Domination of Nephrotic Problems among Diabetic Patients of Bangladesh
Department of Pharmacy, World University of Bangladesh, Dhaka, Bangladesh
*Corresponding Author: Mohiuddin AK, Department of Pharmacy, World University of Bangladesh, 151/8, Green Road Dhanmondi, Dhaka-1205, Bangladesh
Received: 29 November 2018; Accepted: 14 December 2018; Published: 20 December 2018
Citation: Mohiuddin AK. Domination of Nephrotic Problems among Diabetic Patients of Bangladesh. Archives of Nephrology and Urology 1 (2018): 009-016.Share at Facebook
Nearly 80% of people with diabetes live in low- and middle-income countries. It increases healthcare expenditure and imposes a huge economic burden on the healthcare systems. The International Diabetes Federation estimated more than 7 million people with diabetes in Bangladesh and almost an equal number with unexplored diabetes. This number is estimated to double by 2025. It is a costly condition and may cause 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 taken treatment from an unqualified provider. These are mostly because concern over medical costs, and pronounced socioeconomic disparities found for care-seeking behavior in both urban and rural Bangladesh.
Diabetic Patient, Glycemic Control, kidney Function, Stroke, Blood Sugar, Albuminuria
ADA-American Diabetes Association; ACCOMPLISH-Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension; ALLHAT-Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; ACE-Angiotensin converting enzyme Inhibitors; ARBs-Angiotensin Receptor Blockers; BIRDEM-Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders; CDiC-Children and adolescent in Changing Diabetes in Children; CCBs-Calcium Channel Blockers; CAD-Coronary Artery Disease; CVD-Cardiovascular Disease; CHF-Congestive Heart Failure; DM-Diabetes Mellitus; DAB-Diabetic Association of Bangladesh; DN-Diabetic Nephropathy; NIDDM-Non-insulin Dependent Diabetes Mellitus; CKD-Chronic kidney disease; DKD-Diabetic Kidney Disease; ESRD-End Stage Renal Disease; eGFR-estimated Glomerular Filtration Rate; ESAs-Erythropoiesis Stimulating Agents; MGN-Membranous Glomerulonephritis; FCPD-Fibro-Calculous Pancreatic Diabetes; HbA1C-Hemoglobin A1C; IDNT-Irbesartan Diabetic Nephropathy Trial; IgA-Immunoglobulin A; FSGN-Focal Sclerosing Glomerulonephritis; IDF-International Diabetes Federation; HD-Hemodialysis; SPRINT-The Systolic Blood Pressure Intervention; RAAS-Renin-Angiotensin-Aldosterone System; SGLT2-Sodium-glucose co-transporter 2
During 90s, 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 damaged. When the blood vessels in the kidneys are damaged, 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 undergo kidney failure. The primitive 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. DKD is a progressive condition and is the chief cause of 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 microalbuminuria should be treated with a most factual arbitration to retard the progression of DKD.
2. 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 pharma 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.
3. Results and Discussion
3.1 General pathophysiology and prevalence of diabetes complications
CKD was defined in terms of kidney deterioration (albuminuria) and decreased kidney activities (decreased [eGFR])  Albuminuria was defined as an albumin-to-creatinine ratio greater than 2.5 mg/mmol or 3.5 mg/mmol for men and women, respectively, on at least two occasions . Type 2 DM globally affects approximately 20% of adults over the age of 65 years. DKD is one of the most frequent and dangerous complexity of DM2, affecting about one-third of the patients with DM2 . The current 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 most common cause of ESRD in the USA. ESRD incidence due to Type 2 DN is 35%-50%, according to the US Renal Data System , The next most common cause is hypertension . The third most common element is glomerulionephritis. The important subgroups of glomerulonephritis include: MGN, IgA nephritis, and FSGN. Among all the complexities of diabetes mellitus, nephropathy is the diabetes-specific complication with the greatest mortality . Recently, there appears to have been a blast in the incidence of DN, which is most often type II, or NIDDM. The increased incidence of NIDDM appears linked to a virtual predominant of obesity in the USA .
3.2 Prevalence of diabetes in Bangladesh
An estimated 10 million people in Bangladesh have diabetes . WHO stated 83% population of age group 25-65 never checks for diabetes . A different report says almost similar thing. For an effective control and prevention of diabetes; 87% of Bangladeshis were non-compliant, compared to 71% of Indians and 52% Europeans . Interesting thing is compliance is not improved in the last 14 years. 33% people age over 35 are diabetic or pre-diabetic, less than 15% of them have their condition under control . According to the WHO-Diabetes country profile of Bangladesh in 2016, the physical inactivity was prevailing among more than 25% of population .
