ACUTE KIDNEY INJURY & CHRONIC KIDNEY DISEASE IN CHILDREN

BY- DR. SAMEEKSHYA PRADHANGUIDE- ASSOC. PROF. DR. J .R CHAMPATIRAY

ACUTE KIDNEY INJURY

DEFINITION

Rapid deterioration of renal function resulting in retention of nitrogenous wastes and inability of kidney to regulate fluid and electrolyte homeostasis.

In year 2000 the acute dialysis quality initiative (ADQI) proposed RIFLE criteria for defining AKI .

Later, Acute Kidney Injury Network (AKIN)

classified AKI based on the RIFLE system.

> 3 months

INCIDENCE The precise incidence of AKI in children is not well known. 4-6 % case of AKI seen in general ward and upto 40% in

PICU AGE with dehydration & shock is a common cause. In India, malaria, snake bite are also common causes. In PICU, commonly affects children who have sepsis and

multiorgan failure. Children undergoing major cardiac surgery and organ

transplantation are also at considerable risk. HUS and AGN are important renal causes. Post renal causes of AKI are rare.

ETIOLOGY

Pre renal Intrinsic or renal Post renal

- Both pre and post renal aki are potentially reversible in early stages but if prolonged can cause renal parenchymal damage.

(A) PRE RENAL

Also called prerenal azotemia, is characterized by diminished effective circulating arterial volume, which leads to inadequate renal perfusion and a decreased GFR .

CAUSES OF PRERENAL AKI

Acute gastroenteritis Hemorrhage Shock Congestive cardiac failure Hepatorenal syndrome (renal vasoconstriction) Sepsis (peripheral vasodilaton) Profound third space loss (burns, Ac. Pancreatitis,

nephrotic syndrome, massive ascites) NSAID’s & ACE inhibitors

Renin

Angiotensin II

Aldosterone

Renal Tubular Na Reabsorption

Vasopressin

Renal Tubular H2O Reabsorption

Urine Volume

Concentrated Urine

Urine Sodium

Decreased Renal Perfusion

Mechanisms of Sodium and Water Conservation in Prerenal Azotemia

(B) RENAL CAUSES – Obstruction of renal artery or veins - renal vein thrombosis , renal arterial obstruction, Involvement of renal microvasculature – HUS , HSP, polyarteritis , collagen vascular disease Glomerular causes- AGN ( PSGN ,other infections ), cresentic GN Interstitial causes- acute tubulointerstitial nephritis Tubular causes (ATN) Prolongation of pre-renal insult , intravascular hemolysis , sepsis ,

nephrotoxic agents , multiorgan failure , rhabdomyolysis , snakebite , other envenomations , falciparum malaria , leptospirosis

1.OBSTRUCTION OF RENAL ARTERIES AND VEINS

Bilateral renal arterial thrombosis may occur after umbilical artery catheterization in neonates (rarely causes aki usually causes intractable hypertension).

Renal vein thrombosis may be a complication of infant of diabetic mother especially following dehydration.

In older children renal vein thrombosis may occur with nephrotic syndrome with anasarca and dehydration.

Gross hematuria, enlargement of kidney and azotemia are typical manifestation.

2.INVOLVEMENT OF RENAL MICROVASCULATURE

HUS is a common cause of AKI in chidren. Causes thrombotic microangiopathy 2 types- D+HUS and D-HUS Common causes of D+HUS – EHEC(in developed

countries),Shigella dysentriae type I (in India) Following dysentery shigella-toxin enters the circulation

and leads to endothelial injury in microvasculature . Localized coagulation and deposition of platelet thrombi

and fibrin occurs in glomeruli causing decrease in GFR.

3.GLOMERULAR DISEASES

PSGN, Post infectious GN, Cresentric GN, Renal vasculitis, IgA nephropathy are important causes in this group.

