What is a vascular access? dialysis cathete?


What is a vascular access?

A vascular access is a hemodialysis patient’s lifeline. A vascular access makes life-saving hemodialysis treatments possible. Hemodialysis is a treatment for kidney failure that uses a machine to send the patient’s blood through a filter, called a dialyzer, outside the body. The access is a surgically created vein used to remove and return blood during hemodialysis. The blood goes through a needle, a few ounces at a time. The blood then travels through a tube that takes it to the dialyzer. Inside the dialyzer, the blood flows through thin fibers that filter out wastes and extra fluid. The machine returns the filtered blood to the body through a different tube. A vascular access lets large amounts of blood flow continuously during hemodialysis treatments to filter as much blood as possible per treatment. About a pint of blood flows through the machine every minute. A vascular access should be in place weeks or months before the first hemodialysis treatment. Two types of vascular access designed for long-term use include the arteriovenous (AV) fistula and the AV graft. A third type of vascular access—the venous catheter—is for short-term use.


What is an arteriovenous fistula?

An AV fistula is a connection, made by a vascular surgeon, of an artery to a vein. Arteries carry blood from the heart to the body, while veins carry blood from the body back to the heart. Vascular surgeons specialize in blood vessel surgery. The surgeon usually places an AV fistula in the forearm or upper arm. An AV fistula causes extra pressure and extra blood to flow into the vein, making it grow large and strong. The larger vein provides easy, reliable access to blood vessels. Without this kind of access, regular hemodialysis sessions would not be possible. Untreated veins cannot withstand repeated needle insertions. They would collapse the way a straw collapses under strong suction.
Health care providers recommend an AV fistula over the other types of access because it
  • provides good blood flow for dialysis
  • lasts longer than other types of access
  • is less likely to get infected or cause blood clots than other types of access
Before AV fistula surgery, the surgeon may perform a vessel mapping test. Vessel mapping uses Doppler ultrasound to evaluate blood vessels that the surgeon may use to make the AV fistula. Ultrasound uses a device, called a transducer, that bounces safe, painless sound waves off organs to create an image of their structure. A specially trained technician performs the procedure in a health care provider’s office, an outpatient center, or a hospital. A radiologist—a doctor who specializes in medical imaging—interprets the images. A patient does not need anesthesia. A Doppler ultrasound shows how much and how quickly blood flows through arteries and veins so the surgeon can select the best blood vessels to use. A surgeon performs AV fistula surgery in an outpatient center or a hospital. The vascular access procedure may require an overnight stay in the hospital; however, many patients go home afterward. A health care provider uses local anesthesia to numb the area where the surgeon creates the AV fistula.

 An AV fistula frequently requires 2 to 3 months to develop, or mature, before the patient can use it for hemodialysis. If an AV fistula fails to mature after surgery, a surgeon must repeat the procedure.



At the start of a hemodialysis session, a health care provider or the patient inserts two needles into the vascular access. One needle carries blood from the body to the dialyzer. The other carries filtered blood back to the body. To tell the needles apart, the needle that carries blood away from the body is called the arterial needle. The needle that carries blood back to the body is called the venous needle. Some patients prefer to insert their own needles into the vascular access, which requires training to learn how to prevent infection and protect the vascular access. No matter who inserts the needles, the patient should know how to take care of the needle insertion area to prevent infection.
If an AV fistula does not mature, an AV graft is the second choice for a long-lasting vascular access.


What is an arteriovenous graft?

An AV graft is a looped, plastic tube that connects an artery to a vein. A vascular surgeon performs AV graft surgery, much like AV fistula surgery, in an outpatient center or a hospital. As with AV fistula surgery, the patient may need to stay overnight in the hospital, although many patients can go home after the procedure. A health care provider uses local anesthesia to numb the area where the surgeon creates the AV graft.
A patient can usually use an AV graft 2 to 3 weeks after the surgery. An AV graft is more likely than an AV fistula to have problems with infection and clotting. Repeated blood clots can block the flow of blood through the graft. However, a well-cared-for graft can last several years.


Set Up the Vascular Access Well before Starting Hemodialysis

Patients should set up a vascular access well before starting hemodialysis, as AV fistulas and AV grafts both need time to mature before they are ready for use. A health care provider can help schedule an appointment with a vascular surgeon well before the patient starts hemodialysis, even if the patient is feeling fine. Giving a vascular access time to mature can help prevent problems with narrow veins, low blood flow, and blood clots.
Before the procedure, health care providers should use the back of the patient’s hand for drawing blood to preserve the blood vessels in the arm. A health care provider can teach the patient simple exercises that help the blood vessels grow larger for the surgeon’s use. The same exercises help the AV fistula grow larger after the procedure.


What is a venous catheter?

A venous catheter is a tube inserted into a vein in the neck, chest, or leg near the groin, usually only for short-term hemodialysis. The tube splits in two after the tube exits the body. The two tubes have caps designed to connect to the line that carries blood to the dialyzer and the line that carries blood from the dialyzer back to the body. A person must close the clamps on each line when connecting and disconnecting the catheter from the tubes.
 If kidney disease has progressed quickly, a patient may not have time for placement of an AV fistula or AV graft before starting hemodialysis treatments. A nephrologist—a doctor who specializes in kidney problems—or an interventional radiologist—a doctor who uses medical imaging equipment to perform operations—performs the venous catheter placement procedure in a hospital or an outpatient center. The patient receives local anesthesia and sedation to stay calm and relaxed during the procedure.
Venous catheters are not ideal for long-term use. With a venous catheter, a patient may develop a blood clot, an infection, or a scarred vein, causing the vein to narrow. However, if a patient needs to start hemodialysis right away, a venous catheter will work for several weeks or months until a surgeon can perform a long-term access surgery and the AV fistula or AV graft has time to mature. If fistula or graft surgery is unsuccessful, then a patient will need a long-term venous catheter access. When a patient needs a venous catheter for more than 3 weeks, the surgeon will “tunnel” the catheter under the skin, rather than insert it directly into the vein. A tunneled catheter is more comfortable and has fewer problems. Even tunneled catheters, however, may become infected.

What problems could a vascular access cause?

All three types of vascular access—AV fistula, AV graft, and venous catheter—can cause problems that require further treatment or surgery. The most common problems include access infection and low blood flow due to blood clotting in the access.
Infection and low blood flow happen less frequently in properly formed AV fistulas than in AV grafts and venous catheters. Still, having an AV fistula does not guarantee the access will be problem-free.
AV grafts more often develop low blood flow, an indication of clotting or narrowing of the access. The AV graft may then require angioplasty, a procedure to widen the narrow part. Another option involves surgery on the AV graft to replace the narrow part.
Venous catheters are the most likely to cause infection and clotting problems. If these problems develop, medication may help. Antibiotics are medications that fight bacteria that can cause infection. Blood thinners such as warfarin keep blood from clotting. If these treatments fail, a nephrologist or an interventional radiologist will need to replace the catheter.


How does a patient care for and protect a vascular access?

