Changes in pulmonary restrictive parameters by intensive home hemodialysis: a case report

Background Patients with End-Stage Renal Disease (ESRD) are at an increased risk for restrictive lung disease due to accumulation of uremic toxins and volume overload. Hemodialysis is the preferred treatment for improving lung function in dialysis patients. However, the effects of fluid removal and solute clearance by hemodialysis on lung function remain unclear. Case presentation We report a case of restrictive lung disorder in a hemodialysis patient, who showed improvement in both clinical and spirometric lung function after initiation of intensive home hemodialysis (32 h per week). Conclusion Intensive hemodialysis augments fluid removal and solute clearance, which in turn may improve restrictive lung function.


Background
Patients with end-stage renal disease (ESRD) commonly present with pulmonary complications related to uremia and volume overload [1]. Kidney failure reduces pulmonary mechanical and ventilatory functions. Restrictive lung defect (defined as percent forced vital capacity (FVC) < 80 with a reduced total lung capacity (TLC)) is the most common pulmonary dysfunction in ESRD and is associated with poor quality of life and clinical outcome [1].
The prevalence of restrictive lung disorder in chronic kidney disease (CKD) patients is 36% and increases to 64% in CKD patients with protein-energy wasting (PEW) [2][3][4]. Other important risk factors include older age, tobacco smoking, higher body mass index (BMI), and diabetes. Despite the high prevalence of restrictive lung disorder in the CKD population, its pathogenetic mechanisms remain unclear. Several studies have explored the effect of hemodialysis on lung function with mixed results, and longitudinal data are lacking [2,5,6].
We report in a patient with restrictive lung disorder and ESRD, who demonstrated gradual improvement in clinical and pulmonary function parameters after conversion from conventional hemodialysis to nocturnal home hemodialysis (4nights per week, 8 h per session).

Case presentation
A 62-year-old man with ESRD secondary to diabetes presented to Toronto General Hospital with shortness of breath on exertion for 3 years. His co-morbidities include type 2 diabetes, coronary artery disease, gout, hypertension, hyperlipidemia, hypothyroidism, asthma, and obstructive sleep apnea treated by continuous positive airway pressure (CPAP). His mobility was limited by dyspnea (especially with stairs). Given his poor functionality, he was unable to complete any formal exercise program. He denied any chest pain, orthopnea, and paroxysmal nocturnal dyspnea.
He was diagnosed with asthma 10 years ago with pulmonary function testing (PFTs). His pulmonary obstruction was not substantiated by a methacholine challenge. At that time, he presented with shortness of breath on exertion, chest tightness, and occasional cough. He had a remote history of smoking and occasional alcohol use. He was regularly seen in our chronic kidney disease program 3 years prior to the initiation of renal replacement therapy. At that time, PFTs showed a decrease in lung volumes and airflow obstruction with normal diffusive capacity. Based on symptom severity, his inhaler regime included salbutamol (100 mcg) 2 puffs twice daily, ipratropium (17 mcg) 2 puffs twice daily, salmeterolfluticasone (50/500) 2 puffs twice daily, montelukast 10 mg once daily, ciclesonide (160 mcg) 2 puffs once daily and tiotropium (1.25 mcg) 2 puffs once daily ( Table 2).
At the time of hemodialysis initiation, his vital signs were stable, body weight was 99 kg, and there was pronounced bilateral edema. His cardiac examination revealed normal heart sounds with no audible murmurs. There were no abnormal pulmonary findings.
He was initiated on conventional hemodialysis (4 h per session, 3 times a week) in February 2018 due to volume overload. He adhered to his dialysis treatment schedule, and his weight gradually decreased by 7 kg in 3 months. His respiratory symptoms improved, and he was able to exercise using a stationary bicycle without exertional dyspnea. However, he remained dependent on bronchodilators (Table 2). PFTs were repeated in April 2018 (see Table 1). Of note, there was no evidence of airflow limitation. Additional diagnostic tests included a normal electrocardiogram and chest X-ray (Fig. 1). Transthoracic echocardiogram showed an ejection fraction of 55%. Ventricular and atrial assessments showed normal geometry and function bilaterally. CT scan of thorax demonstrated no evidence of interstitial thickening, air trapping, pulmonary edema, or bronchiectasis.
During 8 weeks of home hemodialysis training, his weight decreased by another 5 kg. The patient's symptom gradually improved, he denied dyspnea on exertion, or asthmatic attack. His asthmatic medication was tapered as shown in Table 2. He was converted to nocturnal home hemodialysis in June 2018. His hemodialysis prescription was 8 h per session, 4 times a week via left radio-cephalic AV fistula with bicarbonate base dialysate.
The remaining dialysis treatment parameters were noted below: Revaclear®; Polyethersulfone membrane, surface area of 1.8 m 2 , urea mass transfer area coefficient (KoA) 1439 mL/min, ultrafiltration coefficient (UFC) 54 ml/hr./ mmHg, Blood flow rate (Qb) 350 ml/min and dialysate flow rate (Qd) 500 ml/min.  Fig. 1 Chest X-ray showed stable mild elevation of the right hemidiaphragm. There is no lung consolidation or pulmonary edema. The cardio-pericardial silhouette is normal in size Within 3 months of home hemodialysis, our patient reported further improvement of dyspnea. He indicated that his activities were no longer limited by his respiratory symptoms, and he was able to climb 2 flights of stairs.
His asthma medications were subsequently tapered completely as shown in Table 2.
Routine hemodialysis laboratory data were collected after 3 months of home hemodialysis initiation. His results reflected his intensive hemodialysis prescription (urea 18 mmol/L, creatinine 554 mmol/L, hemoglobin 123 g/L, bicarbonate 23 mmol/L, albumin 41 g/L, calcium 2.29 mmol/L, phosphate 1.35 mmol/L and PTH 37.9 pmol/L.) His urea reduction ratio was 85% with a single-Pool Kt/V of 2.53. Moreover, the patient had a diagnostic methacholine test, and excluded any pulmonary obstruction. His pulmonary function is shown in Table 1.

