Dialysis

Number: 0541

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses dialysis.

1. Medical Necessity

   1. Medically Necessary Procedures

      Aetna considers the following procedures medically necessary:

      1. Hemodialysis or intermittent peritoneal dialysis for renal failure up to 3 times per week;
      2. Hemodialysis and intermittent peritoneal dialysis performed more than 3 times per week for renal failure for hyperkalemia, hypophosphatemia, pregnancy, fluid overload, acute pericarditis, congestive heart failure, pulmonary edema, or severe catabolic state when these conditions are refractory to dialysis 3 times per week;
      3. Home hemodialysis when prescribed by a physician for members with end stage renal disease - the following conditions/equipment and supplies are considered medically necessary for administration of hemodialysis in the home:

         1. Skilled Nursing

            Periodic monitoring of the member's condition by a nurse (skilled nursing visit) in accordance with a care plan that is prepared and periodically reviewed by a physician; and

         2. Dialysis Equipment and Supplies

            1. Equipment: Note: Because Medicare primary coverage of the dialysis equipment listed below commences after the person's first 30 months of hemodialysis, this equipment is usually covered by Aetna on a rental basis during the member's first 30 months of hemodialysis, because 30-month's rental is usually less expensive than purchase:

               1. Adjustable reclining chairs, when required as a component of the home dialysis system;
               2. Delivery system accessories:
                  
                  
                  1. Blood pumps
                  2. Heparin infusion pumps
                  3. Monitoring devices
                  4. Water purification systems (either a deionization system or a reverse osmosis system are considered medically necessary, but not both in the same member at the same time)
                  5. Water softening systems for members who have a reverse osmosis purification system if the member's water is of a lesser quality than required for the reverse osmosis purification system;

               3. Dialyzers and dialysis delivery systems;

            2. Supplies: The following hemodialysis supplies may be considered medically necessary:

               1. Activated carbon filters used as a component of water purification systems to remove unsafe concentrations of chlorine or chloramines
               2. Antibiotic ointment
               3. Blood pressure monitors
               4. Blood tubing
               5. Centrifuge readacrit (hematocrit measuring equipment)
               6. Cleansing agents
               7. Dialysates
               8. Dialysate testing supplies
               9. Fistula cannulation sets
               10. Fluid administration sets
               11. Gun to secure tubing
               12. Heparin
               13. Needles
               14. Nylon locking ties
               15. Reagents (to detect residual traces or cleansing and sterilizing agents)
               16. Saline solution components
               17. Sterile dressing
               18. Sterile saline
               19. Sterilizing agents
               20. Stethoscope when needed for blood pressure monitoring
               21. Syringes
               22. Winthrop tubes.

         Aetna considers the NxStage System (NxStage Medical, Inc.) or the Tablo Hemodialysis System (Outset Medical, Inc.) portable/mobile hemodialysis machine an equally acceptable alternative to standard hemodialysis machines for medically necessary home hemodialysis. 

         Aetna considers professional staff to assist home hemodialysis medically necessary for members with end-stage renal disease who meet all of the following criteria:

         1. Member is stable on dialysis as shown by meeting the criteria of the National Kidney Foundation; and
         2. Member has good functioning vascular access; and
         3. Member has medical contraindications to leaving home for hemodialysis; and
         4. Member or non-professional care-giver is unable to perform home hemodialysis following hemodialysis training.

   2. Peritoneal Dialysis

      Aetna considers continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD) medically necessary when prescribed by a physician for persons with end-stage renal disease.

   3. Other Dialysis Equipment and Supplies

      1. Back up equipment supplied in anticipation of the need for substitution or replacement is not considered medically necessary. Rental of equipment is considered medically necessary while member-owned equipment is being repaired.
      2. Peridex filter sets are not considered medically necessary for peritoneal dialysis.
      3. Short-wave (radiofrequency) diathermy machines are not covered as they are not appropriate for home use. See CPB 0540 - Heating Devices.
      4. Spare deionizing tanks are not considered medically necessary since they are essentially a precautionary supply.
      5. Ultrafiltration monitors are not considered medically necessary when ultrafiltration is independent of conventional hemodialysis. 
         Note: Charges for repair and maintenance of rented equipment are included in the rental fees. Charges for repair of rented equipment will be denied as included in the rental charges.
      6. Emergency reserve supplies are usually provided when a member initiates dialysis in anticipation of short-term increases in use of supplies or delays in supply delivery. Up to 1 month's supplies in reserve in case of emergency are considered medically necessary; this is a one-time allowance.

2. Experimental and Investigational

   1. The Crit-Line In-Line Monitor is a device used to measure a member's hematocrit and oxygen saturation during hemodialysis.  This device is considered experimental and investigational as there is inadequate evidence of the Crit-Line In-Line Monitor in improving the management of persons receiving hemodialysis. See also CPB 0373 - Crit-Line In-Line Monitor.
   2. Aetna considers the following experimental and investigational because their effectiveness has not been established:
      
      
      1. Bioengineered human acellular vessels for dialysis access;
      2. Drug-coated balloon angioplasty for dialysis access stenosis;
      3. Peritoneal dialysis as a treatment for heart failure in persons without renal failure;
      4. The use of multiple-frequency bio-impedance devices for fluid management in persons receiving dialysis;
      5. The use of nasal antibiotic for the prevention of peritonitis in peritoneal dialysis individuals;
      6. The use of vitamin E-coated membranes for hemodialysis;
      7. Wearable hemodialysis machines.

3. Related Policies

   1. CPB 0373 - Crit-Line In-Line Monitor
   2. CPB 0540 - Heating Devices
   3. CPB 1028 - Difelikefalin Injection (Korsuva)

