Available online on 15.01.2024 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright   © 2024 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access  Full Text Article                                                                                                                                                    Research Article

To Conduct a Prospective Study on Pioglitazone Induced Kidney Injury in Tertiary Care Hospital

B. Archana*¹, Palla Vishwada¹, Yallapragada Sahithi Sri Charani ², Dadi Sneha Shri ²

1. Department of Pharmacology, Bojjam Narasimhulu Pharmacy College for Women, 17-1-382, Vinaynagar Campus, Saidabad, Hyderabad – 500059, Telangana.
2. Bojjam Narasimhulu Pharmacy College for Women, 17-1-382, Vinaynagar Campus, Saidabad, Hyderabad – 500059, Telangana.

 

 

INTRODUCTION

It was Apollonius of Memphis who first used the term diabetes about 250–300 BC. When the sugary urine state was discovered by the ancient Greek, Indian, and Egyptian civilizations, the term diabetes mellitus was created. Hyperglycemia, a collection of metabolic illnesses known as diabetes mellitus, is caused by deficiencies in either insulin action or secretion, or both. Greek Diabetes means "syphon," meaning to pass by, and Latin Mellitus means "sweet" are the roots of the phrase Diabetes Mellitus. Over time, hyperglycemia can cause several organs, including the kidney, heart, kidney, eyes, nerves, and blood vessels, to fail, malfunction, or be destroyed¹. Metabolic defects are caused by reduced insulin synthesis to achieve the proper response and/or insulin resistance in particular tissues, primarily the liver, adipose tissue, and skeletal muscles at the level of effector enzymes, signal transduction system, and/or insulin receptors. Genes are also responsible for these abnormalities. The assessment of hyperglycemia involves multiple morbidities. These include malformations that grow resistant to the effects of insulin, as well as autoimmune destruction of the pancreatic beta cells, which leaves the body without insulin. A decrease in tissue response to insulin or insufficient insulin synthesis can lead to abnormalities in the metabolism of proteins, fats, as well as carbohydrates in hyperglycemia. The extremities of manifestations depend on the time span of the hyperglycemia. Some patients of hyperglycemia are less symptomatic mainly people who are having type – 2 hyperglycemia during the initial stage of disorder². Symptoms include polyurea, polyphagia, polydipsia, weight loss, blurred vision. Unrestrained hyperglycemia results to stupor, coma, and leads to death if not treated due to ketoacidosis or rare from non ketotic hyper osmolar syndrome. Chronic complications of hyperglycemia involve retinopathy with possible loss of eyesight, neuropathy can cause the renal damage, peripheral neuropathy leads to foot ulcers, dissever, diabetic neuropathy osteoarthropathy, and autonomic neuropathy leads to GI, urogenital, cardiovascular, peripheral arterial and cerebro vascular disease. High blood pressure and deficiency of lipoproteins are normal in patients who are suffering from hyperglycemia³.

Etiology

Alpha cells that secrete glucagon as well as beta cells that produce insulin make up the majority of the endocrine cells found in the pancreatic islets of Langerhans. Beta and alpha cells alternate in their secretion depending on the glucose's occupant. Unsuitably skewed glucose levels occur when there is an imbalance between glucagon and insulin⁴. Hyperglycemia is caused by insulin resistance in diabetes, which results in neither producing insulin nor weakening its effects.

Type 1 DM is occurs due to damage of beta cells in the pancreas due to auto immune reactions which results in the low levels of insulin or out of insulin.

Type 2 DM is seen most commonly in elderly and obesity people. It occurs mainly due to variation of insulin levels and insulin sensitivity which leads to functional deficiency of insulin.

Type 2 DM involves a more complex interaction between genetics and lifestyle. There is clear evidence suggesting the Type 2 DM is has a stronger hereditary profile as compare to Type 1 DM. The majority of patients with the disease have at least one parent of Type 2 DM⁵.

