Intradialytic parenteral nutrition improves nutritional status in a complex cystic fibrosis patient with redo double lung transplant and end-stage renal disease

Abstract

This case study reports on the use of intradialytic parenteral nutrition (IDPN) to address severe malnutrition in a 38-year-old woman, redo double lung transplant recipient with a complex medical history including cystic fibrosis and end-stage renal disease (ESRD) on haemodialysis. Gastroparesis and severe postprandial abdominal pain limited oral/enteral nutrition input. The addition of IDPN resulted in a dry weight increase of 13.6% over a 12-month period and an improvement in the patient’s malnutrition status from severe (Patient-Generated Subjective Global Assessment (PG SGA) C24) to moderate (PG SGA B7). The patient stated she would recommend IDPN to others in a similar situation. Management of patients with coexisting cystic fibrosis and ESRD with or without haemodialysis requires patient engagement in treatment planning and a multidisciplinary team approach for clinical judgement in the absence of guidelines. As advances in medical care see more patients with these coexisting conditions, IDPN may provide an increasingly useful adjunct therapy.

Background

Cystic fibrosis and end-stage renal disease (ESRD) are both hypercatabolic states that result in increased incidence of malnutrition that can be difficult to treat and which leads to increased morbidity and mortality.^{1 2} Clinical guidelines for nutrition in chronic kidney disease (CKD) provide prescriptions for appropriate nutritional intervention(s) to optimise nutritional status and prevent malnutrition, and address targets for increased energy and protein, fat and carbohydrate intake, and restricted sodium, potassium, phosphate and fluid.^{1 3 4} For cystic fibrosis, clinical guidelines for nutritional management provide recommendations for energy, protein, fat, sodium and the treatment of pancreatic insufficiency.^{2 5} Malnutrition is common in patients with cystic fibrosis, and nutritional status is strongly associated with pulmonary function and survival.² Cystic fibrosis guidelines do not recommend parenteral nutrition for routine use or long-term treatment due to the requirement for centrally placed catheters, the risk of complications such as line sepsis and the challenges associated with administering parenteral nutrition outside the hospital setting, although it may be considered for severely compromised patients awaiting transplantation or in exceptional cases when enteral feeding is not possible.^{2 5}

The provision of calories and amino acids via intradialytic parenteral nutrition (IDPN) can acutely reverse the net negative whole-body and forearm muscle protein balances and may provide a convenient and safe option for nutritional support in patients with ESRD.⁶ IDPN uses the fistula/permacath for delivery of partial parenteral nutrition into the venous line during regular dialysis sessions. This eliminates the increased infection risk posed by the additional access lines of traditional home parenteral nutrition and avoids any additional treatment time burden on the patient. However, the evidence is equivocal for IDPN in relation to risk of harms, economic cost and extent of benefit over standard nutritional interventions. IDPN may be useful as an adjunct strategy for patients with reduced dietary intake where intensive dietetic input and oral supplementation have failed.^{4 7}

Advances in healthcare have resulted in improved life expectancy for people with cystic fibrosis, and consequently in our centre we have an increasing number receiving haemodialysis and requiring nutritional management and monitoring. The management of patients with both CKD and cystic fibrosis is complex due to the contradicting nutritional requirements of these conditions, and there is very little guidance available for clinicians. In particular, there are challenges in balancing salt requirements, managing fluid restrictions and reaching high energy and protein requirements while minimising potassium and phosphate levels. A search of the literature found no reports on the use of IDPN for management of ESRD in patients with cystic fibrosis, either with or without lung transplant. This case study shares the experiences and learnings from the nutritional management of an immunosuppressed patient with both ESRD and cystic fibrosis, and reports on the effectiveness of using IDPN to manage severe malnutrition.

