Review Article - Archives of Pharmacology and Therapeutics (2019) Volume 1, Issue 1
Domination of Nephrotic Problems among Diabetic Patients of Bangladesh
Faculty of Pharmacy, World University of Bangladesh, Dhaka-1205, Bangladesh
- *Corresponding Author:
- Mohiuddin AK
Received date: November 21, 2018; Accepted date: December 05, 2018
Citation: Mohiuddin AK. Domination of Nephrotic Problems among Diabetic Patients of Bangladesh. Arch Pharmacol Ther. 2018; 1(1):8-13.
Copyright: © 2018 Mohiuddin AK. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Nearly 80% of people with diabetes live in low and middle-income countries. It increases healthcare use and expenditure and imposes a huge economic burden on the healthcare systems. The International Diabetes Federation estimated 7.1 million people with diabetes in Bangladesh and almost an equal number with undetected diabetes. This number is estimated to double by 2025. It is a costly condition and can lead to stroke, heart attack, chronic kidney diseases, neuropathy, visual impairment and amputations. Bangladesh is a developing country where 75% of total population lives in rural area. Subsequently they have poor healthcare access as 26% of rural professionals remain vacant and nearly 40%, absent. Nearly 45% rural people take medical assessment from unqualified health workers including medical assistants, mid-wives, village doctors, community health workers in comparison to that by qualified medical graduates (only 10%-20%). More than 75% women having complications sought treatment from an unqualified provider. These are mostly because concern over medical costs, and pronounced socioeconomic disparities found for care-seeking behaviour in both urban and rural Bangladesh.
Diabetic patient; Diabetic kidney disease (DKD); End stage renal disease (ESRD); Diabetic nephropathy (DN);
Chronic kidney disease (CKD); Diabetes mellitus (DM)
During 90’s, the country has a relatively low diabetes affected population. According to the International Diabetes Federation, the prevalence will be around 15% by 2030. With diabetes, the small blood vessels in the body are injured. When the blood vessels in the kidneys are injured, they cannot filter blood properly. About 30% of patients with Type 1 (juvenile onset) diabetes and 10%-40% of those with Type 2 (adult onset) diabetes eventually will suffer from kidney failure. The earliest sign of diabetic kidney disease is an increased excretion of albumin in the urine. This happens long before the usual tests done after seeing a physician. Diabetic kidney disease (DKD) is a progressive condition and is an important cause of end stage renal disease (ESRD) as well as a risk factor for cardiovascular morbidity and mortality. There is general agreement that people with diabetes should be screened regularly to detect early markers of kidney damage. People with diabetes and micro-albuminuria should be treated with a multifactorial intervention approach to retard the progression of DKD.
Materials and Methods
A comprehensive review of literature search including books, journal, newsletters, newspaper, magazine column and many more; some physicians, technical experts, industry high officials, hospital authority, nurses and employees of pharmacy companies stated their valuable observation. Projections were based on nephrotic disorders prevalent in diabetic patients, their treatment and statistical evaluation in several institutions of Bangladesh.
Results and Discussion
General pathophysiology and prevalence of
Chronic kidney disease (CKD) was defined in terms of kidney damage (albuminuria) and decreased kidney function (decreased estimated glomerular filtration rate (eGFR)) . Albuminuria was defined as an albumin-tocreatinine ratio greater than 2.5 mg/mmol or 3.5 mg/ mmol for men and women, respectively, on at least two occasions . Type 2 diabetes mellitus (DM) globally affects 18%-20% of adults over the age of 65 y. Diabetic kidney disease (DKD) is one of the most frequent and dangerous complications of DM2, affecting about onethird of the patients with DM2 . The conventional treatments for DKD are control of blood glucose and blood pressure levels by inhibiting the renin-angiotensin system. However, the prevalence of DKD continues to increase and additional therapies are required to prevent or ameliorate the condition. Many drugs have been, or are being, developed to target the molecular mechanisms in play in DKD . Diabetic nephropathy is the commonest cause of end-stage renal disease (ESRD) in the USA. End-stage renal disease (ESRD) incidence due to type-2 diabetic nephropathy (DN) is 35%-50%, according to the United States Renal Data System . The next most common cause is hypertension . The third most common cause is glomerulionephritis. The important subgroups of glomerulonephritis include: immunoglobulin A nephritis (IgA), membraneous glomerulonephritis (MGN) and focal sclerosing glomerulonephritis (FSGN). Among all the complications of diabetes mellitus, nephropathy is the diabetes-specific complication with the greatest mortality . Recently, there appears to have been an explosion in the incidence of diabetic nephropathy (DN), which is most often type II, or non-insulin dependent diabetes mellitus (NIDDM). The increased incidence of NIDDM appears linked to a virtual epidemic of obesity in the USA .