Epidemiology

In every 11 adults 1 person is having hyperglycemia (mainly type 2) throughout the world. The onset of Type 1 DM is starts from birth and ends at age of 4 to 6 years and again from 10 – 14 years. The prevalence of people with Type 1 DM underage of 20 is 2.3 per 1000. Most of the autoimmune diseases occurs in females but there is no gender difference for onset of Type 1DM at young age. The ratio of onset of Type1DM is 3 :2 (male to female). The incidence of Type 1DM is increasing globally and raising to 2 to 5 % yearly in Europe, Asia, Middle East. Nearly 2% of incidence is increases in youth of US⁶.

The Onset of Type 2DM is usually occurs in the later life through obesity in adolescents has lead to an increase in Type 2DM in younger population. Upto 9% of total population are having Type 2DM in US 25% in those are above 65 years.

The International Diabetes Foundation evaluates that 1 in 11 adults if age 20 - 25 yrs had hyperglycemia throughout the world in 2015. The specialists anticipate that the prevalence of hyperglycemia is going to increase from 415 to 642 million by 2040 with increase in population change over from low to middle income levels. Type 2DM is varies among the community groups and it is 2 to 6 times more common in blacks, Native Americans, Pima Indians and Hispanic Americans compare to whites in US. Not only community plays a major role in Type 2DM environmental factors also risk factors for Type 2DM. For example,Pima Indians in USis more likely to develop Type 2DM when compare to Pima Indians in Mexico (38% vs 6.9%)⁷.

MATERIALS AND METHODS

Study site

The current study was carried out in the general medicine department of the 1000-bed tertiary care teaching hospital.

Study design

We used a prospective observational study design for our research⁸.

Source of data

Blood samples, patient case papers, and also patient interviews.

Study regulation

350 members, including those who are not patients.

Patient selection criteria

The inclusion and exclusion criteria were used to determine the patients who were enrolled in the trial⁹.

1. Inclusion criteria ¹⁰
2. Diabetes Patients on Pioglitazone with hypertension as well as kidney co-morbidities are included.
3. The study includes patients who are willing to participate.
4. Patients between the ages of 35 and 90 are eligible.                       
5. Exclusion criteria 
6. Patients under the age of twenty are not eligible.
7. Mothers who are pregnant or nursing are not allowed.
8. Patients using insulin are not allowed¹¹.
9. Patients with COVID-19 are not accepted.
10. Individuals who do not take pioglitazone are not eligible.
11. Patients who decline to take part in the research will not be accepted.
12. Hepatic and central nervous system impairment patients are not accepted.
13. The study's qualified patients will provide their informed permission¹².

Study procedure

1.    The Institutional Ethics Committee of Saastra College of Pharmacy, Nellore, and the Department of General Medicine, ACSR Medical College & Govt. General Hospital, Nellore, approved the study after a common data entry format was created for the collection of patient information.

2.    The study's eligible participants provided information on their demographics, history of diabetes and hypertension co-morbidities, use of pioglitazone, and social history in diabetes patients¹³. 

3.    After starting treatment, the patient will have a three-month follow-up to determine the prognosis.

4.    The impact of pioglitazone on patients with diabetic kidney damage will be tracked, and information will be gathered.

5.    A questionnaire containing information about any drinking, smoking, and other behaviours as well as social history will be used¹⁴.

6.    Forms for patient counselling were provided.

7.    Patients get counselling regarding the use of pioglitazone and lifestyle changes related to their complaints at each follow-up visit¹⁵. 

8.    Patients are followed up with continuously, the effects of pioglitazone are monitored, and quality of life is assessed.

9.    Formatting the results, sending them in, and publishing the data in suitable journals with high impact and indexing¹⁶.

RESULTS AND DISCUSSION

Table 1: Study population distribution according to elevated serum creatinine levels

 

 

 

Figure 1: Study population distribution according to elevated serum creatinine levels

Thirty of the 350 participants had elevated serum creatine levels; the remaining subjects' serum creatine levels were normal.

The 350 participants in the study are shown in blue, while the number of people with elevated serum creatinine readings is shown in red.

