Management In Early Onset Of Diabetes Nephropathy In ... · related to altered blood pressure profiles. Youths with type 1 diabetes showed significantly increased nocturnal blood

Journal of Ayurveda Official publication of National Institute of Ayurveda, Jaipur, Rajasthan134

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ORIGINAL REASEARCH ARTICLE - LITERARY REVIEWS

Ayurveda Management In Early Onset Of Diabetes Nephropathy In Children And Adolescent

*Dr. Rakesh Kumar Nagar, **Dr. Trupti Motghare, *** Dr. Kamla R Nagar

*Assistant Professor, Department of Kaumarbhritya, NIA Jaipur, **Ayurveda Medical Officer, Govt. of Maharastra, *** Professor Dept. of Dravya Guna Vigyana, Faculty of Ayurveda Science, Jyoti Vidyapeeth Women’s University Jaipur, Rajasthan

ABSTRACTDiabetic nephropathy (DN) is characterized by persistent proteinuria, decline in renal glomerular function,

hypertension, and progression to end stage renal disease. Diabetic nephropathy (DN) develops in 15–20% of subjects with Type1 Diabetes Mellitus and in similar or higher percentage of Type2 Diabetes Mellitus patients, causing increased morbidity and premature mortality. Although overt Diabetic Nephropathy or kidney failure caused by either type of diabetes are very uncommon during childhood or adolescence, diabetic kidney disease in susceptible patients almost certainly begins soon after disease onset and may accelerate during adolescence, leading to micro albuminuria or incipient Diabetic Nephropathy.Therefore, all diabetics warrant ongoing assessment of kidney function and screening for the earliest manifestations of renal injury and Pediatric health care professionals ought to understand about risk factors, strategy for prevention, and treatment of early Diabetic Nephropathy.This reviewconsiders risk factors for its development, screening for early manifestations, prevention and treatment in the form of pathya–apathya and oral intervention of anti diabetic and Reno protective Ayurveda drug (Gokshur, Punarnava, Mahanimba, Shilajit Kakmachi,) by its diuretic, antihypertensive, immunomodulatary, hypoglycemic and hypo-lipidemic activity, helpful in treating diabetes mellitus and its complication (diabetic nephropathy) and progression in early stage.

Keywords : Diabetic nephropathy, diabetes mellitus proteinuria, hypertension gokshur, punarnava

Address of Correspondence: Dr. Rakesh Kumar NagarAssistant Professor,Department of Kaumarbhritya, NIA, Jaipur

Email ID : [email protected]

Contact No : 9414062099

How to Site the Article : Nagar RK, Motghare T, Nagar KR, Ayurveda Management In Early Onset Of Diabetes Nephropathy In Children And Adolescent, JOA XIII-4, 2019; 134 - 139

Introduction :

JOAjournalofayurveda.in ISSN No:2321-0435

Diabetes mellitus is a complex disorder that characterized by hyperglycemia resulting from malfunction in insulin secretion and/or insulin action both causing by impaired metabolism of glucose, lipids and protein.[1] The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction and failure of various organs.[2]


Nagar RK, Motghare T, Nagar KR, Ayurveda Management In Early Onset Of Diabetes Nephropathy In Children And Adolescent, JOA XIII-4, 2019; 134 - 139

Over the last century human life style and food habits have drastically changed which lead to various chronic diseases. Around 200 million people around the world are being diagnosed with diabetes. According to WHO statistics diabetes is the sixth leading cause of disease-related death in the world.

On long standing it leads to many micro and macro vascular complications. The microvascular complications of diabetes include nephropathy, retinopathy, and neuropathy. In type-1 diabetes the first signs of these complications may develop during adolescence, particularly if insulin is insufficient in the body. Diabetic nephropathy (DN) develops in 15–20% of subjects with Type1 Diabetes Mellitus and in similar or higher percentage of Type2 Diabetes Mellitus patients, causing increased morbidity and premature mortality. Although overt Diabetic Nephropathy or kidney failure caused by either type of diabetes are very uncommon during childhood or adolescence, diabetic kidney disease in susceptible patients almost certainly begins soon after disease onset and may accelerate during adolescence, leading to micro albuminuria or incipientDiabetic Nephropathy.

