# Timing and Modality Option for Renal Replacement Therapy

Steps in calculation

Example of calculation or formula

Calculate the urea clearance for a 24-h period

Urea clearance = Uurea/Purea ∗ urine volume/1440 = Urea mL/min

Determine urea clearance in liters, which is equivalent to Kt

L/week = Urea mL/min ∗ number of minutes in week (10,080)/1000 mL/1 L

Determine the urea distribution volume (V) in liters (L)

V (L) men = 2.5 + 0.34 ∗ Wt (kg) + 0.118 ∗ ht (cm) − 0.095 ∗ age (years)

V (L) women = −35.3 + 0.18 ∗ W + 0.34 ∗ H or

V (L) men = 0.6 ∗ (Wt in kg)

V (L) women = 0.5 ∗ (Wt in kg)

Calculate the weekly Kt/V (Kt/Vweek) week/V (L)

Kt/Vweek = Urea (mL/min) ∗ number of minutes in week (10,080)/1000 mL/1 L/V (L)

Example: a 70-kg man with 24-h urea clearance of 10 mL/min

Uurea/Purea ∗ urine volume = Urea mL/min = 10 mL/min

10 mL/min ∗ 10,080 min/week ∗ 1 L/1000 mL = 100.8 Urea clearance

Assess total body water (V) (approx. 0.6 ∗ Wt) = 42 L

Kt/Vweek = 100.8/42 = 2.4

Abbreviations: Wt weight, ht height (Reproduced with permission from Bessie Ann Young [8])

A stage-based paradigm that utilizes either eGFR calculated using the Modification of Diet in Renal Disease (MDRD) study equation or an actual measurement of glomerular filtration rate (GFR) have been suggested to apply for the decision of the initiation time of dialysis by the current KDOQI guidelines [9]. These guidelines specifically interpret that patients at stage 4 CKD should be educated about dialysis and that referral for dialysis should be considered after the GFR declines to 15 mL/min/1.73 m2 (see Table 16.1) [2]. According to these guidelines, it was shown that dialysis was initiated at a higher mean GFR in 2006 than that in 1994, occurring at a conspicuous cost and also with early loss of residual renal function. Study of the Initiating Dialysis Early and Late randomized trial showed that there was no evident difference in mortality between early initiation of dialysis (eGFR, 10–14 mL/min/1.73 m2) and late initiation of dialysis (eGFR, 5–7 mL/min/1.73 m2). Current formulas for the calculation of eGFR are listed in the KDOQI guidelines for CKD, and most laboratories currently include serum creatinine-based eGFR calculated using the four-variable MDRD study equation proposed by Levey et al. (Table 16.2). Table 16.3 shows the KDOQI recommendations for the initiation of dialysis.

Table 16.2

Chronic Kidney Disease Epidemiology Collaboration equation for estimating GFR

Race

Sex

Serum creatinine level, μmol/L

Equation

Black

Female

≤62 μmol/L (≤0.7 mg/dL)

GFR = 166 ∗ (SCr/0.7)−0.329 ∗ (0.993)Age

Female

>62 μmol/L (>0.7 mg/dL)

GFR = 166 ∗ (SCr/0.7)−1.209 ∗ (0.993)Age

Black

Male

≤80 μmol/L (≤0.9 mg/dL)

GFR = 163 ∗ (SCr/0.7)−0.411 ∗ (0.993)Age

Male

>80 μmol/L (>0.9 mg/dL)

GFR = 163 ∗ (SCr/0.7)−1.209 ∗ (0.993)Age

White

Female

≤62 μmol/L (≤0.7 mg/dL)

GFR = 144 ∗ (SCr/0.7)−0.329 ∗ (0.993)Age

or other

Female

>62 μmol/L (>0.7 mg/dL)

GFR = 144 ∗ (SCr/0.7)−1.209 ∗ (0.993)Age

Male

≤80 μmol/L (≤0.9 mg/dL)

GFR =141 ∗ (SCr/0.7)−0.411 ∗ (0.993)Age

Male

>80 μmol/L (>0.9 mg/dL)

GFR = 141 ∗(SCr/0.7)−1.209 ∗ (0.993)Age

Abbreviations: GFR glomerular filtration rate, SCr serum creatinine (Reproduced with permission from Bessie Ann Young [8])