Case presentation

This case study reports on a 38-year-old woman with a supportive family who maintains a busy lifestyle, including working part time. Her complex medical history included cystic fibrosis (F508 homozygous), immunosupression due to double lung transplants (2012, redo lung transplant 2013) resulting in the development of atypical haemolytic uremic syndrome, CKD secondary to thrombotic microangiopathy and ESRD. Other complications include pancreatic insufficiency, steatohepatitis, cardiac failure, gastro-oesophageal reflux requiring nissan fundoplication, gastroparesis, cystic fibrosis-related diabetes (CFRD), anaemia of chronic disease, severe cushing syndrome secondary to long-term steroid use, osteoporosis, hypertension (improved with dialysis) and an episode of Clostridium difficile colitis in 2016. Following an extended intensive care admission in December 2017 due to ruptured diverticulum requiring laparotomy and Hartmann’s procedure, the patient developed renal failure and was commenced on haemodialysis. The patient was deconditioned and severely malnourished, and a percutaneous endoscopic gastrostomy (PEG) was inserted to assist in meeting her nutritional needs. Multiple nutrition impact symptoms including severe postprandial pain, early satiety, chronic nausea and anorexia precluded any increase in nutritional intake via enteral nutrition or oral diet. With malnutrition an ongoing and pressing issue, IDPN was introduced as a supplementary management option (figure 1).

Figure 1.

Timeline of nutritional management in patient with cystic fibrosis and ESRD. ESRD, end-stage renal disease; HD, haemodialysis; IDPN, intradialytic parenteral nutrition; MCT, medium chain triglyceride.

Treatment

The patient was reviewed regularly by dietitians in the haemodialysis unit and during hospital admissions while on IDPN. The goal nutrition requirements were calculated using the Schofield equation with a stress factor of 1.5–2 and activity factor of 1.5 and protein as 15%–20% of estimate energy requirements.⁵ Dry weight, biochemical results, nutrition impact symptoms and intake (oral, enteral, IDPN) were monitored (table 1). The patient had a strong aversion to oral nutrition supplements; as a result these were not included in nutritional management. Medium chain triglyceride (MCT) oil was provided via PEG two times per day for added energy. A supplementary renal specific enteral feed (Nepro HP) (low electrolyte, concentrated, high energy, high-protein formula) was prescribed for the patient to administer overnight via the PEG. However, the patient continued to experience severe abdominal pain, and a PEG with jejunal extension (PEG-J) was inserted secondary to gastroparesis. The patient enountered difficulties in managing the required pancreatic enzyme replacement therapy (PERT). Oral aministration was insufficient and resulted in steathorrea. PERT dissolved in 10 mL 8.4% sodium bicarbonate solution administered via PEG-J was trialled; however, the patient found this laborious and time consuming and thus decided to return to PEG feeding. Adherence to prescribed PEG feed regimens was variable.

Table 1.