Discussions and conclusions
This is the first case report of a patient who had improvements in pulmonary function after conversion to intensive hemodialysis (32 h per week). It is tempting to speculate that enhanced removal of fluid and uremic toxins by augmenting hemodialysis dose may modify pulmonary mechanics and ventilatory function.
Our patient's respiratory symptoms improved incrementally from the time of initiating hemodialysis to transition to home intensive hemodialysis. It is reasonable to hypothesize that pulmonary interstitial edema and bronchial wall congestion (via salt and water retention) may result in pulmonary restriction. Elevation in alveolar capillary permeability increases hydrostatic pressure of pulmonary vessels. As a result, ventilatory dysfunction within large and small airways may also lead to impaired lung compliance and diffusion defect [1]. Our patient's initial improvement may be explained primarily by fluid removal, which correlated with a reduction in his body weight. There is a consistent body of literature which associated volume overload with pulmonary dysfunction in ESRD. Yilmaz et al. demonstrated that FEV1 and FVC were significantly lower in dialysis patients with fluid overload. Consequently, increased ultrafiltration volume was independently associated with higher FVC [7]. Similarly, Chase and colleagues demonstrated that increased extravascular lung water, impaired gas exchange and lung compliance was modifiable by enhanced fluid removal [8]. Similarly, Alves et al. demonstrated that sessional ultrafiltration was associated with an acute increase in FEV1 and FVC [9].
After conversion to intensive home hemodialysis, our patient continued to have improvement in lung function without significant changes in his target weight. It is tempting to speculate that other physiologic mechanisms apart from extracellular volume removal may account for the observed changes in lung function. The uremic milieu in ESRD patients may play a role in the pathogenesis of restrictive lung disease. Rahgoshai and colleagues demonstrated an increase in FVC after hemodialysis without significant changes in target weight [10]. Similarly, Navari et al. reported a significant increase of FVC and FEV 1 in patients using bicarbonate based hemodialysis independent of ultrafiltration [11]. It was postulated that the uremic milieu may impair respiratory muscles leading to a reduced vital capacity in dialysis patients [12][13][14]. It is also plausible that chronic inflammation and malnutrition caused by uremia [15] may compound the severity of restrictive lung disease [3]. Intensive hemodialysis may modulate inflammatory cytokines levels. Indeed, in another observational study, reduction in endothelin-1 is associated with amelioration bronchoconstriction and pulmonary hypertension in dialysis patients [16]. Unfortunately, we did not measure inflammatory markers in our patient, which warrants further prospective examination. In summary, restrictive lung disorder is a common complication in the ESRD population. We reported gradual improvement in lung function in a patient undergoing intensive hemodialysis. Our case suggests that chronic accumulation of uremic toxins and volume overload may contribute to the pathogenesis of restrictive lung disorder in dialysis patients. Conversion from conventional hemodialysis to intensive hemodialysis augments fluid removal and solute clearance which may represent a viable option in the treatment of restrictive lung dysfunction in patients with ESRD.