HYPERTENSION IN CHILDREN (3) FINAL DOCUMENT-2-1.pptx

Hypertension in children

1. HYPERTENSION IN CHILDREN PRESENTED BY DR THIPPANI NARESH PG-1 ST YEAR DEPARTMENT OF PAEDIATRICS

2. INTRODUCTION Hypertension is an abnormally high blood pressure especially arterial blood pressure. Blood pressure is the force exerted by the blood against the walls of blood vessels. SBP or DBP values >95PERCENTILE or >=130/80 mm hg for adolescents >13 yr old age should be REPEATED ON ATLEAST 2 0r MORE OCCASION is confirmed the diagnosis of HYPERTENSION

3. Standardized BP recording is essential in children; it should be taken in a relaxed state to avoid stress-induced elevations and white coat hypertension, preferably using a Mercury sphygmomanometer on the right arm at heart level with appropriate cuff size. Measurement of blood pressure

4. MEASUREMENT OF BLOOD PRESSURE Regulation of normal blood pressure is carried out by; BLOOD PRESSURE = CARDIAC OUTPUT * SYSTEMIC VASCULAR RESISTANCE SYSTEMIC VASCULAR RESISTANCE is an index of arteriolar compliance Or constriction throught the body it is the resistance that left ventricle must overcome to pump blood through the systemic circulation . CARDIAC OUTPUT is an amount of blood pump out by the heart /min.

5. Cardiac output CARDIAC OUTPUT = HEART RATE * STROKE VOLUME HEART RATE is the number of contraction of the heart /min . STROKE VOLUME is the volume of blood pumped from the left ventricle per beat.

6. • Severe hypertension is usually secondary to an underlying cause; essential hypertension is increasingly detected in OBESE CHILDREN • All children >3-year-old who are seen in a medical setting should have their blood pressure measured • The preferred method of measurement is AUSCULTATION • Correct measurement by RIGHT ARM AT HEART LEVEL WITH APPROPRIATE CUFF SIZE . • Measures obtained by oscillometry that exceed the 90th percentile should be verified on auscultation MEASUREMENT OF BLOOD PRESSURE

7. AMBULATORY BLOOD PRESSURE MONITORING ABPM is TOOL to assess paediatric hypertension. The patient wears a device that records BP every 20- 30 minutes throughout a 24- hour period, during usual daily activities, including sleep. This monitoring allows calculation of the mean daytime BP, sleep BP, and mean BP over 24 hours. It minimizes the white-coat effect , provides accurate readings through multiple measurements,and evaluates circadian BP profiles effectively.

8. STAGING OF PAEDIATRIC HYPERTENSION [ aap ] DEFINATIONS NORMAL BLOOD PRESSURE BP <90 percentile for age , sex, height OR SBP/DBP <120/<80 mm hg for adolescent >=13 YR ELEVATED BP BP >=90 percentile AND <95 percentile OR >120-129/<80 mm hg for adolescents >13yr HYPERTENSION BP >95th percentile or ≥130/80 mm Hg for adolescents ≥13 years old. STAGE 1 HYPERTENSION : BP >95th percentile -up to the 95th percentile + 11 mm Hg or 130- 139/80- 89 mm Hg for adolescents ≥13 year. STAGE 2 HYPERTENSION : BP ≥95th percentile + 12 mm Hg or >140/90 mm Hg for adolescents ≥13 years of age

9. WHITE COAT HYPERTENSION ELEVATED OFFICE BP but NORMAL AMBULATORY BP May be incraesd risk of developing to sustained hypertension MASKED HYPERTENSION NORMAL OFFICE BP but ELEVATED AMBULATORY BP HYPERTENSIVE URGENCY RAISED BP WITHOUT END ORGAN DAMAGE or SYMPTOMS, such as headache, nausea, blurred vision. HYPERTENSIVE EMERGENCY RAISED BP elong with presence of END ORGAN DAMAGE, such as ENCEPHALOPATHY,SEIZURES,CONGESTIVE HEART FAILURE, ACUTE KIDNEY INJURY,PAPIL EDEMA or PULMONARY EDEMA.

10. SIMPLIFIED TABLE FOR SCREENING BP VALUES MALE FEMALE AGE[year] SYSTOLIC DIASTOLIC SYSTOLIC DIASTOLIC 1 98 52 98 54 2 100 55 101 58 3 101 58 102 60 4 102 60 103 62 5 103 63 104 64 6 105 66 105 67 7 106 68 106 68 8 107 69 107 69 9 107 70 108 71 10 108 72 109 72 11 110 74 111 74 12 113 75 114 75 >=13 120 80 120 80

11. Acute hypertension is linked to conditions such as GN, HUS, HEAD INJURY, GBS, and SEVERE BURNS, while neonatal RENAL ARTERIAL OCLUSION can result from umbilical artery catheterization. Persistent hypertension in children often results from RENAL PARENCHYMAL DISEASE, RENOVASCULAR LESIONS, CGN, and various nephropathies like those seen in SLE and Henoch- Schönlein syndrome. ETIOLOGY

12. ETIOLOGY Endocrine causes TAKAYASU DISEASE or RENAL ARTERY STENOSIS, HYPERTENSION IN INFANCY because of COARCTATION OF AORTA .