A patient can care for and protect a vascular access by
  • ensuring that the health care provider checks the access for signs of infection or problems with blood flow before each hemodialysis treatment, even if the patient is inserting the needles.
  • keeping the access clean at all times.
  • using the access site only for dialysis.
  • being careful not to bump or cut the access.
  • checking the thrill in the access every day. The thrill is the rhythmic vibration a person can feel over the vascular access.
  • watching for and reporting signs of infection, including redness, tenderness, or pus.
  • not letting anyone put a blood pressure cuff on the access arm.
  • not wearing jewelry or tight clothes over the access site.
  • not sleeping with the access arm under the head or body.
  • not lifting heavy objects or putting pressure on the access arm.

Hemodialysis Technique ...what is dialysis .....

Hemodialysis Technique
what is dialysis

Hemodialysis Technique---  As discussed in the previous chapter, the clearance of a solute is dependent on the Qb, Qd, and membrane efficiency. The dialyzer membranes have different pore sizes that are variably distributed, larger pores being fewer than smaller pores. Small solutes like urea can be transported through all pore sizes whereas the larger molecules such as vitamin B12 or beta-2-microglobulin can only pass through the larger pores. Thus the clearance of the larger solutes, unlike urea, is more influenced by the membrane and less by Qb and Qd.

1.1 Blood Flow Rate
 what is dialysis

Because clearance is calculated using Qb, it would be understandable to mistakenlyassume that the relationship between urea clearance and Qb is linear. However, al though urea clearance increases steadily as Qb is increased from zero, at faster flow rates, the dialyzer is unable to continue to transport urea with the same efficiency and the urea concentration at the dialyzer outlet increases. In other words, the urea removed as a percentage of urea inflow into the dialyzer decreases and (as clearance is Qb multiplied by the fractional decline in urea) the clearance curve plateaus

1.2 Dialysate Flow Rate
 what is dialysis

An increase in Qd generally increases the urea clearance. This effect is negligible, however, as long as Qd is 150−250 ml/min faster than Qb. With high-efficiency dialyzers, there is little (<10%) increase in urea clearance if Qd is increased from 500 ml/min to 800 ml/min, provided that Qb remains 350 ml/min.

1.3 Dialyzer Efficiency and Mass Transfer Area Coefficient (KoA)
 what is dialysis

Dialyzer efficiency is measured in terms of clearance at a given Qb and Qd. Usually, these values are measured for urea and other solutes at a Qb of 200 ml/min and a Qd of 500 ml/min. Another measure of dialyzer efficiency is solvent removal in terms of the ultrafiltration coefficient (K uf ). However, dialyzer efficiency is more accurately measured as the mass transfer coefficient (KoA). The KoA of a solute is defined as the maximum (theoretical) ability of a membrane to allow the transfer of a solute through its pores when Qb and Qd are unlimited. Thus, KoA is the clearance of a solute when dialysate and blood flow are not the limiting factors. The higher the value of KoA, the more permeable the membrane for that solute. Thus, the higher KoA of a dialyzer for a solute, the more that solute would be cleared, and this value is proportional to the surface area and porosity of a membrane. However, if the surface area becomes too large, the relationship will not remain linear (this will be further discussed later).

1.4   Different Hemodialysis Techniques

1.4.1.   Different Hemodialysis Techniques
what is dialysis



diffusion is the predominant method of solute clearance. There is a very small
amount of hydrostatic UF to remove the excess fluid volume  gained between dialysis sessions, contributing a small solute clearance by convection.


1.4.2.  Hemofiltration 
 what is dialysis

 The technique of hemofiltration (HF) uses a large quantity of hydrostatic UF. Plasma ultrafiltrate is replaced with plasma-like electrolyte solution. Solute removal is  Hemofiltration The technique of hemofiltration (HF) uses a large quantity of hydrostatic UF. Plasma ultrafiltrate is replaced with plasma-like electrolyte solution. Solute removal is

1.4.3.  Hemodiafiltration
 what is dialysis

 In order to improve solute clearance, hemofiltration (convective transport) may be combined with diffusive transport by allowing dialysate to flow on the ultrafil-
trate side. Intermittent use of this technique is called hemodiafiltration (HDF) , while continuous use (commonly used in acute renal failure) is called continuous arteriovenous hemodiafiltration (CAVHD) or continuous venovenous hemodiafiltration (CVVHD), depending on the location of the catheter(s)

1.4.4.  Slow Low Efficiency Dialysis (SLED)
 what is dialysis

Slower removal of solutes is better tolerated than rapid removal. Thus, in an acutel yill patient, sometimes the slow removal is achieved by reducing the dialysate flow to 300 ml/min or lower with blood flow not exceeding 200 ml/min, and the treatment time is prolonged to 8–24 h. This technique, slow low efficiency dialysis (SLED), is better tolerated with less hemodynamic instability.

1.4.5. Ultrafiltration
what is dialysis

If volume removal alone is needed, it can be achieved by intermittent UF (IUF) or
slow and continuous UF (SCUF), without replacement of ultrafiltrate.

1.5  Hemodialysis Setup
 what is dialysis

Hemodialysis apparatus can be divided in two major components Blood circuit
Dialysate circuit



1.5.1.Blood Circuit

The blood circuit comprises: 

1-Tubing set with ports,
2- drip chambers, and an access device
3- Blood pump
4 -Hemodialyzer
 
1.5.1.1 Tubing Set
Blood is drawn from the patient into the blood tubing, either through a central venous catheter or through a needle inserted into the patient’s vascular access (fistula or graft). Blood tubing can be divided into two major segments. The segment that carries blood from the patient to the hemodialyzer is traditionally called the “arterial segment,” while the segment that carries blood from the dialyzer back to the patient is called the “venous segment.” Usually, each of these segments has a drip chamber into which blood flows and any air rises to the top. Blood drains from the drip chamber into the blood tube, continuing its course toward the dialyzer from the arterial and to the patient from the venous drip chamber. Pressure in these segments is monitored (arterial pressure monitor 1 in arterial drip chamber located before the blood pump and venous pressure monitor in the venous drip chamber), and if it goes beyond the set ranges, the alarm sounds and the blood pump stops. The venous drip chamber also has a level and air detector. If the blood level drops below the detector
level because of too much air, an air alarm sounds, the pump stops, and the tubing segment below the drip chamber is clamped to prevent any air being introduced into the patient. Some systems have an additional arterial pressure monitor between the blood pump and the dialyzer (arterial pressure monitor 2) that enables the reading of pressure between the pump and the dialyzer. The pressure in the arterial segment before the pump (monitor 1) is negative and after the pump (monitor 2) is positive, reflecting the resistance caused by the dialyzer. Pressure in the venous segment is positive, reflecting the resistance caused by the vascular access. The drop in pressure between post pump pressure and venous pressure represents the effect of ultrafiltration. For the calculation of transmembrane pressure (TMP), either the average of the two pressures (if post pump arterial pressure is measured) or the venous pressure is
used. The TMP is the pressure on the blood side of the dialyzer membrane minus the pressure on the dialysate side. The blood tubing is usually sterilized using ethyleneoxide (Eto), thus, the blood tubing needs to be thoroughly rinsed prior to connecting the tubing to the patient