IDPN management and assessment data

Date		Week 0 Pre-IDPN March 2018	1 week IDPN March 2018	1 month IDPN April 2018	3 months IDPN July 2018	6 months IDPN October 2018	12 months IDPN April 2019
Anthropometry
Dry weight (kg)		35.5	35.5	36.5	38.5	40.5	40
Preweight (kg)		38.55	37	38.65	41.35	42.9	42
Postweight (kg)		36	35.7	36.6	39.05	40.5	40.2
Ultrafiltration (UF in L)		3.45	2.3	2.95	3.55	3.1	2.7
PG SGA		C24		B14	–	B14	B7
Blood biomarkers (pre-HD)
Sodium (mmol/L)		136	129 L	129 L	124 L	131 L	134 L
Potassium (mmol/L)		3	4	4.9	3.6	4.3	4.9
Chloride (mmol/L)		102	–	94 L	92 L	94 L	98
Urea (mmol/L)		10.6	–	38.0 H	21.1	20.8	17.3 L
Albumin (g/L)		30 L	30 L	27 L	27 L	31 L	31 L
Liver function tests (U/L)		WNL	WNL	WNL	WNL	WNL*	WNL*
Triglyceride (mmol/L)		–	–	–	2.6 H	–	0.8
Phosphate (mmol/L)		1.88 H	3.76 H	3.11 H	1.80 H	2.01 H	2.14 H
Clinical
Pre-HD blood glucose levels (mmol/L)		7.7	13.4	13.4	15.2	7.1	7.7
Post-HD blood glucose levels (mmol/L)		9.4	16	16.9	11.4	–	9.9
Pre-HD blood pressure (mm Hg)		127/87	156/88	153/98	117/78	129/90	152/109
Post-HD blood pressure  (mm Hg)		116/80	109/71	105/73	98/66	100/55	120/90
Oedema		Nil	Nil	Nil	Nil	Nil	Nil
Appetite		Poor	Poor	Poor	Poor	Poor	Poor
Stoma output		Active	Yellow colour	Steatorrhea	Active	Active	Active
Diet (per cent of minimum energy requirements met)
Oral diet	Energy (kJ)	3000 (28%)	3000 (28%)	1500 (14%)	2000 (19%)	2000 (19%)	4500 (42%)
	Protein	25 g	25 g	10 g	15 g	15 g	40 g
PEG-J (Nepro+/-MCT oil†)	Energy (kJ)	6914 (65%)	6914 (65%)	7792 (72%)	8860 (83%)	8860 (83%)	3800 (36%)
	Protein	62 g	62 g	68 g	79 g	79 g	40 g
	Fluid volume	770 mL	770 mL	840 mL	980 mL	980 mL	495 mL
IDPN	Energy (kJ)	0	1866 (17%)	2332 (22%)	1866 (17%)	1866 (17%)	1866 (17%)
	Protein	0	20 g	25 g	20 g	20 g	20 g
Total nutrition	Energy (kJ)	9914 (93%)	11 780 (110%)	11 624 (108%)	12 726 (119%)	12 726 (119%)	10 166 (95%)
	(kJ/kg)	249	302	300	330	315	255
	Protein	87 g	107 g	103 g	114 g	114 g	100 g

EER calculated using Schofield equation with activity factor of 1.5 and stress factor of 1.5–2.0=10 700–14 300 kJ/day. Low range requirement (ie, 10 700 kJ) was used for calculation of percentage of total nutrition. Estimated protein requirement to meet 15%–20% of EER=100–134 g/day. UF, ultrafiltration total fluid removed from dialysis.

*Lactate dehydrogenase elevated.

†MCT oil was included at 30 mL/day (1054 kJ) increasing to 40 mL/day (1406 kJ) 1 month post-IDPN. Other caloric increases were attained by increased Nepro. Body composition measurements were not made.

EER, estimated energy requirement; H, above normal range; HD, haemodialysis; IDPN, intradialytic parenteral nutrition; L, below nomal range; MCT, medium chain triglyceride; PEG-J, percutaneous endoscopic gastrostomy with jejunal extension; PG-SGA, Patient-Generated Subjective Global Assessment; UF, ultrafiltration total fluid removed from dialysis; WNL, within normal limits.

To address continued malnutrition, IDPN (SmofKabiven 986 mL; amino acids 5.1%, lipids 3.8%, glucose 12.7%, electrolytes 0.7%) was commenced during scheduled dialysis sessions, three times per week. IDPN is in regular use at our centre but is provided to only a small proportion of haemodialysis patients based on clinical judgement. The conflicting nutritional requirements for cystic fibrosis and ESRD (table 2) created multiple challenges in managing the addition of IDPN. Particularly problematic was prioritisation between the very high sodium requirements of cystic fibrosis and the lower limits on sodium intake indicated for ESRD. In line with ESRD guidelines, the renal team ceased the patient’s usual sodium supplementation for cystic fibrosis (gastrolyte and/or salt tablets adding up to 4000 mg sodium/day). Further, the patient had reduced sodium intake due to anorexia and the low sodium content of Nepro HP. Hyponatraemia developed and the patient reported nausea and increased nocturnal abdominal pain when prehaemodialysis sodium levels fell below 124 mmol/L. It was unclear whether these symptoms were a direct result of insufficient sodium, or from other aspects of the patient’s complex medical history, thus as posthaemodialysis sodium levels remained within normal limits (137 mmol/L), concerns of fluid overload precluded reinstatement of medicinal salt supplementation. The patient elected to include salty foods and add salt to meals and drinks.

Table 2.