Prevalence of diabetes in Bangladesh
An estimated 10 million people in Bangladesh have diabetes . WHO stated 83% population of age group 25-65 y never checks for diabetes . A different report says almost similar thing. For an effective control and prevention of diabetes; 87% of Bangladeshis were noncompliant, compared to 71% of Indians and 52% Europeans [ 11]. Interesting thing is compliance is not improved in the last 14 y. 33% people age over 35 y are diabetic or prediabetic, only 12% of them have their condition under control . According to the WHO-diabetes country profile of Bangladesh in 2016, the physical inactivity was prevailing among 25.1% of population .
Diabetes patients in Bangladesh with renal
Glomerulonephritis was found to be the leading cause of end stage renal disease (ESRD) and diabetic nephropathy was the second common cause. Hypertension was the most common associated co morbid disease . As kidney function deteriorates, patients develop complications related to fluid overload, electrolyte and acid-base imbalances, and the build-up of nitrogenous waste products. To survive, some patients eventually need haemodialysis or kidney transplantation . 40%-50% of patients with type 1 diabetes and 20%-30% of patients with type 2 diabetes developed diabetic nephropathy . In BIRDEM 2014, prevalence of nephropathy was found in 25% patients; male 27% and female 22% found among 400 type-2 diabetic patients . +35A>C polymorphism possibly responsible for nephropathy in Bangladeshi type-2 diabetic subjects which is predominant in male ; Micro-albuminuria was found in 24% of type 1 diabetes, 27% of fibrocalculous pancreatic diabetes, and nearly 70% of type 2 diabetes children and adolescent in Changing Diabetes in Children (CDiC) clinic, BIRDEM . In Bangladesh, the causes of CKD G5 among 954 patients who were on HD in 2012-2013 were chronic glomerulonephritis (25.5%), diabetic nephropathy (41%) and hypertensive renal disease (33%) .
Non-adherence to preventive and therapeutic
Diabetic Association of Bangladesh selected 374 type 2 diabetic patients diagnosed for at least one year. Nonadherence rate of diet was 90% and exercise was 25%. About 32% patients non-adhered to self-blood glucose monitoring, 70% to foot care and 6% had smoking habits. The main barriers to adherence to blood glucose monitoring was that they did not believe it is useful (65%) and barriers to do exercise were always being busy (44%) and coexisting diseases (9%) .
Almost one in ten adults in Bangladesh was found to have diabetes, which has recently become a major public health issue. A recent meta-analysis showed that the prevalence of diabetes among adults had increased substantially, from 4% in 1995 to 2000 and 5% in 2001 to 2005 to 9% in 2006 to 2010. International Diabetes Federation stated the prevalence will be 13% by 2030 . According to the WHO, at least 2.8% of the population worldwide suffer from diabetes. Considering the increasing rate of type 2 diabetes it is understood that, by the 2030 the prevalence of diabetes mellitus will be double .
Healthcare expenditure for diabetes in
A recent study by World Bank found $160 per year in household expenses for diabetes care (2013 dollars) in Bangladesh . The annual cost of diabetes care per person in the outpatient department of a tertiary care facility was $314. Based on this finding, it is estimated that the total annual burden of some 5.1 million diabetic patients will be $1.5 billion, which is a large burden for a developing country like Bangladesh . In 2016, approximately 55,703 diabetic individuals received in-hospital care, with an estimated 2,641,000 outpatient visits. The total annual estimated cost of diagnosed diabetes was approximately $217.71 million . The median monthly cost of diabetes maintenance was close to USD 10, approximately 10% of the median monthly income .
Management of nephrotic complication in
Blood pressure control: Blood pressure is one of the most important factors influencing progression of diabetic kidney disease and therefore should be aggressively controlled. The SPRINT trial showed reduced mortality in people with non-diabetic CKD with lower blood pressure targets (<120 href="#28" title="28">28,29].
