Complex Technological and Biological Research of Solutions for Peritoneal Dialysis

Abstract

Objective: The purpose of our work was to conduct technological, analytical, and biological investigations and stability studies of peritoneal dialysis (PD) solutions containing glucose and sodium lactate in single-chamber containers.Methods: Different formulations of PD solutions were prepared and sterilized at a temperature of 121 °C during 15 m. UV-spectrophotometric determination was performed using purified water as a blank. The spectra of the solutions were run in the range of 220 to 400 nm for the identification of an absorption maximum (λmax) and measuring the absorbance at 228-230 nm and λmaxbefore and after heat sterilization. λmax of the most PD solutions after sterilization was found in the range of 273 to 281 nm. The potentiometric determination was done for pH measuring PD solutions before and after sterilization. Alternative analytical procedure of direct argent metric method was employed for fast measuring content of chloride ions. Viability of Vero cells was evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test, neutral red (NR) uptake assay, and sulforhodamine B (SRB) test.Results: The results showed that the absorbance of the most laboratory batches of PD solutions augments significantly with increasing an autoclave heating time to the sterilization temperature and time of its cooling after sterilization. The longer these parameters, the higher is the absorbance at 228-230 and 273-281 nm indicating 3,4-dideoxyglucoson-3-en (3,4-DGE) and 5-hydroxymethylfurfural (5-HMF) contents, respectively. Glucose degradation is practically absent at short terms of heating and cooling an autoclave while sterilized samples are preserved sterile. Stability studies showed a significant decrease in the absorbance at 228-230 nm during storage with the achievement of a nadir and the following weak increase; an elevation or decrease in the absorption maximum; a substantial decline in the pH of the solution after sterilization and an insignificant pH decrease during storage. The viability of kidney cells was the highest in the SRB test and the lowest one was in the MTT test.Conclusion: The influence of sterilization regimes on the quality of conventional PD solutions and their stability during storage were studied. The highest cytotoxicity was detected in the MTT test, and the lowest one was done in the SRB test, indicating the largest vulnerability of mitochondria under the influence of PD solutions compared to the membranes permeability, functioning of kidney cell lysosomes and the ability of cells to synthesize proteins. Our studies could be useful in the context of planning development of PD solutions with the purpose of authorization and domestic manufacture of these solutions in low-and-middle-income countries.

Approach of the State Pharmacopeia of Ukraine to Analytical Procedures Validation on the Example of Chloride Ions Assay in Peritoneal Dialysis Solutions

“…Each mL of 0.1 M silver nitrate is equivalent to 3.545 mg of Cl -. The content of chloride ions (X 1 ), in mmol/L, in a solution, is calculated according to the following formula: X 1 = V 1 ∑ K ∑ 3.545 ∑ 1000 : 10 : 35.45 = V 1 ∑ K ∑ 10, where V 1 is a volume of 0.1 M solution of silver nitrate used in the titration of a tested solution, in ml, respectively; K is a correction coefficient to the molarity of 0.1 M solution of silver nitrate (7).…”

“…Peritoneal dialysis (PD) is an essential life-sustained treatment modality of renal replacement the-rapy, which is documented to cost less to health care systems in the world compared with hemodialysis (7,8). To the best of our knowledge, scientific papers do not provide information on pharmaceutical development including analytical aspects of PD solutions of the first or second generations despite increasing the prevalence of PD patients in developed and developing countries.…”

“…The total chloride content is one of the critical quality attributes of PD solutions (7,9). According to the British Pharmacopeia (9), an assay of chlorides is carried out using the two titrants: 0.1 M silver nitrate and 0.1 M ammonium thiocyanate for titration of silver nitrate excess.…”

Chronic kidney disease and dialysis therapy: incidence and prevalence in the world

“…The availability of RRT is limited in many countries with a high burden of CKD (Hill et al 2016;Hudz et al 2018a;Lv and Zhang 2019). The development and manufacture of solutions for dialysis therapy (concentrates for HD and solutions for PD) in a country will permit to reduce their cost mainly because of the absence of international deliveries.…”

The Association of Hemoglobin Levels With Quality of Life and Physical Activity in Hemodialysis Patient in Wangaya Regional General Hospital, Denpasar

“…Data also showed that there were 2 million death cases of CKD because of the limited access in renal replacement therapy [6]. CKD is often associated with reduced quality of life due to its complications [7]. Hemodialysis in CKD is performed to replace kidney function in end-stage renal disease.…”