Table 2: Study population distribution according to age group and length of pioglitazone use.

 

Figure 2: Study population distribution according to age group and length of pioglitazone use

Blue denotes a period of one to five years, red-six to ten years, green-eleven to fifteen years, and violet-sixteen to twenty years.

The Y axis shows the age range of the population, and the X axis shows the number of individuals at risk for kidney damage. Kidney injury is most frequently observed in people who have been using pioglitazone for 10 to 15 years. Males in the 50–60 year age range are more commonly affected.

 

Table 3: Age group as well as length of pioglitazone use (less than 5 years) were used to distribute the study population

 

Figure 3: Age group as well as length of pioglitazone use (less than 5 years) were used to distribute the study population

The Y axis shows the number of patients, and the X axis shows age.

One year is indicated by the colour blue, two years by the colour red, three years by the colour green, and sixteen to twenty-four years by the colour violet. Five years is shown by the light blue colour.

The Y axis shows the age range of the population, and the X axis shows the number of individuals at risk for kidney damage.

Table 4: Study population distribution according to age group and length of pioglitazone use (6 – 10 yrs)

 

Figure 4: Study population distribution according to age group and length of pioglitazone use (6 – 10 yrs)

The Y axis shows the number of patients, and the X axis shows age.

The colours blue, red, green, and violet denote lengths of six, seven, nine, and ten years, respectively. The light blue tint denotes a duration of ten years.

The Y axis shows the age range of the population, and the X axis shows the number of individuals at risk for kidney damage.

Table 5: Study population distribution according to age group and length of pioglitazone use (11–15 years)

 

Figure 5: Study population distribution according to age group and length of pioglitazone use (11–15 years)

The Y axis shows the number of patients, and the X axis shows age.

The periods in blue, red, green, violet, and light blue denote 11, 12, 13, and 15 years, respectively. The Y axis shows the age range of the population, and the X axis shows the number of individuals at risk for kidney damage.

 

Table 6: Distribution of study population based on age group and duration of Pioglitazone  usage (16 – 20 yrs)

 

Figure 6: Study population distribution according to age group and length of pioglitazone use (16–20 years)

The Y axis shows the number of patients, and the X axis shows age.

Blue denotes sixteen years, orange, seventeen, eighteen, and nineteen years, yellow, nineteen, and twenty years, are indicated by the colours. Light blue denotes twenty years.

The Y axis shows the age range of the population, and the X axis shows the number of individuals at risk for kidney damage.

 

 

CONCLUSION

According to the prospective study "Kidney injury caused by pioglitazone." The long-term use of pioglitazone in diabetic patients has been found to raise serum creatinine levels by up to 11% in 350 trial participants. Additionally, patients on pioglitazone for six to ten years have a higher risk of kidney injury, which is usually observed in males between the ages of fifty as well as sixty.

ACKNOWLEDGEMENT

we would like to express my deepest appreciation you our management and principal Dr. P Mani chandrika, M. Pharmacy, PhD. I am extremely grateful to Bojjam Narasimhulu pharmacy college for women for their support without which it would not be possible for completion of our dissertation.

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

REFERENCES

1. Torella R, Lunetta M, Vitali L, Repaglinide plus bedtime insulin is as effective as premixed insulin twice daily but more safe than insulin alone in Type 2 diabetes mellitus inadequately controlled with oha therapy. Diabetologia, 2002; 45:765.

2. Diana LR, Ira CS. Evaluation of the Quality of Life of Chronic Kidney Failure Patients Undergoing Hemodialysis at General Hospital in Jakarta. International Journal of Experimental and Biomedical Research, 2022; 1(1):6-13.

