Dialysis Solutions
Sub-sections
Dialysis Solutions
Drug Nomenclature
Dialysis and Haemofiltration
Dialysis and filtration solutions are solutions of electrolytes formulated in concentrations similar to those of extracellular fluid or plasma. They always contain sodium and chloride and bicarbonate or a bicarbonate precursor. In addition, they often contain calcium and magnesium, and rarely potassium. Glucose may be added as an osmotic agent. These solutions allow the removal of water and metabolites and the replacement of electrolytes.
In haemodialysis, the exchange of ions between the solution and the patient's blood is made across a semi-permeable membrane, primarily by diffusion. Excess fluid is removed by ultrafiltration achieved by a pressure gradient. Membranes are either derived from cellulose (e.g. cuprophane) or are synthetic. Bicarbonate rather than a bicarbonate precursor is increasingly preferred as the bicarbonate source in haemodialysis since the problems of precipitation of calcium and magnesium have been overcome by changes in dialysis technique. Acetate is still used in some dialysers, but is thought to have vasodilator and cardiodepressant actions, and may not be converted to bicarbonate fast enough for high-flux haemodialysis or in patients with liver disease. Haemodialysis solutions are provided in a sterile concentrated form for dilution with water before use; this water need not be sterile.
In peritoneal dialysis, the exchange is made across the membranes of the peritoneal cavity primarily by diffusion. Excess fluid is removed by ultrafiltration achieved by the use of osmotic agents such as glucose. The problems of calcium bicarbonate precipitation have not yet been overcome, and lactate is generally used as the bicarbonate precursor. Peritoneal dialysis solutions must be sterile and apyrogenic.
In haemofiltration, blood is filtered rather than dialysed. Metabolites are removed by convective transport, and excess water by hydrostatic ultrafiltration. Fluid and electrolytes are replaced by direct intravenous infusion. Most haemofiltration solutions use acetate or lactate as the bicarbonate source. Haemofiltration solutions must be sterile and apyrogenic.
Adverse Effects
Adverse effects occurring during haemodialysis include nausea, vomiting, hypotension, muscle cramps, and air embolus. Effects related to vascular access include infection, thrombosis, and haemorrhage. Adverse effects occurring during haemofiltration are similar to those for haemodialysis.
The most common adverse effects associated with peritoneal dialysis include peritonitis, hernias, hyperglycaemia, protein malnutrition, and catheter complications.
Long-term complications in dialysed patients, some of which may relate to renal failure itself, include haemodialysis-related amyloidosis, acquired cystic kidney disease, and accelerated atherosclerosis. Dialysis dementia is a special hazard of aluminium overload. Long-term peritoneal dialysis results in progressive structural changes to the peritoneal membrane ultimately resulting in dialysis failure.
References.
- 1. Himmelfarb J. Hemodialysis complications. Am J Kidney Dis 2005; 45: 1122–31. PubMed
Aluminium overload.
Accumulation of aluminium in patients on dialysis may result in
dialysis dementia, anaemia, and aluminium-related bone disease (see also
). Sources of aluminium include the water used for preparation
of dialysis fluids and aluminium-containing phosphate binders used in
treating renal osteodystrophy (
). It is therefore
important that water used for the preparation of dialysis fluids has a
low aluminium concentration; Ph. Eur. 5.5 specifies a limit
for aluminium of 10Â micrograms/litre. Non-aluminium-containing
phosphate binders such as calcium acetate or calcium carbonate may be
preferred for long-term therapy. Aluminium overload in patients on
dialysis has been treated with desferrioxamine (
).
Copper toxicity.
Haemodialysis-induced cramp.
Muscle cramps commonly occur during haemodialysis procedures, and
are often associated with hypotension as a result of inappropriate
volume removal. In addition, they may be exacerbated by
cellulose-derived membranes or the use of acetate as a bicarbonate
precursor.
Sodium chloride tablets (
), intravenous
sodium chloride 0.9%, intravenous hypertonic
glucose (
), and quinine (
)
have been used in the prevention or treatment of
haemodialysis-induced cramp.
Hypersensitivity.
Infections.
