)

9. GRADING OF CHRONIC KIDNEY DIESEASE

10. INDICATIONS OF DIALYSIS IN CKD
• GFR <15ml/min/1.73m2 BSA.
• Growth Failure
• Severe HTN
• Intractable intravascular volume overload
• Profound electrolyte abnormalities {hyperkalemia , hyperphosphatemia
etc.}

11. RENAL REPLACEMENT THERAPY
• Renal replacement therapy (RRT) replaces non endocrine kidney function
in patients
• It is used when the kidneys are not functioning well i.e in conditions like
Acute or Chronic Kidney Disease.

12. HISTORY
• In 1861, Thomas Graham Bell in Glasgow, Scotland, coined the term dialysis
and predicted that this technique could have medical application
• Willem Kolff and then Belding Scribner, who made HD a feasible treatment
in the early 1960s.

13. RENAL REPLACEMENT
PRINCIPLE

14. MODALITIES OF RRT
HEMODIALYSIS
PERITONEAL DIALYSIS
RENAL TRANSPLANTATION

15. DIALYSIS
• All dialyses modalities can be used to ensure equivalent solute clearence
and ultrafiltration.
• Choice of procedure depends on
• a) Age & size of the patient
• b) Cardiovascular status
• c) Availability of vascular status
• d) Integrity of peritoneal membrane and abdominal cavity.
• e) Expertise available.

16. HEMODIALYSIS
• Most common to treat advanced and permanent kidney failure
• blood flows to and from a semipermeable large surface area membrane
• After filtration to remove wastes and extra fluid, the cleansed blood is
returned to the patient.
• Biocompatibility of the dialyzer membrane is an essential requirement
because of high surface areas and long contact times.

17. SCHEMATIC
REPRESENTATION
OF
HEMODIALYSER

18. COMPLICATIONS
1.Dialysis disequilibrium syndrome: Manifested as seizures
2.Muscle Cramps
3.Hypotension.
4. Nausea & Vomiting
5.Itching.

19. PERITONEAL DIALYSIS
• Peritoneal dialysis uses the peritoneum as a natural permeable membrane
through which water and solutes can equilibrate.
• peritoneal dialysis is
• Less physiologically stressful
• Does not require vascular access
• Can be done at home
• Allows patients much greater flexibility

20. TYPES
Manual - Continuous ambulatory peritoneal dialysis (CAPD)
- Intermittent peritoneal dialysis (IPD)
Automated - Continuous cyclic peritoneal dialysis (CCPD)
-Tidal peritoneal dialysis (TPD)
-Nocturnal intermittent peritoneal dialysis (NIPD)

21. COMPLICATION
• Bleeding after catheter insertion
• Perforation of gut.
• Abdominal pain
• Leakage around catheter
• Difficult Drainage
• Exit site infections.
• Peritonitis
• Metabolic problems

22. ADVANTAGES
• Ability to perform dialysis at home.
• Technically easy than hemodialysis, especially in infants
• Ability to live a greater distance from medical center
• Freedom to attend school
• Less restrictive diet
• Less expensive than hemodialysis

23. TYPES OF CONTINOUS
RENAL REPALCEMENT
THERAPY

24. SLOW CONTINUOUS
ULTRAFILTRATION
• Remove plasma water in
patients without significant
electrolyte or other acid-
base abnormalities.
• Blood is pumped through
the fibres of the dialysis filter
at a pressure higher than
that surrounding the fibres.
• The hydostatic pressure
determines the rate of fluid
removal.