3.3 Diabetes patients in Bangladesh with renal dysfunction
Glomerulonephritis was found to be the preeminent cause of ESRD and DN was the second common cause. Hypertension was trivial associated co morbid disease . As kidney function declines, patients develop complexities related to fluid overload, electrolyte and acid-base imbalances, and the build-up of nitrogenous waste products. To survive, some patients ultimately need hemodialysis 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 . Microalbuminuria was found in 24% of type 1 diabetes, 27% of FCPD, and nearly 70% of type 2 diabetes in CDiC clinic, BIRDEM . In Bangladesh, the causes of CKD G5 (End-Stage Renal Failure) among 954 patients who were on HD in 2012-13 were chronic glomerulonephritis (25.5%), diabetic nephropathy (41%) and hypertensive renal disease (33%) .
3.4 Non-adherence to preventive and therapeutic lifestyle
DAB selected 374 type 2 diabetic patients diagnosed for at least one year. Non-compliant diet was 90% and exercise was 25%. Nearly 35% patients non-adhered to self-blood glucose monitoring, 70% to foot care and 6% had smoking habits. The main barriers to adherence to blood sugar monitoring was that they did not believe it is useful (65%) and barriers to do exercise were always being busy (45%) and coexisting diseases (10%) .
3.5 Diabetic forecast
Almost 10% 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 5% in 1995 to 2005 and nearly 10% in 2006 to 2010. IDF 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 .
3.6 Healthcare spending for diabetes in Bangladesh
A recent study by World Bank found $160 per year in household expenditures 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 US$314. Based on this finding, it is estimated that the total annual burden of more than 5 million diabetic patients will be US$1.5 billion, which is a large burden for a developing country like Bangladesh . In 2016, approximately 55,703 diabetic individuals received in-hospital care, with an estimated 2,641,000 outpatient visits. The total annual estimated cost of diagnosed diabetes was approximately US$ 217.71 million . The median monthly cost of diabetes maintenance was close to USD 10, approximately 10% of the median monthly income .
4.1 Diet modification, exercise and statins for blood pressure/sugar control
Glycemic control is critical for the management of kidney patients with diabetes. Blood pressure should be aggressively controlled. SPRINT trial should target (<120/80). Exercise interventions improve the overall functional status and quality of life which also improve hyperlipidemia. Resistance exercise reduces visceral and trunk fat mass, as predictors of hypertension . KDIGO (global NGO developing and implementing evidence-based clinical practice guidelines in renal disease) recommends treatment for a blood pressure of <140/90 in absence of proteinuria and <130/80 mm Hg in presence of proteinuria [28-30]. ADA recommends a HbA1C goal of <7%. Glycemic target should be higher for elderly patients with comorbidity issues [3, 31, 32]. Therapy with a Statin should be contemplated if the LDL cholesterol is >100 mg/dl with an LDL treatment goal of <100 mg/dl. A modest protein limitation of 0.8 g/kg body weight per day has found to be advantageous to control albuminuria/proteinuria and loss of GFR. Diet modification is more accepted than diet restriction. Fruits, fiber and vegetables are encouraged as well as red meat and refined sugar opposed [33-34].
4.2 Combination therapy
The first-line treatment options for hypertension in people with type 1 diabetes are ACE-Inhibitors or ARBs (for both type 1 or 2 diabetes). Diuretics or/and calcium channel blockers can 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 .
4.3 Use of RAAS inhibitors and diuretics
The RAAS plays a vital role in the pathogenic progression of DKD. 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. Aldosterone antagonists (Spironolactone) and direct renin inhibitors (Aliskerin) reduce proteinuria but they cannot prevent progression of DKD or CVD [36, 37]. Diuretics and RAAS inhibitors are co-operative in terms of effect on BP. In the diabetic subgroup of ALLHAT, chlorthalidone reduced the primary endpoint of detrimental coronary heart disease and myocardial infarction to the same degree as lisinopril or amlodipine and was supercilious for prevention of heart failure .
4.4 Dihydropyridine/non-dihydropyridine CCBs and beta-blockers
Non-dihydropyridine CCBs (e.g. diltiazem, verapamil) decline proteinuria in momentary studies but have not been revealed to prevent the advancement of DKD or CVD. Dihydropyridine CCBs (e.g. amlodipine, felodipine) as a chief agent have proved to increase proteinuria in the IDNT study. They are more potent in BP control (as demonstrated by ACCOMPLISH study) than the Non-dihydropyridine CCBs but more effective in combination with ACE inhibitors than ACE inhibitors with diuretics. Beta blockers have proven contribution for controlling comorbidities that often follow diabetes, including CAD, stroke, and CHF. In the absence of these conditions, the utility of beta blockers for BP control in diabetes is not clear .