Patients undergoing haemodialysis are at risk of infections from microbial contamination of dialysis fluid, and from inadequate care of vascular access sites. Maximum microbial counts and limits for endotoxins have been specified for water used in dialysis fluids. Bicarbonate-based dialysis solutions are more susceptible to microbial growth than acetate-based solutions.
Peritonitis is common in patients receiving peritoneal dialysis.
The risk of infection may be minimised by using disconnect systems, good
aseptic technique, and by good care of catheters. Treatment of bacterial
peritonitis requires intraperitoneal antibacterials,
which are usually added to the dialysis fluid (see
).
Dialysis equipment should be regularly disinfected with agents such
as formaldehyde (
) or ethylene oxide (
), but
for mention of ethylene oxide anaphylactoid reactions,
see
.
Metabolic complications.
The high concentrations of glucose in peritoneal dialysis solutions
required to form an osmotic gradient can lead to weight gain,
hyperglycaemia, hyperlipidaemia, and increased protein loss. Alternative
osmotic agents such as icodextrin (
) can be used,
and amino acid-based solutions are also available.
References.
- 1. Burkart J. Metabolic consequences of peritoneal dialysis. Semin Dial 2004; 17: 498–504. PubMed
Precautions
Peritoneal dialysis is not appropriate for patients with abdominal sepsis, previous abdominal surgery, or severe inflammatory bowel disease.
Haemodialysis should be used with caution in patients with
unstable cardiovascular disease or active bleeding.
During haemodialysis and haemofiltration, heparin (see
Extracorporeal Circulation,
)
or epoprostenol (Uses,
) are required to
prevent clotting of the blood in the extracorporeal circuit.
Dialysis solutions should be warmed to body temperature with dry heat because wet heat carries a risk of microbial contamination.
Interactions
The effects of dialysis and
filtration procedures on drug concentrations in the body
can be complex.
More drug may be
removed by one dialysis technique than another. In general, drugs of low
molecular weight, high water solubility, low volume of distribution, low
protein binding, and high renal clearance are most extensively removed by
dialysis. For example, aminoglycosides are extensively
removed by dialysis procedures, and extra doses may be needed to replace
losses. Specific drug
dosage adjustments for dialysis procedures may be used where these
are known. For drugs where the effect of dialysis is unknown, it is usual
to give maintenance doses after dialysis. Dialysis has been
used to remove some drugs in the treatment of overdosage
and poisoning (see
).
Dialysis-induced changes in fluids and electrolytes have the potential to alter the effects of some drugs. For example, hypokalaemia predisposes to digoxin toxicity.
In patients undergoing peritoneal dialysis, drugs such as insulin and antibacterials may be added to the dialysis fluid. Consideration should be given to the possibility of adsorption of drugs onto the PVC bags.
References.
- 1. Aronson JK. The principles of prescribing in renal failure. Prescribers' J 1992; 32: 220–31.
- 2. Cotterill S. Antimicrobial prescribing in patients on haemofiltration. J Antimicrob Chemother 1995; 36: 773–80. PubMed
- 3. et al. Drug prescribing in renal failure: dosing guidelines for adults. 4th ed. Philadelphia: American College of Physicians, 1999.
Uses and Administration
Dialysis and filtration procedures are used in renal failure to correct electrolyte imbalance, correct fluid overload, and remove metabolites. They also have a limited role in the treatment of overdosage and poisoning. The two main techniques are haemodialysis and peritoneal dialysis; haemofiltration is used less frequently. The choice of technique will depend on the condition to be treated, the clinical state of the patient, patient preference, and availability.
Haemodialysis is more efficient than peritoneal dialysis at clearing small molecules such as urea, whereas peritoneal dialysis may be better at clearing larger molecules. Haemodialysis is considered to be less physiological as it alternates periods of high clearance with periods of no clearance.
Haemodialysis is usually performed intermittently (often 3 times a week); a typical session takes 3 to 5 hours. More recently high-flux dialysers have been developed which have reduced the time required for dialysis sessions.