25. CONTD…
Advantage :
• Decreased complexity and less nursing staff required
• Majorly fluid removal
Disadvantage
• Lower efficiency solute clearance

26. Continuous veno-
venous hemofiltration
• Uses convection
• The porosity of the membrane determines
which solutes are removed. (small
molecule:urea, and middle-size
molecules:inflammatory cytokines,are cleared).
• Intravascular volume must be maintained
using a replacement fluid.
• Decision based on patient’s serum
potassium and acid-base balance.
(Eg: bicarbonate containing fluids are used for
metabolic acidosis and normal saline in metabolic
alkalosis)

27. CONTINUOUS VENO-
VENOUS HEMODIALYSIS
• counter-current dialysate flow(diffusion
acc.to conc. gradient).
• Solute clearance can be increased with higher
dialysate or blood flow rates.
• Dialysates - physiologic concentrations of
sodium, chloride, magnesium, and glucose.
• The potassium concentration vary - 0 to 5
mmolL
• Buffered with either bicarbonate or a
bicarbonate precursor (lactate, citrate, or
Acetate) ,
• Impaired in liver failure or shock states.

28. Continuous veno-venous
hemodiafiltration
• combines hemodialysis (diffusive
dialysis) and hemofiltration (convective
dialysis).
• The ultrafiltrate can be replaced by
either replacement fluid and the
counter-current/co-current dialysate
flow.
• CRRT mode is determined by the
patient’s volume, serum urea, and
potassium and acid-base balance status.

29. SUMMARY

30. ANTICOAGULATION
MODES OF ANTICOAGULANTS DURING RENAL REPLACEMENT THERAPY

31. ASSESSMENT OF DIALYSIS
• Clinical assesment, cardiovascular risk, nutritional status, and degree of achievable ultrafiltration.
• Estimation hemoglobin, phosphate, and albumin, and clearance of the small solutes, urea and
creatinine
• Urea removal assessed by Kt/v
k - amount of plasma cleared of urea
t - duration of the session
v - urea distribution in body( total body water)
• most precise and accurate measure of dialysis/ session.
• In clinical scenario URR (Urea Reduction Ratio)is calculated
[(Pre dialysis urea) – (post dialysis urea)/ pre dialysis urea]x100

32. AIM OF DIALYSIS
• 30% reduction in BUN during the 1s dialysis(1.5-2hrs)
• 50% during the 2nd treatment. (3hrs)
• >70% reduction during subsequent treatments (3.5-
4hrs)

33. LABORATORY ROLE IN
DIALYSIS MANAGEMENT

34. RENAL TRANSPLANTATION
• Most effective form of renal replacement
therapy
• long-term survival and quality of life.
• Procedure: The donor kidney is usually
placed extraperitoneally in the right or left
iliac fossa.
• The recipient native kidneys are left in situ
in most cases.

35. HISTORY
• Joseph Murray in Boston performed the first successful transplant in 1954
• In 1963, maintenance AZA and corticosteroids was the standard regimen for kidney
transplantation(1 year graft survival approx. 40% )
• Cyclosporin-based protocols improved graft survival(80% - 90%)
• Mid- to late 1990s -Tacrolimus, mycophenolate mofetil (MMF), sirolimus (Rapamycin),
and everolimus (Ever)
• Current agents (monoclonal or polyclonal antibodies directed against immune response
cellular targets)are being studied(1-year graft survival of approx.> 90% )
• At present half life of graft is 14 years

36. PREOPERATIVE ASSESSMENT
• Two important psychological issues remain to be considered:
concept of organ receipt
 potential difficulty in complying with immunosuppressive therapies.
• Age is no longer a primary issue in an healthy individual

37. EXCLUSION CRTERIA FOR KIDNEY
TRANSPLANTATION

38. LABORATORY
ASSESSMENT OF
POTENTIAL KIDNEY
TRANSPLANT
RECIPIENT

39. POST OPERATIVECOMPLICATIONS
• Graft rejection
• Immunosuppressive drug toxicity
• Acute tubular damage.
• Relative hypotension and dehydration may also contribute.
• Renal artery and venous thromboses are rare complications
• Ureteric obstruction