Table 16.3

Kidney Disease Outcomes Quality Initiative recommendations for the initiation of dialysis

CKD stage

Recommendation

Stages 1 and 2

• Diagnosis of CKD and initiation of risk factor reduction

Stage 3

• Referral from PCP to nephrologist for the evaluation of CKD and assessment of risk factors for progression

Stage 4

• CKD education, including education about transplant and dialysis

• Referral to vascular surgery for AV fistula once estimated GFR <20 mL/min/m2

• Preemptive transplantation

Stage 5

• Cadaveric transplant wait-listing

• PD catheter placement

• AV graft placement

• Initiation of hemodialysis if uremic symptoms exist

Abbreviations: CKD chronic kidney disease, PCP primary care provider, AV arteriovenous, GFR glomerular filtration rate, PD peritoneal dialysis (Reproduced with permission from Bessie Ann Young [8])

Therefore, even if the weekly Kt/V decreases to 2.0, it is not necessary to immediately start dialysis if the following conditions exist:

1. 1.

Absence of edema and no weight gain

2. 2.

Nutrition indexes indicating no need for dialysis

3. 3.

Absence of clinical symptoms and signs of uremia

However, the initiation of dialysis in patients with CKD in practical works is always later than the KDOQI recommendation. The Netherlands Cooperative Study on the Adequacy of Dialysis investigated the average Kt/V upon initiation of dialysis in the Netherlands from 1993 to 2000 and reported that the average Kt/V was 0.5 in 1993 and 0.8 in 2000 [10]. In China, Yang et al. surveyed the conditions of patients in Peking University First Hospital in 2000 and reported that the average creatinine clearance upon initiation of dialysis was 4.2 mL/min. In addition, many patients had complications such as hyperkalemia and acute pulmonary edema when they started dialysis. Liu et al. compared the timing for the initiation of dialysis in 2000 and 2006 in the same hospital and showed that dialysis was initiated earlier in 2006; however, complications were present.

Controversy exists as to whether earlier dialysis can improve the quality of life and prolonged the lifespan. Kazmi et al. analyzed the US Medicare data and showed that a higher eGFR at the initiation of dialysis indicated a higher risk of death, possibly implying that patients had much more serious complications. However, Beddhu et al. examined the risk of death adjusted for complications and obtained the same results [11]. Current clinical practice guidelines have suggested the timing for the initiation of dialysis according to renal function, nutritional status, and symptoms and signs of uremia. However, the key factor to determine when to institute dialysis is the existence of complications in clinical practice, especially in patients with diabetes. The measurement of residual renal function is helpful for doctors to evaluate the complications of patients and to determine the timing for the initiation of dialysis. More studies are required to confirm the advantages of earlier-onset dialysis.

### 16.3.2 Malnutrition

RRT should be considered if malnutrition cannot be corrected using standard non-dialysis treatment. According to the KDOQI guidelines, maintenance dialysis or kidney transplantation is recommended for non-dialysis patients with CKD (GFR <15 mL/min/1.73 m2) if protein–energy malnutrition is persistent or progresses despite treatment in which reasons for malnutrition are absent (viewpoint).

Extensive data showed that mortality and the incidence of complications were significantly increased in patients with protein–energy malnutrition at the initiation of dialysis [12, 13]. Supplementary evidence indicated that the survival rate of patients with ESRD closely correlated with nutritional status. This is true not only in patients on maintenance dialysis but also in patients who are to undergo dialysis. A study investigating 683 patients undergoing dialysis between 1970 and 1989 showed that hypertension, coronary artery disease, and hypoalbuminemia preexisting before dialysis were independent risk factors for mortality. Another study that included 1982 hemodialysis patients indicated that hypoalbuminemia at the start of dialysis was correlated with the risk of death. A study that included 680 PD patients also reported similar results.

Moreover, one study reported the opposite and observed no correlation between serum albumin level and survival rate of patients starting on hemodialysis. However, the sample size was small (n = 139), and 94% were black (83%) or Hispanic (11%) in this study.

Despite controversial conclusions, there was evidence showing that nutritional status improved after dialysis treatment in malnourished patients; however, the improvement in nutritional status did not improve the prognosis. Conversely, in patients with good nutritional status, their nutritional status remained unchanged after dialysis. Accordingly, despite the absence of evidence, the KDOQI guidelines suggest that maintaining good nutrition before dialysis could be helpful for the prognosis of patients.