Peritoneal dialysis may be performed continuously or intermittently. Continuous ambulatory peritoneal dialysis (CAPD) is the most commonly used technique. Patients remain mobile, except during exchanges, and can carry out the procedure themselves. There is always dialysis solution in the peritoneal cavity, and this is drained and replaced 3 to 5 times daily. Continuous cycle peritoneal dialysis (CCPD) is similar, except that exchanges are carried out automatically overnight, and patients do not have to carry out any exchanges during the day. Intermittent peritoneal dialysis (IPD) requires the patient to be connected to a dialysis machine for 12 to 24 hours 2 to 4 times a week. During this time, dialysis solution is pumped into and out of the peritoneal cavity, with a dwell time of about 10 to 20 minutes.
Haemofiltration is usually performed as a continuous technique and, as it is not portable, its principal use is in intensive care units. It may also be used intermittently as an adjunct to haemodialysis in patients with excess fluid weight gain. Continuous arteriovenous or venovenous haemodiafiltration (CAVHD or CVVHD) combines dialysis and filtration.
Assessing serum concentrations of urea or creatinine before the next dialysis session is not a good measure of the adequacy of the dialysis, so various other measures have been developed including the urea reduction ratio and urea kinetic modelling. The use of such measures is more established for haemodialysis than for peritoneal dialysis.
References.
- 1. Zucchelli P, Santoro A. How to achieve optimal correction of acidosis in end-stage renal failure patients. Blood Purif 1995; 13: 375–84. PubMed
- 2. Carlsen DB, Wild ST. Grams to milliequivalents: a concise guide to adjusting hemodialysate composition. Adv Ren Replace Ther 1996; 3: 261–5. PubMed
- 3. Passlick-Deetjen J, Kirchgessner J. Bicarbonate: the alternative buffer for peritoneal dialysis. Perit Dial Int 1996; 16 (suppl 1): S109–S113. PubMed
- 4. Pastan S, Bailey J. Dialysis therapy. N Engl J Med 1998; 338: 1428–37. PubMed
- 5. Ifudu O. Care of patients undergoing hemodialysis. N Engl J Med 1998; 339: 1054–62. PubMed
- 6. Mallick NP, Gokal R. Haemodialysis. Lancet 1999; 353: 737–42. PubMed
- 7. Gokal R, Mallick NP. Peritoneal dialysis. Lancet 1999; 353: 823–8. PubMed
- 8. Fischbach M, et al. Hemodialysis in children: principles and practice. Semin Nephrol 2001; 21: 470–9. PubMed
- 9. Schröder CH. The choice of dialysis solutions in pediatric chronic peritoneal dialysis: guidelines by an ad hoc European committee. Perit Dial Int 2001; 21: 568–74. PubMed
- 10. Teehan GS, et al. Update on dialytic management of acute renal failure. J Intensive Care Med 2003; 18: 130–8. PubMed
- 11. Locatelli F, et al. Optimal composition of the dialysate, with emphasis on its influence on blood pressure. Nephrol Dial Transplant 2004; 19: 785–96. PubMed
- 12. Lameire N. Volume control in peritoneal dialysis patients: role of new dialysis solutions. Blood Purif 2004; 22: 44–54. PubMed
- 13. Maduell F. Hemodiafiltration. Hemodial Int 2005; 9: 47–55. PubMed
- 14. Nanovic L. Electrolytes and fluid management in hemodialysis and peritoneal dialysis. Nutr Clin Pract 2005; 20: 192–201. PubMed
- 15. Saxena R. Peritoneal dialysis: a viable renal replacement therapy option. Am J Med Sci 2005; 330: 36–47. PubMed Correction. ibid.; 110.
- 16. Ikizler TA, Schulman G. Hemodialysis: techniques and prescription. Am J Kidney Dis 2005; 46: 976–81. PubMed
Acute renal failure.
Acute renal failure is characterised by a rapid decline in kidney
function, and has a variety of causes.1-7 It is
often classified by origin as prerenal (e.g. due to hypovolaemia such as
that associated with shock, burns, or dehydration; congestive heart
failure; or renal artery obstruction), renal (such as acute tubular
necrosis or interstitial nephritis of various causes, including
nephrotoxic drugs and infections), or postrenal (acute urinary tract
obstruction). The prognosis depends on the underlying disease, which
should be identified and treated if possible, but the mortality may
still be as high as 60%, particularly after
surgery or trauma and in patients who become oliguric.