13. CAUSES OF PERSISTANT HYPERTENSION IN CHILDREN Renal parenchymal disease Chronic glomerulonephritis, reflux nephropathy, obstructive uropathy Polycystic kidney disease, renal dysplasia, segmental renal hypoplasia Renovascular disease Idiopathic aortoarteritis (Takayasu disease) Renal artery stenosis, renal artery thrombosis Renal tumors Wilms tumor , nephroblastoma, hemangiopericytom Cardiovascular disease Coarctation of aorta Endocrine disease Pheochromocytoma, neuroblastoma, primary hyperaldosteronism Cushing syndrome, congenital adrenal hyperplasia Primary (essential) hypertension

14. Chidren with hypertension are Asymptomatic. Headache, Abdominal pain, Nausea, Vomiting and Weight loss . In the newborn period, hypertension manifests with features suggesting sepsis, intracranial hemorrhage or cardiorespiratory distress. Accurate blood pressure recording must be carried out in all sick neonates. Clinical features

15. HTN-DX

16. Investigations for hypertension depends on its PERSISTANCY AND SEVERITY. High normal BP values are common in obese and adolescent children, often with a family history of essential hypertension. Initial evaluations include chest X-ray, urinalysis, and kidney/urinary tract ultrasound. Persistent hypertension -ECG, echocardiography, and retinal examination are crucial. For suspected high MNERALOCORTICOID STATES or RENOPVASCULAR STATES. PLASMA RENIN ACTIVITY Diagnostic evaluation

17. • Urinalysis: Cells, protein, 24-hour protein excretion • Urine culture • Blood urea, creatinine, electrolytes, bicarbonate, uric acid, calcium • Fasting cholesterol, triglycerides • Chest X-ray film • Electrocardiogram, echocardiogram, fundus examination • Abdominal ultrasound ,99m Tc –DMSA. • 99mTc-DMSA scan . Preliminary investigation in sustained hypertension

18. ADDITIONAL INVE IN CHILDREN WITH SUSTAINED HTN GLOMERULONEPHRITIS REFLUX NEPHROPATHY RENOVASCULAR DISEASE PHEOCHROMOCYTOMA OTHER ENDOCRINE CAUSES COARCTATION OF AORTA SERUM C3,C4,ASO AUTOANTIBODIES,[ ANA,anti-dsDNA,ANCA ] MCU,DMSA scan,INTRAVENOUS UROGRAM DOPPLER ULTRA SOUND,CAPTOPRIL PRIMED ISOTOPE SCAN[DTPA/MAG-3] RENAL ANGIOGRAPHY OR DSA RENIN SAMPLING FROM RENAL VEINS AND IVC URINE AND PLASMA CATECHOLAMINE PLASMA CALCITONIN,PARATHORMONE, MIBG SCAN[I123 METAIODOBENZYLGUANIDINE ],CT,MRI. URINE STEROID SAMPLE PLASMA RENIN,ALDOSTERONE,CORTISOL DEXAMETHASONE AND ACTH TEST ECHOCARDIOGRAM,ANGIOGRAPHY

19. TREATMENT LIFE STYLE MODIFICATIONS –DIETARY CHANGES , REGULAR EXERCISE WEIGHT LOSS DASH DIET-- low Na intake and increasing K- , Ca- , and Mg- containing foods, such as 6-8 servings of whole grains, 4-5 servings of fruits, and 4-5 servings of vegetables per day and low- fat dairy foods. For adults, the standard DASH diet contains 2,300 mg of Na (also recommended by the AHA) and the low- sodium DASH diet recommends up to 1,500 mg of sodium per day. In addition, regular aerobic physical activity for at least 30- 60 minutes on most days along with a reduction of sedentary activities to <2 hr /day.

20. Clinical treAtment These are following class of drugs useful for the treatment of hypertension; ANTI HYPERTENSIVE DRUG THERAPY 1.ANGIOTENSIN CONVERTING ENZYME INHIBITORS[ACEI] 2. ANGIOTENSIN RECEPTOR BLOCKERS 3. DIURETICS 4. CALICIUM CHANNEL BLOCKERS 5. BETA-BLOCKERS 6.ALPHA BLOKERS 7.CENTRALLY ACTING AGENTS 8.DIRECT VASODILATORS

21. ANGIOTENSIN CONVERTING ENZYME INHIBITORS These agents control of BP by blocking the renin angiotensin system[RAS] . They do this by preventing conversion of angiotensin -1 to blood pressure raising hormone angiotensin-11 They also increase availability of the vasodilator bradykinin by blocking its breakdown.

