Ayurveda and Diabetic nephropathy
Dr Praveen Kumar ChoudharyAssociate ProfessorA & U Tibbia College, New Delhi
Definition
Progressive rise in urine albumin excretion (UAE) coupled with increasing BP and leading to declining GFR and CKD
1. Abnormal urine albumin excretion >30 mg/24 hours
2. Diabetic Glomerular Lesion
3. GFR ↓
American Diabetes Association (ADA) recommendations, Diabetes Care, January 2012
Appearance
Diabetic Nephropathy
Goals Early Diagnosis1. Routine screening: BP (Systolic and diastolic), Pre-
diabetics and diabetics (Morning hyperglycemia, evening normoglycaemia, PP, HBA1C), Lipid profile
2. Urine Albumin excretion (UAE), ACR Microhaemoglobinuria
3. Sensitization for further work up Treatment: 1. Diet2. Regime3. Drugs Prevention of complications
Susceptible patients/risk factors
Genetics: Pre-hypertensives, Cardiovascular disease, hyperglycaemics
Onset of diabetes – Type 2 – Mild to moderate hypertension
Persistent raise in BP – Lack of nocturnal dipping – Prior to appearance of microalbuminuria
Onset of DM – Raised UAE Inefficient control of hyperglycaemia –
continuous raised HBA1C above 8 Dyslipidaemia Associated Retinopathy and Neuropathy
Risk
Albumin excretion rate – 10mg/24 hr HBA1C - >8 Retinopathy
Chances are more over a decade
Chances are very less in absence of these factors
OTHERS Low birth weight (British med. Jour. 2004) Oral contraceptives Cardiovascular risk factors
Diagnostic protocol
Persistent Proteinuria in DM
AER > 300mg /day Type 1 : after 10 years Type 2 : At the time of diagnosis
With Hypertension Diabetic retinopathy Renal function deterioration
05/02/2023
9
SCREENING FOR NEPHROPATHYWHEN: Type 1 - annually after puberty and 5 years of DM
Type 2 - at diagnosis and then annually
WHAT: random urine ACR;
and random urine dipstick
Normal< 2.0 mg/mmol men
< 2.8 mg/mmol womenRescreen in 1 year
Microalbuminuria2.0 - 20 mg/mmol men
2.8 - 28 mg/mmol women
Macroalbuminuria> 20 mg/mmol men
> 28 mg/mmol womenDiabetic nephropathy
diagnosed
Up to 2 repeat random urine ACRs performed 1 week to 2
months apart
Suspicion of nondiabetic
renal disease?Yes
Workup or referral fornondiabetic renal
diseaseNo
Check ACR results
Only 1 abnormal ACR: Repeat screen
in 1 year
Any 2 abnormal out of 3 ACRs: Diabetic
nephropathy diagnosed
DN AND DM Type 1 : Rare before 10 years Type 2: May be in newly diagnosed
Peak incidence : 10 to 20 years, starts declining after 20 years
DM > 30 years with normoalbuminuria > Very low risk of Overt DN
ABNORMAL UAE
Normoalbuminuria <30mg/day Microalbuminuria : 30 – 300 mg/day Macroalbuminuria: >300 mg /day
Albumin Excretion
SPECIMEN COLLECTED
24hr collection (mg/24h)
Timed collection (μg/min)
First voided morning specimen
Urine Albumin concentration
(mg/l)
Urine Albumin:Creatinine
ratio* (mg/mmol)
Normoalbuminuria <30 <20 <20 <3.5 (F)<2.5 (M)
Microalbuminuria 30-300 20-200 20-200 3.5 to 35 (F) 2.5 to 25 (M)
Overt proteinuria >300 >200 >200 >35 (F)>25 (M)
Stages of Renal Involvement According to the Urinary Albumin Level
Natural history of DN
HYPERTENSION Kidney is a villain and victim More BP more rapid deterioration
Effect on glomerulus: Dilatation of afferent arteriole – increase in
intra-glomerular pressure – hyper-filtration – damage
Hypertension is most important aggravating factor for DN
RETINOPATHY
80% of Type 1 DM with RP – DN 50% of Type 2 DM with RP – DN
PROGRESSIVE DETERIORATION OF KIDNEY FUNCTION
Initially GFR is increased – hyper filtration Serum Creatinine is normal – Till overt DN in