Diabetic nephropathy (DN) is characterized by persistent proteinuria, decline in renal glomerular function, hypertension, and progression to end stage renal disease. Diabetic nephropathy accounts for approximately 14% of all deaths in diabetic patients, and some 25% of those developing diabetes under the age of 30 die from renal failure due to diabetic nephropathy.

Diabetic complications

Diabetic nephropathy is a specific form of renal complication of Diabetes Mellitus (DM), a major cause of death and disability among diabetics. It is observed that even patients having well-controlled diabetes suffer from diabetic nephropathy.Diabetes mellitus also causes "microvascular" complications leading to the small blood vessels damage.

Micro vascular Complications-

a) Diabetic Retinopathy

b) Diabetic Nephropathy

c) Diabetic Neuropathy

PathogenesisDiabetic nephropathy presents with

ê

hyper filtration firstê

followed by renal hypertrophyê

microalbuminuria, and hypertension (HTN)ê

later proteinuria and ESRD

In Ayurveda, direct nomenclature of DN is not found. Regarding the manifestation of Upadrava (complications) in Madhumeha patients it’s stated as, the Dushita Medas (improperly formed fat tissue) along with Kapha, does Dooshana of Kleda and gets transformed to Mootra (urine). This cause obstruction at the Mootravaha Srotas and transforms Madhumeha into incurable form leading to manifestations of Upadrava

Risk factors for development of Diabetic Nephropathy

A number of risk factors may influence the onset or progression of Diabetic Nephropathy.

¾ Duration of diabetes

¾ Metabolic control

¾ Puberty

¾ Hypertension

¾ Hyperlipidemia

¾ Genetic influence

Duration of diabetes

Resident and nonresident renal cells are stimulated by hyperglycemia in producing humoral mediators, cytokines, and growth factors that are responsible for structural alterations such as increased deposition of ECM and functional alterations such as increased permeability of glomerular basement membrane or shear stress. These alterations contribute to diabetic nephropathy.



Puberty

Puberty enhances the development of micro vascular diseases. There is a significance of pubertal association of duration of diabetes with kidney volume and the prevalence of micro-albuminuria. However, nephromegaly found in the prepubertal age indicating the importance of prepubertal course of diabetes for the development of diabetic nephropathy during and after puberty.

Hypertension

There is a link between the quality of metabolic control and altered blood pressure regulation and showed that age, diabetes duration, sex, BMI, A1C, and insulin dose were related to altered blood pressure profiles. Youths with type 1 diabetes showed significantly increased nocturnal blood pressure (systolic blood pressure +0.51, diastolic blood pressure +0.58, mean arterial pressure +0.80), which primarily contributes to micro albuminuria.High normal or high blood pressure in adolescence leads to development of incidence of micro albuminuria and predispose to later development of sever form of diabetic nephropathy.

Geneticinfluence

The likewhood of development of DN is increased in patients with diabetic siblings or parents who have DN. Genotype of angiotensin converting enzyme gene is associated with both increased risk of development of DN and reduced responsiveness to ACE inhibitors.

Aims and objectives

1. Early screening of various parameters and risk factors for the earliest manifestations of renal injury and its progression.

2. To rule out the efficacy of antidiabetic and Renoprotective drug as an alternative and supportive treatment in preventing the development and its progression of diabetic nephropathy in adolescence.

Material and Methods

Various ayurveda classics and studies published in

journals related to effect of study drugs on diabetes mellitus and its complication are reviewed and analyzedTherapeutic Strategies

¾ Early screening of various parameters responsible for progression of DN

¾ Glycemic control

¾ Reduction of blood hypertension,

¾ Lipid control

¾ Dietary management in early stage

Early screening

• Albumin excretion rate in upper normal range between 20-200 microgram/ min.

• AER determination should be started in 6-12 monthly interval in 11-12 years child who show puberty and with diabetic duration 4-5 years.

• BP Should be monitored for the early detection altered BP with Microalbuminiuria.