22. ACEI USES - heart failure ,post-myocardial infection, left ventricular systolic dysfunction ,and diabetic and non diabetic chronic kidney disease. SIDE EFFECTS – They are well tolerated . dry cough. Angioedema These drugs can increase serum creatinine by 30% due to reduce pressure within the renal glomerulus which is not harmful . These dugs not used in pregnancy . Drugs ; RAMIPRIL CAPTOPRIL ENALAPRIL PERINDOPRIL

23. ANGIOTENSIN RECEPTOR BLOCKERS DRUGS— LOSARTAN VALSARTAN TELMISARTAN CANDESARTAN ARBS Antagonises the renin angiotensin system[RAS] They reduses BP by blocking action of angiotensin -11 on its AT1 receptor and thus prevent the vasoconstrictor effect of this receptor.

24. aRBS USES; These drugs have the same benefits on cardiovascular and renal outcome as ACEI like heart failure , post-myocardial infraction , left ventricular systolic dysfunction ,and diabetic and non diabetic chronic kidney disease . SIDE EFFECT ; ANGIOEDEMA. These drugs must not used in pregnency

25. DIURETICS These agents work by increasing excretion of sodium by the kidney and additionally vasodilator effect 2 types of diuretics used in treatment of hypertension ; thiazide diuretics Loop diuretics

26. diuretics Clinical outcome benefit have been best established with CHLOROTHALIDONE,INDAPAMIDE, AND HYDROCHLOROTHIAZIDE . CHLOROTHALIDONE has more powerful effect on BP than HYDROCHLOROTHIAZIDE and has longer duration of action . S/E ; HYPOKALEMIA, HYPER GLYCEMIA , HYPERURICEMIA. The metabolic problem can be reduced by using low doses or by combining with ACEI OR ARBS ,which have been shown to reduce the metabolic changes . Diuretics are most effective with potassium sparing agents also help to prevent hypokalemia and with CCB are also effective .

27. Calicium channel blockers These agents reduce blood pressure by blocking the inward flow of calicium ions through the L Channel of arterial smooth muscle Eg ; 2 types CCBs Dihydropyridones nifedipine amlodipine Which work by dilating arteries Non Dihydropyridines Diltiazem Verpamil Which dilates arteries some what less but also reduce heart rate and contractility . Hence nondihydropyridine are not recommended in patient with heartfailure

28. CCBs SIDE EFFECT The main S/E of CCBS is peripheral edema ,which is most prominent at high doses They are powerful BP reducing effect s, when combined with ACEI or ARBS.

29. Beta adrenoreceptor blockers Beta blockers reduces cardiac output and also decrease the release of renin from the kidney Eg Propranolol Atenolol Metoprolol Carvediol Acebutalol

30. Beta receptor blockers USES MYOCARDIAL INFRACTION HEART FAILURE ANGINA PECTORIES S/E FATIGUE REDUCED SEXUAL FUNCTION REDUCED EXERCISE TOLERANCE Many cause ADVERSE EFFECT ON GLUCOSE METABOLISM –NOT RECOMMENDED IN DIABETIC PATIENTS Combined alpha and beta blocker ,LABETALOL ,I.V. ,used in HYPERTENSIVE EMERGENCIES . ORALL – Trearting HYPERTENSION IN PREGNANT AND BREAST FEEDING WOMEN.

31. ALPHA ADRENERGIC BLOCKERS DRUGS PRAZOSIN TERAZOSIN DOXAZOSIN They reduce BP by blocking atrial adrenergic receptors and thus preventing the vasoconstrictor action of these receptors

32. USES Less widely used as first step agents. RESISTANT HYPERTENSION when combining with diuretics, beta blockers, and ACEI For maximally effective usually combine with diuretics IN ADULTS – BENIGN PROSTATIC HYPERTROPHY

33. CENTRALLY ACTING AGENTS DRUGS METHYLDOPA CLONIDINE Work primarly by reducing the sympathetic outflow from the CNS. S/E DROWSINESS DRY MOUTH

34. DIRECT VASODILATORS DRUGS HYDRALAZINE MINOXIDIL These agents cause fluid retention and tachycardia,they are most effective in reducing BP when combined with diuretics and betablockers or sympatholytic agents. Hydralazine most widely used of these agents. Minoxidil used in patient whose BP difficult to control. S/E Fluid retention ,tachycardia Unwanted hair growth [women]

35. Drugs in longterm treatment of htn DRUG INITIAL DOSE[KG/DAY] MAX DOSE[KG/DAY] DIVIDED DAILY VASODILATORS HYDRALAZINE 1-2 mg 5-8mg 3-4 MINOXIDIL 0.1-0.2mg 1mg 1-2 PRAZOSIN 50-100mg 500ug 2-3 CENTRAL ALPHA AGONIST CLONIDINE 5-7ug 25ug 3 ADRENERGIC BLOCKERS ATENOLOL 1mg 2mg 1 PROPRANOLOL 1-2mg 4mg 3 METAPROLOL 1-2mg 6mg 2 LABETALOL 1-3mg 10-12mg 2 PHENOXYBENZAMINE 0.2mg 1-2mg 2