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Hemodialysis:
CPT codes covered if selection criteria is met:
90935	Hemodialysis procedure with single evaluation by a physician or other qualified health care professional
90937	Hemodialysis procedure requiring repeated evaluation(s) with or without substantial revision of dialysis prescription
90999	Unlisted dialysis procedure, inpatient or outpatient
99512	Home visit for hemodialysis
CPT codes not covered for indication listed in the CPB:
Bioengineered human acellular vessels for dialysis access, use of vitamin E-coated membranes for hemodialysis - no specific code :
HCPCS codes covered if selection criteria is met:
A4216	Sterile water, saline and/or dextrose, diluent/flush, 10 ml
A4217	Sterile water/saline, 500 ml
A4651	Calibrated microcapillary tube, each
A4652	Microcapillary tube sealant
A4657	Syringe, with or without needle, each
A4660	Sphygmomanometer/blood pressure apparatus with cuff and stethoscope
A4663	Blood pressure cuff only
A4670	Automatic blood pressure monitor
A4672	Drainage extension line, sterile, for dialysis, each
A4673	Extension line with easy lock connectors, used with dialysis
A4674	Chemicals/antiseptics solution used to clean/sterilize dialysis equipment, per 8 oz
A4680	Activated carbon filters for hemodialysis, each
A4690	Dialyzer (artificial kidneys), all types, all sizes, for hemodialysis, each
A4706	Bicarbonate concentrate, solution, for hemodialysis, per gallon
A4707	Bicarbonate concentrate, powder, for hemodialysis, per packet
A4708	Acetate concentrate solution, for hemodialysis, per gallon
A4709	Acid concentrate, solution, for hemodialysis, per gallon
A4728	Dialysate solution, non-dextrose, containing, 500 ml
A4730	Fistula cannulation set for hemodialysis, each
A4736	Topical anesthetic for dialysis, per gm
A4737	Injectable anesthetic, for dialysis, per 10 ml
A4740	Shunt accessory, for hemodialysis, any type, each
A4750	Blood tubing, arterial or venous, for hemodialysis, each
A4755	Blood tubing, arterial and venous combined, for hemodialysis, each
A4770	Blood collection tube, vacuum, for dialysis, per 50
A4771	Serum clotting time tube, for dialysis, per 50
A4772	Blood glucose test strips, for dialysis, per 50
A4773	Occult blood test strips, for dialysis, per 50
A4774	Ammonia test strips, for dialysis, per 50
A4802	Protamine sulfate, for hemodialysis, per 50 mg
A4860	Disposable catheter tips for peritoneal dialysis, per 10
A4890	Contracts, repair and maintenance, for hemodialysis equipment
A4911	Drain bag/bottle, for dialysis, each
A4913	Miscellaneous dialysis supplies, not otherwise specified
A4918	Venous pressure clamps, for hemodialysis, each
A4927	Gloves, non-sterile, per 100
A4928	Surgical mask, per 20
A4929	Tourniquet for dialysis, each
A4930	Gloves, sterile, per pair
A6010 - A6457	Dressings
C1881	Dialysis access system (implantable)
E1500	Centrifuge, for dialysis
E1510	Kidney, dialysate delivery system kidney machine, pump recirculating, air removal system, flowrate meter, power off, heater and temp control with alarm, IV poles, pressure gauge, concentrate container
E1520	Heparin infusion pump for hemodialysis
E1530	Air bubble detector for hemodialysis, each, replacement
E1540	Pressure alarm for hemodialysis, each, replacement
E1550	Bath conductivity meter for hemodialysis, each
E1560	Blood leak detector for hemodialysis, each, replacement
E1570	Adjustable chair, for ESRD patients
E1575	Transducer protectors/fluid barriers, for hemodialysis, any size, per 10
E1580	Unipuncture control system for hemodialysis
E1590	Hemodialysis machine
E1600	Delivery and/or installation charges for hemodialysis equipment
E1610	Reverse osmosis water purification system, for hemodialysis
E1615	Deionizer water purification system, for hemodialysis
E1620	Blood pump for hemodialysis, replacement
E1625	Water softening system, for hemodialysis
E1629	Tablo hemodialysis system for the billable dialysis service
E1636	Sorbent cartridges, for hemodialysis, per 10
E1699	Dialysis equipment, not otherwise specified
G0299	Direct skilled nursing services of a registered nurse (RN) in the home health or hospice setting, each 15 minutes
G0300	Direct skilled nursing services of a license practical nurse (LPN) in the home health or hospice setting, each 15 minutes
J1643	Injection, heparin sodium (pfizer), not therapeutically equivalent to J1644, per 1000 units
J1644	Injection, heparin sodium, per 1,000 units
J7030	Infusion, normal saline solution, 1,000 cc
J7040	Infusion, normal saline solution, sterile (500 ml = 1 unit)
S9123	Nursing care, in the home; by registered nurse, per hour (use for general nursing care only, not to be used when CPT codes 99500-99602 can be used)
S9124	Nursing care, in the home; by licensed practical nurse, per hour
S9335	Home therapy, hemodialysis; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing services coded separately), per diem
HCPCS codes not covered for indications listed in the CPB:
E1632	Wearable artificial kidney, each
E1635	Compact (portable) travel hemodialyzer system
ICD-10 codes covered if selection criteria are met:
N18.6	End stage renal disease
Peritoneal Dialysis:
CPT codes covered if selection criteria are met:
90945	Dialysis procedure other than hemodialysis (eg, peritoneal dialysis, hemofiltration, or other continuous renal replacement therapies), with single physician evaluation [CAPD, CCPD]
90947	Dialysis procedure other than hemodialysis (eg, peritoneal dialysis, hemofiltration, or other continuous renal replacement therapies) requiring repeated physician evaluations, with or without substantial revision of dialysis prescription [CAPD, CCPD]
90999	Unlisted dialysis procedure, inpatient or outpatient
HCPCS codes covered if selection criteria is met:
A4216	Sterile water, saline and/or dextrose, diluent/flush, 10 ml
A4217	Sterile water/saline, 500 ml
A4651	Calibrated microcapillary tube, each
A4652	Microcapillary tube sealant
A4653	Peritoneal dialysis catheter anchoring device, belt, each
A4657	Syringe, with or without needle, each
A4660	Sphygmomanometer/blood pressure apparatus with cuff and stethoscope
A4663	Blood pressure cuff only
A4670	Automatic blood pressure monitor
A4671	Disposable cycler set used with cycler dialysis macine, each
A4672	Drainage extension line, sterile, for dialysis, each
A4673	Extension line with easy lock connectors, used with dialysis
A4674	Chemicals/antiseptics solution used to clean/sterilize dialysis equipment, per 8 oz
A4714	Treated water (deionized, distilled, reverse osmosis) for peritoneal dialysis, per gallon
A4720	Dialysate solution, any concentration of dextrose, fluid volume greater than 249 cc, but less than or equal to 999 cc, for peritoneal dialysis
A4721	Dialysate solution, any concentration of dextrose, fluid volume greater than 999 cc, but less than or equal to 1999 cc, for peritoneal dialysis
A4722	Dialysate solution, any concentration of dextrose, fluid volume greater than 1999 cc, but less than or equal to 2999 cc, for peritoneal dialysis
A4723	Dialysate solution, any concentration of dextrose, fluid volume greater than 2999 cc, but less than or equal to 3999 cc, for peritoneal dialysis
A4724	Dialysate solution, any concentration of dextrose, fluid volume greater than 3999 cc, but less than or equal to 4999 cc, for peritoneal dialysis
A4725	Dialysate solution, any concentration of dextrose, fluid volume greater than 4999 cc, but less than or equal to 5999 cc, for peritoneal dialysis
A4726	Dialysate solution, any concentration of dextrose, fluid volume greater than 5999 cc
A4728	Dialysate solution, non-dextrose, containing, 500 ml
A4736	Topical anesthetic for dialysis, per gm
A4737	Injectable anesthetic for dialysis, per 10 ml
A4760	Dialysate solution test kit, for peritoneal dialysis, any type, each
A4765	Dialysate concentrate, powder, additive for peritoneal dialysis, per packet
A4766	Dialysate concentrate, solution, additive for peritoneal dialysis, per 10 ml
A4770	Blood collection tube, vacuum, for dialysis, per 50
A4771	Serum clotting time tube, for dialysis, per 50
A4772	Blood glucose test strips, for dialysis, per 50
A4773	Occult blood test strips, for dialysis, per 50
A4774	Ammonia test strips, for dialysis, per 50
A4860	Disposable catheter tips for peritoneal dialysis, per 10
A4911	Drain bag/bottle, for dialysis, each
A4913	Miscellaneous dialysis supplies, not otherwise specified
A4918	Venous pressure clamps, for hemodialysis, each
A4927	Gloves, non-sterile, per 100
A4928	Surgical mask, per 20
A4929	Tourniquet for dialysis, each
A4930	Gloves, sterile, per pair
A6010 - A6457	Dressings
C1881	Dialysis access system (implantable)
E1500	Centrifuge, for dialysis
E1510	Kidney, dialysate delivery system kidney machine, pump recirculating, air removal system, flowrate meter, power off, heater and temp control with alarm, IV poles, pressure gauge, concentrate container
E1570	Adjustable chair, for ESRD patients
E1592	Automatic intermittent peritoneal dialysis system
E1594	Cycler dialysis machine for peritoneal dialysis
E1630	Reciprocating peritoneal dialysis system
E1634	Peritoneal dialysis clamps, each
E1699	Dialysis equipment, not otherwise specified
G0299	Direct skilled nursing services of a registered nurse (RN) in the home health or hospice setting, each 15 minutes
G0300	Direct skilled nursing services of a license practical nurse (LPN) in the home health or hospice setting, each 15 minutes
S9123	Nursing care, in the home; by registered nurse, per hour
S9124	Nursing care, in the home; by licensed practical nurse, per hour
S9335	Home therapy, hemodialysis; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing services coded separately), per diem
S9339	Home therapy; peritoneal dialysis, administrative services, professional pharmacy services, care coordination and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
HCPCS codes not covered for indications listed in the CPB:
Multiple-frequency bio-impedance devices - no specific code:
A4870	Plumbing and/or electrical work for home hemodialysis equipment
E1637	Hemostats, each
E1639	Scale, each
Other HCPCS codes related to the CPB:
C7513	Dialysis circuit, introduction of needle(s) and/or catheter(s), with diagnostic angiography of the dialysis circuit, including all direct puncture(s) and catheter placement(s), injection(s) of contrast, all necessary imaging from the arterial anastomosis and adjacent artery through entire venous outflow including the inferior or superior vena cava, fluoroscopic guidance, with transluminal balloon angioplasty of central dialysis segment, performed through dialysis circuit, including all required imaging, radiological supervision and interpretation, image documentation and report
C7514	Dialysis circuit, introduction of needle(s) and/or catheter(s), with diagnostic angiography of the dialysis circuit, including all direct puncture(s) and catheter placement(s), injection(s) of contrast, all necessary imaging from the arterial anastomosis and adjacent artery through entire venous outflow including the inferior or superior vena cava, fluoroscopic guidance, with all angioplasty in the central dialysis segment, and transcatheter placement of intravascular stent(s), central dialysis segment, performed through dialysis circuit, including all required imaging, radiological supervision and interpretation, image documentation and report
C7515	Dialysis circuit, introduction of needle(s) and/or catheter(s), with diagnostic angiography of the dialysis circuit, including all direct puncture(s) and catheter placement(s), injection(s) of contrast, all necessary imaging from the arterial anastomosis and adjacent artery through entire venous outflow including the inferior or superior vena cava, fluoroscopic guidance, with dialysis circuit permanent endovascular embolization or occlusion of main circuit or any accessory veins, including all required imaging, radiological supervision and interpretation, image documentation and report
C7530	Dialysis circuit, introduction of needle(s) and/or catheter(s), with diagnostic angiography of the dialysis circuit, including all direct puncture(s) and catheter placement(s), injection(s) of contrast, all necessary imaging from the arterial anastomosis and adjacent artery through entire venous outflow including the inferior or superior vena cava, fluoroscopic guidance, with transluminal balloon angioplasty, peripheral dialysis segment, including all imaging and radiological supervision and interpretation necessary to perform the angioplasty and all angioplasty in the central dialysis segment, with transcatheter placement of intravascular stent(s), central dialysis segment, performed through dialysis circuit, including all imaging, radiological supervision and interpretation, documentation and report
E1632	Wearable artificial kidney, each
G0491	Dialysis procedure at a medicare certified esrd facility for acute kidney injury without esrd
G0492	Dialysis procedure with single evaluation by a physician or other qualified health care professional for acute kidney injury without esrd
J1642	Injection, heparin sodium, (Heparin Lock Flush), per 10 units
ICD-10 codes covered if selection criteria are met:
E83.39	Other disorders of phosphorous metabolism [Hypophosphatemia]
E87.5	Hyperkalemia
E87.70 - E87.79	Fluid overload
I30.0 - I30.9	Acute pericarditis
I50.1 - I50.9	Heart failure
J81.0 - J81.1	Pulmonary edema
N18.6	End stage renal disease
O00.0 - O9A.53	Pregnancy, childbirth and the puerperium
R54	Age-related physical debility [severe catabolic state]
Z33.1	Pregnant state, incidental
Z33.3	Pregnant state, gestational carrier
Z3A.00 - Z3A.49	Weeks of gestation
Drug-coated balloon angioplasty:
CPT codes not covered for indications listed in the CPB:
Drug-coated balloon angioplasty - no specific code
ICD-10 codes not covered for indications listed in the CPB (not all inclusive):
T82.858A - T82.858S	Stenosis of other vascular prosthetic devices, implants and grafts [dialysis access stenosis]