Oral intervention

Punarnava

The diabetic hyperglycemia induces elevation of the serum levels of urea and decrease protein level which were considered as significant markers of renal function.21 The diabetic hyperglycemia induces elevation of the plasma levels of urea, uric acid and creatinine which are significant markers of renal dysfunction and reflecting a decline in the glomerular filtration rate were significantly recovered by Boerhaa via diffusa.The Boerhaa via diffusa increased the protein level in blood Histopathological studies reinforce the healing of pancreas, by Boerhaa via diffusa aqueous extract, as a possible mechanism of their antidiabetic activity.[3] Ruksha quality of Punarnava and honey may help to reduce the Kleda. Punarnava help in reduction of Bahudrava Shlesma and in turn reduction of vitiated Meda and Kleda.[4]

When compared to glibenclamide (anti-diabetic drug), the aqueous solution of Punarnava leaf extract is shown more prominent result. It act as a rejuvenator and can be used in relieving impaired urinary condition. They



are very useful in the reduction of excess body fluids, congestion and edema due to excess Kapha.

Gokshur

The diuretic action of T. terrestrismakes it useful as an anti-hypertensive agent.[5] The diuretic properties of T. terrestrisare due to large quantities of nitrates and essential oil present in its fruits and seeds. The diuretic activity can also be attributed to the presence of potassium salts in high concentration.Saponin from T. terrestrispossess hypoglycemic properties[6] T. terrestris significantly reduced the level of serum glucose, serum triglyceride, and serum cholesterol, while serum superoxide dismutase (SOD) activity was found to be increased in alloxan-induced diabetic mice.It was found that dietary intake of the herb significantly lowered the serum lipid profile, decreased endothelial cellular surface damage as well as ruptures, and partially repaired the endothelial dysfunction resulting from hyperlipidemia[7]. Gokshuradi Guggulu (a combined Ayurvedic preparation) is a well-known and commonly used medicine in diseases of Mutravaha Srotas. It is specially indicated in Prameha, Mutrakriccha and Mutraghata along with other indications of Mutra and Shukravaha Srotasa. [8] Gokshura, the main ingredient, is well known for its Rasayana effect, especially on Mutravaha Srotas. According to the available literature on TT, the plant could have a potential as a herbal medicine for effective blood pressure control due to its diuretic activity (potassium sparing), anti hyperlipidemic activity, and cardioprotective activity.

Solanum Nigrum

The preliminary phytochemical screening of aqueous extract of Solanumnigrum proved the presence of alkaloids, which has antidiabetic effects by possibly stimulating insulin release from pancreatic beta cells. The efficacy of Solanumnigrum on antihyperlipidemic activity due to the presence of glycoprotein, which increases the activity of antioxidant enzymes. The reason for the hypocholesterolemic effect is through phospholigation of cAMP-dependent protein kinase (PKA), which is activated by the Solanumnigrum glycoprotein. Solanum

nigrum administration can improve lipid profile and decrease blood glucose levels, Ca/Mg ratio, and vascular reactivity to vasoconstrictor agents in diabetic animals. It can also decrease vessel atherosclerosis and prevent diabetic vessel complications.

Mahanimba (Melia azedarach)

Nephroprotective activity –Ethnolic extract of Melia azedarach has significantly decreased the concentration of urea and creatinine in Acetaminophen induced nephrotoxicity.[9]

Antihyperglycemic activity – The ethanolic extract of leaves of Melia azedarach in alloxan induced diabetic rat shows marked decrease in the blood glucose level , shows significant reduction in blood glucose level in glucose tolerance test.[10]

Andrographis paniculata

Andrographolide appears to reduce plasma glucose concentration dose-dependently in streptozotocin-induced diabetic and normal rats, with the potential effect observed in normal rats rather than in diabetic (Yu rats BC, Hung CR 2003). An aqueous extract (50 mg/kg body weight) administered to streptozotocin-diabetic rats resulted in a 52.9% reduction in blood glucose levels. Dry powder of the plant material significantly decreased blood glucose levels by 61.8% at a lower dose of 6.25 mg/kg body weight (Husen R2004;)

Shilajatu

The active principle in Shilajatu is fulvic acid. Fulvic acid significantly increased superoxide dismutase activity. Experimental studies showed that fulvic acids diminished the development and progression of diabetes, and assisted in the treatment. (Bhattacharya SK1995;9(1):41–4.)

Hyperglycemia is the principal factor responsible for the structural alterations at the renal level glycemic control remains the main target for therapy in patients with potential development of diabetic nephropathy. Intensive blood glucose control is the best approach in reducing the risk for micro vascular complications. In addition, early treatment of blood glucose in young people with diabetes



has a dramatic effect on the survival because there is an increased life expectancy.