36. CCBs NIFEDIPINE 0.25 3 1-2 AMLODIPINE 0.05-0.2 0.6 1-2 ACEI CAPTOPRIL 0.3 5 ENALAPRIL 0.1 0.5-1 3 LISINOPRIL 0.05 0.6 1-2 RAMIPRIL 5-6 1 ARBs LOSARTAN 0.5-0.6 1 1 IRBESARTAN 150-300 1 VALSARTAN 1.3 2.7 1 DIRETICS HYDROCHLOTHIAZIDE CHLOROTHALIDONE 0.5-1 0.25 2-4 2 2 1 FUROSEMIDE SPIRONOLACTONE 0.5 1 5-6 3 1-2 1-2

37. STEPPED CARE APPROCH TO ANTI-HYPERTENSIVE TREATMENT

38. Hypertensive emergencies BP levels 5-10 mm above the 99th centile or DBP >110 mm Hg are considered ‘severe hypertension and end organ damage. Patients with severe hypertension are likely to manifest clinical features of end organ involvement and need urgent attention. The condition can be life threatening with serious sequelae if therapy is inadequate.

39. c/f Encephalopathy Headache Vomithing Ataxia Sensorial disturbances Stupor Seizure Focal neuroligical deficit –hemiparesis, blurring, transient loss of vision. TREATMENT OF HYPERTENSIVE EMERGENCY Constant infusion of labetalol

40. Tretment of hypertensive emergencies Drug dosage Sodium nitroprusside 0.5-8 μ g/kg/min IV infusion Labetalol Infusion: 0.5-3 mg/kg per hour, or Bolus: 0.2-1 mg/kg bolus IV Nifedipine 0.25-0.5 mg/kg oral or sublingual (bite and swallow); maximum single dose 5-10 mg Nicardipine 1-3 μ g/kg/min IV infusion Hydralazine 0.1-0.5 mg/kg/dose slow IV; can be repeated after 4 hours

41. Drug Onset of action Duration sodium nitroprusside Immediate short half life labetalol 2-10 min 2-3 hours nifedipine 5-30 min upto 6 nicardipine 1-2 min 10-15 mins hydralazine 5-20 min 4-12hrs

42. PRIMARY[ESSENTIAL] HYPERTENSION • Primary hypertension is identifiable in children and adolescents, often in association with obesity This type HTN diagnosed after a doctor notices that your BP is high on 3 or more visits and eliminate all other causes of HTN. C/F- No symptoms, but experiences frequent headache , tiredness, dizziness or nose bleed.

43. PRIMARY[ESSENTIAL ]HTN Causes- unknown,researchers do know that obesity,smoking,alchohol,diet,herediety . • Weight reduction and regular physical activity are important components of therapy • Dietary modifications should be strongly encouraged • The presence of target organ damage (chiefly left ventricular hypertrophy) is an indication to initiate or intensify pharmacologic therapy

44. Monogenic forms of hypertension Condition Inheritance Gene locus Gene product Liddle syndrome AD 16P GAIN OF FUNCTION MUTATION ENAC Syndrome of apparent AR 16q MUTATION IN GENE ENCODING11 beta hydroxysteroid dehydrogenase-2 mineralocorticoid excess Glucocorticoid remediable AD 8q chimeric gene from 11Betahydroxylase n aldosteronism aldosterone synthase gene,CYP11B2,result in ACTH stimulating aldosterone synthesis. Gordon syndrome AD 12p MUTATION IN GENE ENCODING WNK1 n 17q WNK4 Congenital adrenal AR 8q DEFICIENCY OF 11 BETA hydroxylase n hyperplasia 10q 17 alpha hydroxylase

45. Syndromes with hypertension,hypokalemia,metabolic alkalosis LIDDLE SYNDROME APPARENT MINERALOCORTICOID EXCESS GLUCOCORTICOID REMEDIABLE ALDOSTERONISM[GRA] ADRENAL ENZYMATIC DISORDER

46. GORDON SYNDROME AD disorder characterised by HYPERTENSION, HYPERKALEMIA, and HYPER CHLOREMIC METABOLIC ACIDOSIS with normal GFR. Some patient may have short stature, intellectual impairment, muscle weakness, hyper calciuria , and renal stones. Plasma renin , aldosterone are reduced . TRATMENT HYDROCHLOROTHIAZIDE OR FUROSEMIDE SODIUM BICARBONATE.