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Background

This policy on dialysis was adapted from Medicare DMERC Local Medical Policy. 

Hemodialysis or intermittent peritoneal dialysis (PD) is necessary up to 3 times per week.  Hemodialysis and intermittent PD performed more than 3 times per week may be necessary for hyperkalemia, hypophosphatemia, pregnancy, fluid overload, acute pericarditis, congestive heart failure, pulmonary edema, or severe catabolic state when these conditions are refractory to dialysis 3 times per week.  

Home Hemodialysis

NxStage System

NxStage Medical, Inc., a subsidiary of Fresenius Medical Care, offers the NxStage System One portable hemodialysis machine, which is FDA cleared for the treatment of acute and chronic renal failure or fluid overload using hemofiltration, hemodialysis, and/or ultrafiltration, in an acute or chronic care facility. The NxStage System is also indicated for home hemodialysis, including home nocturnal hemodialysis. All treatments must be administered under physician's prescription, and must be performed by a trained and qualified person, considered to be competent in the use of this device by the prescribing physician (FDA, 2014).

More frequent hemodialysis has the potential to improve survival as well as quality of life of patients with chronic kidney disease.  New means of delivering hemodialysis are being explored.  Kraus et al (2007) carried out a feasibility study to examine the safety of center-based versus home-based daily hemodialysis with the NxStage System One portable hemodialysis device.  These investigators also performed a retrospective analysis to determine if clinical effects previously associated with short-daily dialysis were also seen using this novel device.  They conducted a prospective, 2-treatment, 2-period, open-label, cross-over study of in-center hemodialysis versus home hemodialysis in 32 patients treated at 6 centers.  The 8-week In-Center Phase (6 days/week) was followed by a 2-week transition period and then followed by the 8-week Home Phase (6 days/week).  These researchers retrospectively collected data on hemodialysis treatment parameters immediately preceding the study in a subset of patients.  Twenty-six out of 32 patients (81 %) successfully completed the study.  Successful delivery of at least 90 % of prescribed fluid volume (primary endpoint) was achieved in 98.5 % of treatments in-center and 97.3 % at home.  Total effluent volume as a percentage of prescribed volume was between 94 % and 100 % for all study weeks.  The composite rate of intra-dialytic and inter-dialytic adverse events per 100 treatments was significantly higher for the In-Center Phase (5.30) compared with the Home Phase (2.10; p = 0.007).  Compared with the period immediately preceding the study, there were reductions in blood pressure, anti-hypertensive medications, and inter-dialytic weight gain.  The authors concluded that daily home hemodialysis with a small, easy-to-use hemodialysis device is a viable dialysis option for end-stage renal disease (ESRD) patients capable of self/partner-administered dialysis.

The Canadian Agency for Drugs and Technologies in Health's report on portable home hemodialysis for kidney failure (Scott, 2007) stated that while home hemodialysis is less costly than conventional in-center programs, it is unknown if these savings extend to portable devices.  Presently, the NxStage System One is the only really portable hemodialysis system licensed in the United States.  It weighs 30 kg and is the size of an older style computer monitor.  This device operates on standard electric current; do es not require any water supply, plumbing, or disinfection; and is portable enough for travel.  The NxStage System consists of a computer-controlled delivery unit and a disposable cartridge containing the dialyser and fluid circuits.  The dialysate comes in sterile, pre-mixed bags, which eliminates the need for a water purification system.  An optional accessory can produce dialysate from purified home tap water.  Another manufacturer, Home Dialysis Plus Ltd., has developed a portable hemodialysis machine that is smaller and more efficient than existing systems.  The Home Dialysis Plus machine weighs approximately 14 kg and is the size of a large suitcase. 

The CADTH (Scott, 2007) stated that the only publications on the NxStage System are brief reports and conference presentations of case series studies, some of which pooled results from different dialysis machines. One anecdotal report and three conference abstracts provided separate results.  Furthermore, it is not yet clear if the use of the portable hemodialysis machine (e.g. the NxStage System) improves long-term survival and quality of life.

The CADTH report noted that the FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study may address this lack of evidence by comparing clinical outcomes and cost-effectiveness data from 500 patients on NxStage daily hemodialysis with a matched conventional in-centre hemodialysis cohort from the U.S. Renal Data System database (Scott, 2007). The results of this and other ongoing trials will influence the uptake of portable hemodialysis devices.

An assessment by the National Horizon Scanning Centre (NHSC, 2007) found a lack of evidence for the NxStage and other portable systems that utilize new means of generating dialysate from tap water. An assessment of the NxStage System by the Adelaide Health Technology Assessment National Horizon Scanning Unit (Purins and Hiller, 2008) found that the evidence for the NxStage System was from small, low to medium quality studies.