Discussion

Hyperglycemia induces renal damage directly or through hemodynamic modifications, responsible for hemodynamic alterations such as glomerular hyperfiltration, shear stress, and microalbuminuria. These alterations induce an abnormal activation of protein kinase C (PKC) inducing meningeal expansion and glomerular basement membrane thickening. Because hyperglycemia is the principal factor responsible for structural alterations at the renal level, glycemic control remains the main target of the therapy. Study shows clear link between the quality of metabolic control and altered blood pressure regulation and showed that age, diabetes duration, were related to altered blood pressure profiles which primarily contributes to microalbuminuria

Early screening (microalbuminuria, serum creatinine, GFR, blood pressure) and close monitering with onset of DM in adoloscence age is effective in preventing its complication (DN) in later age.

The study drugs T. terrestrisand B diffusa act as ACE Inhibitor, anti hypertensive agent by its diuretic property, prevent and treat diabetic nephropathy and its progression.

Study drug posses hypoglycemic and hypolipidemic activity, decreases endothelial cellular surface damage (T. terristeris), alter the erythrocyte membrane composition (Punarnava), prevent diabetic vessel complications (Solanum nigrum), decreased the concentration of urea and creatinine (Mananimba), reduce plasma glucose concentration (Andrographis paniculata), effective in reducing microal buminuria (Gokshura-Punarnava basti ) in DM as compared to enalapril.(ACE inhibitor)

Shilajatu, Punarnava, are drugs said as Naimittika Rasayanas beneficial in Prameha, Shotha, and in renal disorders. Hence, act as an adjuvant to the specific Vyadhihara Chikitsa prescribed for the disease and enhances their effect.

Conclusion

Considering all ayurveda classics and various research works analyzed in present study suggest that combination of early screening of risk factors and oral intervention of anti-hypertensive, anti-hyperglycemic, renoprotective,effective in reducing microalbuminuria along with shodhan and rasayan property present with in study drugs (Gokshur, Punarnava, Mahanimb, Shilajatu, Kakmachi,) found effective to stabilize the risk factors of DN like blood glucose levels, HTN and effective enough to prevent the disease from further progression.

1. Babu V, Gangagadevi T, Subramaniam A. 2003. Diabetes induced by STZ in rats. Ind J of Pharmacol., 35: 290-96.

2. Bajpay A, editor. 1993. Ecological Studies of Boerhaavia verticillata poir with special reference to phytochemical and therapeutic importance. Ph.D. Thesis, Banaras Hindu University, Varanasi, India.

3. Mrs.U.Kanagavalli et al Anti-Diabetic Activity of Boerhaavia Diffusa Against Alloxan Induced Diabetic Rats. International Journal Of Pharma And Bio Sciences Issn0975-6299

4. Rajkala S. Ramteke et alClinical efficacy of Gokshura-Punarnava Basti in the management of microalbuminuria in diabetes mellitus. Ayu 2012 oct-dec; 33(4)537-541

5. Saurabh Chhatre et al Phytopharmacological overview of Tribulus terrestris Medknow Publications

6. Li M, Qu W, Wang Y, Wan H, Tian C. Hypoglycemic effect of saponin from Tribulus terrestris. Zhong Yao Cai. 2002;25:420–2.

7. Tuncer MA, Yaymaci B,et al. Influence of Tribulus terrestris extract on lipid profile and endothelial structure in developing atherosclerotic lesions in the aorta of rabbits on a high-cholesterol diet. Acta Histochem. 2009;111:488–500.

8. Bhatta harishankara., editor. Shri Sarangadharacharya, Sarangdhara Samhita (gujarati bhasantara sahita), Madhyamakhanda, Adhyaya. 2nd ed. Vol. 7. Mumbai: Pandit Narayan Mulaji Sanskrit pustakalaya; 1928. pp. 85–88.

9. V.Srinivasan, Ethanolic extract of Melia Azadirachta against Acetaminophen induced Nephrotoxicity,International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.6, No.1, pp 70-79, Jan-March 2014

10. Prashant Kumaret alAntihyperglycemic Effect of the Leaves Of Melia Azedarach Onalloxan Induced Diabetic Rats, International Journal Of Pharma Professional’s Research Research Article Volume-5, Issue-4, Oct-2014 1121

References



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Management In Early Onset Of Diabetes Nephropathy In ... · related to altered blood pressure profiles. Youths with type 1 diabetes showed significantly increased nocturnal blood