This study enrolled patients who underwent peritoneal dialysis or CVVHDF as a CRRT method. As far as we know, our study is the largest newborn study to date that compared the PD and CVVHDF methods in MSUD. Our results indicated that leucine levels were more rapidly eliminated by the CVVHDF than PD and that CVVHDF did not increase mortality.
Maple syrup urine disease presents with coma in the newborn period; accumulation of toxic metabolites, especially leucine and its metabolites, causes acute metabolic crisis, severe neurological and developmental injury, or even death[1, 8]. It has been shown that cerebral leucine accumulation causes neurotransmitter consumption and replaces other essential amino acids, leading to impaired normal brain growth and development; thus, its levels should be effectively lowered as quickly as possible[9]. Patients may present with inability to suck, poor feeding, intolerance to feeding, vomiting, hypotonia, apnea, respiratory failure, and convulsions[4, 5]. Infants with MSUD are at risk of metabolic decompensation and should be treated with an emergency protocol[9]. The goal of acute therapy is to reduce catabolism and to increase protein anabolism[9]. Severe cases should be aggressively treated (e.g. dialysis, hemofiltration, parenteral feeding, and/or orogastric feeding) [9]. The acute dietary therapy should be aggressive and contain adequate energy (up to 150% of normal energy expenditure) provided by a formula, which is free of BCAA, and fluids[].9 The most common cause of admission among our patients was feeding problems and respiratory failure. In these patients, as the leucine reduction rate per hour increases, the time to starting complete enteral feeding decreases.
Lowering the concentrations of BCAA and their metabolites can prevent neurological injury and save lives[5]. Patients need a rapid diagnosis and urgent elimination of toxins with specific therapy[1]. In recent years, recommendations about the use of CVVHDF have been increasing thanks to technological advances and to an increasing, albeit still limited, number of case reports discussing the CRRT methods[5, 7, 10]. Renal replacement therapies have been successfully used to lower the plasma levels of low molecular weight substances[7]. While peritoneal dialysis has been frequently used in the newborn, the rate of using intermittent hemodialysis (IHD) and continuous hemofiltration methods has been constantly rising[7, 10]. In newborn babies, it may be difficult to perform CRRT due to difficulties related to catheter placement and hemodynamic instability[10]. In our unit, five patients with a failed catheter placement attempt had to undergo PD. Peritoneal dialysis has a limited capacity to increase renal clearance and to remove the solute burden and fluid overload, which makes CRRT a more favorable method[7]. Phan et al[7]. showed the efficacy of IHD in acute MSUD crisis in children. However, IHD may lead to a greater rate of hemodynamic instability[7, 8, 10]. Arterial blood pressure and cerebral blood flow disorders may increase the extent of neurological injury[7, 8, 10]. Newborn infants are more susceptible to this side effect[10]. In MSUD, leucine levels may increase if the catabolic process persists or when they show a rebound increase after IHD[5, 7, 10]. It is believed that thanks to allowing a safer electrolyte replacement and a lower risk of rebound leucine increase, CVVD, CVVHD, and CVVHDF, among other continuous modalities, may offer an advantage over IHD[7, 10, 12, 13]. There has been a recent increase in the number of studies that dealt with the technique and frequency of RRT[5, 10–12]. Studies on patients with congenital metabolic disorders have shown that CVVHDF was effective and provided a rapid reduction in toxic metabolites[1, 14]. Jouvet et al[15]. compared the three methods (CVVHDF, CVVH, and CVVHD) in three infants with MSUD and demonstrated that CVVHDF was more effective in eliminating leucine. Kornecki et al[16]. showed that leucine levels more rapidly fell with CVVHDF compared with CVVH. Çelik et al[5]. reported that the short-term outcomes of patients with MSUD were favorable with both dialysis methods, although longer leucine exposure with PD may increase the risk of irreversible brain injury. There are a limited number of studies, mostly in the form of case reports, examining acute detoxification therapy in newborn infants with MSUD[5, 10, 15].
Since leucine is not an osmotic molecule, its rapid removal does not cause any problem; furthermore, since brain blood flow is constant, there is no risk of brain edema[10]. However, CRRTs are associated with several complications. Previous studies have widely reported a number of complications in patients treated with CVVHDF, particularly in the newborn, such as serum electrolyte abnormalities, hemodynamic instability, hemorrhage, and catheter obstruction[17, 18]. In our study, 11 (68.75%) patients received mechanical ventilation support. Hypotension, filter obstruction, and some serum electrolyte abnormalities were the most common complications in our study. Six of 11 patients who underwent CVVHDF developed hypotension, three patients hypokalemia, one patient hypothermia, and two patients filter obstruction in dialysis set, while one patient underwent SVC replacement due to catheter obstruction. A patient in the PD group underwent catheter revision due to obstruction. Eight (72.7%) patients in the CVVHDF group and 3 (60%) in the PD group received mechanical ventilation support. Our study did not find any significant difference between the CVVHDF and PD groups with regard to the leucine reduction rate. However, the leucine reduction rate per hour was significantly higher in the CVVHDF group than in the PD group (p < 0.05). These results indicate that CVVHDF is much more effective than PD in newborn MSUD patients. However, one must exercise caution about hypotension and electrolyte imbalance; additionally, when a patient develops hypothermia, body temperature should be carefully observed. One of our patients died in the second week after RRT.