More recently, and assessment from the National Health Service (Gossage-Worrall, et al., 2010) found that “the evidence for the use of portable hemodialysis devices is limited. The available evidence consists of comparison studies, case series, poster presentations, product specific reviews and editorials.... There is a paucity of evidence on the use of this device in relation to its portability.”

A report by the National Horizon Scanning Centre (NHSC, 2012) found no published evidence comparing the compact transportable home hemodialysis machines (NxStage or Selfcare+)  to standard hemodialysis machines. "Research comparing the costs associated with transportable machines and standard home haemodialysis machines would be needed to further understand and quantify any potential benefits or risks of these machines. The results of the Freedom study and further research into adolescents and children are awaited, as are trials of the Selfcare+ system. Further long-term studies of various possible treatment regimes on these transportable machines compared with standard machines are needed to assess whether they offer improvements in health outcomes for patients."

Jaber et al (2009) noted that conventional thrice-weekly hemodialysis (HD) has limited the ability to generate further improvements in patient quality of life, morbidity, and mortality. Daily HD (DHD) offers the promise of providing clinical and economical benefits. The authors reported that the objectives of the FREEDOM Study, and observational study with a lack of control arm, were to evaluate outcomes of DHD (6 times/week) with the NxStage System One device. The DHD group will include up to 500 participants at 70 clinical sites, enrolling for 3 years with a minimum of 1-year follow-up. Study candidates include adult patients (age greater than or equal to 18 years) with ESRD who are considered suitable candidates for DHD with the NxStage System One device by the treating physician and who have Medicare as their primary insurance payer. The control group will consist of a matched thrice-weekly in-center HD cohort derived from the U.S. Renal Data System database using a 10:1 ratio, totaling 5,000 patients. The primary intent-to-treat analysis compares hospitalization days/patient-year between the DHD and thrice-weekly HD groups. Other outcomes recorded in both groups include non-treatment-related medical expenditures. In addition, in the DHD cohort, changes in quality-of-life measures (baseline, 4 and 12 months, and every 6 months thereafter); urea kinetics; parameters related to anemia, bone and mineral metabolism, and nutrition; vascular access interventions; and use of medications will be examined. This authors concluded that this study has the potential to elucidate the health and economic benefits of DHD and complement results of current clinical trials.

In an interim report from the FREEDOM study, Jaber et al (2010) reported on the impact of daily hemodialysis on depressive symptoms and post-dialysis recovery time.  The authors found that daily hemodialysis is associated with long-term improvement in depressive symptoms and postdialysis recovery time.  In this interim report, as part of an a priori planned analysis, the investigators examined the long-term impact of daily hemodialysis on depressive symptoms, measured using the Beck Depression Inventory (BDI) survey, and post-dialysis recovery time, measured using a previously validated questionnaire, in adult patients initiating daily hemodialysis.  The BDI survey and postdialysis recovery time question were administered at baseline, and changes were assessed at months 4 and 12.  The investigators reported that 239 participants were enrolled (intention-to-treat cohort) and 128 completed the study (per-protocol cohort).  Mean age was 52 years, 64 % were men, 55 % had an arterio-venous (AV) fistula, and 90 % transitioned from in-center hemodialysis therapy.  In the per-protocol cohort, there was a significant decrease in mean BDI score over 12 months (11.2 [95 % confidence interval [CI]: 9.6 to 12.9] versus 7.8 [95 % CI: 6.5 to 9.1]; p < 0.001).  For robustness, the intention-to-treat analysis was performed, yielding similar results.  The percentage of patients with depressive symptoms (BDI score greater than 10) significantly decreased during 12 months (41 % versus 27 %; p = 0.03).  Similarly, in the per-protocol cohort, there was a significant decrease in post-dialysis recovery time over 12 months (476 [95 % CI: 359 to 594] versus 63 minutes [95 % CI: 32 to 95]; p < 0.001).  The intention-to-treat analysis yielded similar results.  The percentage of patients experiencing prolonged post-dialysis recovery time (greater than or equal to 60 minutes) also significantly decreased (81 % versus 35 %; p = 0.001).

A retrospective study using a matched population-based cohort by Weinhandl et al (2012) suggests that relative to thrice-weekly in-center hemodialysis, daily home hemodialysis with the NxStage System associates with modest improvements in survival.  The investigators used a matched-cohort design to assess relative mortality in daily home hemodialysis using the NxStage System and thrice-weekly in-center hemodialysis patients between 2005 and 2008.  The investigators matched 1,873 home hemodialysis patients with 9,365 in-center patients (i.e., 1:5 ratio) selected from the prevalent population in the U.S. Renal Data System database.  Matching variables included first date of follow-up, demographic characteristics, and measures of disease severity.  The cumulative incidence of death was 19.2 % and 21.7 % in the home hemodialysis and in-center patients, respectively.  In the intention-to-treat analysis, home hemodialysis using the NxStage was associated with a 13 % lower risk for all-cause mortality than in-center hemodialysis (hazard ratio [HR], 0.87; 95 % CI: 0.78 to 0.97).  Cause-specific mortality HRs were 0.92 (95 % CI: 0.78 to 1.09) for cardiovascular disease, 1.13 (95 % CI: 0.84 to 1.53) for infection, 0.63 (95 % CI: 0.41 to 0.95) for cachexia/dialysis withdrawal, 1.06 (95 % CI: 0.81 to 1.37) for other specified cause, and 0.59 (95 % CI: 0.44 to 0.79) for unknown cause.  Findings were similar using as-treated analyses.  The investigators reported that they did not detect statistically significant evidence of heterogeneity of treatment effects in subgroup analyses.

Walker et al (2014) sought comparative cost-effectiveness studies of home versus facility HD for people with end-stage kidney failure (ESKF).  These investigators conducted a systematic review of literature from January 2000 to March 2014.  Studies were included if they provided comparative information on the costs, health outcomes and cost-effectiveness ratios of home HD and facility HD.  They searched medical and health economic databases using MeSH headings and text words for economic evaluation and hemodialysis.  A total of 6 studies of economic evaluations that compared home to facility HD were identified – 2 studies compared home nocturnal HD, 1 home nocturnal and daily home HD, and 3 compared contemporary home HD to facility HD.  Overall, these studies suggested that contemporary home HD modalities are less costly and more effective than facility HD.  Home HD start-up costs tend to be higher in the short-term, but these are offset by cost savings over the longer term.  The authors concluded that contemporaneous dialysis modalities including nocturnal and daily home HD are cost-effective or cost-saving compared to facility-based HD.  This result is largely driven by lower staff costs, and better health outcomes for survival and quality of life.  Expanding the proportion of HD patients managed at home is likely to produce cost savings.

Palmer et al (2014) stated that home hemodialysis is associated with improved survival and quality of life (QOL) in uncontrolled studies.  However, relative benefits and harms of home versus in-center hemodialysis in randomized controlled trials (RCTs) are uncertain.  In a Cochrane review, these investigators evaluated the benefits and harms of home hemodialysis versus in-center hemodialysis in adults with end-stage kidney disease (ESKD).  The Cochrane Renal Group's Specialised Register was searched up to October 31, 2014; RCTs of home versus in-center hemodialysis in adults with ESKD were included.  Data were extracted by 2 investigators independently.  Study risk of bias and other patient-centered outcomes were extracted.  Insufficient data were available to conduct meta-analyses.  These researchers identified a single cross-over RCT (enrolling 9 participants) that compared home hemodialysis (long hours: 6 to 8 hours, 3 times/week) with in-center hemodialysis (short hours: 3.5 to 4.5 hours, 3 times/weeks) for 8 weeks in prevalent home hemodialysis patients.  Outcome data were limited and not available for the end of the first phase of treatment in this cross-over study which was at risk of bias due to differences in dialysate composition between the 2 treatment comparisons.  Overall, home hemodialysis reduced 24 hour ambulatory blood pressure and improved uremic symptoms, but increased treatment-related burden of disease and interference in social activities.  Insufficient data were available for mortality, hospitalization or dialysis vascular access complications or treatment durability.  The authors concluded that insufficient randomized data were available to determine the effects of home hemodialysis on survival, hospitalization, and QOL compared with in-center hemodialysis.  They stated that given the consistently observed benefits of home hemodialysis on QOL and survival in uncontrolled studies, and the low prevalence of home hemodialysis globally, RCTs evaluating home hemodialysis would help inform clinical practice and policy.