47. Chronic kidney disease The terms CRF and CHRONIC RENAL INSUFFICIENCY have now been replaced by the more appropriate and useful title of “CHRONIC KIDNEY DISEASE’ (CKD). This term was proposed by the National Kidney Foundation-Kidney Disease and Outcome Quality Initiative (NKF-KDOQI) group to classify any patient who has KIDNEY DAMAGE >=3 months with or without a decreased GFR, or KIDNEY FUNCTION GFR < 60 ml/min per 1.73 m2 lasting for 3 months with or without kidney damage. The severity of CKD has been graded on the basis of GFR

48. Criteria for def ckd [ nkf-kdoqi ] Patient has chronic kidney disease (CKD) if either of the following criteria are present: 1. Kidney damage for ≥3 mo , as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by one or more of the following features: • Abnormalities in imaging tests • Abnormalities in the composition of the blood or urine • Abnormalities on kidney biopsy 2. GFR < 60 mL/min/1.73 m2 for ≥3 mo , with or without the other signs of kidney damage described previously

49. Stages of chronic kidney disease CKD can be divided in 5 stages, based on the level of GFR , which is estimated in children from the level of serum creatinine and height, using the Schwartz formula . The CKD classification is criticized in two respects: stages 1 and 2 are defined better by the Associated abnormalities (e.g. proteinuria, hematuria, structural anomalies) than By The Estimated GFR; secondly, GFR varies with age, gender, and body size, increasing with renal maturation from infancy to reach adult values at 2 years of age. Hence, the GFR ranges defining the CKD stages apply only to children >2-year-old. Previously, the terms chronic renal insufficiency GFR levels between 50 and 25% chronic renal failure GFR level <25%

50. CKD STAGES[NKF-KDOQ1] ACCORDING TO NATIONAL KIDNEY FUNDATION-KIDNEY DISEASE AND OUTCOME QUALITY INITIATIVE. Stage GFR, ml/min/1.73 m2 Description 1 >= 90 KIDNEY DAMAGE WITH NORMAL OR INCREASED GFR 2 60-89 KIDNEY DAMAGE WITH MILD DECREASE OF GFR 3 30-59 MODERATE DECREASE OF GFR 4 15-29 SEVERE DECREASE OF GFR 5 <15 KIDNEY FAILURE 5D <15 ,0n dialysis KIDNEY FAILURE, DIALYSIS DEPENDENT

51. ETIOLOGY Prevalence of CKD in children <16: 1.5-3.0 per 1,000,000. Preterminal CKD. Incidence 4-12 cases/year/MARP, prevalence 21-82 cases/MARP. ESRD rates higher in boys, older children, African-Americans. North India reports show 12-50% ESRD in pediatric nephrology patients.

52. Etiologies of ckd NON GLOMERULAR Aplastic, hypoplastic, and dysplastic kidneys Cystinosis Medullary cystic kidney disease/ juvenile nephronophthisis Obstructive uropathy (e.g., PUV, cloaca, neurogenic bladder) Oxalosis Autosomal dominant and autosomal recessive polycystic kidney disease (ADPKD, ARPDK) Pyelonephritis/interstitial nephritis/reflux nephropathy Renal infarct Syndrome of agenesis of abdominal musculature (Eagle-Barrett syndrome) Wilms tumor GLOMERULAR Chronic glomerulonephritis (including focal segmental glomerulonephritis [FSGS]) Congenital nephrotic syndrome (CNS) Hemolytic uremic syndrome (HUS) Idiopathic crescentic glomerulonephritis IgA nephritis IgA nephropathy (IGAN) Membranoproliferative glomerulonephritis (MPGN) Membranous nephropathy Sickle cell nephropathy Systemic immunologic disease (e.g., SLE, granulomatosis with polyangiitis) Hereditary nephritis (Alport syndrome)

53. RISK FACTORS FOR CKD VUR associated with recurrent urinary infections and renal scarring Obstructive uropathy Prior history of acute nephritis or nephrotic syndrome Children with history of renal failure in perinatal period Family history of polycystic kidneys or genetic renal conditions Renal dysplasia or hypoplasia Low birth weight infants Prior history of Henoch- Schönlein purpura Presence of diabetes, hypertension Systemic lupus erythematosus, vasculitis

54. DIAGNOSIS AND STAGING OF CKD ;KEY POINTS The term ‘chronic kidney disease’ is preferable to ‘chronic renal failure’. Any STRUCTURAL ABNORMALITY or FUNCTIONAL IMPAIRMENT of kidney(s) that persists for 3 MONTHS is termed chronic kidney disease, regardless of severity CKD is staged according to estimated GFR, from normal RENAL FUNCTION (stage 1) to severe kidney disease, previously termed ESRD (stage 5) The terminology is applicable to children above 2 YEARS of age

55. DX AND STAGING CKD;KEY POINTS The GFR is estimated by the Schwartz or modified Schwartz formulae Glomerulonephritis, congenital renal and urological anomalies and reflux nephropathy account for majority of pediatric CKD burden Children with history of AKI, recurrent UTIs, corrected obstructive uropathy, and U/L or B/L structural abnormalities require follow-up in view of risk of development of renal impairment in future

56. RENAL RESPONSE TO NEPHRON LOSS The kidneys have the ability to maintain chemical homeostasis in spite of the loss of a large proportion of nephrons. This adaptation involves changes in the remnant glomerular and tubular function and structure. FUNCTIONAL CHANGES 1 INCRESE IN SINGLE NEPHRON GFR[SNGFR] .Loss of nephrons is associated with an increase in glomerular blood flow in the remaining normal nephrons. There is dilatation of the afferent and the efferent arterioles, the Afferent dilating more than the Efferent. This Enhances the Transcapillary Hydrostatic Pressure and increases the GFR. Thus, the whole kidney GFR is augmented.