4.5 SGLT2 inhibitors for type 2 DM
Empagliflozin has been found to reduce exacerbate DKD, where, Canagliflozin declines the albuminuria aggravation, reduction in GFR and need for renal replacement therapy. SGLT2 inhibitors are, however, not indicated for patients with reduced GFR (eGFR<60 ml/min for Dapagliflozin and eGFR<45/min for Canagliflozin and Empagliflozin) .
4.6 HbA1c control in DKD
Chronic kidney disease, ESRD and treatment with ESAs found to be beneficial for RBC turnover. Studies reveal that HbA1c levels may not be the sole predictor of glycemic control in patients with CKD or ESRD. With progressive GFR loss, typically <20 mL/min/1.73m2 or ESRD, insulin catabolism is diminished and gluconeogenic capability by the kidney is impaired. Therefore glucose-lowering therapy often requires diminution to avoid hypoglycemia .
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: Ethics approval and consent to participate
Animal and Human experiment: N/A
Human Data Submission Approval: N/A
Consent for Publication
Consent to publish Individual Person’s data: N/A
Availability of Data and Materials
Data sharing: Please contact author for data requests
The authors declare that they have no competing interests
Funding from individual/Organization: N/A
The individual contributions of authors: N/A
- Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Ann Intern Med 139 (2003):137-147.
- Viberti GC, Mogensen CE, Passa P, et al. St Vincent declaration: Guidelines for the prevention of diabetic renal failure. In Eds.: Mogensen CE. The kidney and hypertension in diabetes mellitus. Dordrecht Kluwer Academic Publishers (1994): 515-527.
- Roberto Pecoits-Filho, Hugo Abensur, Carolina CR Betonico, et al. Interactions between kidney disease and diabetes: Dangerous liaisons Diabetol Metab Syndr. Diabetol Metab Syndr 8 (2016): 50.
- Kim MK. Treatment of diabetic kidney disease: Current and future targets. Korean J Intern Med 32 (2017): 622-630.
- 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 10 (2017): 257-262.
- Allen IA. Diabetic Nephropathy and Treatment of Hypertension. In Eds.: De Groot LJ, Chrousos G, Dungan K, et al. Endotext, South Dartmouth (MA): MDText.com (2000-2013).
- Nathan DM. Long-term complications of diabetes mellitus. New Engl J Med 328 (1993): 1676-1685.
- Abdulrhman A. Prevalence of diabetic nephropathy among Type 2 diabetic patients in some of the Arab countries. Int J Health Sci (Qassim) 11 (2017): 1-4.
- Chaity AJ. Obesity blamed for alarming rise in childhood diabetes. DhakaTribune (2017).
- Star Online Report. 80 lakh Bangladesh is suffering from diabetes: State minister. The Daily Star (2016).
- Hayes L, White M, Unwin N, et al. Patterns of physical activity and relationship with risk markers for cardiovascular disease and diabetes in Indian, Pakistani, Bangladeshi and European adults in a UK Professiona population. J Public Health Med 24 (2002): 170-178.
- Abrar SMA. Diabetes management service launched in Bangladesh. Dhaka Tribune (2018).
- Tareq S. Obesity is increasing among the younger generation in Bangladesh. The Daily Star (2018).
- Ahmed ST, Rahim MA, Ali MZ, et al. Prevalence of primary renal diseases among patients on maintenance haemodialysis: A hospital based study. KYAMC Journal 2 (2012): 182-186.
- Ahmed SS, Khan MAH, Laila TR. Treatment and Prevention of Common Complications of Chronic Kidney Disease. Journal of Enam Medical College 4 (2014): 45-55.
- Position Statement American Diabetic Association. Standards of medical care in diabetes-2015. Diabetes care 38 (2015): 8-93.
- Sayama H, Muttalib MA, Islam MI, et al. Prevalence of Nephropathy with Evaluation of HbA1c Level and other Associated Risk Factors in Type 2 Diabetic Patients in a Tertiary Level Hospital. KYAMC Journal 8 (2017): 21-26.
- Laily AA, Promita D, Manisha D, et al. Superoxide dismutase 1 gene +35A>C (intron3/exon3) polymorphism in diabetic nephropathy patients among Bangladeshi population. J Mol Pathophysiol 3 (2014): 52-57.
- Zabeen B, Nahar J, Islam N, et al. Risk Factors Associated with Microalbuminuria in Children and Adolescents with Diabetes in Bangladesh. Indian Journal of Endocrinology and Metabolism 22 (2018): 85-88.