1.5.1.2 Blood Pump
 what is dialysis

The most common type of blood pump is the roller design. Rotating rollers compress the pump segment of the tubing and sweep the blood forward. The speed of rotation determines Qb. The usual Qbs range from 200 to 500 ml/min in adults (median rate about 350 ml/min). If the pump is set at a certain rate but access is unable to provide blood at that rate, the pressure in the arterial chamber 1 drops below the set range and the alarm stops dialysis. Similarly, any excessive resistance to blood being returned to the patient increases pressure in the venous drip chamber and the system will stop if the set range is exceeded. There are two access-related reasons for insufficient blood flow—that the arterial segment is not receiving the desired blood flow or that the venous side cannot return the flow back to the patient. The former means that
the pump is causing too much negative pressure. This pressure limit is usually set at −200 mmHg, with any drop below this limit sounding the alarm. Problems with the return of blood cause the pressure in the venous drip chamber to increase and a pressure greater than 200 mmHg is usually considered unsafe.
The blood pump is a “demand driven” pump; thus, the blood pump rotation (flow
rate) is set at a fixed rate and the pump “demands” blood at this rate. The design of the pump is inflexible, leading to frequent alarm interruptions. The other commonproblem with the blood pump is the trauma the rollers cause to the pump segment of the blood tubing (spalling), limiting the tubing’s useful life [1]. The pump segment tubing material is silicone rubber and the rest of the blood tubing is usually made of polyvinyl chloride. The diameter of the pump tubing segment determines the “stroke volume” of blood per sweep. This requires that the rollers completely occlude the tubing segment, incomplete occlusion would reduce the stroke volume and Qb. At a very high pump speed, often the arterial pressure becomes too negative and tubing may partially collapse, again reducing the stroke volume and Qb. To get the reliable Qb, the pump needs to be frequently checked and calibrated.


1.5.1.3 Hemodialyzer
 what is dialysis


The dialyzer is the site of the movement of molecules (dialysis process) and is
the critical part of the dialysis apparatus. It contains a semipermeable membrane, through one side of which flows blood and the other side dialysate. This membrane consists of either thousands of capillary fibers (hollow fiber dialyzers) or of a sheet that is arranged in parallel plates (parallel plate dialyzers). The hollow fiber design is the version used most frequently  The major components of this are: Blood ports—carry blood into (arterial port) and out of (venous port) the dialyzer Headers—from the blood port, the blood enters the arterial header space and dialyzed blood enters the venous header space (before entering the venous blood port)


Potting material—the hollow capillary fibers are anchored to the dialyzer casing
with a potting material, separating the blood from the dialysate compartment
Space between header and fibers—this critical space is where clotting most often occurs
Capillary fibers—about 10,000 capillary fibers made of permeable material are
contained within the dialyzer casing. The blood flows inside the fibers and the
dialysate flows on the outside
Dialysate ports—there are two ports on the side of the casing, one for dialysate
inflow and one for the outflow 

Space between ports and potting material—this space is critical because dialysate flow (and thus clearance) in this space is relatively poor
Dialyzer Characteristics
Selection of a dialyzer is based on material and performance characteristics:
Membrane: The material that constitutes the membrane can be divided into four
broad groups:
(i) Cellulose membrane

Early material derived from plant polysaccharide was called cellophane. Later, other forms of cellulosic materials (based on the manufacturing process) were used; these included cuprophan (cuprammonium cellulose), saponified cellulose ester, and regenerated cellulose. The cellulosic membranes were widely used and are less expensive than the other membrane materials but cause more immunoactivation. Their use in the USA over recent years has declined because of being less bio-compatible.
(ii) Substituted cellulose membrane: 

The cellulose membranes described above
contain free hydroxyl groups that are thought to activate complements when
exposed to blood. In an attempt to reduce this, free hydroxyl groups have been
bonded to materials like acetate to form substituted cellulose membranes such
as cellulose acetate, diacetate, and triacetate. These are thought to be more bio-
compatible.
(iii) Mixed cellulosic–synthetic membrane: 

 During the manufacturing process, a tertiary amine compound is added to the cellulose thus the membrane surface becomes more biocompatible. These membranes are called Hemophan (Cellosyn).
(iv) Synthetic membrane: 

Several synthetic membranes are currently in use. These differ from cellulosic membrane in several aspects. The synthetic membranes are generally more biocompatible, have higher hydraulic permeability, and are more expensive. Some of these membranes also adsorb plasma proteins, immunoglobulins, and complements. Common synthetic membranes materials include polysulfone (PS), polyacrylonitrile (PAN), polycarbonate, polymethylmethacrylate (PMMA), and polyamide. Biocompatibility of the membrane: The dialyzer membranes cause activation of blood cells, complement blood cells, and complement cascade. This is thought to occur mostly by free hydroxyl moieties present on the surface of cellulosic membranes. The activated cells produce cytokines and lead to various clinical sequelae and dialytic reactions. Antioxidants are also produced during dialysis and new dialyzers are being produced in which the membrane is coated with antioxidant materials such as vitamin E. The use of these dialyzers has been reported to be associated with less production of oxidants. The biocompatibility is attributed to the membrane material, with cellulosic membranes being the least biocompatible, synthetic membranes the most biocompatible, and others in between. The potting materials as well as the middle layer (the layer between the two skins of the membrane) can also cause bio-incompatibility.

• Dialyzer performance: 
 Dialyzer performance is judged by solute clearance and

UF characteristics:
 (i) Solute clearance: 
The solute removal characteristic of a dialyzer is one of the key measures of its performance. It is reported in terms of clearance of solutes such as urea, creatinine, phosphate (PO 4 ), uric acid, beta-2-microglobulin, and vitamin B 12 . Clearance depends on the thickness and surface area of the membrane and on the density, characteristics, and size of the pores. Urea clearance is the most commonly used measure, since it is used in the calculation of the dose of dialysis. The clearance data provided by the manufacturer usually comes from in vitro experiments using water and is always higher than the blood clearance obtained in vivo. Therefore, the manufacturer’s in vitro data must not be used to determine the dialysis prescription using urea kinetics. Generally, creatinine clearance is 70–95% of urea clearance. PO 4 and uric acid clearances are not always reported but can be useful in treating markedly elevated PO 4 or uric acid levels (e.g., those encountered with tumor lysis syndrome and acute renal failure). However, PO 4 is an intracellular ion and, using a dialyzer with a high PO 4 clearance, the plasma value can fall quickly without a major impact on total body removal of this ion. Vitamin B 12 (with a molecular weight of 1355) has lower clearance and helps in defining the permeability of the dialyzer for larger (middle) molecules. Recently, beta-2-microglobulin clearance has also been used as a method of assessing membrane characteristics, particularly the flux of the membrane.
(ii) UF characteristic: 

The UF characteristic of a dialyzer is measured as the K uf , the
volume of plasma water removed per hour per mmHg of TMP, and is reported
in terms of the ultrafiltration rate (ml/h/mmHg). Thus, the UF rate (UFR) can be
accurately calculated for each treatment from the K uf of the dialyzer and TMP
during the procedure.