57. MAINTANENCE OF TUBULOGLOMERULAR BALANCE Increased filtration in normal glomeruli is matched by a proportionate increase in reabsorption in the corresponding tubule. The absorption of sodium, glucose and amino acids is adjusted similarly. The tubular handling of substances that are excreted by secretion .

58. Structural changes There is an increase in glomerular volume secondary to the hemodynamically mediated increase in capillary lumen volume and hypertrophy of cellular and matrix constitutents of the glomerulus. There is also an increase in the size and volume of the tubules involving predominantly the proximal tubules .

59. Progression of kidney damage Regardless of the etiology of CKD, once there is a critical loss of nephron mass, the renal failure is progressive. As a significant proportion of nephrons are damaged, the remaining compensate for the loss of renal function. These nephrons undergo progressive HYPERPERFUSION and HYPERFILTRATION that gradually causes increasing GLOMERULAR INJURY and SCLEROSIS . As GFR , there is an Sr.CREATININE . Without major intervention or additional renal damage, the reciprocal of serum creatinine decreases with time in a relatively linear manner. The rate of decline in GFR, however, varies in different individuals and diseases. Risk Factors Associated with Diseases. Reduction of GFR risk factor for renal progression.

60. Progression of ckd -pathophysiology Hypertension and proteinuria are independent risk factors for CKD progression. Residual proteinuria, post-ACE inhibition correlates with GFR decline. Hypertension disrupts glomerular autoregulation by arteriolar nephrosclerosis and hyper filtration injury, inducing intraglomerular hypertension and proteinuria. . Hyperphosphatemia can increase progression of disease by leading to calcium phosphate deposition in the renal interstitium and blood vessels. Hyperlipidemia, a common condition in CKD patients, can adversely affect glomerular function through oxidant- mediated injury. Vasoactive signaling triggered by proteinuria promotes inflammation and fibrosis pathways, accelerating CKD.

61. Progression of ckd Vasoactive signaling triggered by proteinuria releases angiotensin-II, aldosterone, and endothelin-I, promoting inflammation and fibrosis. This cascade involves RANTES, NFkB , and MCP-1, mediating macrophage invasion and fibrotic transformation. Dyslipidemia , hyperglycemia , and oxidative stress exacerbate renal injury and fibrosis. RAAS activation contributes significantly to CKD progression via angiotensin II-mediated effects. Genetic factors, including polymorphisms in RAAS and inflammatory genes, influence CKD progression.

62. Progression of ckd

63. PATHOPHYSIOLOGY OF CKD MANIFESTATIONS MECHANISMS ACCUMILATION OF NITROGENOUS WASTE DECREASE OF GFR ACIDOSIS Decreased ammonia synthesis Impaired bicarbonate reabsorption Decreased net acid excretion SODIM WASTING Solute diuresis Tubular damage URINARY CONCENTRATING DEFECT Solute diuresis Tubular damage

64. HYPERKALEMIA Decrease in glomerular filtration rate Metabolic acidosis Excessive potassium intake Hyporeninemic hypoaldosteronism RENAL OSTEODYSTROPHY Impaired renal production of 1,25-dihydroxycholecalciferol (1,25OH2D) Hyperphosphatemia Hypocalcemia Secondary hyperparathyroidism GROWTH RETARDATION Inadequate caloric intake Renal osteodystrophy Metabolic acidosis Anemia Growth hormone resistance ANAEMIA Decreased erythropoietin production Iron, folate, and/or vitamin B12 deficiency Decreased erythrocyte surviva BLEEDING TENDENCY Defective platelet function INFECTION INFECTION Defective granulocyte function, Impaired cellular immune functions Indwelling dialysis catheters

65. Decreased academic achievement, attention regulation, or executive functioning HYPERTENSION LOW BIRTH WEIGHT Gastrointestinal symptoms (feeding intolerance, abdominal pain) GASTROESOPHAGEAL REFLUX DECRESED GASTROINTESTINAL MOTILITY HYPERTENSION Volume overload Excessive renin productio HYPERLIPIDEMIA Decreased plasma lipoprotein lipase activity Abnormal HDL-C CARDIOMYOPATHY Hypertension Anemia Fluid overload GLUCOSE INTOLERANCE Tissue insulin resistance

66. Systemic features The clinical features in patients with advanced CKD (stage 3-5) include anorexia, failure to thrive, growth retardation, fatigue, anemia, hypertension and bone disease. The late features, with extreme reduction of GFR, are itching, severe acidosis, hyperkalemia, left ventricular failure and pulmonary edema, pericarditis and altered sensorium.