Tablo Hemodialysis System

Outset Medical, Inc. offers the Tablo Hemodialysis System, which is FDA cleared for use in patients with acute and/or chronic renal failure, with or without ultrafiltration, in an acute or chronic care facility. Treatments must be administered under physician’s prescription, with a trained individual available as needed who is considered competent in the use of the device by the prescribing physician. The Tablo Hemodialysis System is also indicated for use in the home (FDA, 2020). The Tablo Hemodialysis System is a compact mobile unit on wheels that includes wireless connectivity and touchscreen guidance. 

In an investigational device exemption (IDE) study, Plumb et al (2020) evaluated the safety and efficacy of the Tablo hemodialysis system managed in‐center by health care professionals and in‐home by patients and/or caregivers. The authors conducted a prospective, multicenter, open‐label, crossover trial comparing in‐center and in‐home hemodialysis using Tablo. There were 4 treatment periods during which hemodialysis was prescribed 4 times per week: 1‐week Run‐In, 8‐week In‐Center, 4‐week Transition, and 8‐week In‐Home. The primary efficacy endpoint was weekly standard Kt/Vurea ≥ 2.1. The secondary efficacy endpoint was delivery of ultrafiltration (UF) within 10% of prescribed UF. Thirty participants enrolled and 28 completed all trial periods. The authors found that adherence to the protocol requirement of 4 treatments per week was 96% in‐center and 99% in‐home. The average prescribed and delivered session lengths were 3.4 hours for both the In‐Center and the In‐Home periods. The primary efficacy endpoint for the intention‐to‐treat cohort was achieved in 199/200 (99.5%) of measurements during the In‐Center period and 168/171 (98.3%) In‐Home. The average weekly standard Kt/Vurea was 2.8 in both periods. The secondary efficacy UF endpoint was achieved in the ITT cohort in 94% in both in‐center and in‐home. Two prespecified adverse events (AEs) occurred during the In‐Center period and 6 in the In‐Home period. None of the AEs were deemed by investigators as related to Tablo. The median resolution time of alarms was 8 seconds in‐center and 5 seconds in‐home. The authors concluded that the primary and secondary efficacy and safety endpoints were achieved during both In‐Center and In‐Home trial periods. The authors state that their study confirms that Tablo is safe and effective for home hemodialysis use. The authors note several limitations to their study, which included that the number of patients was relatively small, and the duration of each study period was relatively brief. The average age of the patients was younger than the average age of the patients receiving dialysis in the United States, although consistent with other studies on in‐home hemodialysis. Given that the willingness to do hemodialysis at home was an inclusion criterion, study participants were more likely to have an ease with medical technology and an interest in self‐care which may also contribute to selection bias. Other, less motivated patients may not have achieved similar results.

Bioengineered Human Acellular Vessels for Dialysis Access

Lawson and colleagues (2016) stated that for patients with end-stage renal disease (ESRD) who are not candidates for fistula, dialysis access grafts are the best option for chronic HD.  However, polytetrafluoroethylene arterio-venous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis.  These researchers developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access.  They performed 2 single-arm phase II clinical trials at 6 centers in the US and Poland.  These investigators enrolled adults with ESRD.  A novel bioengineered human acellular vessel was implanted into the arms of patients for HD access.  Primary end-points were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events [AEs]), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months.  All patients were followed-up for at least 1 year, or had a censoring event.  Human acellular vessels were implanted into 60 patients; mean follow-up was 16 months (SD 7.6).   One vessel became infected during 82 patient-years of follow-up.  The vessels had no dilatation and rarely had post-cannulation bleeding.  At 6 months, 63 % (95 % CI: 47 to 72) of patients had primary patency, 73 % (57 to 81) had primary assisted patency, and 97 % (85 to 98) had secondary patency, with most loss of primary patency because of thrombosis.  At 12 months, 28 % (17 to 40) had primary patency, 38 % (26 to 51) had primary assisted patency, and 89 % (74 to 93) had secondary patency.  The authors concluded that bioengineered human acellular vessels appeared to provide safe and functional HD access, and warrant further study in RCTs.

Combined Blockade of Renin-Angiotensin-Aldosterone System

Li and co-workers (2018) stated that full blockade of the renin-angiotensin-aldosterone system (RAAS) is believed to decrease morbidity and mortality of patients with chronic kidney disease (CKD).  In non-dialysis patients, combined RAAS blockade with 2 different RAAS blockers causes more AEs without improving survival, but its role in maintenance dialysis patients is still unclear.  These investigators conducted a systematic review and mediation analysis to examine the safety and efficacy of combined RAAS blockade in dialysis patients.  Comprehensive search was conducted in PubMed, Embase, Web of Science and Cochrane Library database to June 2017 to identify relevant studies.  Studies comparing combined with single RAAS blockade and reporting all-cause death, cardiovascular death, hypotension or hyperkalemia in dialysis patients were included.  Effect sizes were calculated with randomized effects model and summarized as odd ratios (OR).  A total of 9 studies with 13,050 dialysis patients were included.  Compared with single blockade, combined blockade significantly reduced all-cause mortality (OR 0.71, 95 % CI: 0.54 to 0.93, p = 0.01), while cardiovascular mortality remained unchanged (OR 0.85, 95 % CI: 0.45 to 1.59, p = 0.61).  Combined blockade tended to increase odd of hypotension but not odd of hyperkalemia (OR 1.54, 95 % CI: 1.00 to 2.38, p = 0.05; OR 0.89, 95 % CI: 0.76 to 1.05, p = 0.17).  Further mediation analysis indicated that hypotension might exert a suppression effect on the survival benefit of angiotensin-converting enzyme (ACE) inhibitor plus angiotensin receptor blocker (ARB) treatment on cardiovascular mortality.  The authors concluded that combined RAAS blockade might be a promising treatment in dialysis patients to further reduce mortality if blood pressure (BP) was well-controlled.

Drug-Coated Balloon Angioplasty for Dialysis Access Stenosis

Wee and colleagues (2019) noted that arterio-venous fistulas for patients undergoing HD are at high risk of stenosis.  Despite conventional balloon angioplasty (CBA), re-stenosis rates are high.  The use of a drug-coated balloon (DCB) may offer an alternative to reduce re-stenosis.  This study was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.  An electronic search on Medline, Embase, and the Cochrane Library was conducted to identify articles evaluating DCB angioplasty for patients with HD access stenosis; RRs of primary patency were pooled, and relevant subgroup and sensitivity analyses were conducted.  There were 17 studies (8 RCTs, 9 cohort studies) included, comprising a total of 1,113 stenotic dialysis accesses, of which 54.7 % underwent DCB angioplasty and 45.3 % underwent CBA.  There was a significantly superior 6-month (RR, 0.57; 95 % CI: 0.44 to 0.74; p < 0.00001; I2 = 62 %) and 12-month (RR, 0.73; 95 % CI: 0.63 to 0.84; p < 0.0001; I2 = 53 %) primary patency in the DCB angioplasty group in comparison to the CBA group (71.0 % versus 49.2 % at 6 months; 44.2 % versus 20.6 % at 12 months).  Subgroup analyses of study design (RCTs, cohort studies) showed similar trends.  Sensitivity analyses by excluding 1 poor-quality RCT and those employing the cross-over analysis design also showed similar results.  Studies investigating central venous stenosis showed significantly better 6-month (RR, 0.57; 95 % CI: 0.41 to 0.79; p = 0.0009; I2 = 67 %) and 12-month (RR, 0.69; 95 % CI: 0.56 to 0.85; p = 0.0004; I2 = 64 %) primary patency in the DCB angioplasty group in comparison to the CBA group.  The pooled rate of minor complications was low in both the DCB (1.1 %) and CBA (0.9 %) groups.  The authors concluded that DCB angioplasty appeared to be a better and safe alternative to CBA in treating patients with HD stenosis in terms of 6- and 12-month primary patency.  Moreover, these researchers stated that a larger trial is needed to establish these findings.