Example
 
A dialyzer with a K uf of 4 ml/h/mmHg is used for a treatment. The prepump arterial pressure is −100, the post-pump arterial pressure is not measured, the venous pressure is 100 mmHg, and the patient needs to lose 2.7 kg during a 3-h run. What should be the dialysate pressure to achieve the above UF goal
if no UF modeling is used? TMP = P b –P d and UFR = TMP × K uf ; UFR = 2, 700 ml/3 h, or 900 ml/h where P b is the pressure on the blood side and P d is the pressure on the
dialysate side of the membrane 900 ml/h = TMP × 4 ml/h/mmHg; or TMP = 900 ml/h ÷ 4 ml/h or 225 mmHg 225 mmHg = P b –P d , or 225 = 100−P d ; or P d = −125 mmHg, or the dialysate side would have to supplement the blood side pressure by having a negative pressure
If a dialyzer with a K uf of 15 is used and rest of the variables remain
unchanged, the 100 mmHg venous pressure would cause more UF than
desired, in this case, the P d would be positive to slow down the UFR by
countering the P b
TMP = 60 and P d = 40(P b remains 100).

From the above example, it is clear that dialyzers with a high K uf can cause excessive UF and need fine balancing of pressure from the dialysate side in order to prevent over ultrafiltration. Thus the dialyzers with a K uf of >8 ml/h/mmHg should only be used with machines with volumetric control ability. In dialyzers with a very high K uf (such as 100 ml/h/mmHg), a large pressure drop occurs along the length of the capillary fiber and often a back-leak of dialysate occurs or even a small leak in the membrane can cause infusion of dialysate from the venous end of the fibers into the blood. For this reason, very porous dialyzers may be safe only with ultrapure dialysate. Surface area and porosity of the membrane: Dialyzer clearance is dependent on the porosity of the dialyzer and the total surface area of the dialyzer membrane. The surface area of most dialyzer membranes ranges from 0.8 to 2.1 m 2 . For the less biocompatible membranes such as cuprophan, the larger the surface area, the more
potential there is for immunoactivation (see below). Priming volume: Priming volume is the volume of the blood compartment of the dialyzer and is therefore equal to the volume of blood that will fill this compartment. For dialyzers used with adults, this volume ranges from 50 to 150 ml.
Membrane thickness: Usually, thin membranes are more permeable than thicker membranes. However, thinner membranes cannot withstand as high a TMP as
thicker membranes. In addition to dialyzer performance characteristics, the dialyzer sterilization technique may be of importance. The most common method of sterilization is with Eto. Removal of Eto prior to use of the dialyzer is very important because some patients experience a severe anaphylactic reaction to small amounts of Eto, which is difficult to remove from the potting material without thorough rinsing. In Eto-sensitive patients, only dialyzers sterilized by alternative methods (e.g., gamma radiation or
steam autoclaving) should be used. Because of the risk of severe reaction to Eto,
this method is becoming less commonly used and gamma radiation and steam sterilization are becoming more popular.

High-Efficiency High-Flux Dialyzers
Dialyzers that are more efficient and contain high flux membranes have become
very popular during the last two decades. It is worthwhile to clarify the various
membrane characteristics because confusion regarding the definitions and terminology is prevalent. Flux: The term flux defines the ability to ultrafilter plasma water, or the K uf of a membrane. Thus, a membrane with K uf of <10 ml/h/mmHg is called a low-flux membrane and a membrane with >20 ml/h/mmHg is called a highflux membrane. Efficiency: Efficiency denotes the solute removal by diffusion based on the KoA of urea; membranes with a KoA urea of <500 ml/min are called low efficiency membranes and those with >600 ml/min are called high-efficiency membranes. Generally, the high-flux dialyzers also have high-efficiency membranes and vice versa. However, theoretically, the two could be very different Mass transfer area coefficient (KoA): As discussed in Chapter 1, the KoA is the clearance of a solute at infinite Qb and Qd, usually expressed in terms of urea clearance or KoA urea . This theoretical value can be calculated from clearance and blood and dialysate flows:  KoA = (Qb × Qd)/(Qb − Qd) × ln[(1 − Ks/Qb) ÷ (1 − Ks/Qd)],  where Ks = the dialyzer clearance of a solute such as urea. Thus, the KoA value is more affected by clearance than Qb or Qd.

Traditionally, dialyzers have always been reprocessed and reused—mainly for convenience and to save time. With the popularity of the more expensive high-efficiency dialyzers, cost saving has become the major factor for reuse. However, recently, the interest has shifted from reuse to no reuse, because of the concern about the process and its effect on the treatment and patient. Although there is no clear evidence of reuse having any adverse effect on patients or treatment, some reports even have cited the possible benefit of reuse. With no reuse, the cost of dialysis supplies increases, and the impact on the environment by increasing the amount of contaminated waste is of major concern.
The reuse technique involves rinsing with clean water and/or cleaning agents
such as sodium hypochlorite (bleach), hydrogen peroxide, or peracetic acid. Af-
ter thorough cleaning, the dialyzer is sterilized; formaldehyde is the most common agent used but glutaraldehyde has also been used for this purpose, and there has been interest in using heat. Before the dialyzer is used again, several safety checks are mandatory:
Dialyzers are tested chemically to ensure that no sterilizing agent remains.
Membrane patency is checked by the use of a pressure test. Dialyzer efficacy is tested to ensure that enough membrane surface is still avail able for dialysis. This is done by measuring the fiber bundle volume (FBV). If the FBV is >80–85% of the baseline value, the dialyzer is deemed to have an adequate number of patent fibers. Any dialyzer with a lower value should be discarded.

1.5.2 Dialysate Circuit

The major components of the dialysate circuit
1-Dialysate
2-Dialysate delivery system

1.5.2.1 Dialysate
These days, bicarbonate dialysates are almost exclusively used for dialysis. Concentrated dialysate that is proportioned by mixing with treated water in the machines is the most common form. However, mixing of concentrated NaHCO 3 and CaCl 2 leads to the precipitation of CaCO 3 .
CaCl 2 + NaHCO 3 → Ca(HCO 3 ) 2 + NaCl → CaCO 3 + H 2 O + CO 2
The precipitation is avoided by separating the concentrated NaHCO 3 
(B-concentrate) from the rest of the constituents of the dialysate (A-concentrate). To further reduce the risk of CaCO 3 formation, an acid is added to the A-concentrate,this keeps the pH of the final dialysate below 7.4 after the proportioning and mixing of the A- and B-concentrates. The lower pH drives the equation to the left, resulting in more soluble calcium chloride and calcium bicarbonate instead of less soluble calcium carbonate formation. Based on the acidifying agent, two types of A-concentrates are available:
Acetate-containing acid concentrate (acetate dialysate): The acid concentrate
contains acetic acid, usually 4 mEq/l (in liquid concentrate) or 8 mEq/l (in powdered concentrate, Granuflo R Fresenius) in the final dialysate.
Citrate-containing acid concentrate (citrate dialysate): The predominant acid is
citric acid, usually 2.4 mEq/l, with 0.3. mEq/l acetic acid (Citrasate R , Advanced
Renal Technologies). The composition of the rest of the constituents is identical in the two forms of dialysate. Clinical effects: The presence of citric acid has been reported to have some beneficial effects, mostly related to its anticoagulant properties  During the recent years, there have been concerns about acetate causing activation of cells and inflammatory markers. There is a lot of interest in further reducing or removing acetate from the dialysate.
Liquid versus dry concentrate: Both acetate- and citrate-containing concentrates
are available in either dry form or liquid form. The dry concentrate is dissolved
in appropriate volume of treated water before connecting it the machine. Exam-
ples of dry forms are Granuflo R (8 mEq/l acetate) by Fresenius, and DRYalysate R (2.4 mEq/l citrate) by Advanced Renal Technologies. Examples of liquid formulations are Naturalyte R and Citrasate R , by Fresenius and Advanced Renal Technologies, respectively. 