67. DIAGNOSTIC EVALUATION A comprehensive history should include signs like polyuria, polydipsia, and family history of renal disease. Clinical examination involves blood pressure measurement, growth evaluation, and screening for anemia and rickets. Estimating GFR in children typically employs the Schwartz formula . Alternative formulas, like those proposed by the CKD study, consider additional parameters for accuracy.

68. Diagnostic evaluations Lab investigations include urinalysis, blood urea, electrolytes, and creatinine measurement. Additional tests like lipid profile, PTH, and iron studies may be required. Further investigations for CKD causality include imaging and renal histological examination. GFR= K*HEIGHT[IN CM]/SERUM CREATININE[mg/dl] GFR =K*HEIGHT[eGFR= 39.1 [ Ht (m)/ SCr ]0.516 ×[1.8/ CysC ]0.294 ×[30/BUN]0.169 ×[1.099male] ×[ Ht /1.4]0.188

69. Diagnosis and assessment of severity Ultrasonography is useful for examining renal size, anomalies and obstruction • Radionuclide imaging is usually not helpful if GFR <20-30 ml/min/1.73 m2 • Glomerular disorders are suggested by proteinuria, hematuria and casts • Blood levels of urea, creatinine, electrolytes, and appropriate tests to evaluate anemia, bone disease and acid-base status are necessary.

70. management RETARDING PROGRESSION OF CKD Control of hypertension Reduction in proteinuria • Other strategies– --Management of anemia – Prevention and management of dyslipidemia – Prevention of acidosis – Non- hypercalcemic doses of vitamin D analog

71. Retarding progression of ckd Optimizing blood pressure control and reducing proteinuria are key to slowing renal disease progression. Intensified blood pressure management targeting 50-75th percentile levels and reducing proteinuria by ≥1 g/day are recommended. Renin-angiotensin system blockade with ACE inhibitors or ARBs is the preferred strategy for renal protection, reducing both proteinuria and hypertension.

72. Retarding progression of ckd ….. These effects are mediated through decrease in glomerular vascular tone that decrease intraglomerular pressure,proteinuria and local release of cytokines and chemokines, while attenuating activation of inflammatory pathways. Thus, glomerular hypertrophy and sclerosis, tubulointerstitial inflammation and fibrosis are diminished .

73. Fluid and electrolytes In children with CKD, maintaining water and sodium balance is crucial. There's typically no need to restrict salt and water intake, but careful monitoring is necessary to avoid volume and salt derangements. Sodium intake is typically around 2 g daily, adjusted based on blood pressure; hypervolemia and hypertension risk necessitate salt restriction. Fluid intake should match urine output, with adjustments for dialysis; hypokalemia risks from diuretics may require potassium supplementation, but it's restricted in advanced CKD stages. Hyperkalemia may require potassium exchange resins for management.

74. growth Despite optimal management, many infants and young children with CKD fail to reach their genetic height potential. Growth impairment typically initiates when GFR drops to 50% of normal, necessitating correction of nutritional deficiencies, acid-base balance, and salt, calcium, and vitamin D deficiencies to promote steady growth, especially in children with GFR >25 ml/min/1.73 m2.

75. growth In cases of persistent growth retardation despite interventions, children with CKD may undergo recombinant human growth hormone ( rhGH ) therapy , potentially achieving a normal final height. Studies show significant increases in height velocity and standard deviation score with rhGH , typically starting at 0.05 mg/kg per day subcutaneously , although long-term effects and necessity in pubertal patients are uncertain, and side effects such as hyperglycemia and hypertension should be monitored.

76. NUTRITION Intakes of calories, proteins, vitamins and minerals should be appropriate for age Children with malnutrition need up to 130% calories to allow catch up growth Supplemental enteral nutrition often required through nasogastric or gastrostomy tube There is no role for protein restriction in children with CKD Proteins with higher biologic value should be used in children with CKD Restriction of dietary phosphorus intake is required in advanced CKD

77. Ckd -mbd CKD-MBD involves systemic disruptions in calcium, phosphorus, PTH, and vitamin D metabolism. Can lead to bone disorder[renal osteodystrophy] Elevated FGF-23 levels, alongside reduced vitamin D activation, contribute to bone disorders and secondary hyperparathyroidism. Renal osteodystrophy presents with high or low bone turnover, impacting mineralization and bone volume. High-turnover bone disease, or OSTEITIES FIBROSA CYSTICA common in advanced pediatric CKD, leads to hypocalcemia , hyperphosphatemia, and elevated PTH. Clinical signs include bone pain, fractures, and radiographic abnormalities. Low-turnover bone disease, seen in adynamic renal osteodystrophy, exhibits PTH over-suppression and hypercalcemia. Vascular calcification in CKD-MBD primarily occurs in the vascular media. Understanding these complexities aids in managing CKD-MBD's multifaceted impact on patients' skeletal and vascular health.

