Surgery, Gastroenterology and Oncology

Background:Hemodialysis remains the standard therapy for end-stage renal disease (ESRD), the final stage of chronic kidney failure often caused by diabetes mellitus (DM). Evaluating liver enzymes—vital markers of hepatic function—is complicated in ESRD due to uremia, dialysis effects, and accompanying illnesses. The specific contribution of DM to these enzyme changes in ESRD is not well defined. This study aimed to assess liver enzyme levels in hemodialysis patients and distinguish the influence of ESRD alone from ESRD combined with DM.

Methods: A cross-sectional analysis included 140 subjects, comprising 70 ESRD patients and 70 healthy controls. Patients were further stratified into diabetic (n=14) and non-diabetic (n=56) groups. Post-dialysis blood samples were examined for hepatic enzymes, albumin, bilirubin, urea, creatinine, electrolytes, coagulation markers, hematologic parameters, and random blood glucose.

Results: Relative to controls, ESRD patients demonstrated significantly increased aspartate transaminase (AST) (p=0.012) and alkaline phosphatase (ALP) (p<0.001) levels, together with a pronounced decrease in serum albumin (p<0.001). Alanine aminotransferase (ALT) showed a slight, non-significant rise, while total bilirubin remained unchanged. Within the ESRD group, diabetics displayed significantly higher AST (p=0.017), ALT (p=0.003), ALP (p=0.013), and albumin (p=0.034) levels compared with non-diabetics. Dialysis adequacy indicators, including urea reduction ratio and Kt/V, were markedly lower in diabetic patients (p=0.005 and p=0.039, respectively).

Conclusion: Post-dialysis liver enzyme levels are elevated in ESRD, particularly when diabetes is present, compared with healthy individuals. These findings highlight the importance of careful interpretation of liver enzyme data in this population.

INTRODUCTION

End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD) and requires renal replacement therapies such as haemodialysis (HD). Globally, the prevalence of ESRD is increasing, largely due to rising rates of diabetes mellitus (DM) and hypertension (HTN). DM accounts for nearly half of ESRD cases, underscoring the strong link between metabolic disorders and progressive renal failure (1).

Liver function is commonly assessed by measuring aspartate aminotransferase (AST), alanine amino-transferase (ALT), and alkaline phosphatase (ALP). In ESRD, however, the accuracy of these markers is affected by uremia, dialysis treatment, and multiple comorbidities (2).

Abnormal liver enzyme profiles are frequently observed in ESRD patients. Uremic toxins can interfere with hepatic metabolism, while haemodialysis may alter enzyme activity by removing inhibitory substances (3,4). The independent impact of DM on these alterations remains uncertain. Although DM is known to elevate liver enzymes in otherwise healthy individuals, few studies have examined its role in ESRD, forming the rationale for this investigation (5).

The timing of blood sampling relative to dialysis strongly influences aminotransferase levels. Pre-dialysis samples often show reduced values due to vitamin B6 deficiency and uremic suppression, whereas post-dialysis measurements generally reveal higher levels once inhibitors are cleared (6). Such pre-dialysis reductions suggest that even modest post-dialysis increases may be clinically relevant (7) and do not necessarily indicate intrinsic liver pathology (8).

Furthermore, DM is frequently associated with liver conditions such as non-alcoholic fatty liver disease (NAFLD), steatohepatitis, and cirrhosis, complicating the management of ESRD. Chronic hyperglycemia promotes oxidative stress and inflammation, which aggravate hepatic injury and alter enzyme activity, with insulin resistance playing a key role (9).

Therefore, this study aimed to evaluate liver enzyme levels in ESRD patients receiving haemodialysis and to explore the specific effect of coexisting diabetes mellitus on these biochemical markers.