The clinical effects of the two currently used acid concentrates
Type of dialysate              Disadvantages                      Advantages
 
Acetate-containing                                                                
bicarbonate dialysate          Intradialytic compli-
                                             cations,
                                            Activation of cells
                                            Activation of inflam-
                                            matory proteins

Citrate-containing
bicarbonate dialysate         Decrease in Ca and
                                            Mg                                        Reduced clotting:
                                                                                         • Increase in the
                                                                                            dose of dialysis
                                                                                         • Heparin-free
                                                                                            acute/chronic
                                                                                             dialysis
                                                                                         • Reduced heparin
                                                                                            chronic dialysis
                                                                                          • Increase in reuse
                                                                                             of dialyzer

Bicarbonate concentrate: Bicarbonate is available in powder form. The powder is either mixed manually with appropriate volume of water prior to connecting to the machine, or the powder comes filled in a cartridge and is attached to the machine. With the cartridge form, the water is delivered to the cartridge and the concentrated solution is used directly from the cartridge by the machine.
Lactate-containing dialysate: In a small number of home dialysis patients using
frequent and slower rate dialysis, the NxStage machine uses a dialysate that contains lactate in place of bicarbonate as a basic anion. Thus, currently used dialysates contain bicarbonate as the predominant basic anion (used for the vast majority of patients) or lactate (used for only a small number of patients).

1.5.2.2 Dialysate Delivery System

The dialysate delivery system blends and provides dialysate to the dialyzer, monitors dialysate quality, and controls and monitors UF from the patient. It can be divided into four 
major components:
Water preparation system: Treated (purified) water  is delivered to the machine, where it is heated to an appropriate temperature (34–39 ◦ C) by a heater and deaerated (usually by subjecting the heated water to a negative pressure, using a pump). Water is then delivered to the proportioning system.
Proportioning system: There are different types of proportioning systems based
on whether dialysate, water, or both are metered. Simply stated, the proportioning system takes appropriate volumes (based on how concentrated the concentrate is) of parts A and B of the concentrate and mixes them with the appropriate volume of (in the appropriate ratio) treated water to form the final A and B dialysates, the final mixing of the two diluted parts A and B makes the final dialysate; the composition is shown in Table 2.2. The final dialysate is then checked for proper mixing (proportioning) by measuring the conductance of electricity through the final dialysate. The rate of flow of an electric current through any solution is proportional to the concentration of electrolytes present in the solution, thus, distilled water is a very poor conductor of electricity, and the salt solution is a good conductor. Thus, from the rate of electrical conductance, the concentration of salt in the solution can be verified. Roughly, the conductance is about 1/10th of the sodium concentration, thus
a dialysate of 135 mEq/l sodium concentration should have a conductivity value
of 13.5 ms/s. If the conductivity of the dialysate is in the acceptable range, the
dialysate is allowed to proceed to the dialyzer. If the conductivity is out of range,
the dialysate is diverted to the bypass loop. The temperature of the dialysate is also monitored prior to its passage through the dialyzer, if the temperature is out of range, the dialysate is diverted to bypass. It is important to have separate and independent sensors monitoring and controlling the proportioning units.

Volumetric-controlled machines: These machines have two integral parts to 
ensure accurate ultrafiltration,
(1) the balancing chamber 
(2) the UF controller

1. Balancing chamber: 

 The risk of over-ultrafiltration because of the use of per- meable dialyzers required the development of a machine that could accurately track the ultrafiltration and control the rate. This was achieved by ensuring that dialysate inflow into and outflow out of the dialyzer were same. The “balancing” of the two flows is most commonly achieved by allowing the inflow and outflow into a rigid chamber and keeping the two volumes separated by a diaphragm that deflects an equal distance from the middle. This balancing chamber concept works by inflowing a fixed volume into the chamber, and the fixed deflection of
the diaphragm pushes an equal volume out of the chamber. The interplay of the
four sets of one-way valves ensures that an equal volume of dialysate goes into
and comes out of the dialyzer. Two sets of these balancing chambers acting in
alternate cycles achieve a more continuous flow of the dialysate.

2. UF controller: 
A separate line branches out of the dialysate outflow line, the flow in this line is controlled by a UF pump. The pump in turn is controlled by a central computer unit that gets information from the dialyzer inlet and outlet pressures for both blood and dialysate; the unit also gets information about the required rate and net volume of UF fed into the machine prior to the treatment. This computer unit then controls the UF rate by controlling the UF pump. Monitors and detectors: For safety, several monitors and detectors are used in the
dialysate delivery system:

(i) Conductivity monitor: As discussed earlier, the appropriate mixing of concentrate with water is monitored by conductivity. Because this monitor essentially checks the electrolyte concentrations in the final dialysate, any malfunction that is accompanied by abnormal proportioning can be potentially fatal for the patient. Any deviation from the narrow set range leads to the sounding of an alarm and the interruption of dialysis.
(ii) Temperature monitor: Patients need to be dialyzed with dialysate at 36–42 ◦ C. Dialysis at <36 ◦ C is associated with the patient feeling cold and uncomfortable, and a dialysate temperature of >42 ◦ C is associated with severe hemolysis and cardiopulmonary arrest. The dialysate temperature is monitored and a thermostat controls the water heater. Any increase in temperature beyond the set range triggers an alarm and dialysis is stopped (usual safe range set between 35–39 C).
(iii) Blood leak detector: Blood leak sensors are placed on the dialysate outflow line. These are usually flow-through photo-optical or blue frequency spectrum sensors.
(iv) pH sensors: Some machines have a pH electrode as part of the proportioning system. These are generally used to prevent any mistake in connecting the appropriate concentrates to the machine (e.g., B concentrate not being connected).
(v) Arterial and venous pressure monitors: Both arterial and venous drip chambers are connected to a pressure sensor through a filter. The pressure ranges are set in the safe range to monitor the blood delivery to and from the system. The prepump arterial pressure would usually be a negative number representing the demand by the pump. Generally, the safe lower limit of the arterial pressure is no lower than −100 mmHg. The venous pressure is generally kept below 200 mmHg.
(vi) Air detector: An air detector is located on the venous drip chamber. If too much air collects, an alarm sounds, the pump stops, and a blood line below the drip chamber is clamped to prevent an accidental infusion of air.

1.5.2.3 Dialysis Water
Drinking water contains chemical, microbiological, and other contaminants. A
healthy adult drinks about 10–12 l of water per week, this water goes across a selective barrier of the gastrointestinal tract, and excess chemicals are removed by the healthy kidney. In contrast, during dialysis, a dialysis patient is exposed to more than 350 l of water weekly, the water passes through the nonselective dialyzer membrane, and there is no kidney to maintain the normal balance of chemicals. More over, the highly permeable high-flux membrane used today increases the risk of ontaminants passing through the membrane and into the blood gives the commonly present contaminants and medical syndrome caused by these in dialysis patients. Some common contaminants have been shown to be injurious to patients. Contaminants include aluminum (causing bone and brain problems and anemia), copper (causing hemolytic anemia and febrile reactions), and chloramine (causing hemolytic anemia). If the large quantities of salt and electrolytes that are normally present in the water are allowed to remain, higher concentrations of these occur in the final dialysate. The Association for the Advancement of Medical Instrumentation (AAMI) has recommended minimum standards for the water used in dialysis Thus, the water for dialysis must be purified of these contaminants prior to its use by the proportioning system of the dialysis machine.