Liao and associates (2020) noted that re-stenosis remains a significant problem in endovascular therapy for HD vascular access; and DCB angioplasty decreases re-stenosis in peripheral and coronary artery diseases. In a systematic review and meta-analysis, these researchers examined the patency outcomes following DCB angioplasty, as compared to CBA for the stenosis of HD vascular access.  They carried out a comprehensive search in the Medline, Embase, and CENTRAL databases to identify eligible RCTs evaluating DCB angioplasty for HD vascular access dysfunction.  The primary end-point was the 6-month target lesion primary patency and the secondary end-points were 12-month target lesion primary patency and procedure-related complications; RR were pooled and relevant subgroups were analyzed separately.  A total of 11 RCTs comprised of 487 patients treated with DCB angioplasty and 489 patients treated with CBA were included.  There were no significant differences in the target lesion primary patency at 6 months [RR, 0.75; 95 % CI: 0.56 to 1.01; p = 0.06] and at 12 months (RR 0.89; 95 % CI: 0.79 to 1.00; p = 0.06).  The absence of benefit for the DCB group remained, even in the arterio-venous fistula subgroup or the subgroup of studies excluding central vein stenosis.  The risk of procedure-related complication did not differ between the 2 groups (RR 1.00; 95 % CI: 0.98 to 1.02; p = 0.95).  The authors concluded that DCB angioplasty did not demonstrate significant patency benefit for the treatment of HD vascular access dysfunction; wide variations in patency outcomes across studies were noted.  Moreover, these researchers stated that further studies focusing on specific types of access or lesions are needed to clarify the value of DCB for HD vascular access.

An UpToDate review on techniques for angioplasty of the arteriovenous hemodialysis access (Beathard, 2020) states that small trials and single-center observational studies had suggested a benefit for drug-coated balloon angioplasty compared with standard balloon angioplasty. The review states, however, that in multicenter trials, drug-eluting balloon angioplasty has not improved patency rates (citing Abdul Salim, et al., 2020; Moreno-Sánchez, et al., 2020).

Measurement of Serum Uric Acid for Prediction of Cardiovascular or All-Cause Mortality in Hemodialysis Patients

Rohn and associates (2020) stated that in the general population, hyperuricemia is associated with increased morbidity and mortality.  Data on this association in hemodialysis patients is controversial.  Moreover, it remains elusive whether serum uric acid (SUA) lowering therapy is associated with mortality.  These researchers carried out a retrospective analysis of 601 patients on chronic hemodialysis therapy in 5 outpatient centers with a maximum follow-up of 100 months and a mean follow-up of 41 months.  Death was defined as primary endpoint.  Cumulative survival was analyzed by Kaplan-Meier analysis and Cox regressions adjusted for age.  Cumulative survival rates were higher for those subjects with a higher than median SUA concentration both based on mean annual and baseline measurements (p < 0.05 each).  There was no survival difference anymore after adjustment for age (p > 0.05 each).  Stratification for SUA lowering therapy (allopurinol/febuxostat) had no impact on cumulative survival, neither in Kaplan Meier nor in Cox regression analyses (p > 0.05 each).  Furthermore, Cox regression analysis excluded an increased cardiovascular mortality in subjects with hyperuricemia.  The authors concluded that in contrast to the general population, hyperuricemia was not associated with increased mortality in patients undergoing hemodialysis.  Moreover, xanthine oxidase inhibition was not associated with a survival benefit in this analysis.  These data did not support the use of SUA lowering medication in hemodialysis patients with asymptomatic hyperuricemia.

Wang and colleagues (2021) noted that studies have reported inconsistent findings regarding the association between SUA levels and mortality in hemodialysis patients.  In a meta-analysis, these researchers examined if higher SUA values comprised a risk factor of cardiovascular or all-cause mortality in maintenance hemodialysis patients.  PubMed, Embase and the Cochrane library were searched up to August 31, 2020 for the longitudinal studies that examined the association between the elevated SUA and cardiovascular or all-cause mortality risk in maintenance hemodialysis patients.  Pooled adjusted HR and corresponding 95 % CI were calculated using a random-effects model.  These investigators included 10 studies with an overall sample of 264,571 patients with hemodialysis in this meta-analysis.  Patients with the highest SUA were associated with a decreased risk of cardiovascular mortality (HR = 0.72, 95 % CI: 0.59 to 0.87) compared with patients with the lowest SUA after adjustment for potential confounders in a random effects model.  Moreover, for each increase of 1 mg/dL of SUA, the overall risks of all-cause and cardiovascular mortality decreased by 6 % and 9 %, respectively (HR = 0.94, 95%  CI: 0.90 to 0.99; HR = 0.91, 95 % CI: 0.89 to 0.94).  The authors concluded that elevated SUA levels were strongly and independently associated with lower risk of cardiovascular mortality in maintenance hemodialysis patients.  Moreover, these researchers stated that further investigations, especially RCTs, are needed to examine if high SUA levels is an independent risk factor of all-cause mortality in hemodialysis patients.

Multiple-Frequency Bio-Impedance Devices for Fluid Management in Persons Receiving Dialysis

Scotland and associates (2018) stated that CKD is a long-term condition requiring treatment such as conservative management, kidney transplantation or dialysis.  To optimize the volume of fluid removed during dialysis (to avoid under-hydration or over-hydration), individuals are assigned a “target weigh”', which is commonly assessed using clinical methods, such as weight gain between dialysis sessions, pre- and post-dialysis BP and patient-reported symptoms.  However, these methods are not precise, and measurement devices based on bio-impedance technology are increasingly used in dialysis centers.  Current evidence on the role of bio-impedance devices for fluid management in people with CKD receiving dialysis is limited.  In a systematic review, these investigators evaluated the clinical effectiveness and cost-effectiveness of multiple-frequency bio-impedance devices versus standard clinical assessment for fluid management in people with CKD receiving dialysis.  These researchers searched major electronic databases [e.g., Medline, Medline In-Process & Other Non-Indexed Citations, Embase, Science Citation Index and Cochrane Central Register of Controlled Trials (CENTRAL)] conference abstracts and ongoing studies.  There were no date restrictions.  Searches were undertaken between June and October 2016.  Evidence was considered from RCTs comparing fluid management by multiple-frequency bio-impedance devices and standard clinical assessment in people receiving dialysis, and non-randomized studies evaluating the use of the devices for fluid management in people receiving dialysis.  One reviewer extracted data and assessed the risk of bias of included studies.  A second reviewer cross-checked the extracted data.  Standard meta-analyses techniques were used to combine results from included studies.  A Markov model was developed to assess the cost-effectiveness of the interventions.  A total of 5 RCTs (with 904 adult participants) and 8 non-randomized studies (with 4,915 adult participants) assessing the use of the Body Composition Monitor [(BCM) Fresenius Medical Care, Bad Homburg vor der Hohe, Germany] were included.  Both absolute over-hydration and relative over-hydration were significantly lower in patients evaluated using BCM measurements than for those evaluated using standard clinical methods [weighted MD [WMD] -0.44, 95 % CI: -0.72 to -0.15, p = 0.003, I2 = 49 %; and WMD -1.84, 95 % CI: -3.65 to -0.03; p = 0.05, I2 = 52 %, respectively].  Pooled effects of bio-impedance monitoring on systolic BP (SBP) (MD -2.46 mmHg, 95 % CI: -5.07 to 0.15 mmHg; p = 0.06, I2 = 0 %), arterial stiffness (MD -1.18, 95 % CI: -3.14 to 0.78; p = 0.24, I2 = 92 %) and mortality (HR = 0.689, 95 % CI: 0.23 to 2.08; p = 0.51) were not statistically significant.  The economic evaluation showed that, when dialysis costs were included in the model, the probability of bio-impedance monitoring being cost-effective ranged from 13 % to 26 % at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained.  With dialysis costs excluded, the corresponding probabilities of cost-effectiveness ranged from 61 % to 67 %.  The authors concluded that BCM used in addition to clinical assessment may lower over-hydration and potentially improve intermediate outcomes, such as SBP, but effects on mortality have not been demonstrated.  They stated that if dialysis costs are not considered, the incremental cost-effectiveness ratio fell below £20,000, with modest effects on mortality and/or hospitalization rates, and the current findings are not generalizable to pediatric populations nor across other multi-frequency bio-impedance devices.  These researchers stated that services that routinely use the BCM should report clinically relevant intermediate and long-term outcomes before and after introduction of the device to extend the current evidence base.  The main drawbacks of this review were the lack of evidence on clinically relevant outcomes, children receiving dialysis, and any multi-frequency bio-impedance devices, other than the BCM.