which macroalbuminuria is present After DN – GFR starts to decrease @ 1ml/min/
month
OTHER CAUSES OF INCREASED UAE Exercise Pyrexia Infection Pyuria CCF Hyperglycaemia Hypertension Haematuria Menstruation Pregnancy
Decreased in ACE inhibitors and NSAIDS intake
PATHOGENESIS Functional changes कफजन्य Increased renal plasma flow Hyperperfusion Afferent vessel dilatation and efferent vessel
contraction (Atherosclerosis) Intraglomerular hypertension Increased glomerular hydrostatic pressure Hyperfiltration स्रोतोदुष्टि� प्रकार – संग एवं विवमाग�गमन
PATHOPHYSIOLOGICAL STAGESStage increased GFR Increased filtration pressure as result of
increased intraglolerular pressure Increased UOP and low s.cra, ureaPathological change but no clinically evident disease
Proteinuria Mesangial expansion and increased matrix change in pore sizes leading to leakage of proteinStarling Foces: increased plasma flow, increased glomerular capillary hydrostatic pressure
Microhematuria Ischemic injury of tubules due to constriction and stenosis of efferent arteriole
Decreased GFR Atrophy and death of nephrons
CKD and ESKD Loss of compensation mechanisms of nephrons
METABOLIC CHANGES AGEs Advanced glycation end products Pro fibrogenic and pro inflammatory cytokines
(transforming growth factor – beta TGF Beta) Protein kinase C Polyol pathway – Sorbitol aldose reductase
pathway – sorbitol cannot cross cell membrane – accumulation – osmotic stress on cells – insulin entry restricted - hyperinsulinaemia
ROS (Reactive oxygen species) by hypertension Endothelial dysfunction – vascular damage Angiotensin II सभी inflammatory changes वि�त्तजन्य होते हैं
INTRAGLOMERULAR MESANGIAL CELLS: AXIS HOLDING THE EDOTHELIAL AND EPITHELIAL CELLS, CONSTRICTION AND DILATATION LEADING TO FENESTRATION - CHANGE THE FILTRATION
Atherosclerosis of efferent arteriole
Increased HTN in glomerulus
PATHOGENESISROS, hyperinsulinaemia, HTN
AGEs,
Mesangial matrix expansion
Fibrin collagens deposition in GBM
Influence of cytokines C and mesangial expansion
STRUCTURAL CHANGES Mesangial expansion Renal hypertrophy Thickening of GBM (glomerular basement
membrane) Glomerulosclerosis (Kimmelsteil Wilson
nodules) Glomerulus में होने वाले सभी विवकार जिजस्मे वृक्क ऊतक का
क्षय होता है वह वातजन्य हैं
Endothelium Fenestration (60 – 100 nm) Glycocalyx (network of proteoglycans with
neg. charge Endothelial cell injury:
Increased permeability Impaired nitric oxide production Up-regulation of adhesion molecules
Defects of the glycocalyx: Decrease of negativity associated with
increased albumin clearance
GBM It is 300 – 400 nm thick gel like structure and 90% water Critical membrane for filtration barrier The narrow gaps 30 – 40 nm permeable for water and solutes It contains cytoskeleton The apical membrane contains podocalyxin, podoplanin and
podoendin which are responable of the negative charge It contains: collagen IV, heparan sulfate proteoglucans, laminin,
nidogen Podocytopenia:
Loss of negative charge (loss of podocalyxin) Change in the pores size due to damage in the diagram integrity
Causes of reduced number of podocytes: Podocyte detacement Podocyte apoptosis Inability to proliferate and restore podocyte number
Silt diaphragm abnormalities: Abnormalities of nephrin Foot process widening and effacement
GBM Heparan sulfate reduction correlates with
degree of proteinuria Its degradation is mediated by heparanase This theory approved in Type 1 and 2 DM but in
advanced human cases but not in the early stage where there is also proteinuria.