1.5.2.4 Water Treatment System
Two major types of water purification systems are in common use: (1) reverse os- mosis (R/O) and (2) deionizer (D/I). However, to protect and prolong the lives of R/O membrane or the D/I resins, water goes through several steps of “pretreatment”. Pretreatment system: The first component of the pretreatment system is a sediment filter that removes sediments such as silt, rust, and clay as water percolates through the filter. Next, there is a water softener that is filled with resin charged with NaCl; as water passes around these resin beads, the Ca and Mg in the water are exchanged with NaCl, thus, water coming out has less Ca and Mg. The softner is periodically recharged by flushing it with brine. The water next is passed through a set of activated charcoal columns. Some organic contaminants and especially the chlo-rine and chloramines are adsorbed on the charcoal surface and removed from the water. This is important because chloramines can damage the R/O membranes and are not effectively removed by the D/I. Exhaustion of the charcoal column has led to several significant incidences of chloramine toxicity. It is, therefore, required that treated water is checked for chloramines at least three times a day to ensure proper functioning of the charcoal columns. Sets of several gradually decreasing sizes of filters (from 5 to 2 μm) are placed to remove smaller particles. The pretreated water
is then passed through the final water treatment system, either R/O or D/I.
Reverse osmosis system (R/O): Membranes with very small holes are arranged
in a cartridge either in the form of a parallel plate or capillary fibers. The holes
are so small that they only allow water molecules to pass through, retaining any-
thing larger, including sodium and urea. The pretreated water is forced through these holes by a pump that generates enough pressure to squeeze water molecules against higher osmolar pressure, thus, the name, reverse osmosis. The membrane separates the pure water or permeate from the “rejected” water, the pure water is allowed to circulate through the dialysis unit to be used for the dialysate proportioning; the rejected water is drained out. The R/O membranes are made from either cellulosic or synthetic materials. Cellulosic membranes are prone to be damaged by bacteria, whereas the synthetic membranes (polyamide, polysulfones, etc.) are more vulnerable to chemicals such as chloramines and chlorine. The efficacy of the membrane is continuously monitored by measuring the resistance to electrical current through the product (permeate) and feed water. A membrane that rejects >85% of conductant water is considered to be functioning well, if this rejection rate goes below 85%, the membrane needs to be changed. The rejection ratio = (1− [conductivity permeate/conductivity feed water]) ×100. Deionization (D/I): Removal of inorganic ions by exchanging the inorganic ions with H + and OH − ions is the process of D/I. The most common type is a mixed-bed D/I that consists of resins fixed with H + (cation)
and other resins coated with OH − ions (anion). As water with dissolved inorganic ions percolates first through the cation exchange resin, the dissolved cations (Na, Ca, Mg, etc.) are exchanged for H + . Water then passes through the anion exchange resins and anions (Cl, Fl, NO 3 , etc.) are exchanged with OH − , H + , and OH − , then forming pure water that, after going through submicron filters and often ultraviolet light, is permitted to loop around the unit. The product water coming out of D/I is monitored by checking the resistivity, which should be greater than 1 mΩ /cm to be
acceptable. Most of the major catastrophies afflicting groups of patients have been caused by improperly treated water delivering contaminants to the blood. Thus, it is mandatory to use an effective water treatment system and to continuously monitor the quality of the water. Moreover, the increased use of highly permeable high-flux dialyzers increases the potential for the transfer of contaminants into the blood, thus, the water needs to be further purified. Some units use a tight membrane filter (dialyzer); the dialysate passes across this first dialyzer prior to its delivery to the patient dialyzer. This “ultrapure” dialysate further protects the patient.

Chronic kidney disease .. (CKD)

Chronic kidney disease (CKD)

 can be defined in a variety of ways. The US Preventive Health Service defines it as decreased kidney function, with size-adjusted estimated glomerular filtration rate (eGFR/1.73 m 2 ) <60 mL/min, or as kidney damage that persists for at least 3 months. The management of a patient with CKD involves the following considerations: screening,etiologic diagnosis, and staging of the CKD severity; identifying and managing patients at high risk of progression; management of complications of CKD; and preparing the patient for transplantation or renal replacement therapy.













I.SCREENING, DIAGNOSIS, AND STAGING.
 
Screening should include monitoring for the presence of proteinuria and measurement of kidney function. Screening should focus on patients with CKD risk factors. These in-clude diabetes mellitus, hypertension, cardiovascular disease, history of smoking,obesity, age >60 years, indigenous racial origin, and a family history of CKD.

A. Urinary protein measurement.

US Preventive Health Service recommends urinary protein measurement as
a screening test in all high-risk individuals. The American Diabetes Association (ADA) recommends that an evaluation for microalbuminuria be performed in all type 2 diabetic patients at the time of diagnosis and in all type 1 diabetic patients 5 years after initial evaluation. Screening can be done by urine dipstick, but a more reliable method is an early morning meas-urement of the albumin-to-creatinine ratio in a spot urine sample. The dipstick used should be able to detect both albumin and evidence of blood or white cells. If the dipstick test suggests either blood or white cell activity, thena microscopic analysis of the urinary sediment should be performed.   One problem with urine dipstick tests is that they measure concentration only, and can give falsely negative results in a dilute urine. The urine albumin-to-creatinine ratio (UACR) overcomes this problem by looking at the ratio of albumin to creatinine, as both will be affected by dilution, and the effects of dilution will tend to cancel out. In terms of milligrams albumin per gram or millimole of creatinine, normoalbuminuria is
defined as <30 mg/g (<3 mg/mmol); microalbuminuria as 30–300 mg/g (3–30 mg/mmol); and macroalbuminuria as >300 mg/g (>30 mg/mmol). These cutoffs correspond only roughly to albuminuria measured in terms of milligrams per day (e.g., 30 and 300 mg per day), and they assume that 1 gof creatinine is being excreted per day. In fact, the average amount of creatinine excreted per day is actually high- er, and as discussed elsewhere in this chapter, creatinine excretion is greater in men than in women and in young people versus older people. However, fine-tuning these “cutoff” UACR ratios is not of great clinical importance, as the risk of increased urine albumin excretion is continuous, and risk is increased even when the albumin excretion is <30 mg per day. The UACR can be done at any time, but a morning test may increase sensitivity and will tend to exclude the relatively benign condition of orthostatic proteinuria, where,
proteinuria is present during the day, but ceases while the subject is sleeping
supine. A positive UACR test should be repeated at least twice over 3
months to exclude acute kidney injury and to confirm a positive test.