- George C, Goedecke JH, Crowther NJ, et al. The Role of Body Fat and Fat Distribution in Hypertension Risk in Urban Black South African Women. PLoS One 11 (2016): 0154894.
- Mumu SJ, Saleh F, Ara F, et al. Non-Adherence to Lifestyle Modification and its Determinants among Bangladeshi type 2 Diabetic Patients. International Journal of Epidemiology 44 (2015): 148-149.
- Shamima Akter, M Mizanur Rahman, Sarah Krull Abe, et al. Prevalence of diabetes and prediabetes and their risk factors among Bangladeshi adults: A nationwide survey. Bulletin of the World Health Organization 92 (2014): 204-213.
- Lambert P, Bingley PJ. What is Type 1 Diabetes?. Medicine 30 (2002): 1-5.
- Shariful Islam SM, Lechner A, Ferrari U, et al. Healthcare use and expenditure for diabetes in Bangladesh. BMJ Glob Health 2 (2017): 000033.
- Afsana A, Samira HH, Hasina AC, et al. Healthcare cost of type 2 diabetes mellitus in Bangladesh: A hospital-based study. International Journal of Diabetes in Developing Countries 36 (2015): 235-241.
- Sarker AR, Marufa S. Letter To The Editor Health and economic burden of diabetes in Bangladesh: Priorities for attention and control. Journal of Diabetes 9 (2017).
- Lana V, Shahnawaz A, Farzana F. Self-care practices and barriers to compliance among patients with diabetes in a community in rural Bangladesh. Int J Diabetes Dev Ctries 36 (2016): 320-326.
- Ainslie MH, Amit XG. Blood pressure targets in chronic kidney disease: Does proteinuria dictate how low we go?. CMAJ 185 (2013): 941-942.
- Eric J, David AC. Management of Hypertension in CKD: Beyond the Guidelines. Adv Chronic Kidney Dis 22 (2015): 116-122.
- Susanne B, Nosratola DV, Keith CN. What should be the blood pressure target for patients with chronic kidney disease?. Curr Opin Cardiol 28 (2013): 439-445.
- Faqah A, Jafar TH. Control of Blood Pressure in Chronic Kidney Disease: How Low to Go?. Nephron Clin Pract 119 (2011): 324-332.
- Vikram P, Adam WC, George B. Hypertension Management in Diabetic Kidney Disease Diabetes. Spectr 28 (2015): 175-180.
- Daniel EW, Mark JS. Managing Dyslipidemia in Chronic Kidney Disease. J Gen Intern Med 19 (2004): 1045-1052.
- Kalaitzidis RG, Elisaf MS. The Role of Statins in Chronic Kidney Disease. Am J Nephrol 34 (2011): 195-202.
- Sanjay K, Bharti K, Navneet A. Combination therapy in hypertension: An update. Diabetol Metab Syndr 2 (2010): 44.
- Rabi Y, Kirk NC. Inhibition of RAS in diabetic nephropathy. Int J Nephrol Renovasc Dis 8 (2015): 29-40.
- Luz LM, Adriana PG. Renin-Angiotensin-Aldosterone System Blockade in Diabetic Nephropathy. Present Evidences J Clin Med 4 (2015): 1908-1937.
- Susan S. Management of Hypertension in Diabetic Patients With Chronic Kidney Disease. Diabetes Spectrum 21 (2008): 30-36.
- Care Process Model Management of High Blood Pressure (2018).
- Daniel SH, Owen G, William TC. An Update on SGLT2 Inhibitors for the Treatment of Diabetes Mellitus. Curr Opin Endocrinol Diabetes Obes 24 (2017): 73-79.
- Sun MK, Kyeong MK, Soon KK, et al. Erythropoiesis-stimulating Agents and Anemia in Patients with Non-dialytic Chronic Kidney Disease. J Korean Med Sci 31 (2016): 55-60.
- Kawanami D, Matoba K, Takeda Y, et al. SGLT2 Inhibitors as a Therapeutic Option for Diabetic Nephropathy. Int J Mol Sci 18 (2017): 1083.
- Global Health Insights. Understanding risk factors for stroke death in Bangladesh (2017).
- Abraham G, Varughese S, Thandavan T. Chronic kidney disease hotspots in developing countries in South Asia. Clin Kidney J 9 (2016): 135-141.
- Van Huffel L, Tomson CR, Ruige J, et al. Dietary Restriction and Exercise for Diabetic Patients with Chronic Kidney Disease: A Systematic Review. PLoS One 9 (2014): 113667.
- Phipps MS, Jastreboff AM, Furie K, et al. The diagnosis and management of cerebrovascular disease in diabetes. Current Diabetes Reports 12 (2012): 314-323.