Guidance from the National Institute for Health and Care Excellence (NICE, 2017) concluded: [t]here is currently not enough evidence to recommend the routine adoption of the BCM – Body Composition Monitor to guide fluid management in people with chronic kidney disease having dialysis in the NHS. Further research is recommended to show the effect of using the BCM – Body Composition Monitor on clinical outcomes. The guidance also concluded: "[t]here is currently not enough validation or clinical-outcome data to recommend the routine adoption of the InBody S10 or the MultiScan 5000 to guide fluid management in people with chronic kidney disease having dialysis in the NHS."

Nasal Antibiotic for the Prevention of Peritonitis in Peritoneal Dialysis Individuals

Campbell and colleagues (2017) noted that PD is an important therapy for patients with ESKD and is used in more than 200,000 such patients globally.  However, its value is often limited by the development of infections such as peritonitis and exit-site and tunnel infections.  Multiple strategies have been developed to reduce the risk of peritonitis including antibiotics, topical disinfectants to the exit site and anti-fungal agents.  However, the effectiveness of these strategies has been variable and are based on a small number of RCTs.  The optimal preventive strategies to reduce the occurrence of peritonitis remain unclear.   This is an update of a Cochrane review first published in 2004.  These investigators evaluated the benefits and harms of anti-microbial strategies used to prevent peritonitis in PD patients.  They searched the Cochrane Kidney and Transplant's Specialized Register to October 4, 2016 through contact with the Information Specialist using search terms relevant to this review.  Studies contained in the Specialized Register are identified through search strategies specifically designed for CENTRAL, Medline, and Embase; hand-searching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.  Selection criteria were RCTs or quasi-RCTs in patients receiving chronic PD, which evaluated any anti-microbial agents used systemically or locally to prevent peritonitis or exit-site/tunnel infection.  Two authors independently assessed risk of bias and extracted data.  Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratio (RR) with 95 % CI.  A total of 39 studies, randomizing 4,435 patients, were included; 20 additional studies have been included in this update.  The risk of bias domains were often unclear or high; risk of bias was judged to be low in 19 (49 %) studies for random sequence generation, 12 (31 %) studies for allocation concealment, 22 (56 %) studies for incomplete outcome reporting, and in 12 (31 %) studies for selective outcome reporting.  Blinding of participants and personnel was considered to be at low risk of bias in 8 (21 %) and 10 studies (26 %) for blinding of outcome assessors.  It should be noted that blinding of participants and personnel was not possible in many of the studies because of the nature of the intervention or control treatment.  The use of oral or topical antibiotic compared with placebo/no treatment, had uncertain effects on the risk of exit-site/tunnel infection (3 studies, 191 patients, low quality evidence: RR 0.45, 95 % CI: 0.19 to 1.04) and the risk of peritonitis (5 studies, 395 patients, low quality evidence: RR 0.82, 95 % CI: 0.57 to 1.19).  The use of nasal antibiotic compared with placebo/no treatment had uncertain effects on the risk of exit-site/tunnel infection (3 studies, 338 patients, low quality evidence: RR 1.34, 95 % CI: 0.62 to 2.87) and the risk of peritonitis (3 studies, 338 patients, low quality evidence: RR 0.94, 95 % CI: 0.67 to 1.31).  Pre-/peri-operative intravenous vancomycin compared with no treatment may reduce the risk of early peritonitis (1 study, 177 patients, low quality evidence: RR 0.08, 95 % CI: 0.01 to 0.61) but has an uncertain effect on the risk of exit-site/tunnel infection (1 study, 177 patients, low quality evidence: RR 0.36, 95 % CI: 0.10 to 1.32).  The use of topical disinfectant compared with standard care or other active treatment (antibiotic or other disinfectant) had uncertain effects on the risk of exit-site/tunnel infection (8 studies, 973 patients, low quality evidence, RR 1.00, 95 % CI: 0.75 to 1.33) and the risk of peritonitis (6 studies, 853 patients, low quality evidence: RR 0.83, 95 % CI: 0.65 to 1.06).  Anti-fungal prophylaxis with oral nystatin/fluconazole compared with placebo/no treatment may reduce the risk of fungal peritonitis occurring after a patient has had an antibiotic course (2 studies, 817 patients, low quality evidence: RR 0.28, 95 % CI: 0.12 to 0.63).  No intervention reduced the risk of catheter removal or replacement.  Most of the available studies were small and of suboptimal quality; only 6  studies enrolled 200 or more patients.  The authors concluded that in this update, they identified limited data from RCTs and quasi-RCTs that evaluated strategies to prevent peritonitis and exit-site/tunnel infections.  This review demonstrated that pre-/peri-operative intravenous vancomycin may reduce the risk of early peritonitis and that anti-fungal prophylaxis with oral nystatin or fluconazole reduced the risk of fungal peritonitis following an antibiotic course.  However, no other anti-microbial interventions have proven efficacy.  In particular, the use of nasal antibiotic to eradicate Staphylococcus aureus, had an uncertain effect on the risk of peritonitis and raised questions about the usefulness of this approach.  They stated that given the large number of patients on PD and the importance of peritonitis, the lack of adequately powered and high quality RCTs to inform decision-making about strategies to prevent peritonitis is striking.

Nicotinic Acid and Related Compounds for the Treatment of Hyperphosphatemia in Dialysis Persons

Liu and colleagues (2018) noted that studies indicated that nicotinic acid and related compounds may decrease phosphorus concentrations effectively by reducing the absorption in the gastro-intestinal (GI) tract.  However, the efficacy and safety of oral niacin treatments have only been investigated in a limited number of small-scale studies.  These investigators performed a meta-analysis by pooling 12 qualified relevant pre-clinical and clinical trials to evaluate the association of nicotinic acid (and its related compounds) treatment and hyperphosphatemia among dialysis patients.  Baseline and after treatment data were collected from the studies to evaluate drug efficacy, effect on lipid profile, and drug safety.  To evaluate drug efficacy, subgroups were created based on different exposure time (i.e., 4 weeks, 8 weeks, 12 weeks, and 24 weeks) and each subgroup was compared against baseline data.  In the assessment of lipid profile and drug safety, results of 8-week treatment were compared against baseline data.  This study showed that in the efficacy assessment of drug treatment, serum phosphorus concentration was only significantly reduced in the 4-week (SMD, 0.68; 95 % CI: 0.40 to 0.97; p = 0.000; n = 8), and 8-week (SMD, 1.05; 95 % CI: 0.68 to 1.42; p = 0.000; n = 10) treatment groups.  The calcium × phosphorus product showed significantly reduced concentration in all the drug exposure time settings, and no rebound was detected (4-week treatment: SMD, 0.61; 95 % CI: 0.18 to 1.04; p = 0.005; n = 5; 8-week treatment: SMD, 0.76; 95 % CI: 0.32 to 1.18, p = 0.001; n = 8; and 12-week treatment: SMD, 0.28, 95 % CI: -0.06 to 0.61; p = 0.103; n = 3).  Lipid profile monitoring showed that HDL and triglycerides (TG) significantly changed after 8 weeks of treatment (HDL: SMD, -0.63; 95 % CI: -1.03 to 0.24; p = 0.002; n = 5) and TG: SMD, 0.25; 95 % CI: 0.02 to 0.49; p = 0.033; n = 5).  Assessment of drug safety detected significant association for incidence of diarrhea (8 % incidence rate; 95 % CI: 4 % to 12 %; p = 0.001) and total AE (41 % incidence rate, 95 % CI: 12 % to 69 %, p = 0.001).  The authors concluded that nicotinic acid and related compounds could significantly reduce serum phosphorus concentration with additive anti-lipemic effects.  Moreover, they also recommended that the safety of this drug be further studied since these findings suggested significant incidence of AEs.