1.1  Limitations of Urine Dipstick


False Negatives
        Low urine-specific gravity (<1.010)
        High urine salt concentration
        Acidic urine
        Nonalbumin proteinuria
False Positives
       Presence of blood or semen
       Alkaline urine
       Detergents/disinfectants
       Radiocontrast agents
       High urine-specific gravity (>1.030)

B. Measurement of kidney function

1. Glomerular filtration rate (GFR) .

The GFR, usually expressed in terms of milliliters per minute, is the
volume of serum cleared by the kidneys per unit of time. The GFRdepends on body size and age, and so an isolated value of GFR needs to be evaluated in context. One usually normalizes GFR to body surface area, specifically, per 1.73
m 2 . In healthy subjects, GFR/1.73 m 2 is similar in men and women,
but GFR/1.73 m 2 declines with age, averaging about 115 mL/minin young adults, 100 mL/min in the middle-aged, and then dwindling to 90, 80, and 70 mL/min as patient age increases to 60, 70, and 80 years, respectively.
 
2.  Serum creatinine.

Creatinine is produced at a relatively constant rate from creatine in muscle and is excreted by the kidneys by both glomerular filtration and tubular secretion. Normal creatinine concentrations range from 0.6 to 1.0 mg/dL (53–88 mcmol/L) in womenand from 0.8 to 1.3 mg/dL (70–115 mcmol/L) in men. Measurement of
the serum creatinine concentration is one way to obtain a rough estimate of the level of renal function, because as renal function falls, creatinine will continue to be produced, and the serum levels will rise. The relationship between serum creatinine and renal function is nonlinear: a doubling of the serum creatinine will reflect a decline in GFR of approximately 50%. Doubling of serum creatinine from aninitially low value can result in a serum creatinine still in the “normal range” despite a substantial loss of kidney function. Serum creatinine levels are influenced by muscle mass, recent dietary intake, especially of cooked meat, and
concomitant drug therapy (e.g.treatment with cimetidine, a drugthat blocks tubular secretion of creatinine and which will slightly increase the serum creatinine without any effect on GFR). In patients with cirrhosis and ascites, estimation of renal function from serum creatinine is particularly difficult.
There can be a very low creatinine production rate due to extremely low muscle mass (low creatinine production rate), plus it often is difficult to determine ascites-free body weight for normalization. In such patients, serum creatinine
levels in the 0.5–1.0-mg/dL range (44–88 mcmol/L), nominally “normal,” may reflect moderately to markedly impaired levels of renal function. Even in patients without cachexia, the serum creatinine level must always be interpreted in the context of a patient’s muscle mass. For example, a serum creatinine of 1.3 mg/dL (115 mcmol/L) can represent a creatinine clearance of 94 mL/min in a young 80-kg male, or a creatinine clearance of only 28 mL/min in an elderly,
50-kg female (Macgregor and Methven, 2011). Until recently the serum creatinine was measured by a variety of methods, some of which, due to interfering substances in the blood, deviated substantially from “true” values of creatinine concentration as determined by isotope dilution mass spectrometry (IDMS). In the United States and many other countries, laboratories are now
normalizing their measurement methods to IDMS, and the normalized values tend to be lower than those obtained using other methods.

3. Creatinine clearance by timed urine


collection. A timed (usually 24 hours) urine collection of creatinine excretion can be used to calculate the creatinine clearance (C Cr ), which is defined as the volume of serum cleared of creatinine per minute. Normal C Cr is approxim-
ately 95 ± 20 mL/min in average size adult women and 125 ± 25 mL/min in average-size adult men. Patients are instructed to urinate in to the toilet on arising, and to mark this time as the start of the collection period. Next they are to pass all of their urine into a container during the ensuing day and night.
The following morning, the patients are to urinate into the container one last time, and to note this time as the end of the collection period. By dividing the amount of creatinine in the collected urine bythe number of minutes in the col-
lection period (start time to finish time), the laboratory can calculate
the per minute rate of creatinine excretion. A sample of blood must
be drawn at some point during the urine collection period in which the
serum creatinine level is measured. To calculate creatinine clearance,
one simply divides the per minute creatinine excretion rate by the serum value. This gives the volume per minute of serum that had to have been “cleared” of creatinine by the kidneys. For example, if the per minute creatinine excretion rate is 1.0 mg/min, and the serum creatinine level is 1 mg/dL, or 0.01 mg/mL, then 1.0/0.01 = 100 mL/ min of serum were on average being cleared of creatinine by the kidneys during the collection period. Despite the technical challenge ofcollecting urine properly, timed urine collections are a very useful
means of estimating kidney function in cachectic patients, including those with cirrhosis and ascites, as well as markedly obese patients. The completeness of the urine collection for creatinine can be estimated by comparing the amount of
creatinine recovered per day based on the expected daily creatinine excretion rate for a given patient based on sex and body weight. Thus, one expects daily creatinine excretion to be about 15–20 mg/ kg lean body weight in women and
20–25 mg/kg lean body weight in men. A more exact estimate of daily creatinine excretion rate can be obtained from the use of an equation incorporating
body weight, gender, age, and race, such as that developed by Ix (2011), and which is detailed as a nomogram in Appendix A. A creatinine excretion rate that is significantly less than expected usually indicates an incomplete urine collection. Because creatinine is cleared by the renal tubules in addition to being filtered at the glomerulus, the creatinine clearance is greater than GFR. When GFR/1.73 m 2 is very low (e.g., less than 10–15 mL/min), the proportion of
creatinine excretion due to tubular secretion is high. To get a more reliable estimate of GFR when GFR is low, one can measure the amounts of both creatinine and urea in the timed urine sample, and measure the serum urea level as well as the creatinine level during the collection period. The per minute clearance of urea is calcu-lated in the same way as for creatinine. Urea is filtered at the glomerulus, but then some urea is reabsorbed by the renal tubules, so with urea, the situation is opposite to that with creatinine; due to tubular reabsorption, the urea clearance will be less than the GFR, where as the creatinine clearance will be greater than the GFR. Averagingthe urea and creatinine clearances has been shown to give a good estimate of GFR in patients with GFR less than 10–15 mL/min.


4.  Estimated creatinine clearance. To


avoid the inaccuracies and incon venience of timed urine collections, creatinine clearance (C Cr ) can be estimated by using equations that estimate the per minute creatinine excretion rate based on age, body size, gender, and in some
equations, race. One equation thathas been used for this is the Cock croft–Gault equation: where W is body weight. This equation provides a quick and
reasonably accurate estimate of renal function at the bedside. The
more recently developed Ix equation (Ix, 2011), described in Appendix A, also can be used. The Ixequation was developed and validated in a much larger sample of individuals, including blacks, and was based on modern, IDMS-cal-ibrated laboratory measures of creatinine. Neither equation is very
accurate in markedly obese or cachectic patients. Some have sug-gested that the accuracy of the Cockcroft–Gault equation can be increased by using actual body
weight for cachectic patients, ideal body weight for normal weight
patients, and adjusted body weight for markedly obese patients (Brown, 2013). See Appendix B for more details.


5 . Estimated GFR


a . Modification of Diet in Renal Disease (MDRD) equation.