MW: < 40 kDa free to pass
> 100 kDa totally restricted
Albumin mw 69 kDa
Microalbuminuria:Change in electric charge
Macroalbuminuria: Change in electric chargeIncreased pores size
MECHANISMS OF PROTEINURIA Site of injury
Glomerular hemodynamics Glomerular hyperfiltration
Afferent arteriole vasodilatation Efferent arteriole vasoconstriction glomerular capillary pressure
glomerular endothelial cell
Endothelial cell injury Diminished endothelial glycocalyxAltered VEGF signaling
Hyperglycemia< AGE, ROS Endothelial cell injury or enzymatic cleavagePodocyte injury or loss
GBM Irregular thickeningDecreased negative charge
production and/or degradation of extracellular matrix proteins production and/or degradation of HSPG
podocyte
proximal tubule
PodocytopeniaLoss of slit diaphragm integrity Foot process widening and effacement
Loss negative charge
Decrease protein reabsorption
Detachment, apoptosis, lack of proliferation Decrease or changes in subcellular localization of nephrin Disrupted actin cytoskeletonLoss of slit diaphragm integrityImpaired podocyte GBM interaction Podocalyxin
Tubular injury and interstitial fibrosis
AGE, advanced glycosylation end products; HSPG, heparan sulfate proteoglycan; ROS, reactive oxygen species; VEGF, vascular endothelial growth factor.
PATHOLOGICAL CLASSIFICATION OF DNClass Description Inclusion Criteria
I Mild or nonspecific LM changes and EM-proven GBM thickening
Biopsy does not meet any of the criteria mentioned below for class II, III, or IVGBM > 395 nm in female and >430 nm in male individuals 9 years of age and older, Podocyte hypertrophy
IIaMild mesangial expansion
Biopsy does not meet criteria for class III or IVMild mesangial expansion in >25% of the observed mesangium
IIb Severe mesangial expansion
Biopsy does not meet criteria for class III or IVSevere mesangial expansion in >25% of the observed mesangium
III Nodular sclerosis (Kimmelstiel–Wilson lesion)
Biopsy does not meet criteria for class IV
At least one convincing Kimmelstiel–Wilson lesion
IV Advanced diabetic glomerulosclerosis
Global glomerular sclerosis in >50% of glomeruliLesions from classes I through III
STAGES OF DIABETIC NEPHROPATHY Stage 1: Glomerular hypertension and
hyperfiltration, Normoalbuminuria, Raised GFR and normal serum creatinine
Stage 2: Silent phase (No clinical menifestation, only structural changes detected by biopsy), Normoalbuminuria
Stage 3: Micro-albuminuria, BP may be raised, Normal serum creatinine
Stage 4: Macro-albuminuria, Hypertension, serum creatinine may be raised or normal
Stage 5: Above and increasing serum creatine, End stage kidney disease
TREATMENT GOAL Screening and prevention of type 2 DM Screening and prevention of DN Screening and prevention of
Microalbuminuria to DN Management of Hypertension Management of dyslipidaemia
PREVENTIVE MEASURES Screening of diabetic nephropathy Prevention of diabetic nephropathy
Screening:1. Blood pressure : <130/802. UAE: Type 2 – Annual after diagnosis, type 1
– annual 5 year post diagnosis (normal range - <30mg/day, <20µg/min, < 30 µg/mg creatinine)
3. Lipid profile – Annual (LDL <100mg/dl, HDL >40mg/dl, TG <150mg/dl)
TABLE 2. RECOMMENDATIONS FOR THE COMPREHENSIVE MANAGEMENT OF T2DM PATIENTS WITH CKDFactor Recommendations Lifestyle factors diet, exercise, smoking,and alcohol intake
Blood glucose Treatment goal: HbA1c <6.5%Preprandial plasma glucose 90-130 mg/dlPostprandial plasma glucose <180 mg/dl