Management is essentially supportive in the
hope that renal function will recover. Complications of acute renal
failure include extracellular volume overload and hyponatraemia,
hyperkalaemia, metabolic acidosis, hyperphosphataemia and hypocalcaemia.
Those complications requiring urgent treatment, often including the use
of dialysis, are severe hyperkalaemia (
), pulmonary
oedema, pericarditis, and severe metabolic acidosis (
).
The use of dialysis before clinical signs of uraemia is a matter of
debate since it does not appear to hasten recovery
per se,1 but all save the shortest episodes of
acute renal failure will require some form of renal replacement therapy
with dialysis or filtration. Intermittent haemodialysis and peritoneal
dialysis are both used, but the newer haemofiltration techniques have
theoretical advantages in terms of volume control and cardiovascular
stability, and are increasingly preferred.2,8,9
Numerous drugs have been tried in attempts to attenuate renal injury or hasten recovery in patients with acute tubular necrosis due to ischaemia or nephrotoxins.1,5,10,11 These include drugs to increase renal blood flow (e.g. low-dose dopamine, atrial natriuretic peptide, or prostaglandins), drugs to increase urine flow and protect the epithelial cells (mannitol and loop diuretics, calcium-channel blockers), or the use of chelating agents or antidotes against specific nephrotoxins. Consistent clinical benefit has not, however, been demonstrated.
Acute renal failure is reversible in about 95% of patients who
survive the complications. A few patients who survive acute renal
failure will require long-term dialysis or kidney transplantation
(
).
For further information on the substances mentioned above, see:
- Atrial Natriuretic Peptide,
- Calcium-channel Blockers,
- Dialysis Solutions,
- Dopamine,
- Loop Diuretics (see Furosemide,
)
- Mannitol,
- 1. Brady HR, Singer GG. Acute renal failure. Lancet 1995; 346: 1533–40. PubMed
- 2. Morgan AG. The management of acute renal failure. Br J Hosp Med 1996; 55: 167–70. PubMed
- 3. Evans JHC. Acute renal failure in children. Br J Hosp Med 1994; 52: 159–61. PubMed
- 4. Klahr S, Miller SB. Acute oliguria. N Engl J Med 1998; 338: 671–5. PubMed
- 5. Dishart MK, Kellum JA. An evaluation of pharmacological strategies for the prevention and treatment of acute renal failure. Drugs 2000; 59: 79–91. PubMed
- 6. Ashley C, Holt S. Acute renal failure. Pharm J 2001; 266: 625–8.
- 7. Lameire N, et al. Acute renal failure. Lancet 2005; 365: 417–30. PubMed
- 8. McCarthy JT. Renal replacement therapy in acute renal failure. Curr Opin Nephrol Hypertens 1996; 5: 480–4. PubMed
- 9. Joy MS, et al. A primer on continuous renal replacement therapy for critically ill patients. Ann Pharmacother 1998; 32: 362–75. PubMed
- 10. Albright RC. Acute renal failure: a practical update. Mayo Clin Proc 2001; 76: 67–74. PubMed
- 11. Pruchnicki MC, Dasta JF. Acute renal failure in hospitalized patients: part II. Ann Pharmacother 2002; 36: 1430–42. PubMed
Chronic renal failure.
Chronic renal failure is the irreversible, usually progressive, loss
of renal function that eventually results in end-stage renal disease
(ESRD) and the need for renal replacement therapy (dialysis or renal
transplantation). The rate of decline in renal function is generally
constant for each patient and is usually monitored by measuring
serum-creatinine concentrations as an indirect index of the glomerular
filtration rate (GFR). In its early stages when the patient is
asymptomatic, progressive loss of renal function is described as
diminished renal reserve or chronic renal insufficiency. When the limits
of renal reserve have been exceeded and symptoms become apparent, it is termed
chronic renal failure or overt renal failure. When renal function is
diminished to such an extent that life is no longer sustainable (GFR
less than 5Â mL/minute), the condition is termed ESRD or uraemia.
Many diseases can lead to ESRD, the most common being diabetes
(
), glomerulonephritis (
), and
hypertension (
).