PATIENTS AND METHOD

This cross-sectional study was designed to evaluate liver enzyme levels in patients with end-stage renal disease (ESRD) undergoing haemodialysis and to assess the influence of concurrent diabetes mellitus (DM). A total of 140 participants were recruited from Benha Teaching Hospital and divided into two groups: 70 ESRD patients and 70 healthy controls free from diabetes or renal disease. The patient group was further separated into diabetic (n=14, all on insulin therapy) and non-diabetic (n=56) subgroups. Inclusion criteria required participants to be 18 years or older, have a confirmed ESRD diagnosis, and receive haemodialysis for at least six months. Exclusion criteria included a Body Mass Index (BMI) above 27 or any illness other than chronic kidney disease that could influence metabolic state or hepatic enzyme activity. Specifically excluded were chronic viral hepatitis, malignancy, haemochromatosis, autoimmune hepatitis, non-alcoholic fatty liver disease, metabolic syndrome, alcoholic liver disease, active smoking, recent surgery, pregnancy, lactation, alcohol intake, or use of hepatotoxic medications such as statins.

The protocol received approval from the Institutional Review Board (IRB) of the Faculty of Medicine, Menoufia University. Written informed consent was obtained from all subjects, ensuring confidentiality and the option to withdraw at any point. Comprehensive data were collected for each participant, including demographic details, medical and medication history, laboratory results, and abdominal ultrasonography findings.

Laboratory investigations for all individuals included measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phospha-tase (ALP), serum albumin, total bilirubin, urea, creatinine, sodium (Na), and potassium (K). Coagulation parameters were assessed using prothrombin time (PT) and international normalized ratio (INR). Hematologic tests included hemoglobin (Hb), total leukocyte count (TLC), and platelet count (PLT). Random blood glucose (RBG) was used to evaluate glycemic control, while dialysis adequacy was determined by calculating the urea reduction ratio (URR) and single-pool Kt/V.

For ESRD patients, blood specimens were drawn immediately after the haemodialysis session.

Statistical Analysis

Data were analyzed using IBM SPSS Statistics version 26 (Armonk, NY, USA). The distribution of quantitative variables was checked with the Kolmogorov-Smirnov and Shapiro-Wilk tests, supported by visual inspection. Normally distributed data were presented as mean ± standard deviation, and categorical variables were summarized as counts and percentages. Group comparisons of continuous data used the independent samples t-test for parametric variables or the Mann-Whitney U test for non-parametric data. Associations between categorical variables were examined with the Chi-square or Fisher’s exact test as appropriate. A two-tailed p-value <0.05 was considered statistically significant.

RESULTS

Of 150 initially screened patients, 10 did not meet the inclusion criteria, leaving 140 participants who were enrolled and analyzed (fig. 1).

Figure 1 - Flowchart of the enrolled participants.

Participants were allocated to an ESRD group (n=70) and a control group of healthy individuals (n=70) free of diabetes or kidney disease. Patients with ESRD were significantly older and had a higher frequency of hypertension than controls (p<0.001), whereas gender distribution was comparable. Prothrombin time (PT), international normalized ratio (INR), and random blood glucose (RBG) were all markedly elevated in the patient group (all p<0.001). Conversely, hemoglobin (Hb), total leukocyte count (TLC), and platelet count (PLTs) were significantly lower (p<0.001, p=0.007, and p<0.001, respectively; table 1).

Table 1 - Baseline characteristics and laboratory tests of ESRD patients and healthy controls

Evaluation of hepatic and renal parameters showed significantly higher aspartate transaminase (AST) and alkaline phosphatase (ALP) in ESRD subjects (p=0.012 and p<0.001, respectively) along with a pronounced reduction in serum albumin (p<0.001). Alanine aminotransferase (ALT) and total bilirubin displayed no significant differences. As anticipated, serum urea, creatinine, and potassium were markedly elevated in patients, whereas serum sodium was significantly reduced (all p<0.001; table 2).

Table 2 - Liver function and Kidney function tests of ESRD patients and healthy controls.

Within the ESRD group, subgroup analysis compared diabetics (n=14) to non-diabetics (n=56). The two subgroups were similar in age, sex distribution, and hypertension prevalence. Diabetic patients had significantly higher PT, INR, and RBG values (p=0.006, p=0.003, and p<0.001, respectively), while Hb, TLC, and PLT counts were not significantly different (table 3).

Table 3 - Baseline characteristics and laboratory tests of diabetic and non-diabetic ESRD patients

Regarding liver enzymes, diabetic ESRD patients showed significantly greater AST, ALT, serum albumin, and ALP levels than non-diabetic peers (p=0.017, p=0.003, p=0.034, and p=0.013, respectively). Total bilirubin remained unchanged between groups, and no significant differences were found in serum urea, creatinine, sodium, or potassium (table 4).