Patients with CKD are usually prescribed with a “low-protein diet.” An inappropriate low-protein diet could result in malnutrition and poor prognosis. Hence, if the nutritional status of patients with CKD (GFR <20 mL/min/1.73 m2) is aggravated with no firm causes and cannot be corrected by interventions, RRT should be considered even though pericarditis or hyperkalemia is absent.

### 16.3.3 Indications for Emergency Dialysis

Severe hyperkalemia, acidosis, and acute pulmonary edema are indications for emergency dialysis.

## 16.4 Modality Option for RRT

### 16.4.1 Medical Consultations for Patients and Relatives

The purpose of management of patients with CKD in different stages is distinct. Stage 3 CKD is followed by renal anemia, renal osteopathy, electrolyte disturbance, acidosis, cardiovascular disease, and malnutrition. Patients with these must be intensively monitored by renal physicians. Moreover, endocrine and cardiovascular specialists are involved in the management of patients. Dietitians are required to evaluate the nutritional status and institute a low-protein diet plan to delay the progression of kidney disease. As kidney disease progresses, mental disorders are always accompanied by physical conditions. Therefore, psychologists and social workers are required to participate in the management of patients. Treatments for stage 4 CKD include retardation of progression, management of complications, and physical and psychological preparations for RRT. Studies have shown that quality of life and survival rates were better in patients undergoing appropriate management before dialysis than in those without rational treatment by nephrologist [1416].

The physical preparations for RRT include correction of anemia, treatment of bone disease, maintenance of electrolyte and acid–base balance, and preservation of good nutritional status [17]. Patients with stage 4 CKD should be followed up every 2 or 3 months if diagnosed with diabetic or nondiabetic nephropathy, respectively.

With respect to psychological preparations for RRT, first of all, doctors should assist patients in eliminating their fear, depression, and anxiety about RRT, and information on CKD, renal failure, and modalities of RRT should be subsequently introduced to them. In addition, patients could be introduced to the hemodialysis or PD settings to help eliminate RRT rejection. Unhealthy mental condition before dialysis correlates with poor prognosis of patients.

### 16.4.2 Modalities of RRT

Patients at stage 4 CKD should make a decision of dialysis modality with respect to RRT, which is expected to be made during a relatively short period of time, such as during a clinic visit. Many educational facilities such as DVDs, videos, or Internet programs can be used to assist patients and their families in considering which modality best fits their lifestyle and needs. Moreover, to acquire sufficient exposure to diverse available dialysis options, patients are advised to discuss dialysis option selection with a patient peer who is on dialysis or has a transplant and with a trained dialysis social worker who is familiar with all aspects of RRT (transplant, hemodialysis, and peritoneal dialysis). In addition, the economic status of patients should be considered when modality selection is decided. Therefore, patients are suggested to consult with a financial specialist who can evaluate current health insurance dialysis coverage and help patients decide which modality is suitable for them. In China, although majority of dialysis-related healthcare is paid by the China Health Care, it may not cover all care, which may be province-dependent. Transplantation is still the best therapy for irreversible kidney failure, so evaluation for preemptive transplantation before initiating dialysis should be considered for all patients, as should registering for transplantation as soon as possible or simultaneously as patients are being prepared for dialysis.

#### 16.4.2.1 Hemodialysis

Dialysis substitutes two major kidney functions: solute removal and fluid removal. The passive movement of solutes from the blood compartment to the dialysate compartment across a semipermeable membrane, called diffuse, is the predominant mode by which the solute is removed in hemodialysis. The rate of diffusion depends on several coefficients, such as molecular weight of solutes, membrane permeability, blood flow rate, concentration gradient of the solutes between the blood and dialysate, membrane permeability, and flow rate. The clearance of smaller molecules is higher. The greater the concentration gradient between the blood and the dialysate, the more rapidly diffusion occurs. Membrane permeability is determined by several specific membrane characteristics, such as pore size, charge, and quaternary conformation. Higher flow rates facilitate greater solute removal, and the countercurrent of dialysate flow to blood flow will maxim the gradient across the dialysis membrane [18].