3. Jin HM, Pan Y. Renoprotection provided by losartan in combination with pioglitazone is superior to renoprotection provided by losartan alone in patients with type 2 diabetic nephropathy. Kidney Blood Press Res 2007; 30: 203-11. https://doi.org/10.1159/000104089 PMid:17575467

4. Hari Chandana G, Yerikala Ramesh, Venugopalaiah P, Prapurna Chandra Y, Prospective study on meglitinide induced kidney injury in tertiary care hospital, GSC Biological and Pharmaceutical Sciences, 2023; 25(01):211-219. https://doi.org/10.30574/gscbps.2023.25.1.0421

5. Whitelaw DC, Clark PM, Smith JM, Nattrass M. Effects of the new oral hypoglycaemic agent nateglinide on insulin secretion in Type 2 diabetes mellitus. Diabetic Medicine 2000;17(3):225‐9. https://doi.org/10.1046/j.1464-5491.2000.00256.x PMid:10784228

6. Brogard JM, Landin‐Olsson M, Eriksson J. Repaglinide with bedtime insulin improves glycaemic control in poorly controlled type 2 diabetes. Diabetologia 2000;43:716.

7. James MT, Bhatt M, Pannu N, Tonelli M. Long-term outcomes of acute kidney injury and strategies for improved care. Nature Reviews Nephrology, 2020; 16:193-205. https://doi.org/10.1038/s41581-019-0247-z PMid:32051567

8. Reel B, Guzeloglu M, Bagriyanik A, Atmaca S, Aykut K, Albayrak G, The effects of PPAR-γ agonist pioglitazone on renal ischemia/reperfusion injury in rats. Journal of Surgical Research, 2013; 182:176-184. https://doi.org/10.1016/j.jss.2012.08.020 PMid:22981741

9. Sahithi Maroju, Krishna Sumanth K. Prescription Pattern: Diabetes Mellitus in a Tertiary Care Hospital. International Journal of Clinical Pharmacokinetics and Medical Sciences, 2021; 1(3):108-114.

10. Shigeo N, Daisuke K, Sou K, Takuro Y, Koichi T, Toru M, Takashi S, Masaki O, Acute kidney injury: Epidemiology, outcomes, complications, and therapeutic strategies. Seminars in Dialysis, 2018; 31(5):519-527. https://doi.org/10.1111/sdi.12705 PMid:29738093

11. Zhou Y, Huang Y, Ji X, Wang X, Shen L, Wang Y, Pioglitazone for the primary and secondary prevention of cardiovascular and renal outcomes in patients with or at high risk of type 2 diabetes mellitus: a meta-analysis. The Journal of Clinical Endocrinology & Metabolism. 2020; 105:1670-1681. https://doi.org/10.1210/clinem/dgz252 PMid:31822895

12. Zhou D, Li Y, Lin L, Zhou L, Igarashi P, Liu Y. Tubule-specific ablation of endogenous β-catenin aggravates acute kidney injury in mice. Kidney Int. 2012; 82:537-47. https://doi.org/10.1038/ki.2012.173 PMid:22622501 PMCid:PMC3425732

13. Manjunath G Gandage, Kukunuri Dinesh Kumar, Paturu Venkatesh, Basavaraj Kesapur, Effectiveness of Oral Hypoglycaemics in Type-2 Diabetes Mellitus Patients at a Tertiary Care Hospital : A Comparative Observational Study. Future Journal of Pharmaceuticals and Health Sciences, 2022; 2(4):321-327. https://doi.org/10.26452/fjphs.v2i4.330

14. Heerspink HJ, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou F-F, Dapagliflozin in patients with chronic kidney disease. New England Journal of Medicine. 2020; 383:1436-1446. https://doi.org/10.1056/NEJMoa2024816 PMid:32970396

15. Priyamvada PS, Jayasurya R, Shankar V, Parameswaran S. Epidemiology and outcomes of acute kidney injury in critically ill: Experience from a tertiary care center. Indian Journal of Nephrology. 2018; 28:413-420. https://doi.org/10.4103/ijn.IJN_191_17 PMid:30647494 PMCid:PMC6309393

16. Umesh L, Shivaprasad SM, Niranjan MR, Leelavathi V, Sreedhara CG, Rajiv EN. Acute kidney injury: Experience from a state run tertiary care centre in southern India. International Journal of Medical Research and Health Sciences, 2016;5:83-7