Table 4 - Liver function and kidney function tests of diabetic and non-diabetic ESRD patients

Univariate linear regression identified age, platelet count, PT, INR, RBG, serum albumin, serum urea, and serum sodium as significant predictors of AST. Each one-unit rise in age, PT, INR, RBG, and serum urea corresponded to AST increases of 0.24 (0.113-0.365), 4.35 (1.58-7.12), 35.7 (10.1-61.3), 0.05 (0.006-0.09), and 0.04 (0.008-0.07), respectively (table 5). In contrast, one-unit decreases in platelet count, serum albumin, and serum sodium were linked to AST elevations of 0.02 (0.04-0.004), 4.15 (8.07-0.22), and 0.79 (1.22-0.35), respectively. Multivariate analysis retained age as the only independent predictor, where each one-unit increase corresponded to a 0.17 (0.01–0.322) rise in AST (table 6).

Table 5 - Urea-creatinine ratio and kt/v of diabetic and non-diabetic ESRD patients

Table 6 - Univariate and multivariate linear regression analysis of different factors for prediction of changes in AST and ALT in the studied patients.

For ALT, univariate analysis showed that PT, INR, RBG, serum albumin, total bilirubin, and urea reduction ratio (URR) were significant determinants. Increases of one unit in PT, INR, RBG, and total bilirubin were associated with ALT elevations of 6.16 (3.1-9.21), 41.5 (12.7-70.3), 0.07 (0.02-0.11), and 27.3 (13.1-41.5), respectively. Conversely, one-unit reductions in serum albumin and URR predicted ALT increases of 5.2 (9.6-0.79) and 0.25 (0.51-0.002), respectively. In the multivariate model, serum albumin and URR remained independent predictors, with each one-unit decrease linked to ALT elevations of 10.3 (17.3-3.5) and 0.25 (0.5-0.03), respectively (table 6).

DISCUSSION

Understanding the relationship between ESRD, ESRD with DM and liver enzyme levels is crucial. This knowledge can improve clinical follow up of ESRD patients. liver enzymes (AST, ALT and Alp) are part of the routine monthly laboratory follow up of ESRD patients. samples are withdrawn from patients every month in dialysis centres. The knowledge of the change of the levels of these enzymes in ESRD patients are very important in assessing the laboratory results of ESRD patients every month. Also, very important while assessing the ESRD patients in liver morbidities that may occur for them by identifying hepatic complications early and tailoring interventions to reduce liver­related morbidity. AS DM is a main cause of ESRD. So, there was a need to assess its effect on liver enzymes in these patients’ group (ESRD patients). So, we aimed in this study to evaluate liver enzymes (AST, ALT and ALP) levels in ESRD patients in general and those with DM in special.

We studied 140 patients divided into two groups; ESRD group including 70 patients with ESRD and Control group including 70 controls without diabetes or ESRD or any disease that may affect liver enzymes.

In the ESRD group, AST and ALP levels are significantly higher. ALT also is higher, but the elevation didn’t reach significant difference. serum albumin and sodium are significantly lower compared to the control group. Serum urea, creatinine, and potassium levels are significantly elevated, with no significant differences in total bilirubin levels.

The previous studies to our study that studied liver enzymes in (AST, ALT and ALP) in ESRD patients reached two types of results. Some of them showed lower liver enzymes level in ESRD patients (all of these studies samples were withdrawn before dialysis session) and some studies showed significantly higher liver enzymes levels (all samples of these studies were withdrawn after haemodialysis session).

In line with our study results, Latiwesh et al. (10) included 53 HD­CKD patients and 50 healthy controls to estimate the changes in serum ALT, AST and ALP levels in haemodialysis (HD­CKD) patients in comparison to healthy controls and revealed that ALP was significantly higher in both groups of CKD patients when compared to healthy controls (p=0.01) while ALT and AST levels were lower in HD­CKD patients than healthy controls with no significant difference.

Manju et al. (11) identified a statistically significant reduction in AST and ALT levels alongside a marked elevation in ALP among CKD patients when compared to the control group, with a significance threshold of p<0.05. The difference in ALP may be influenced by the severity of kidney disease, the presence of different comorbid conditions, or differences in dialysis status and frequency.