Using multiple agents/combination therapy: The majority of hypertensive patients with diabetes require more than one agent to control blood pressure to the recommended target level; Diuretics or/and calcium channel blockers may be added to ACE-Inhibitors or angiotensin receptor antagonists. Thiazide diuretics, such as chlorthalidone, are similarly effective in reducing coronary heart disease. However, their use in diabetes is less optimal given their metabolic adverse effects, such as hyperglycemia .
Inhibition of the renin-angiotensin system: The RAAS plays a central role in the pathogenesis and progression of diabetic kidney disease. Therefore, inhibition of this system with ACE-Inhibitors or ARBs is one of the most important steps in the treatment of DKD. All hypertensive patients with diabetes should be treated with an ACE-Inhibitor or ARB. Normotensive patients with micro-albuminuria or macro-albuminuria may benefit from treatment with an ACE-Inhibitors or angiotensin receptor antagonists. From a kidney perspective there is no data to support treatment of normotensive, normoalbuminuric patients with ACE-I or ARBs, although there may be some benefit for retinopathy. Patients who are intolerant to ACE inhibitors due to cough usually tolerate an ARB. While angioedema has also been reported with ARBs, it is a rarely seen side effect and much less common that with ACE-Inhibitors. Aldosterone antagonists (spironolactone, epleronone) and direct renin inhibitors (aliskerin) reduce proteinuria in short-term studies but have not been demonstrated to prevent the development or progression of DKD or cardiovascular disease [31,32].
Blood glucose control: It plays an important role in the prevention and progression of DKD and other microvascular diabetes complications. Therefore, good glycemic control is critical for the management of kidney disease and other diabetic complications in these patients. In general, the ADA recommends an HbA1C goal of <7 href="#33" title="33">33].
HbA1c in DKD: Chronic kidney disease, end stage kidney disease (ESRD) and treatment with erythropoiesis stimulating agents (ESAs) have been shown to be associated with decreased red blood cell survival or an increase in red blood cell production/turnover, thereby causing artificially low HbA1C levels in some of these patients. Other reports have shown an increase of HbA1C in CKD through possibly carbamylation of haemoglobin or acidosis. As a result HbA1C levels may not be as accurate in assessing glycemic control in patients with CKD or ESRD. Effects of DKD on glucose control. With advanced GFR loss, typically<20 href="#34" title="34">34].
Sodium-glucose co-transporter 2 (SGLT2) Inhibitors for type 2 DM: SGLT2 inhibitors have emerged as a novel class of medications for the treatment of type 2 DM and have been demonstrated to have beneficial effects beyond their glucose lowering abilities both for cardiovascular and renal endpoints. Empagliflozin has been demonstrated to reduce worsening DKD (defined as progression to macro-albuminuria, doubling of serum creatinine or initiation of renal replacement therapy). The mechanism for this is thought to relate to renovascular effects of the medication. Canagliflozin has been found to reduce the incidence of worsening albuminuria, reduction in GFR and need for renal replacement therapy. SGLT2 inhibitors are, however, not indicated for patients with reduced GFR (eGFR<60 href="#31" title="35">35-37].
Statins and diet modification: Hyperlipidemia is common in diabetic patients with renal disease. Treatment with a statin does not affect progression of kidney disease, but reduces cardiovascular disease risk in people with diabetes and chronic kidney disease. Therapy with a Statin should be considered if the LDL cholesterol is >100 mg/ dl with an LDL treatment goal of <100 href="#37" title="37">37,38].
Dihydropyridine calcium channel blockers (CCBs): Dihydropyridine CCBs (e.g., amlodipine, felodipine) as a sole agent have been shown to increase proteinuria in the IDNT study but are thought to be safe if used in combination with an ACE-Inhibitor or ARB. In fact, the ACCOMPLISH study has demonstrated superiority with regards to progression of chronic kidney disease of the combination of an ACE-Inhibitor with a dihydropyridine CCB as compared to the ACE-Inhibitor combined with hydrochlorothiazide.