The management of patients with chronic renal failure prior to
ESRD involves measures to conserve renal function and compensate for
renal insufficiency. Methods to slow the progression of renal failure
include the treatment of hypertension (
), reduction of proteinuria,
and the reduction of hyperlipidaemia
(
). ACE inhibitors (
) or angiotensin II receptor antagonists
(
) are used for the
reduction of proteinuria and the control of hypertension.
Dietary protein restriction (see Renal Failure,
) has also been used for
control of proteinuria, but conclusive evidence for a renal protective
effect is lacking.
Anaemia
(
), hyperphosphataemia (
),
secondary hyperparathyroidism (
),
and renal osteodystrophy (
) often
require active treatment. Nephrotoxic drugs, including NSAIDs, should be
avoided.
The choice between haemodialysis, peritoneal dialysis, and organ
transplantation is considered, and the patient prepared, before it is
actually required. In patients for whom transplantation is the preferred
option, dialysis may still be required while waiting for a kidney.
Kidney transplantation is discussed on
. There are
differences between countries in the choice of dialysis technique for
patients with ESRD. For example, in-centre haemodialysis is used in about
80% of patients in the USA, whereas CAPD is used in over 50% of patients
in the UK. Overall survival appears to be similar between the 2
techniques, but more patients on CAPD will eventually require
a change to another dialysis method because of treatment
failure.
Unlike renal transplant patients, dialysis patients still require replacement therapy with hormones that are usually produced by the kidney. Thus, recombinant erythropoietin and hydroxylated vitamin D analogues are commonly given.
References.
For further information on the substances mentioned above, see:
- ACE Inhibitors,
- Angiotensin II Receptor Antagonists,
- Dialysis Solutions,
- Erythropoietin (see Epoetins,
)
- Vitamin D Substances,
- 1. NIH. Morbidity and mortality of dialysis. NIH Consens Statement 1993; 11: 1–33. PubMed
- 2. Friedman AL. Etiology, pathophysiology, diagnosis, and management of chronic renal failure in children. Curr Opin Pediatr 1996; 8: 148–51. PubMed
- 3. Steinman TI. Kidney protection: how to prevent or delay chronic renal failure. Geriatrics 1996; 51: 28–35.
- 4. Walker R. General management of end stage renal disease. BMJ 1997; 315: 1429–32. PubMed
- 5. McCarthy JT. A practical approach to the management of patients with chronic renal failure. Mayo Clin Proc 1999; 74: 269–73. PubMed Correction. ibid.; 538.
- 6. Morlidge C, Richards T. Managing chronic renal disease. Pharm J 2001; 266: 655–7.
- 7. Currie A, O'Brien P. Renal replacement therapies. Pharm J 2001; 266: 679–83.
- 8. Ruggenenti P, et al. Progression, remission, regression of chronic renal diseases. Lancet 2001; 357: 1601–8. PubMed
- 9. Renal Association. Treatment of adults and children with renal failure: standards and audit measures. 3rd ed. London: Royal College of Physicians of London and the Renal Association, 2002. Also available at: online (accessed 26/04/05)
- 10. Taal MW. Slowing the progression of adult chronic kidney disease: therapeutic advances. Drugs 2004; 64: 2273–89. PubMed
- 11. Meguid El Nahas A, Bello AK. Chronic kidney disease: the global challenge. Lancet 2005; 365: 331–40. PubMed
Electrolyte disturbances.
Haemodialysis with magnesium-free dialysis solution has been used to
remove magnesium from the body in severe hypermagnesaemia
(
). Similarly, haemodialysis, and sometimes peritoneal
dialysis, has been used in treating hypercalcaemia (
),
hyperkalaemia (
), hypernatraemia (
),
and hyperphosphataemia (
).
Overdosage and poisoning.
Haemodialysis, or less often peritoneal dialysis, can be used to
remove some substances from the body after overdosage or poisoning.
Substances most readily removed have a low molecular weight, low volume
of distribution, low protein binding, high water solubility, and high
renal clearance. Examples of agents for which haemodialysis may have a
role in the treatment of severe overdosage include alcohol
(
), ethylene glycol (
),
methyl alcohol (
), lithium (
),
and salicylates such as aspirin (
). Dialysis may be
particularly important when poisoning with these agents is complicated
by renal failure.