Blood pressure Goal ≤130/80 mm HgUse maximal tolerated dose of ACE inhibitor or ARB before adding a second agent
Cholesterol Goal <4.0 mmol/L for total cholesterol and <2.0 mmol/L for LDL-C Consider use of a statin irrespective of baseline lipid values for the secondary prevention of cardiovascular disease
Platelets Consider use of low dose aspirin for the secondary prevention of cardiovascular disease
Monitoring Annual monitoring of eGFR and ACR
RECOMMENDED TREATMENT Target to keep HBA1C <7% BP < 130/80 Lipid at normal levels Supplements: Stevia rebaudiana : As a sweetner? करेला (Bitter melon - Momordica charantia), सदाबहार
(Vinca rosea/Catharanthus), नीम�त्र (Azadirachta indica), wheetgrass juice /decoction
Juice of root of black pig weed (Trianthema decandra), juice of root of Indian Banyan (Ficus bengalensis) and juice of leaves of Vasa (Adhatoda zeylanica) – to manage DM
मेथी (Fenugreek) and लशुन (garlic) – lipid as well as sugar levels
DIET Oatmeal (यव दलिलया), broccoli (फूलगोभी), green beans (हरी
सेम), strawberries (झडबेर), salmon (मत्स्य), lean meats (अल्� वसा मांस) and cinnamon (दालचीनी)
Avoid high sugar foods and limit protein intake Too much protein intake will increase the kidney burden
and aggravate the kidney damage Limit the salt intake, because too much salt intake will
aggravate hypertension Avoid high potassium content foods such as oranges
and banana Herbal tea - can help repairing kidney damage like
dandelion root tea (ककरौंधा – Taraxicum officinale), nettle leaf tea (विबचू्छ बूटी – Urtica dioica), corn silk tea (मकइ के भुटे्ट के बाल) - Natural diuretics which can remove extra wastes
Drugs
Oral Hypoglycaemics: मेषश्रृंगी (Gymnema sylvestre): Lower blood sugar,
decrease desire of sweet food, maintain lipid levels.
विवजयसार (Pterocarpus marsupium): Hypoglycaemic effect as well as मेदोहर
हरिरद्रा (Turmeric): Hypoglycaemic, anti-inflammatory, Free radical scavenger
दारुहरिरद्रा (Berbaris aristata): Stimulates pancreatic function
मेलिथका (Fenugreek): Hypoglycaemic जम्बू (Syzygium cumini/Eugenia jambolana):
Hypoglycaemic, hypolipidaemic
CONTD आम्र बीज (seeds of Mangifera indica):
Hypoglycaemic , hypolipidaemic नागजिजह्वा (Enicostema littorale): Potent
hypoglycaemic उदुम्बर (Ficus glomerata): Hypoglycaemic विनम्ब लिचरायता
DRUGS FOR PROTEINURIA / RENAL FUNCTION
�ुनन�वा (Boerhavia diffusa): Helps in reducing urea and creatinine as well as renal tissue rejuvenator, hypoglycaemic
गोकु्षर (Tribulus terrestris): Diuretic, renal protector
भूष्टिम आमलकी (Phyllanthus niruri): Anti oxidant and anti infective
मंजिजष्ठा (Rubia cordifolia): Blood detoxifier कासनी (Cichorium intybus): Lowers creatinine
and urea, protects kidney tissue
CONT रुमी मस्तगी (Pistacia lentiscus): Liver and kidney
protector लिशग्रु (Moringa oleifera): Urinary antiseptic
HYPERTENSION अजु�न (Terminalia arjuna) तगर (Valeriana welchii) ब्राह्मी (Bacopa monnieri) स��गन्धा (Rauwolfia serpentina) शंख�ुष्�ी (Convolvulus pluricaulis)
CONTD Diet - 20% carbohydrate, 10 to 15 % protein
and 60-65% vegetables Celery (Ajwain) - lowers pressure by reducing
blood concentration of stress hormones Indian gooseberry (Amla) is effective to lower
it Watermelon - helps in dilating the blood
vessels
योगाभ्यास
सुखासन अथवा वज्रासन में रेचक �ूरक प्राणायाम ध्यान विUया ताडासन, �वनमुक्तासन, भुजंगासन आदिद जलनेवित, शोधन बस्तिस्त वातप्रको� की अवस्था में अनुवासन बस्तिस्त का प्रयोग (गोकु्षरादिद
तैल) से
Thank you