The study has shown the prevalence of Amphotericin B-associated nephrotoxicity and Amphotericin B-associated hypokalemia to be 46.2% and 33.3%, respectively, amongst the patients receiving conventional Amphotericin B in the specified tertiary care centres in Palestine. Several studies have shown an association between the use of conventional Amphotericin B and nephrotoxicity and electrolytes imbalances with liposomal preparations yielding a safer result for kidney function and nephrotoxicity.  Liposomal Amphotericin B, however, carries a significantly higher price in developing countries, such as Palestine and the Middle East, conveying the need to investigate further the relationship between conventional Amphotericin B and the deterioration of the kidney function, risk factors, and the possible protective measures to decrease the possibility of that outcome. [8, 10, 11]
The median age in our present study was 52 years with a slightly predominant male population (54.7%), which isn’t any different from the general population receiving conventional Amphotericin B, especially when compared to other studies with similar sample sizes, as Tuon et al. and Bates et al. found the median age of patients receiving to be 47.87 and 47 with a sample size of 106 and 643, respectively.[14, 15]
Upon investigating the indications for the use of conventional Amphotericin B, it has been noted that the top indications for the use of the antifungal agent, respectively, are the empirical treatment for sepsis (22.2%) and respiratory tract infection (20.5%), which include Candidiasis, Aspergillosis, and various other fungal lung infections. Other articles had a similar indication list for using conventional Amphotericin B. These indications included empirical treatment, confirmed fungal infection by cultures, and malignancy-related infections. [14, 16, 17]
Regarding the dosage of the drug provided to the patients, the subjects’ showed a median cumulative dose of 250 mg within a range of 40 to 2550 mg and a median treatment duration of 6 days within a range of 2 to 220 days compared to Harbarth et al. paper, which constituted of 494 patients, holding a median cumulative dose of 240 mg (interquartile range 113 to 500mg) and a treatment duration of 10 days (interquartile range, 5 to 18 days). 
Nephrotoxicity in our study showed a percentage of 46.2%, which is approaching and slightly lower than results shown in similar articles, as Rocha et al. had a nephrotoxicity percentage of 58.6% under the KDIGO criteria amongst 120 patients from 2006 to 2012 while Tuon et al. had a nephrotoxicity percentage of 60.8% amongst 102 patients from 2006 to 2015. [8, 11] Additionally, in a study published in 2013 by Khalili et al. that aimed to study the effects of various antimicrobial agents, it was determined that conventional Amphotericin B was responsible for a rise in creatinine in 80% of patients receiving it. Thus, such a prevalence in our sample size reemphasizes that nephrotoxicity remains a major issue when opting for conventional Amphotericin B as treatment. Moreover, the slightly lower percentage might be due to a higher rate of ICU participants (70.1%) who received more intensive monitoring than other participants.
Investigating the associations between the variables in our study and the development of conventional Amphotericin B-induced nephrotoxicity has yielded a possible association between nephrotoxicity, hypertension, COVID-19, ICU admission, and mechanical ventilation under a univariable analysis. However, these associations have been found to be insignificant under the multivariable analysis due to a possible confounding bias resulting in no specific individual risk factor for the development of nephrotoxicity. Compared to other articles, this section has had a wide variation, with some researchers finding no significant association between any of the risk factors used in our study and nephrotoxicity. In contrast, other researchers found a significant association between nephrotoxicity and risk factors such as pre-existing renal insufficiency, concomitant nephrotoxic agents, cumulative doses, and volume depletion.[14, 18] Nevertheless, it is important to note that the relationship between COVID-19 infection and nephrotoxicity in the logistic regression table didn't reach a significance level with a broad confidence interval result indicating that a larger sample size of subjects with COVID-19 is needed to explore this relationship. We recommend further investigating the relationship between COVID-19 and conventional Amphotericin B-induced nephrotoxicity in a larger population as that may lead to a better and statistically significant result.
In the current study, hypokalemia was experienced by 33.3% of patients, compared to 74.7% in Rocha et al. article and 62.8% in the Tavakoli-Ardakani et al. study, which included 35 patients undergoing a year-long investigation. [11, 19] With such a low percentage of conventional Amphotericin-B-induced hypokalemia in our research, we believe that various factors may have contributed to this result. These factors include discontinuing concomitant nephrotoxic drugs, increasing IV fluid supplementation, and continuous and frequent electrolyte monitoring and replacement. However, due to the small sample size, our study could not show a significant relationship between the protective factors and the lower incidence of conventional Amphotericin B-induced hypokalemia.
Upon examining the relationship between the variables and conventional Amphotericin B-induced hypokalemia development, we have determined a significant association between conventional Amphotericin B-induced hypokalemia and female gender, with females being at increased risk of developing hypokalemia when treated with conventional Amphotericin B compared to their male counterpart. However, this association has not been observed or studied in other researches. Accordingly, further clinical and biochemical analysis is required to identify the precision and accuracy of this association. Until then, clinicians should be advised to take precautions when administering conventional Amphotericin B to female patients, especially those with previous or documented potassium abnormalities, and to continuously follow up on the serum Potassium levels during the therapy with preparations to intervene and correct the abnormalities accordingly.
Moreover, a larger study with a larger population may lead to significant results between the risk factors and the development of acute kidney injury and electrolytes imbalances since univariable analysis showed significance, but multivariable analysis failed to confirm the significance. As such, we recommend the continuation of the study to assess the relationship between the risk factors and conventional Amphotericin B associated nephrotoxicity and electrolytes imbalance.
The limitations of our study included conducting a retrospective study that involved extracting data from electronic medical records with no routine documentation of the potassium supplementation provided. Furthermore, due to the small number of tertiary care centres in Palestine that use conventional Amphotericin B, we were unable to include a larger sample in our study, which may have limited the study's power to find relationships between risk factors and the development of acute kidney injury and electrolytes imbalances.