DR/Marwa Abokresha
Lecture of internal medicine
Assiut university
Clinical indications of Long-term dialysis :
-Volume overload (Acute pulmonary oedema)
-Inability to control blood pressure
A) Dialysis -Serositis : uremic pericarditis
- Acid–base or electrolyte abnormalities : K↑ and Acidosis
and - Uremic Pruritus
-Uremic encephalopathy and /or uremic convulsions
filtration : -Nausea/vomiting/deterioration in nutritional status
Laboratory Indications of Dialysis :
a) ↑ creatinine > 8mg/dl
b) ↑ urea > 300 mg/dL
c) ↑ K > 6 mg/dl
d) Acidosis : - ↓ PH < 7
- ↓ HCO3 < 12mEq/l
e) GFR ≤ 10 ml/min.
Types of Dialysis
A. Haemodialysis (HD)
Blood is passed over a semi-permeable membrane (cellulose or
polysulphone) against dialysis fluid flowing in the opposite direction.
Diffusion of solutes occurs down the concentration gradient.
A hydrostatic gradient is used to clear excess fluid as required (ultra-
filtration).
HD machine---- control of dialysate temperature and electrolytes
concentrations with transmembrane hydrostatic pressure gradient
Access is preferentially via an arterio-venous fistula which provides
↑blood flow and longevity. This should be created prior to need for RRT to
avoid the infection risk associated with central venous dialysis catheters.
HD is needed 3 times/week or more.
Daily HD increases the ‘dose’ and improves outcomes.
Home HD should be offered to all suitable patients
Two types of dialysate fluid are used
1- Acetate containing dialysate :
a) easier to prepare
b) converts into bicarbonate in liver
c) associated with
- Hypotension and headache during dialysis
- Acetate intolerance
d) not used now
2- Bicarbonate containing dialysate:
preferred in elderly and CVD unstable patients
Complications :
A) Acute complications
Access (arterio-venous fistula) : thrombosis, stenosis, steal
syndrome; tunneled
venous line: infection, blockage, recirculation of blood,
thrombophlebitis ),
Dialysis disequilibrium (between cerebral and blood solutes
leading to cerebral edema ---- start HD gradually),
Bleeding or blood line clotting
Air embolism
Hypotension or cramps
Chest pain , Back painHypersensitivity (Type 1 first use )
Bio-incompatibility of dialyzer membrane --- compliment
activation and hypoxia
Hemorrhage
B)Chronic Complications :
Hepatitis
Psychogenic disorders
Accelerated atherosclerosis
Carpal tunnel syndrome (ẞ 2 microglobulin
Amyloidosis)
C) Complications of inadequate dialysis :
Uremia
Neuropathy
Pericarditis
D) Complications associated with dialysate
Hemolysis
Anemia
Aluminum Toxicity
B. Peritoneal dialysis (PD) : CAPD
Uses the peritoneum as a semi-permeable membrane.
A catheter (soft silicon catheter ) is inserted into the peritoneal cavity and
fluid infused (K free dialysate : 2L one bag)
Solutes diffuse slowly across.
Ultra filtration is achieved by adding osmotic agents (glucose, glucose
polymers) to the fluid. It is a continuous process with intermittent drainage
and refilling of the peritoneal cavity, performed at home.
Dietary protein is increased to 1.3 gm/kg/ day
Problems:
Catheter site infection .
Peritonitis,Hernia.
Excessive weight gain .
loss of membrane function over time.
C. Haemofiltration
Water cleared by positive pressure, dragging solutes into the waste by
convection.
The ultrafiltrate (waste) is replaced with an appropriate volume of (‘clean’)
fluid either before (pre-dilution) or after (post-dilution) the membrane.
↓Hemodynamic instability so used in critical care when HD not possible
due to ↓BP.
Not used for chronic RRT unless in combination with HD for
haemodynamic stability and ↑ middle molecule clearance, eg ẞ2-
microglobulin
Complications of RRT
Annual mortality is significant, mostly due to:
Cardiovascular disease: ↑BP, calcium/phosphate dysregulation, vascular
stiffness, inflammation, oxidative stress, abnormal endothelial function.
Protein-calorie malnutrition: Increases morbidity and mortality.
Renal bone disease: High bone turnover, renal osteodystrophy, osteitis
fibrosa.
Infection: Uremia causes granulocyte and T-cell dysfunction with
↑sepsis-related mortality.
Amyloid: ẞ2-microglobulin accumulates in long–term dialysis causing
carpal tunnel syndrome, arthralgia, visceral effects.
Conservative management is for those who not to receive RRT due to lack
of benefit on quality or quantity of life. Focus is on preserving residual renal
function, symptom control, and advanced planning with patient and family
for end-of-life care
When a patient start dialysis :
1- Examine for fluid overload and check K+ .
2- All patients on dialysis have a target weight at which they are considered euvolaemic.
How much are they above it?
3- Ask about urine output ( that may help them lose volume/K+ )
4- Do not measure BP on fistula arm.
5- Remember ↑risk for CVD but troponin has ↓specificity in ESRF.