Before the initiation of dialysis, Fabrizi et al. (12) evaluated 407 individuals with CKD and 431 healthy controls, revealing that serum AST (p=0.00001) and ALT (p=0.00001) levels in CKD patients were significantly lower compared to those in the control group.

Studies that have shown that CKD patients under­ going HD experience a reduction in serum AST and ALT levels. This decline has been attributed to several factors, including the potential extraction of amino­transferases during HD, elevated lactate levels leading to the rapid consumption of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) during biochemical assays, resulting in lower aminotransferase levels, the inhibitory effect of uremic toxins on enzyme activity, and a deficiency in pyridoxine, which serves as an essential cofactor for aminotransferase synthesis (13,14).

Nazana and coworkers (8) concluded in their study that HD is associated with an increase level of liver enzymes. Despite this increase, most values remain below the upper limit of the normal. Hence in HD population, the diagnosis of liver disease may be missed if based on the comparison between the liver enzyme values and their Upper limit of normal. They included 60 patients The prevalence of liver enzymes above their respective ULN before and after HD were 31 (51.7%) vs 49(81.7%) for ASAT; 6(10.0%) vs 10(16.7%) for ALT (p=0.01). The ratios of AST/ULN, ALT/ULN, before HD were significantly higher than the ratios before HD session.

Oliveira Rebarto and coworkers (15) evaluated 40 hemodialysis patients by collecting blood samples before and after dialysis sessions to assess hematocrit and liver enzyme levels. Post­dialysis samples showed significantly higher values of hematocrit, aminotrans- ferases, and gamma­glutamyl transferase compared to pre­dialysis samples. Based on these findings, they concluded that hemodilution may influence serum liver enzyme concentrations, suggesting that fluid shifts during dialysis could affect their measured levels.

In our study, Diabetic ESRD patients have signifi­ cantly higher AST, ALT, serum albumin, and ALP levels compared to non­diabetic ESRD patients, with no significant differences in total bilirubin, serum urea, creatinine, sodium, and potassium levels.

To the best of our knowledge, there is no previous study assessing liver enzymes in ESRD diabetic patients versus ESRD nondiabetic patients. So, this study is the first to compare liver enzymes in ESRD diabetic patients and in ESRD nondiabetic patients.

But there are some previous studies that assessed liver enzymes in diabetic patients versus non­diabetics. Murtadha et al. (16) found that ALT and AST were higher in diabetic patients either type 1 and 2 than controls (ALT revealed 23.8, 23.2, and 8.9 U/L in T1DM, T2DM, and healthy individuals, respectively. Also, AST found 20.3, 22.85, and 8.94).

Also, Choudhary et al. (17) found that ALP was observed statistically highly significant in DM patients compared to controls (85.7 ± 12.15 vs 71.36 ± 11.17 U/L, p<0.01). Also, ALT level showed significant increase in DM cases compared to controls (28.08 ± 11.25 vs 21.52 ± 7.9, p<0.01).

Islam and coworkers (5) found that elevated liver enzyme levels (ALT, AST, ALP) were significantly more prevalent among individuals with type 2 diabetes compared to non­diabetic participants. In their study, 61.2% of diabetic patients had at least one or more liver enzymes above the upper normal limit, compared to 37.1% in the non­diabetic group. These findings highlight a strong association between diabetes and increased liver enzyme abnormalities.

DM can cause liver conditions such as NAFLD and steatohepatitis, which elevate AST and ALT levels due to hepatic inflammation and damage (18). Elevated ALP levels may reflect both liver and bone turnover issues, exacerbated by metabolic disturbances in diabetes (19). The increase in serum albumin levels in diabetic ESRD patients could be due to a relative increase in hepatic production or changes in protein metabolism related to diabetes (20).

In accordance with our study results, Soleymanian et al. (21) included 532 maintenance HD patients to compare the clinical outcomes in diabetic patients on HD with non­diabetics and revealed that serum albumin and creatinine were significantly higher in diabetic ESRD patients compared to non­diabetic (p value <0.001), while ALP showed no significant difference contrasting us and this may be due to different population sample or dialysis regimen and frequency.