Peritoneal Dialysis for Heart Failure

Chionh and colleagues (2020) stated that heart failure (HF) is a major cause of morbidity and mortality.  Extracorporeal (EC) therapy, including ultra-filtration (UF) and HD, peritoneal dialysis (PD) and peritoneal UF (PUF) are potential therapeutic options in diuretic-resistant states.  In a systematic review, these researchers examined outcomes of PD and compared the effects of PD to EC.  Acomprehensive search of major databases from 1966 to 2017 for studies utilizing PD (or PUF) in diuretic-resistant HF was conducted, excluding studies involving patients with ESRD.  Data were extracted and combined using a random-effects model, expressed as OR.  A total of 31 studies (n = 902) were identified from 3,195 citations, none was randomized trials.  Survival was variable (0 to 100 %) with a wide follow-up duration (36 hours to 10 years).  With follow-up of greater than 1 year, the overall mortality was 48.3 %.  Only 4 studies compared PD with EC.  Survival was 42.1 % with PD and 45.0 % with EC; the pooled effect did not favor either (OR 0.80; 95 % CI: 0.24 to 2.69; p = 0.710).  Studies on PD in patients with HF reported several benefits.  Left ventricular ejection fraction (LVEF) improved after PD (OR 3.76, 95 % CI: 2.24 to 5.27; p < 0.001); 7 of 9 studies saw LVEF increase by more than 10 %; 21 studies reported the New York Heart Association (NYHA) status and 40 to 100 % of the patients improved by greater than or equal to 1 grade; 9 of 10 studies reported reductions in hospitalization frequency and/or duration.  When treated with PD, HF patients had fewer symptoms, lower hospital admissions and duration compared to diuretic therapy.  However, there was inadequate evidence comparing PD versus UF or HD.  These researchers stated that further studies comparing these modalities in diuretic-resistant HF should be conducted.

Furthermore, UpToDate reviews on “Overview of the management of heart failure with reduced ejection fraction in adults” (Colucci, 2020), “Management of refractory heart failure with reduced ejection fraction” (Dunlay and Colucci, 2020), “Right heart failure: Causes and management” (Borlaug, 2020), and “Treatment and prognosis of heart failure with preserved ejection fraction” (Borlaug and Colucci, 2020) do not mention peritoneal dialysis as a management / therapeutic option.

American College of Cardiology guidelines (Hollenberg, et al., 2019) have no recommendation for peritoneal dialysis as a treatment for heart failure. The guidelines state that, for patients with volume overload refractory to diuretics, extracorporeal ultrafiltration or hemodialysis can be considered. The guidelines note that, although ultrafiltration and hemodialysis remove fluid effectively and can improve serum sodium, trials did not show improved clinical outcomes or kidney function. 

Wearable Hemodialysis Devices

There is a lack of evidence supporting wearable hemodialysis devices. In a pilot study, Davenport and colleagues (2007) evaluated the safety and effectiveness of a wearable hemodialysis device.  A total of 8 patients with ESRD (3 women and 5 men, mean age of 51.7 years) who were established on regular hemodialysis were fitted with a wearable hemodialysis device for 4 to 8 hours.  Patients were given unfractionated heparin for anticoagulation, as they would be for standard hemodialysis.  There were no important cardiovascular changes and no adverse changes in serum electrolytes or acid-base balance.  There was no evidence of clinically significant hemolysis in any patient.  Mean blood flow was 58.6 (SD 11.7) mL/min, with a dialysate flow of 47.1 (7.8) mL/min.  The mean plasma urea clearance rate was 22.7 (5.2) mL/min and the mean plasma creatinine clearance rate was 20.7 (4.8) mL/min.  Clotting of the vascular access occurred in 2 patients when the dose of heparin was decreased and the partial thromboplastin time returned towards the normal reference range in both of these patients.  The fistula needle became dislodged in 1 patient, however safety mechanisms prevented blood loss, the needle was replaced, and treatment continued.  The authors concluded that this wearable hemodialysis device shows promising safety and effectiveness results, although more research is needed to confirm these results.

A review of the evidence on the wearable hemodialysis device by the Australia and New Zealand Horizon Scanning Network (Mundy and Hiller, 2009) concluded: "Preliminary evidence of the wearable artificial kidney indicates that it is successful in the clearance harmful solutes and molecules that accumulate in patients with chronic kidney disease. The benefits of more frequent dialysis has been established and therefore a device which would enable patients to undergo dialysis frequently whilst able to participate in normal activities (including work) without being tied to a hospital setting would be advantageous both to the patient and to the health system. Studies where the WAK device is used long-term on a greater number of patients are required".

Vitamin E-Coated Membranes for Hemodialysis

Huang and associates (2015) noted that there is controversy regarding whether vitamin E-coated dialyzer therapy was beneficial for the complications associated with HD.  These researchers performed a systematic review to evaluate the effects of vitamin E-coated dialyzer.  Related trials were searched from multiple electronic databases.  These investigators conducted a meta-analysis to evaluate changes in the pre-defined outcomes using RevMan 5.3 software.  Meta-analysis showed vitamin E-coated dialyzer therapy could decrease erythropoietin (EPO) resistance index (standardized mean difference [SMD], -0.24; 95 % CI: -0.47 to -0.01; p = 0.04).  However, pooled-analysis showed vitamin E-coated dialyzer therapy could not decrease weekly EPO dose (SMD, -0.11; 95 % CI: -0.32 to 0.09; p = 0.28) and intima-media thickness (IMT) of the carotid artery (MD, -0.09; 95 % CI: -0.2 to 0.01; p = 0.09), and vitamin E-coated dialyzer therapy did not improve the serum hemoglobin (MD, -0.03; 95 % CI: -0.18 to 0.13; p = 0.74), albumin levels (SMD, -0.64; 95 % CI: -1.62 to 0.34; p = 0.2), in addition, there was no significant difference in serum cholesterol (SMD, -0.07; 95 % CI: -0.45 to 0.31; p = 0.71), triglycerides (MD, -2.77; 95 % CI: -32.42 to 26.87; p = 0.85), high density lipoprotein (HDL) (SMD, 0.24; 95 % CI: -0.14 to 0.62; p = 0.22) and low density lipoprotein (LDL) (SMD, 0.00; 95 % CI: -0.38 to 0.37; p = 0.98) levels.  The authors concluded that vitamin E-coated dialyzer may reduce the EPO resistance, but there was no conclusive evidence that vitamin E-coated dialyzer can improve the renal anemia, malnutrition, dyslipidemia and atherosclerosis status in HD patients.  However, high-quality trials with hard clinical end-points are needed to fully elucidate the clinical value of vitamin E-coated dialyzer therapy.

D'Arrigo and colleagues (2017) stated that accruing evidence suggests that vitamin E-coated membranes (ViE-m) might improve the clinical management of chronic HD patients.  These investigators conducted a systematic review and meta-analysis of RCTs comparing ViE-m to conventional HD; end-points were a series of biomarkers pertaining to anemia status, inflammation, oxidative stress and dialysis efficacy/status.  A total of 60 studies were included; ViE-m significantly improved the Erythropoietin Resistance Index but had no impact on other anemia parameters.  As for oxidative stress and inflammation, ViE-m produced a significant decrease in interleukin (IL)-6 levels, thiobarbituric acid reactive substances, plasma and red blood cell (RBC) malonylaldehyde and a significant increase in blood and RBC vitamin E.  Conversely, ViE-m use had no impact on lipid profile, dialysis adequacy, blood pressure, albumin and uric acid.  The authors concluded that ViE-m might ameliorated anemia management by reducing oxidative stress and inflammation.  Moreover, they stated that benefits of these bio-membranes on harder clinical outcomes are uncertain and need to be investigated by future, targeted trials.

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References