Diuretics: Diuretics and RAAS inhibitors are synergistic in terms of effect on BP, i.e., the combined effect of agents from these classes on BP is equal to or greater than the sum of individual effects of each medication. Patients with diabetes and normal or near-normal GFR usually respond to thiazide-type diuretics. In the diabetic subgroup of ALLHAT, chlorthalidone reduced the primary endpoint of fatal coronary heart disease and myocardial infarction to the same degree as lisinopril or amlodipine and was superior for prevention of heart failure .
Non-dihydropyridine calcium channel blockers (CCBs): Non-dihydropyridine CCBs (e.g., diltiazem, verapamil) reduce proteinuria in short-term studies but have not been demonstrated to prevent the development or progression of DKD or cardiovascular disease. Nondihydropyridine CCBs tend to have less potent effects on BP than dihydropyridine CCBs.
Beta blockers: Beta blockers have proven benefit for comorbidities that often accompany diabetes, including coronary artery disease, stroke, and congestive heart failure, and are often indicated for these conditions. In the absence of these conditions, the utility of beta blockers for BP control in diabetes is not clear. Beta blockers and RAAS inhibitors are not synergistic in terms of effect on BP, i.e., the combined effect of agents from these classes on BP is often less than the sum of individual effects of each medication [40,41].
Poor compliance, at any point of life creates serious mischiefs. Bangladesh is a country where poor literacy and carelessness never even gives opportunity to the general people to know the reasons behind their health complexities due to non-compliance and non-adherences. The most important thing is patient education, that the modern world is giving the highest priorities. Rich or poor, privileged or unprivileged all segment of population should be brought under the arena of compliance through patient education, at least by health campaign. Both government and profit taking medicine companies should take initiatives regard.
Compliance with the Ethical Issues
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The authors declare that they have no competing interests
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- Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, Hogg RJ, Perrone RD, Lau J, Eknoyan G. National kidney foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003 Jul 15;139(2):137-47.
- Viberti GC, Mogensen CE, Passa P. St Vincent declaration: guidelines for the prevention of diabetic renal failure. The kidney and hypertension in diabetes mellitus. Kluwer Academic Publishers, Dordrecht. 1994; 515-27.
- Roberto PF, Hugo A. Interactions between kidney disease and diabetes: dangerous liaisons. DiabetolMetabSyndr. 2016 Jul 28;8:50.
- Kim MK. Treatment of diabetic kidney disease: current and future targets Korean J Intern Med. 2017 Jul;32(4):622-30.
- Christina MY, Robert N. Diabetic nephropathy as the cause of end-stage kidney disease reported on the medical evidence form CMS2728 at a single center. Clin Kidney J. 2017 Apr;10(2):257-62.
- Allen IA. Diabetic nephropathy and treatment of hypertension. Endotext, South Dartmouth (MA). 2000.
- Nathan DM. Long-term complications of diabetes mellitus. New Engl J Med. 1993;328:1676-85.
- Abdulrhman A. Prevalence of diabetic nephropathy among Type 2 diabetic patients in some of the Arab countries. Int J Health Sci (Qassim). 2017 Jan-Mar;11(1):1-4.
- Chaity AJ. Obesity blamed for alarming rise in childhood diabetes. DhakaTribune. 2017 Nov 13.
- Star Online Report. 80 lakh Bangladesh is suffering from diabetes: State minister. The Daily Star. 2016 Apr 06.
- Hayes L, White M, Unwin N, Bhopal R, Fischbacher C, Harland J, Alberti KG. Patterns of physical activity and relationship with risk markers for cardiovascular disease and diabetes in Indian, Pakistani, Bangladeshi and European adults in a UK population. J Public Health Med. 2002; 24(3):170-78.
- Abrar SMA. Diabetes management service launched in Bangladesh. DhakaTribune. 2018.
- Tareq S. Obesity is increasing among the younger generation in Bangladesh. The Daily Star. 2018.
- Ahmed ST, Rahim MA. Prevalence of primary renal diseases among patients on maintenance haemodialysis: A hospital based study. KYAMC J. 2012;2.
- Ahmed SS, Khan MAH, Laila TR. Treatment and prevention of common complications of chronic kidney disease. J Enam Med College. 2014;4(1):45-55.
- Position Statement American Diabetic Association. Standards of medical care in diabetes-2015. Diabetes Care. 2015;38(1):8-93.