In our study, patients with ESRD are significantly older, have higher HTN, Prothrombin time (PT), INR, and RBG levels, and lower Hb, TLC, and PLT counts, with no significant difference in sex distribution compared to the control group.

Regarding demographics, Manju et al. (11) conducted a study to compare the hepatic and pancreatic enzyme (AST, ALT, ALP, GGT, amylase, and lipase) levels between CKD patients with ESRD including 100 controls, 100 CKD patients and found no significant difference regarding age or sex. The difference in age may be attributed to the sample size or different patient population.

In patients with ESRD undergoing HD or peritoneal dialysis, HTN is common and often inadequately controlled (22). HTN affects nearly 50­60% of HD patients, although some studies have found that 80­ 90% of HD patients are affected (23).

Higher PT and INR levels in ESRD patients are primarily due to impaired liver function and the uremic environment, which affects the synthesis and function of coagulation factors. Additionally, dialysis can influence coagulation parameters (24). Elevated RBG levels are often observed in ESRD patients, especially those with diabetes, due to poor glycemic control, insulin resistance, and alterations in glucose metabolism associated with kidney dysfunction (25).

Lower Hb, TLC, and PLT counts are common in ESRD due to reduced erythropoietin production, chronic inflammation, and bone marrow suppression, high­lighting the complex interplay of metabolic and hema­ tologic disturbances in these patients (26).

Parallel to our results regarding serum urea and creatinine, Latiwesh et al. (10) revealed significantly higher in CKD patients than controls (p<0.05). ESRD leads to significantly elevated serum urea and creatinine levels due to the kidneys' severely reduced ability to filter and excrete waste products. As kidney function declines, the glomerular filtration rate (GFR) decreases, causing an accumulation of these nitro-genous waste products in the blood (27).

ESRD patients were divided into diabetic and non- diabetic groups. Diabetic ESRD patients exhibit significantly higher PT, INR, and RBG levels compared to non­diabetic ESRD patients, despite having similar baseline characteristics such as age, sex, and history of HTN. Hb, TLC, and PLT counts showed no significant differences between the groups.

Diabetic ESRD patients exhibit higher PT, INR, and RBG levels due to poor glycemic control, insulin resistance, and the chronic inflammatory state associated with diabetes. Additionally, coagulation abnormalities, medication use, and metabolic disturbances in diabetic patients further contribute to these elevated levels (28).

Diabetic ESRD patients have significantly lower URR, and kt/v compared to non­diabetic ESRD patients.

This study is considered a pioneering one in assessing urea­creatinine ratio and kt/v between diabetic and non­diabetic ESRD patients. Consistent with our findings, Baloochi Beydokhti evaluated HD adequacy using KT/V > 1.2 and URR > 65% as desirable benchmarks in a study involving 33 participants, stratified into diabetic (n=16) and nondiabetic (n=17) groups. The study revealed that the URR index was below 65% in all diabetic patients and 41.2% of the nondiabetic group. Moreover, 64.7% of nondiabetic patients and 31.3% of diabetic patients had a KT/V index exceeding 1.2, with nondiabetics showing a significantly higher KT/V than diabetics (29).

Concerning regression analyses, age is the most consistent predictor of elevated AST levels, indicating that as patients age, there is a greater likelihood of liver enzyme elevations, potentially reflecting age­related liver function decline or cumulative liver stress.

Increased likelihood of comorbid conditions with aging such as cardiovascular disease, diabetes, and hypertension, which can affect liver health. Additionally, aging may lead to reduced clearance of metabolic byproducts, contributing to elevated AST levels, which is a marker of hepatocellular injury (30).

Regrading regression analyses, decreased levels of serum albumin and urea reduction ratio are strong predictors of increased ALT levels, suggesting that monitoring these markers could help in predicting liver function changes.

Low serum albumin suggests poor nutritional status or compromised liver synthetic function, which is common in ESRD due to chronic inflammation, malnutrition, and liver congestion (31). Meanwhile, a low urea reduction ratio reflects ineffective removal of toxins during dialysis, leading to the accumulation of metabolic waste products that can cause liver stress and hepatocellular injury, thus elevating ALT levels (32). This study has some limitations including its single­center design, which may limit generalizability, and the relatively small sample size. We recommend larger scale studies to follow us for better understanding of liver enzymes profile in ESRD and to determine upper normal level of liver enzymes in ESRD in general and ESRD diabetic in particular. We also recommend assessing gamma­glutamyl transferase (GGT), HBA1C and lipid profile in further assessments.

