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Laboratory role in renal replacement therapy.pptx
1. Laboratory Role in Renal
Replacement Therapy
PRESENTER: DR. JYOTI SHARMA
MODERATOR: DR. PURVI PUROHIT
2. 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.
3. RENAL REPLACEMENT THERAPY
• Replaces the normal blood-filtering function of the kidneys.
• It is used when the kidneys are not working well, (kidney failure and acute kidney
injury and chronic kidney disease)
( "Overview of Renal Replacement Therapy - Genitourinary Disorders". Merck Manuals Professional Edition.)
4. 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.
6. INDICATIONS
• Renal insufficiency (acute or chronic)
• Fluid overload (refractory to diuretics)
• Severe hyperkalemia (>6.5 mEq/L) or rapidly rising potassium levels
• Severe metabolic acidosis (pH <7.1) despite medical management
• Overt manifestations of uremia (pericarditis, encephalopathy)
• eGFR of around 5-7 mL/min/1.73 m2 if there are no symptoms.
• eGFR of 10-14 mL/min/1.73 m2 if there are uremic symptoms.
(Lisa Gemmell, MBChB FRCA FFICM, Robert Docking, MBChB FRCA FFICM, Euan Black, MBChB FRCA FFICM, Renal
replacement therapy in critical care, BJA Education, Volume 17, Issue 3, March 2017,
8. ACUTE KIDNEY INJURY(AKI)
• Definition: Acute kidney injury (AKI) refers to an abrupt decrease in kidney function, resulting in
the retention of urea and other nitrogenous waste products and in the dysregulation of
extracellular volume and electrolytes. - Acute Dialysis Quality Initiative (ADQI) Group
• increase in serum creatinine (≥0.3 mg/dL within 48 h or ≥1.5 times baseline) or urine volume <
0.5 mL/kg/h for 6 h](KDIGO)
10. GUIDELINES FOR AKI ASSESMENT
AKI stage KDIGO RIFLE AKIN
1 (R)
Increase ≥ 0.3 mg/dl within 48 h
or ≥
1.5- to 2-fold from baseline
Increase × 1.5 baseline or
GFR decrease > 25%
Increase 1.5-1.9 times from
baseline or ≥
0.3 mg/dl increase within 48 h
< 0.5 ml/kg/h for 6-12 h
2 (I) 2.0-2.9 times from baseline
Increase × 2 from baseline
or GFR
decreased > 50%
Increase > 2- to 3-fold from baseline < 0.5 ml/kg/h for 12 h
3 (F)
3.0 times from baseline or
increase in serum
creatinine to ≥ 4.0 mg/dl or
initiation of
renal replacement therapy or, in
patients < 18 years,
decrease in eGFR to < 35
ml/min per 1.73 m2
Increase × 3 from baseline,
or serum creatinine > 4
mg/dl)
with an acute rise > 0.5
mg/dl or GFR decreased >
75%
Increased > 300% (> 3-fold) from
baseline, or ≥
4.0 mg/dl with an acute increase of ≥
0.5 mg/dl or
on renal replacement therapy
< 0.3 ml/kg/h for 24 h or anuria for
12 h
Urine output
R: Risk; I: Injury; F: Failure; KDIGO: Kidney Disease Improving Global Outcomes; RIFLE: The Risk, Injury, Failure, Loss, End-Stage;
AKIN: Acute Kidney Injury Network.
11. BIOMARKERS FOR AKI
• Helpful for detecting an injury to the kidney before the increase in serum creatinine during AKI
Cystatin C (CysC)
Neutrophil gelatinase-associated lipocalin (NGAL)
Kidney injury molecule-1 (KIM-1)
L-type or liver-type fatty acid-binding protein (L-FABP)
Interleukin-18 (IL-18)
• The increase in biomarkers as NGAL and KIM-1 is associated with an increased risk of subsequent
renal replacement therapy and/or mortality.
• Cystatin C (CysC) is freely filtered in the glomerulus, almost completely reabsorbed and
catabolized only by kidney .Therefore,it is more accurate than creatinine in determining GFR.
12. GUIDELINES FOR LABORATORIES TO MEASURE CYSTATIN C
• Measure serum cystatin C using an assay with calibration traceable to the international standard reference
material.
• Report eGFR from serum cystatin C in addition to the serum cystatin C concentration in adults and specify
the equation
• Report eGFRcys and eGFRcreat-cys in adults according to CKD-EPI cystatin C and CKD-EPI creatinine-cystatin
C equations, respectively,
• Serum cystatin C concentration rounded to the nearest 100th of a whole number when expressed as
conventional units (mg/l).
• eGFRcys and eGFRcreat-cys be reported and rounded to the nearest whole number and relative to a body
surface area of 1.73m2 in adults using the units ml/min/1.73m2 .
• eGFRcys and eGFRcreat-cys levels less than 60 ml/min/ 1.73m2 should be reported as ‘‘decreased.’’
(KDIGO Guidelines CKD 2012)
13. CHRONIC KIDNEY DISEASE( CKD)
• DEFINITION: abnormalities of kidney structure
or function, present for at least three months,
with implications for health. (KDIGO)
14. CAUSES OF CKD
• Diabetes
• Hypertension
• Polycystic kidney disease (PKD).
• Lupus nephritis
• IgA glomerulonephritis
• Heavy metal poisoning,
• Hemolytic uremic syndrome in children
• IgA vasculitis
• Renal artery stenosis
15. GRADING OF CHRONIC KIDNEY DIESEASE
(KDIGO GUIDELINES)
*Referring clinicians may wish to discuss with their local nephrology service, depending on local arrangements regarding referral and
monitoring.