Nutritional requirements in chronic kidney disease versus cystic fibrosis

	Chronic kidney disease: stage 5 on haemodialysis (1,3,4)	Cystic fibrosis (5)
Energy	125–146 kJ/kg IBW/day	Schofield×activity factor (1.2–2.3)×stress factor (1.1–2.0) (>200 kJ/kg/day)
Protein	1.1–1.4 g/kg IBW/day	15%–20% total energy (>2 g/kg/day)
Fat	≤20% of total kJ	100 g/day>5 years of age 20%–30% energy from fat
Salt	1840–2530 mg/day (80–110 mmol)	>6000 mg/day (261 mmol)
Fluid	500 mL+PDUO	Unrestricted
Potassium	Limit and consider sources	Unrestricted
Phosphate	Limit and consider sources	Unrestricted

IBW, ideal body weight; PDUO, previous day urine output.

Hyperphosphataemia was an ongoing issue. Timing the administration of medications was challenging due to the need to avoid potential interactions between transplant-related immunosuppressants (cyclosporine and mycophenolate) and phosphate binders (lanthanum and sevelamer). It was deemed inappropriate to dissolve phosphate binders in enteral feeds due to the risk of reducing effectiveness of the immunosuppressants. The patient continued to take sevelamer orally when able, 2 hours preimmunosuppresant and postimmunosuppressant doses. Phosphate control improved at 3 months post-IDPN initiation as a result of an increased use of phosphate binders and an increased dialysis time.

High blood glucose levels, presumably related to CFRD, were evident for the first 5 months of IDPN use. The patient was then commenced on insulin (NovoRapid and Levemir) which resulted in improvements in blood glucose control (table 1). Carbohydrate awareness and counting education was also provided.

The patient had elevated blood pressure prehaemodialysis for the first month after IDPN initiation, secondary to excess fluid retention. With the additional IDPN volume incorporated in ultrafiltration targets (target fluid amount to be removed during haemodialysis), the patient was required to maintain a strict fluid restriction (1 L/day) to reduce interdialytic fluid gains and ensure fluid removal could be achieved on haemodialysis. As nutrition status improved, the patient became more uremic, prompting an increase in the duration of haemodialysis from 4 to 4.5 hours to assist with fluid management and urea clearance.

No infections related to the use of IDPN were encountered, and liver function remained stable throughout the 12-month case study period.

Outcome and follow-up

In the 12 months following IDPN initiation, IDPN and PEG feeds were crucial, together providing the majority of nutrition (table 1). Abdominal pain was a major factor in low appetite. Initially, enteral nutrition intake increased from 65% (6914 kJ) to 83% (8860 kJ) of energy requirements; however, the patient reduced this concomitant with an improvement in oral intake towards the end of the case study period. Although the patient continued to report anorexia, her oral intake had improved to 42% (4500 kJ) of energy requirements after 12 months. Nutritional management via this three-pronged strategy continues for the patient at the time of writing. Patient-Generated Subjective Global Assessment (PG SGA), a validated tool for nutrition assessment^{3 8} demonstrated an improvement in status from severe (PG SGA C24) to moderate (PG SGA B7) malnutrition. The patient had substantial dry weight gain of 13.6% (4.5 kg) during this 12-month period.

Discussion

To our knowledge, this is the first report on the use of IDPN for the management of malnutrition in a patient with both cystic fibrosis and ESRD, either with or without lung transplant. The comanagement of these conditions is complicated by the conflicting nutritional requirements and the lack of evidence-based guidelines available. People with cystic fibrosis are hypermetabolic and nutrient malabsorption is common. The energy requirements can be in excess of 200 kJ/kg/day. ESRD further increases caloric need, and the patient was unable to gain weight with an intake of 250 kJ/kg/day from enteral and oral nutrition. It was not until IDPN was introduced and the patient was achieving 300–330 kJ/kg/day that weight gain was attained. It was challenging to achieve repletion without causing electrolyte abnormalities.