40. IMMUNOSUPPRESIVE DRUGS
• In 1970, introduction of immunosuppressive drugs improved success rate of kidney transplantation
• In 1980s, cyclosporin made a dramatic increase in 1-year graft survival and reduction in acute rejection
episodes
• 1990s, tacrolimus ,1-year graft and patient survival rates were equivalent to cyclosporin therapy, but acute
rejection episodes were lower.
• Five-year follow-up suggested improved graft survival with tacrolimus compared with cyclosporin.
• Sirolimus in combination with Mycophenolate mofetil (MMF )is safe and is associated with low rates of
acute transplant rejection at 12 months

41. IMMUNOSUPPRESIVE DRUGS
• Narrow therapeutic window
• Important to monitor the blood concentration
• METHOD: The “trough” concentration (C-0)- just before the next dose.
• The trough level of tacrolimus is correlated with acute rejection episodes
and nephrotoxicity.
.

42. IMMUNOSUPPRESIVE DRUGS
• (MPA), a potent and reversible inhibitor of inosine monophosphate
dehydrogenase isoform 2 (IMPDH)
• It has become the single most used immunosuppressant in solid organ
transplantation.
• Excellent results have been obtained with a fixed-dose regimen

43. MEDICAL ASPECTS OF LONG-TERM RENAL REPLACEMENT
THERAPY
-Diet
-Anemia of renal failure
-Coronary artery disease
-Hyperphosphatemia
-Hypocalcemia and secondary hyperparathyroidism
-Aluminum toxicity
-Bone disease
-Vitamin deficiencies

44. DIET
• serum albumin > 3.5 g/dL (35 g/L); serum albumin is the best predictor of survival in these
patients.
• Calorie- 35 kcal/kg ideal body weight (in children, 40 to 70 kcal/kg/day depending on age and
activity)
• Sodium - 2 g/day (88 mEq [88 mmol]),
potassium - 2.3 g/day (60 mEq [60 mmol]),
phosphate - 800 to 1000 mg/day
• Fluid intake - 1000 to 1500 mL/day and monitored by measuring weight gain between dialysis
• In peritoneal dialysis need a protein intake of 1.25 to 1.5 g/kg/day (compared with 1.0 to 1.2
g/kg/day in hemodialysis patients) to replace peritoneal losses (8.4 +/- 2.2 g/day).

45. ANEMIA OF RENAL FAILURE
• Poor absorption of iron
• Therefore,many patients require IV iron during hemodialysis. (Ferric
carboxymaltose, sodium ferric gluconate, and iron sucrose are preferred
to iron dextran -has a higher incidence of anaphylaxis.)
• Iron stores are assessed using serum iron, total iron-binding capacity, and
serum ferritin.
• Iron stores are assessed before the start of erythropoietin therapy and
thereafter every other month

46. HYPERPHOSPHATEMIA
• Consequence of phosphate retention due to low glomerular filtration rate
(GFR)
• calcium (Ca) × phosphate (PO4) > 50 to 55- risk of coronary artery
calcification
• Initial treatment is calcium-based antacids (eg: calcium carbonate)
• Constipation and abdominal bloating on chronic use.
• Patients should be monitored for calcium levels

47. HYPERPARATHYROIDISM
• impaired renal production of vitamin D and hypophosphatemia.
• Treatment of hypocalcemia is with calcitriol either orally or IV
• Doses are titrated to suppress parathyroid hormone (PTH) level,

48. ALUMINIUM TOXICITY
• Aluminum-contaminated dialysate and aluminum-based phosphate binders.
• S/S – Osteomalacia
Microcytic anemia (iron-resistant)
Dialysis dementia (a constellation of memory loss, dyspraxia,
hallucinations, facial grimaces, myoclonus, seizures
• Treatment - avoidance of aluminum-based binders + IV or
intraperitoneal deferoxamine (chelating agent).

49. VITAMIN DEFICIENCIES
• Dialysis-related loss of water-soluble vitamins (eg, B, C,
folate)
• Daily renal multivitamin supplements