6- Drug dose adjust for renal failure : includes antibiotics, opiates, insulin, and
low-molecular-weight heparin .
7- Care with fluid replacement in sepsis:
* guided by clinical examination and target weight.
* If volume depleted give a 250mL bolus of (non-K+ containing) crystalloid
over 15min with close observation.
8- Avoid maintenance fluids in those who normally have a fluid restriction.
9- Do not use a dialysis line or fistula for IV access
* if a cannula is necessary, preferentially use the back of the hand,
* save other vessels for future fistulas.
10- Surgery : .Aim for pre-op K+ < 5.5 mm0l/L. (< 5mm0l/L if major surgery with risk of
tissue breakdown/ haemolysis). Check K+ urgently post-op . In elective surgery, plan dialysis
provision pre- and post-op.
Transplantation :
should be considered for every patient with, or progressing towards,
stage G5 kidney disease
It is the treatment of choice for kidney failure provided risks do not
exceed benefits.
ABO compatibility is essential
Select donor kidneys on basis of HLA compatibility
Contraindications
• cancer with metastases.
• active infection, HIV with viral replication, unstable CVD.
• congestive heart failure, CVD.
Types of graft
• Living donor: Best graft function and survival, especially if HLA matched. d donor:
1 Donor after brain death (DBD, heart-beating donor).
2 Expanded criteria donor (ECD) is from an older kidney or from a patient
with a history of CVA, BP, or CKD.
3 Donor after cardiac death (DCD, non-heart-beating donor) with ↑ risk of
delayed graft function
Immunosuppression
Aim is to use the minimal effective dose with the lowest drug-
related toxicity.
Protocol used depends upon the immunological risk of the
recipient and type of
donated .
A combination of drugs are used kidney
Monoclonal antibodies: Basiliximab, Daclizumab (selectively block activated T cells via
CD-25), Alemtuzumab (T- and B-cell depletion): Used at the time of transplantation
(‘induction’). ↓Acute rejection and graft loss, ↑ infection risk if non-selective.
Calcineurin inhibitors: Tacrolimus, Ciclosporine (6-8mg/kg in 2 divided doses , then
reduced in 3-4 ms accordig to their blood levels ). These drugs inhibit T-cell activation and
proliferation. ↑Inter-individual variation and narrow therapeutic index mean drug level
monitoring is required. Clearance is dependent on cytochrome p450 isoenzymes, so beware of
drug interactions including: Macrolides and antifungal drugs. Side effects: Nephrotoxicity , ↑
BP, ↑cholesterol, NODAT (new-onset diabetes after transplantation)
Antimetabolites: Mycophenolic acid (1gm/12h) , Azathioprine
(2mg/kg/day) . MPA is now used preferentially due to better prevention of
acute rejection and graft survival . Side effects: Anemia, Leucopenia,
Tratogenicity and GI toxicity.
Glucorticosteroids: ↓Transcription of inflammatory cytokines. First-
choice treatment for acute rejection. Side-effects (↑BP, hyperlipidaemia,
DM, impaired wound healing, osteoporosis, cataracts, skin fragility) have
led to protocols with early withdrawal of steroids and the use of steroid-
free immunosuppression regimens.
Complications of RTx
A. Surgical: Bleeding , thrombosis, infection, urinary leaks, Lymphocele, hernia.
B. Delayed graft function: Affects up to 40% of grafts, more common in DCD.
C. Rejection:
** Hyper acute: due to preformed antibodies in the recipient against the donor kidney ,
or ABO incompatibility ;
- No definite treatment
- Combined plasma exchange , IV immunoglobulin treatment and bortezumib
- Removal of graft
** Acute (in the 1st month) is divided into antibody- mediated (rare unless known
pre-sensitized recipient) or cellular (most common). Causes ↓ renal function,
diagnosed on graft biopsy. Treatment with high-dose steroids and ↑
immunosuppression (antithymocyte globulins.
** Chronic : antibody-mediated rejection causes progressive dysfunction of the graft
and/ or non immunologic causes: long standing HTN , Dyslipidemia , infections, ,
cyclosporine toxicity . Better called interstitial fibrosis and tubular atrophy IFTA
D. Malignancy : Up to 25 x ↑risk of cancer with immunosuppression,
particularly skin, post-transplant lymphoproliferative disorder (PTLD), and gynecological.
E. Infection: ↑Risk of all infections :
Typically hospital acquired/donor derived in month 1, opportunistic in months 1–6,
usual spectrum of community-acquired infection after 6–12 months . Late viral
infection should always be considered: CMV, HSV.
F.CVD: 3–5 x ↑risk of premature CVD compared to general population (but ~80%
less than dialysis). BP, NODAT, rejection, and renal history (uremic cardiomyopathy)
contribute.
Prognosis
Acute rejection <15 %., 1-year graft survival > 90%, Longer-term graft loss ~4%/year.
Factors contributing to graft loss:
• Donor factors: age, comorbidity, living/deceased, DBD/DCD.
• Rejection.
• Infection.
• BP/CVD.
• Recurrent renal disease in graft. Most common outcome is death with a functioning
transplant (ie transplant ‘outlives’ the patient)