This equation was derived from the MDRD trial and reports eGFR normalized
per 1.73 m 2 of body surface area. For laboratories using the new IDMS-standardized serum creatinine values, the version of the MDRD equation
that should be used is what follows:The “175” term in this equation replaces the “186” term in the original published equation to account for the
slightly lower values of IDMS-standardized creatinine assays compared to assays used in the MDRD study. When serum creatinine is measured in SI units (mcmol/ L), one needs to divide the serum creatinine value by 88.5 to
convert to mg/dL prior to inserting into the equation.The MDRD GFR equation differs from the Cockcroft–Gault or Ix estimates of the creatinine clearance in several ways. First, it was developed from data that measuredGFR by iothalamate, a substance which is not secreted by the renal tubules, and so it predicts GFR rather than creatinine clearance. All else being equal, the MDRD equation will give a lower value for renal function (GFR) than creatinine clearance, which includes the tubular secretion component of renal function.
Secondly, the MDRD equation is normalized to body size and is expressed as eGFR/1.73 m 2 of body surface area. Creatinine clearance, whether ob-
tained from a timed urine sample or from the Ix or Cockcroft–Gault equation, is
 raw renal creatinine clearance that has not been adjusted for body size

b. The CKD-EPI GFR equation.


 This is similar to the MDRD equation, but this newer equation was validated in a larger group of subjects, particularly those with only mild degrees of renal impairment. The CKD-EPI equation is listed in Appendix A. The differences between the two equations are usually not of clinical importance, as they occur primarily in patients with GFR levels greater than 60, where the impact of knowing the precise level of renal function is not particularly large.

c. Cystatin C equations. 

An altern-ative method of estimating GFR is based on equations that use the serum cystatin C level. Cystatin C is a 13-kDa protein produced by all cellsthat is filtered by the glomerulus and not reabsorbed. The
production rate of cystatin C is not related to muscle mass or dietary meat intake, and cystatin C–based estimates of GFR correlate better with
CKD-related outcomes than creatinine-based equations in some studies. Some of the newest efforts to predict GFR combine both serum creatinine and cystatin C levels (Levey, 2014). Laboratory methods of measuring cystatin C are not
commonly standardized (this is in progress, similar to IDMS standardization of creatinine), and for the moment, cystatin C equations are not in wide use.

6. Problems with estimated clearances in


acute kidney injury. The estimating equations based on either creatin-ine or cystatin are based on steady state assumptions. If one were to surgically remove both kidneys, the serum creatinine or cystatin C levels would begin to rise, but this would take place over a number of days as opposed to immediately. For this reason, none of the renal function estimating equations described above are useful in situations where the level of kidney function is rapidly changing. The
timed urine collection method can be used to measure creatinine clearance, but then serum creatinine levels need to be measured at both the beginning and end of the collection period, and the per minute excretion rate should be di-
vided by the time-averaged serum value in the calculations.

C. Ultrasound and serum electrolytes.


 In patients found to have CKD, one shouldimage the kidneys, commonly by ultrasound, to look for structural abnor malities and possible obstruction and measure serum electrolytes (Na, K, Cl, HCO 3 ) to screen for metabolic acidosis
and electrolyte disorders, the presence of which may give clues to an underly-
ing renal disease.

D. Looking for an etiologic diagnosis. 


Identiying the underlying cause of CKD is important. The CKD may be revers-
ible, for example in a patient with bilateral renovascular disease or chronic
bladder neck obstruction from prostatic hypertrophy. The cause of CKD may
provide insights into the tempo of disease progression. Since some etiolo-
gies of kidney disease are very likely to recur in a future kidney allograft,
identifying the underlying cause of CKD at the outset may help in later
management decisions.


E.  staging


The National Kidney Foundation’s (NKF) Kidney Disease Outcome
Quality Initiative’s (KDOQI) staging of CKD has been widely adopted. It stages CKD from stage 1 (mildest) to stage 5 (most severe) based on the level of eGFR normalized to body surface area. The two mildest stages—stages 1 and 2, in which the eGFR/1.73 m 2 is still above 60 mL/ min—require evidence for kidney
damage apart from reduced GFR. Kidney damage can be manifest as patho-
logic changes on kidney biopsy; abnormalities in the composition of the
blood or urine (proteinuria or changes in the urine sediment examination), or
abnormalities in imaging tests. The more severe stages of CKD—stages 3,
4, and 5—are present by definition when the GFR is below 60, 30, and
15, respectively. Some elderly patients Staging.with eGFR/1.73 m 2 in the range of 45–60 mL/min may not have obvious
kidney damage, nor an increased risk of an accelerated decline in renal function or mortality. A subsequent staging system developed by KDIGO (Kidney Disease: Improving Global Outcomes) partially takes this into account by sub- dividing stage 3 CKD into two levels: 3a, with eGFR/1.73 m 2 in the range of 45–59 mL/min; and 3b, with GFR levels between 30 and 44 mL/min. Also, the newer staging system adds in the degree of proteinuria as measured by the UACR. One newer staging system is shown in Table 1.2, where a low risk of CKD progression and complic- ations is indicated by “green,” and pro- gressively increased risk is indicated by “yellow,” “orange,” and “red.”

Uremic syndrome
































 Uremic syndrome. The uremic syndrome consists of symptoms and signs that result from toxic effects of elevated levels of nitrogenous and other wastes in the blood.

(Uremic syndrome) Symptoms. Uremic patients commonly become nauseated and often vomit soon after awakening. They may lose
their appetite such that the mere thought of eating makes them feel ill. They often feel fatigued, weak, and/or cold.
Their mental status is altered; at first, only subtle changes in personality may appear, but eventually, the patients become confused and, ultimately, comatose.

(Uremic syndrome) Signs. The classic uremic physical findings of a sallow coloration of the skin due to accumulation of urochrome
pigment (the pigment that gives urine its yellow color) and of an ammonia-like or urine-like odor to the breath are rarely seen unless the degree of uremia is severe. A pericardial friction rub or evidence of pericardial effusion with or
without tamponade reflects uremic pericarditis, a condition that urgently requires dialysis treatment. Foot- or wrist-drop may be evidence of uremic motor neuropathy, a condition that also responds to dialysis. Tremor, asterixis,
multifocal myoclonus, or seizures are signs of uremic encephalopathy. Prolongation of the bleeding time occurs and can be a problem in the patient requiring surgery.

(Uremic syndrome) Signs and symptoms: uremia versus anemia. Several of the symptoms and signs previously ascribed exclusively to uremia may be partially due to the associated anemia. For example, when the anemia of dialysis
patients is corrected with erythropoietin, they experience a marked decrease in fatigue and a concomitant increase in sense of well-being and exercise tolerance. The bleeding time may also improve, and there may be improvement in
angina pectoris and a reduction in left ventricular hypertrophy. There are improvements in cognitive function as well.

(Uremic syndrome) Relationship between uremic syndrome and creatinine clearance. The uremic syndrome predictably develops
when the creatinine clearance falls below 10 mL per minute per 1.73 m 2 . Diabetic individuals appear to be especially suscep-tible and frequently require earlier initiation of chronic dialysis (e.g., when creatinine clearance falls to 15 mL per minute per 1.73 m 2 ). However, in chronic renal failure, decreased spontaneous protein intake, anemia, and derangements in Ca/PO 4 /PTH homeostasis are already demonstrable when clearance is still 30–40 mL per minute per 1.73 m 2 .  (Uremic syndrome)