CONCLUSION

ESRD patients, in general and those with diabetes in particular, have significantly higher liver enzyme profiles in samples collected after dialysis session than general population. So, abnormal high liver enzymes (AST, AlT and ALP) in ESRD patients should be reassessed and upper normal levels should be revised. more and larger studies are needed to confirm these results. These results may change our view to liver enzymes levels in ESRD patients particularly ESRD patients with diabetes in routine monthly follow up and in other occasions.

Conflicts of Interest: Not applicable

Source of Funding: Not applicable

Ethics Approval

The study was approved by the Institutional Review Board (IRB) of Faculty of Medicine, Menoufia University.

REFERENCES

1. Nasri H, Rafieian-Kopaei M. Diabetes mellitus and renal failure: Prevention and management. J Res Med Sci. 2015;20:1112-20.

2. Ray L, Nanda SK, Chatterjee A, Sarangi R, Ganguly S. A comparative study of serum aminotransferases in chronic kidney disease with and without end-stage renal disease: Need for new reference ranges. Int J Appl Basic Med Res. 2015;5:31-5.

3. Sette LH, Almeida Lopes EP. Liver enzymes serum levels in patients with chronic kidney disease on hemodialysis: a comprehensive review. Clinics (Sao Paulo). 2014;69:271-8.

4. Yeung CK, Shen DD, Thummel KE, Himmelfarb J. Effects of chronic kidney disease and uremia on hepatic drug metabolism and transport. Kidney Int. 2014;85:522-8.

5. Islam S, Rahman S, Haque T, Sumon AH, Ahmed AM, Ali N. Prevalence of elevated liver enzymes and its association with type 2 diabetes: A cross-sectional study in Bangladeshi adults. Endocrinol Diabetes Metab. 2020;3:e00116.

6. Clase CM, Ki V, Holden RM. Water-soluble vitamins in people with low glomerular filtration rate or on dialysis: a review. Semin Dial. 2013;26:546-67.

7. Sabouri S, Afzal Aghaee M, Lotfi Z, Esmaily H, Alizadeh M, Mosannen Mozafari H. Evaluation of Liver Enzymes in End-Stage Renal Disease Patients on the Renal Transplant-Waiting List in North-West of Iran. Nephro-Urol Mon. 2020;12:e107859.

8. Nzana V, Kowo M, Maheg A, Maimouna M, Ndjong E, Kaze F, et al. WCN23-0303 liver enzymes assessment in chronic kidney disease patients on maintenance haemodialysis at the yaounde university teaching hospital in cameroon. Kidney International Reports. 2023;8:S313.

9. Frankowski R, Kobierecki M, Wittczak A, Rózycka-Kosmalska M, Pietras T, Sipowicz K, et al. Type 2 Diabetes Mellitus, Non-Alcoholic Fatty Liver Disease, and Metabolic Repercussions: The Vicious Cycle and Its Interplay with Inflammation. Int J Mol Sci. 2023;24.

10. Latiwesh OB, Younis MY, Shakila S, Abdulmalik F, Alammari JA, Min Y, et al. Hepatic enzymes changes in chronic kidney disease patients-a need for modified reference values. J Evolution Med Dent Sci. 2018;7:1949-54.

11. Manju M, Rajendran S, Mishra S, Pavithra M. Serum liver and pancreatic enzymes in chronic kidney disease with and without end-stage renal disease: a comparative study. Indian J Med Biochem. 2019;23:207-12.

12. Fabrizi F, Lunghi G, Finazzi S, Colucci P, Pagano A, Ponticelli C, et al. Decreased serum aminotransferase activity in patients with chronic renal failure: impact on the detection of viral hepatitis. Am J Kidney Dis. 2001;38:1009-15.

13. Ono K, Ono T, Matsumata T. The pathogenesis of decreased aspartate aminotransferase and alanine aminotransferase activity in the plasma of hemodialysis patients: the role of vitamin B6 deficiency. Clin Nephrol. 1995;43:405-8.