78. Ckd -mbd treatment Treatment for CKD-MBD involves normalizing mineral metabolism and reducing bone deformities and vascular calcification. This includes dietary phosphorus restriction, correcting 25OH vitamin D insufficiency, and using phosphate binders to manage hyperphosphatemia. Active vitamin D sterols are prescribed to address low 1,25OH2D levels and elevated PTH, improving calcium and phosphorus absorption and reducing PTH secretion. Careful monitoring and individualized therapy are essential, particularly regarding PTH targets, to optimize outcomes in CKD patients.

79. CKD-MBD Screening should begin in CKD 2, and continue 3-12 monthly according to stage Target values of serum calcium, phosphorus and PTH to be achieved vary by age and stage of CKD Persistent severe bony deformities require orthopedic intervention

80. Anaemia;evaluation and management in ckd

81. Management of anaemia Iron and folic acid supplementation should be routine in advanced CKD Periodic assessment of iron status and peripheral smear are required Intravenous iron should be used to treat iron deficiency in children on hemodialysis, and in those with significant adverse effects with oral iron Subcutaneous or intravenous erythropoietin should be prescribed once iron replete Blood transfusions should be avoided to prevent sensitization Newer erythropoietins , if approved in children, would allow less frequent dosing and better compliance

82. immunization Children with CKD should receive standard immunizations, except live virus vaccines for those on immunosuppressive medications; live virus vaccines should be administered before kidney transplantation. Additionally, yearly influenza vaccination and pneumococcal vaccination with PPSV-23 are recommended, despite potential suboptimal responses to immunizations in children with CKD.

83. Adjustment of drug dose In CKD, drugs excreted by the kidneys may require dose adjustments to optimize efficacy and minimize toxicity, typically involving lengthening dose intervals or reducing absolute doses.

84. esrd End-stage kidney disease (ESKD) necessitates kidney replacement therapy (KRT) like dialysis or transplantation. Discussions for KRT begin at stage 4 CKD, with indications for dialysis including fluid overload, electrolyte abnormalities, and uremic symptoms. Peritoneal dialysis (PD) is predominant, especially for younger children, while hemodialysis (HD) is increasingly used, particularly for older children. Kidney transplantation is the preferred option for improved outcomes in children with ESKD. In the U.S., 75% of children with ESKD undergo dialysis before transplantation .

85. ESRD Peritoneal dialysis (PD) utilizes the peritoneal membrane to remove excess fluid and waste. Access is through a tunneled catheter, with options including continuous ambulatory PD (CAPD) and automated PD (APD), preferred in countries without cost restraints. APD offers uninterrupted daily activities, reduced catheter connections, and less caregiver burden. Hemodialysis (HD) is typically hospital-based, using arteriovenous fistula (AVF), graft (AVG), or catheter access, with options for intensified HD improving outcomes. Pediatric dialysis patients face significantly higher mortality rates, primarily due to cardiovascular disease and infections, with dialysis-associated infections leading to hospitalizations.

86. ESRD

87. questions HYPERTENSION DEFINATION?

88. SBP or DBP values >95PERCENTILE should be REPEATED ON ATLEAST 2 0r MORE OCCASION is confirmed the diagnosis of HYPERTENSION

89. WHAT IS HYPERETENSIVE EMERGENCY----------------

90. Blood pressure levels 5-10 mm above the 99th centile or diastolic blood pressure more than 110 mm Hg are considered ‘severe’. Patients with severe hypertension are likely to manifest clinical features of end organ involvement and need urgent attention.

91. DASH DIET?

92. DASH DIET-- low Na intake and increasing K- , Ca- , and Mg- containing foods, such as 6-8 servings of whole grains, 4-5 servings of fruits, and 4-5 servings of vegetables per day and low- fat dairy foods.

93. CRITERIA FOR DEFINATION OF CKD------

94. 1. Kidney damage for ≥3 mo , as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by one or more of the following features: • Abnormalities in imaging tests • Abnormalities in the composition of the blood or urine • Abnormalities on kidney biopsy 2. GFR < 60 mL/min/1.73 m2 for ≥3 mo , with or without the other signs of kidney damage described previously

95. PATHOPHYSIOLOGY OF CKD INJURY

96. The nephrons undergo progressive HYPERPERFUSION and HYPERFILTRATION that gradually causes increasing GLOMERULAR INJURY and SCLEROSIS . Hypertension disrupts glomerular autoregulation by arteriolar nephrosclerosis and hyper filtration injury, inducing intraglomerular hypertension and proteinuria.

97. WHAT IS ESRD?

98. Kidney failure, also termed end-stage kidney disease (ESKD), represents the state in which a patient’s kidney dysfunction has progressed to the point at which homeostasis and survival can no longer be sustained despite maximal medical management. At this point, kidney replacement therapy (KRT; which is either dialysis or kidney transplantation) becomes necessary. The ultimate goal for children with ESKD is successful kidney transplantation

99. THANK YOU