Patients with ESRD on haemodialysis require sodium restriction for the management of hypertension and interdialytic weight gain, which are associated with adverse patient outcomes.⁹ Due to the primary defect in the cystic fibrosis transmembrane conductance regulator gene, people with cystic fibrosis have abnormally high sodium and chloride losses via sweat glands and are at increased risk of dehydration, hyponatraemia and hypochloridaemia. The recommended adult sodium intake in cystic fibrosis can be in excess of 6000 mg/day (261 mmol/day),⁵ more than two and a half times the upper limit of 2300 mg/day (100 mmol/d) recommended for CKD stage 5.³ The patient continued to experience low serum sodium levels throughout the case study period. No evidence is available on sodium supplementation in cystic fibrosis complicated by ESRD or postlung transplant, and research is needed to guide optimisation of this. People with cystic fibrosis commonly experience symptoms including nausea and/or vomiting, fatigue, anorexia, constipation, difficulty expectorating sputum and headaches when salt intake is insufficient.⁵ Hyponatraemia may have been a contributing factor to the nutrition impact symptoms experienced by the patient. Further, in cystic fibrosis, low sodium levels may result in lung or gut complications, including distal intestinal obstruction syndrome. With this in mind, and providing fluid can be controlled, there may be room for an increase in salt intake in excess of CKD guidelines in this population. Maintenance of a 1 L fluid restriction, incorporating oral and enteral intake alongside IDPN provision, was nearly unattainable. Optimising energy and protein intake took priority for this patient to reduce protein-energy wasting and improve survival.^{2 5} While IDPN enabled nutritional requirements to be met, provision was at the lower end of the required range. Further research is needed to guide optimum salt supplementation in this population group.

People with cystic fibrosis experience a large treatment burden that may further increase post-transplant, and which likely contributed to reduced adherence to prescribed overnight enteral feed regimens. Other challenges included severe postprandial pain, the necessity for multiple medications with potential for interaction which complicated the timing and delivery methods for these, as well as for oral and enteral intake. Hyperphosphataemia was an ongoing issue. While the phosphate binder sevelamer does not appear to have a significant effect on the absorption of cyclosporin, it has been shown to interfere with the pharmacokinetics of mycophenolate mofetil.¹⁰ As a result, it is recommended that the administration of phosphate-binding medications and immunosuppressants are spaced to avoid interactions as it is paramount to prioritise longevity of transplant over phosphate control.

Continued advances in healthcare are resulting in an increasing number of patients with cystic fibrosis requiring management for complex comorbidities. Severe renal dysfunction (creatinine >2.5 mg/dL) develops within 1 year in 5.6% of lung transplant patients, and 8.4% of redo lung transplant patients, with dialysis rates more than doubling by 5 years post-transplant.¹¹ Consequently, the incidence of people with cystic fibrosis living with transplants and experiencing CKD is likely to increase.

During treatment, the patient received care from multiple dietitians. Evidence suggest continuation of care is important for patients with cystic fibrosis given this is a lifelong condition.⁵ This may have impacted on the patient’s adherence to nutrition recommendations. In this case study, the use of IDPN appeared to provide a helpful strategy to address severe malnutrition and improve quality of life for the patient. Further investigations are needed to optimise care for patients with these co-occuring conditions; however, IDPN could be considered as an option for other similar cases.

Patient’s perspective.

I was a little bit hesitant, at first, because I thought IDPN was quite bad for your liver and I was concerned that I would get liver damage especially having CF, as I’ve already got fatty liver.

I was quite desperate to put on some weight and this (IDPN) was giving me extra calories which I so desperately needed. I think it has impacted it (my quality of life) in a positive way in that I have gained some weight since starting IDPN and through gaining weight I’ve got more energy to do things. I’m actually getting out and enjoying some life.

Learning points.

• Intradialytic parenteral nutrition can provide a useful adjunct therapy in the management of malnutrition for patients with both cystic fibrosis and end-stage renal disease (ESRD).

• A multidisciplinary team approach is necessary, with good communication between transplant, renal and respiratory teams along with allied health professionals.

• The involvement of the patient in decision making is crucial, especially when the patient has multiple comorbidities and experiences a large treatment burden.

• There is a need and increasing opportunity for research to enable development of guidelines for the comanagement of cystic fibrosis and ESRD, particularly in relation to guiding optimal salt supplementation in this population.