- Sayama H, Muttalib MA, Islam MI, Khanam PA, Akter N, Akber T. Prevalence of nephropathy with evaluation of HbA1c level and other associated risk factors in type 2 diabetic patients in a tertiary level hospital KYAMC J. 2017 Jul; 8(1):21-26.
- Laily AA, Promita D. Superoxide dismutase 1 gene+35A>C (intron3/exon3) polymorphism in diabetic nephropathy patients among Bangladeshi population. J MolPathophysiol. 2014;3(4):52-57.
- Zabeen B, Nahar J. Risk factors associated with microalbuminuria in children and adolescents with diabetes in Bangladesh. Indian J EndocrinolMetab. 2018 Jan-Feb;22(1).
- Georgi A, Santosh V. Chronic kidney disease hotspots in developing countries in South Asia. Clin Kidney J. 2016 Feb;9(1):135-41.
- Mumu SJ, Saleh F. Non-adherence to lifestyle modification and its determinants among Bangladeshi type 2 diabetic patients. Int J Epidemiol. 2015 Oct 1;44:148-49.
- Shamima A, Mizanur R. Diabetes and prediabetes and their risk factors among Bangladeshi adults: a nationwide survey. Bulletin of the World Health Organization. 2014;92:204-13.
- Lambert P, Bingley PJ. What is type 1 diabetes? Medicine. 2002;30:1-5.
- Shariful MSI, Andreas L. Healthcare use and expenditure for diabetes in Bangladesh. BMJ Glob Health. 2017;2:e000033.
- Afsana A, Samira H. Healthcare cost of type 2 diabetes mellitus in Bangladesh: a hospital-based study. Int J Diabetes. 2016 Jun;36(2):235-41.
- Sarker AR, Marufa S. Letter to the editor health and economic burden of diabetes in Bangladesh: Priorities for attention and control. J Diabetes. 2017 Jul;9(12).
- Lana V, Shahnawaz A, Farzana F, Fahmida D. Self-care practices and barriers to compliance among patients with diabetes in a community in rural Bangladesh. Int J Diabetes Developed Countries. 2016;36:320-26.
- Faqah A, Jafar TH. Control of blood pressure in chronic kidney disease: How low to go? Nephron ClinPract. 2011;119:324-32.
- Vikram P, Adam WC, George B. Hypertension management in diabetic kidney disease. Diabetes Spectr. 2015 Aug;28(3):175-80.
- Sanjay K, Bharti K, Navneet A. Combination therapy in hypertension: An update. DiabetolMetabSyndr. 2010;2:44.
- Luz LM, Adriana PG. Renin-angiotensin-aldosterone system blockade in diabetic nephropathy. Present Evidences. J Clin Med. 2015 Nov;4(11):1908-37.
- Rabi Y, Kirk NC. Inhibition of RAS in diabetic nephropathy. Int J NephrolRenovasc Dis. 2015;8:29-40.
- Farasha Bashir. Understanding risk factors for stroke death in Bangladesh. Global Health Insights. 2017.
- Sun MK, Kyeong MK. Erythropoiesis-stimulating agents and anemia in patients with non-dialytic chronic kidney disease. J Korean Med Sci. 2016 Jan;31(1):55-60.
- Daiji K, Keiichiro M. SGLT2 inhibitors as a therapeutic option for diabetic nephropathy. Int J Mol Sci. 2017 May;18(5):1083.
- Daniel SH, Owen G, William TC. An update on SGLT2 inhibitors for the treatment of diabetes mellitus. CurrOpinEndocrinol Diabetes Obes. 2017 Feb;24(1):73-9.
- Daniel EW, Mark JS. Managing dyslipidemia in chronic kidney disease. J Gen Intern Med. 2004 Oct; 19(10):1045-52.
- Kalaitzidis RG, Elisaf MS. The role of statins in chronic kidney disease. Am J Nephrol. 2011;34:195-202.
- Susan S. Management of hypertension in diabetic patients with chronic kidney disease. Diabetes Spectrum. 2008;21:30-6.
- Care Process Model. Management of high blood pressure. Intermountain Healthcare. 2018.
- Phipps MS, Jastreboff AM. The diagnosis and management of cerebrovascular disease in diabetes. Curr Diabetes Rep. 2012;12(3):314-23.