Preparations
Single-ingredient Preparations
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.
Denmark: Bicbag¤; Finland: Gambrosol; Netherlands: Icodial; Sweden: Altracart II¤; BiCart¤; Bicbag¤; Biosol B¤;
Multi-ingredient Preparations
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.
Australia: Dianeal; Extraneal; Austria: Acetat-Haemodialyse¤; Bicaflac; Dianeal; Extraneal; HAMFL; Hamofiltrasol¤; Monosol; Nutrineal PD4; Peritofundin¤; Physioneal; Brazil: Extraneal¤; HD¤; HF¤; Nutrineal¤; Peritofundin¤; Solurin; Canada: Nutrineal PD4¤; Chile: Concentrado Acido; Czech Republic: CAPD; Dianeal; Extraneal; Gambrosol; Medisol K; Nutrineal PD4; Denmark: balance glucose calcium; Bicaflac; Bicavera Glucose; CAPD/DPCA; Dianeal; Extraneal; Gambrosol; Hemosol Bicar; Lactasol; Lockolys¤; Nutrineal PD4; Physioneal; Prismasol; Finland: Balance; Bicavera; CAPD/DPCA; Dianeal; Extraneal; Lockolys¤; Physioneal; France: Dialysol Acide¤; Dialysol Bicarbonate¤; Dialytan H¤; DPCA 2¤; Germany: Extraneal; Nutrineal PD4; Physioneal; Greece: Peritoneal; Hungary: CAPD; Dianeal; Gambrosol; Peridisol; Israel: CAPD; D-204; D-248; D-300; D-326; Dialine; Dianeal; G-204; G-248; Hemosol BO; Nutrineal PD4; Italy: Extraneal; Icodial; Nutrineal PD4; Physioneal; Mexico: Bipodial¤; Solucion DP; Netherlands: Balance; Bicavera; Duosol; Multibic; Nutrineal; Physioneal; New Zealand: Extraneal; Portugal: Balance; Bicavera; CAPD/DPCA; Dianeal¤; Multibic; Nutrineal¤; Peritofundinas¤; Renofundina¤; South Africa: Sabax Dianeal; Sterisol Peridiasol; Spain: Balance Glucosa Calcio; Bicaflac; Bicavera Glucosa; CAPD/DPCA; CAPD; Dialisis Perit; Dialisol¤; Dianeal; DPCA¤; Extraneal; Gambrosol; Hemofiltracion E2 and E3; Hemofiltracion E4 and E5; Hemofiltracion HF 01¤; Hemofiltracion HF 02¤; Hemofiltracion HF 11 and HF 23¤; Hemosol BO; Icodial¤; Nutrineal PD4; Peritoflex¤; Physioneal Glucosa; Prismasol; Sol Dial Perit¤; Sweden: Balance; BiCart¤; Bicavera; Biorenal¤; Biosol A¤; CAPD/DPCA; Dianeal; Diasol¤; Dicalys 11; Dicalys 17; Duolys A¤; Duolys B¤; Extraneal; Gambrolys¤; Gambrosol; Haemovex 4; Haemovex 8; Hemofiltrasol; Hemofiltrationslosning 401; Hemoset A glucos¤; Hemoset A¤; Hemosol B0; HF-BIC35+HF-EL010¤; HF-BIC35+HF-EL210¤; Nutrineal PD4; Peritolys med glukos¤; Physioneal; Schiwalys Hemofiltration; Spectralys Hemofiltration 19, 20¤; Sterilys B 84¤; Switzerland: Clear-Flex Formula 13, 15, 55, 62, 91, AA, AB, AC¤; Dianeal; DPCA; Extraneal; Gambrosol¤; HF; Multibic; Nutrineal PD4; Physioneal; SK-F, BIC-F¤; Thailand: Dialyte¤; United Kingdom: Dialaflex Solutions¤; Diambulate Solutions¤; Dianeal¤; Difusor¤; Nutrineal PD4; Physioneal; United States: Dialyte; Dianeal¤; Extraneal; Inpersol¤; Venezuela: Dianeal;