16. 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.}
19. SELECTION CRITERIA IN 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.
20. HEMODIALYSIS
• Most common to treat advanced and
permanent kidney failure
• solute clearance is achieved by diffusion
across the 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.
22. INTERMITTENT HEMODIALYSIS
• INDICATION:
• Correct electrolyte and fluid imbalances
• Remove toxins
• REGIME:
• 3 to 5 hours of hemodialysis 3 times a week(most common)
• A ≥ 65% decrease of BUN from predialysis levels – successful session
23. CONTINUOUS RENAL REPLACEMENT THERAPY
• Continuous renal replacement therapy (CRRT) - for critically ill patients with acute kidney
injury, particularly patients who are hemodynamically unstable
• differ in their mode of solute clearance
24. PERITONEAL DIALYSIS
• uses peritoneum as a natural
permeable membrane for
water and solutes
equilibrium
• Less physiologically stressful
• Does not require vascular
access
• Can be done at home
• Allows patients much
greater flexibility
26. COMPLICATION
• Bleeding after catheter insertion
• Perforation of gut.
• Abdominal pain
• Leakage around catheter
• Difficult Drainage
• Exit site infections.
• Peritonitis
• Metabolic problems
27. 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
29. 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)
30. 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. 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.
33. 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
34. EXCLUSION CRTERIA FOR KIDNEY
TRANSPLANTATION
• Serious concomitant illness (particularly if likely to shorten life
• expectancy or to be exacerbated by immunosuppressive treatment)
• Active malignancy
• Inoperable ischemic heart disease
• Severe chronic lung disease
• Active systemic infection (eg, tuberculosis)
• Active immunological disease
• Severe irreversible hepatic disease
• Severe peripheral vascular disease
• Severe obesity (body mass index [BMI] >40 kg/m2
• Lower urinary tract dysfunction not amenable to surgical
• repair
• Substance abuse
• Significant psychiatric disturbance
35. LABORATORY PROFILE FOR THE POTENTIAL KIDNEY
TRANSPLANT PATIENT
• Liver function test
• Kidney function test
• Serum electrolyte
• Acid base status
• Viral markers(HIV ,CMV,VZV, Hep Band C)
• Complete Blood count
• Clotting profile
• ABO compatibility
• HLA Matching
37. 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
38. IMMUNOSUPPRESIVE DRUGS
• Mycophenolate mofetil (MMF ), ester of mycophenolic acid- 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
39. IMMUNOSUPPRESIVE DRUGS AND
MONITORING
• 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.
.
40. COMMONLY USED IMMUNOSUPPRESSENT
DRUGS
DRUGS DOSAGE THERAPEUTIC
WINDOW
SIDE EFFECT
Corticosteroids—prednisone 40 mg daily during first week and
tapering to 5 mg at 6 months and
withdrawal at 12 months
risk of developing
diabetes mellitus
Osteopenia
Osteoporosis
Psychosis
Weight gain
Cyclosporin Depends on weight,
time since transplant
and achieved drug
concentration. Dose
given in 2 divided doses
200–300 µg/L for first
3–12 months.
Thereafter, aim for 100
µg/L.
Nephrotoxicity
Hypertension
Neurotoxicity
Hemolytic-uremic syndrome
Electrolyte abnormalities
Hirsutism
Gingival hyperplasia
Bone pains
Dyslipidemia
Mycophenolate mofetil Initially 2 g daily in divided
doses
Not routinely measured Abdominal pain
Diarrhea
Myelosuppression
Basiliximab and Daclizumab(Anti-
CD25 Ab)
Given at time of transplant
and once thereafter
Well tolerated
42. MEDICAL ASPECT 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
43. 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).
44. 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 initially for 7 days then 2-3 times/week followed by weekly
for 2-3 months and then annually
• Iron stores are assessed before the start of erythropoietin therapy and
thereafter every other month
45. 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
46. HYPERPARATHYROIDISM
• impaired renal production of vitamin D and hypophosphatemia.
• elevated levels of iPTH are observed after transplantation for more
than a year
• Treatment of hypocalcemia is with calcitriol either orally or IV
• Doses are titrated to suppress parathyroid hormone (PTH) level
(Marcén, R., Ponte, B., Rodríguez-Mendiola, N., Fernández Rodriguez, A., Galeano, C.,
Villafruela, J. J., Teruel, J. L., Burgos, F. J., & Ortuño, J. (2009). Secondary
hyperparathyroidism after kidney transplantation: a cross-sectional study. Transplantation
proceedings, 41(6), 2391–2393. https://doi.org/10.1016/j.transproceed.2009.06.047)
47. 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. TAKE HOME MESSAGE
• Renal replacement therapy: replaces the normal blood-filtering function of the kidneys.
• Indication: Renal failure-most common - AKI, CKD
• Modes : Hemodialysis
• Peritoneal dialysis
• Renal transplantation
• Aim :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)
50. CONTD…
• Renal transplantation: kidney is usually placed extraperitoneally in the right or left iliac fossa.
• Evaluation of potential renal transplant patient: clinical, Laboratory and psychological
• Role of immunosuppressants in renal transplants: reduces graft rejection cases, has narrow
therapeutic window
• Trough method : to monitor immunosuppressant drug monitoring
• Long term complications: Anorexia, anaemia , aluminium toxicity, hyperparathyroidism and
vitamin deficiencies