14. Crawford DR, Reyna RS, Weiner MW. Effects of in vivo and in vitro dialysis on plasma transaminase activity. Nephron. 1978;22:418-22.

15. Liberato IR, Lopes EP, Cavalcante MA, Pinto TC, Moura IF, Loureiro Júnior L. Liver enzymes in patients with chronic kidney disease undergoing peritoneal dialysis and hemodialysis. Clinics (Sao Paulo). 2012;67:131-4.

16. Murtadha JH, Abdul Razzaq I, Dawood A, Hajjem Z, Nayif B. Comparative study of abnormal renal function tests and liver function tests in type1 and type2 diabetes mellitus in Iraq. IOSR Journal of Nursing and Health Science (IOSR-JNHS) Ver. 2016;3:5.

17. Choudhary M, Jinger SK, Gahlot G, Saxena R. Comparative study of liver function test in type-1 and type-2 diabetes mellitus. Indian Journal of Scientific Research. 2014;5:143-7.

18. Dharmalingam M, Yamasandhi PG. Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus. Indian J Endocrinol Metab. 2018; 22:421-8.

19. Rafaqat S, Sattar A, Khalid A, Rafaqat S. Role of liver parameters in diabetes mellitus - a narrative review. Endocr Regul. 2023;57:200-20.

20. Raja P, Maxwell AP, Brazil DP. The Potential of Albuminuria as a Biomarker of Diabetic Complications. Cardiovasc Drugs Ther. 2021; 35:455-66.

21. Soleymanian T, Kokabeh Z, Ramaghi R, Mahjoub A, Argani H. Clinical outcomes and quality of life in hemodialysis diabetic patients versus non-diabetics. J Nephropathol. 2017;6:81-9.

22. Kim IS, Kim S, Yoo T-H, Kim J-K. Diagnosis and treatment of hypertension in dialysis patients: a systematic review. Clinical Hypertension. 2023;29:24.

23. Sarafidis PA, Li S, Chen SC, Collins AJ, Brown WW, Klag MJ, et al. Hypertension awareness, treatment, and control in chronic kidney disease. Am J Med. 2008;121:332-40.

24. Lv Y, Liu N, Li Y, Wu J, Zheng J, Li X, et al. Coagulation Dysfunction in Patients with Liver Cirrhosis and Splenomegaly and Its Countermeasures: A Retrospective Study of 1522 Patients. Dis Markers. 2023;2023:5560560.

25. Gianchandani RY, Neupane S, Iyengar JJ, Heung M. Pathophysiology and Management of Hypoglycemiain End-Stage Renal Disease Patients: A Review. Endocr Pract. 2017;23:353-62.

26. Santos EJF, Dias RSC, Lima JFB, Salgado Filho N, Miranda Dos Santos A. Erythropoietin Resistance in Patients with Chronic Kidney Disease: Current Perspectives. Int J Nephrol Renovasc Dis. 2020; 13:231-7.

27. Makris K, Spanou L. Acute Kidney Injury: Definition, Patho-physiology and Clinical Phenotypes. Clin Biochem Rev. 2016;37:85-98.

28. Kovesdy CP, Park JC, Kalantar-Zadeh K. Glycemic control and burnt-out diabetes in ESRD. Semin Dial. 2010;23:148-56.

29. Baloochi Beydokhti T. Dialysis adequacy in diabetic and non-diabetic patients. Med Surg Nurs J. 2014;3:e87779.

30. Jichitu A, Bungau S, Stanescu AMA, Vesa CM, Toma MM, Bustea C, et al. Non-Alcoholic Fatty Liver Disease and Cardiovascular Comorbidities: Pathophysiological Links, Diagnosis, and Therapeutic Management. Diagnostics (Basel). 2021;11.

31. Soeters PB, Wolfe RR, Shenkin A. Hypoalbuminemia: Pathogenesis and Clinical Significance. JPEN J Parenter Enteral Nutr. 2019;43: 181-93.

32. Yamamoto S, Kazama JJ, Wakamatsu T, Takahashi Y, Kaneko Y, Goto S, et al. Removal of uremic toxins by renal replacement therapies: a review of current progress and future perspectives. Renal Replacement Therapy. 2016;2:1-8.