Another principle of hemodialysis is convection, which means the spontaneous transport of solutes across the dialysis membrane. Although the convective mass transfer of solutes may not play a dominant role in conventional hemodialysis, convection is mainly responsible for scavenging macromolecules and plays an important role predominantly in high-flux dialysis and continuous venovenous hemofiltration.

Solvent such as water removal in hemodialysis occurs by the process of ultrafiltration. Fluid can be forced across a semipermeable membrane on a pressure gradient from higher to lower pressures, and the pressure could result from the mechanical hydrostatic pressure or osmotic force. When positive pressure is applied to the blood compartment or negative pressure is applied to the dialysate side of the membrane, ultrafiltration will multiply. The ultrafiltration rate is adjusted to obtain the desired fluid removal during dialysis.

The hemodialysis machine has three main components: (1) the dialyzer (i.e., dialysis membrane); (2) a pump that regulates blood flow; and (3) a dialysate solution delivery system at a constant rate up to approximately 500 mL/min. In addition, the machine has many safety devices to ensure the proper, safe, and reliable delivery of blood and dialysate to the filter where exchange of water and solutes takes place. These devices include monitors to ensure that the pressures inside the extracorporeal circuit are not excessive, a detector for leakage of red blood cells from the blood compartment into the dialysate compartment, an air detector and shut-off device to prevent air embolism, a pump to deliver dialysate, a proportioning system to properly dilute the dialysate concentrate, a heater to warm the dialysate to body temperature, an ultrafiltration controller to precisely regulate fluid removal, and conductivity monitors to check the ionic strength of the dialysate.

Under most conditions, solute removal and fluid removal occur simultaneously. However, if vigorous ultrafiltration is attempted during conventional hemodialysis, patients frequently complain of nausea, muscle cramping, and vomiting. At the same time, systemic vascular resistance may decrease, thereby hypotension develops. Osmotic changes are minimized with isolated fluid removal in the absence of solute removal. Separating ultrafiltration will produce greater hemodynamic stability.

#### 16.4.2.2 Peritoneal Dialysis

In the 1950s and 1960s, peritoneal dialysis (PD) was utilized mainly to treat acute kidney injury. Patients with ESRD were treated almost exclusively by hemodialysis and occasionally by intermittent peritoneal dialysis (IPD). In 1976, the introduction of continuous ambulatory peritoneal dialysis (CAPD) transformed this situation.

Approximately 10% of patients with ESRD in the United States and more than 50% of those in the United Kingdom, Mexico, Canada, and Australia receive CAPD. Compared with hemodialysis, PD obviates the need for vascular access, which is a predominant challenge in patients with diabetes, young children, elders, and patients with severe vascular disease. Furthermore, anticoagulation is not needed in PD so the risk of bleeding decreases. Patients with PD has more stable hemodynamic status as PD is a slow and continuous process compared with hemodialysis, thereby reducing the risk of cardiovascular complications and protecting the residual renal function. PD can be performed by patients at home, thereby giving patients a sense of control and independence. In addition, the diet restriction for salt, potassium, protein, and fluid is not so strict in PD. For children with ESRD, PD is the option of choice because it avoids frequent vascular punctures and, most importantly, allows children to grow. Despite the advantages of PD, there is still controversy about its outcomes compared with those of hemodialysis. PD has been represented with worse, similar, and better mortality compared with hemodialysis, depending on the study design and statistical analysis.

Hemodialysis, PD, and transplantation are the cornerstones of modern renal replacement therapy. It is crucial to understand that these modalities are not mutually exclusive, because patients may transfer from one to another during the course of their treatment. Thus, PD is an excellent option for initial dialysis treatment if a patient will have a transplant within a short period of time. Also, for patients who would like to be in more control of their dialysis, or who intend to do dialysis at home, PD is a good choice.

For PD therapy, the peritoneal membrane is used as the dialyzing surface. Therefore, the function of peritoneal membrane should be evaluated regularly to avoid insufficient dialysis. Unless there is a major contraindication, PD should be considered as the first-line therapy for all patients undergoing preemptive kidney transplantation and other home dialysis therapies.

Table 16.4 lists some recommendations for modality selections (hemodialysis or PD).

Table 16.4

Recommendations for modality selections

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Oct 20, 2020 | Posted by in NEPHROLOGY | Comments Off on Timing and Modality Option for Renal Replacement Therapy

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