4.ACUTE INTERSTITIAL NEPHRITIS

Usually occurs due to hypersensitivity reaction to some drugs (ampicillin, cephalosporins, sulfonamides,quinolones, NSAID’s, phenytoin etc)

The patient may have fever , arthralgia , rash and eosinophilia : urine often shows eosinophils

Renal biopsy should be done if it is strongly suspected.

5.ACUTE TUBULAR NECROSIS

Occurs mostly in critically ill infants and children who have been exposed to nephrotoxic agents and/or prolonged hypoperfusion/hypoxia.

Common causes of ATN include renal hypoperfusion following volume contraction , severe renal vasoconstriction , nephrotoxic agents , sepsis , shock and hypotension.

Renal hypoperfusion prerenal aki(reversible) intermediate stage (slowly reversible) ATN

MECHANISM OF ATN

(C)POST RENAL

It includes a variety of disorders characterized by obstruction of the urinary tract.

In a patient with 2 functioning kidneys, obstruction must be bilateral to result in AKI.

Relief of the obstruction usually results in recovery of renal function except in patients with associated renal dysplasia or prolonged urinary tract obstruction.

CAUSES OF POST RENAL AKI

Posterior urethral valves Ureteropelvic junction obstruction Ureterovesicular junction obstruction Ureterocele Tumor Urolithiasis Hemorrhagic cystitis Neurogenic bladder

CLINICAL EVALUATION HISTORY - H/o blood loss, diarrhea, vomitting – prerenal aki. Past h/o pharyngitis with gross hematuria, edema, hypertension –

acute PSGN. Dysentery, petechiae, pallor- HUS. Sudden passage of dark red urine, pallor and jaundice with h/o drug

exposure – acute intravascular hemolysis (G6PD def.). Rash with arthritis – SLE or HSP. H/o prolonged hypotension or exposure to nephrotoxic drugs – ATN. Exposure to certain drugs f/b fever, rash, arthralgia and rising

S.creat – acute TIN H/o poor urinary stream with palpable UB or kidney – obstructive

uropathy. Abdominal colic,hematuria, dysuria – urinary tract stones.

PHYSICAL EXAMINATION - Obtaining a thorough physical examination is

extremely important . Clues may be found in any of the following –

Skin Eyes Ears Respiratory system Cardiovascular system Abdomen

Skin :- Palpable purpura - Systemic vasculitis Maculopapular rash - Allergic interstitial nephritis

Eye :- Uveitis – interstitial nephritis and necrotizing vasculitis. Ocular palsy - ethylene glycol poisoning or necrotizing vasculitis

Ear :- Hearing loss - Alport disease and aminoglycoside toxicity

Mucosal or cartilaginous ulcerations – Wegener’s granulomatosis

Respiratory system :- rapid and deep breathing – met. Acidosis

basal creps - volume overload

Cardiovascular examination :• Pericardial friction rub - Uremic pericarditis• Increased JVP, Gallop rhythm, pitting edema - CHF

due to volume overload.

Abdomen :• Renal angle tenderness – nephrolithiasis, papillary

necrosis, renal artery or vein thrombosis.• Distended bladder – urinary obstruction.• F/s/o chronic liver disease with ascites with prerenal

aki – hepatorenal syndrome

INVESIGATIONS Urine R/M CBC with CPS 24 hour urinary protien Blood urea and S. creatinine level Serum electrolytes Throat swab C/S ASO titer C3 level Serum calcium Serum phosphate Serum uric acid ANA ABG

IMAGING

Ultrasound of KUB - evaluates renal size, able to detect masses, obstruction, stones

Chest x-ray DTPA DMSA

RENAL BIOPSY

Indicated in Patient in whom the etiology is not identified. Unremitting AKI lasting longer then 2-3 wks or

in assessing the extent of renal damage and outcome.

Suspected drug induced AKI in a patient receiving therapy with a potentially nephrotoxic drugs.

URINARY INDICES

PRE-RENAL INTRINSIC

URINARY SODIUM (mEq/l) < 20 > 40

Urinary osmolality (mOsm/kg) > 500 < 300

Blood urea to creatinine ratio >20:1 < 20:1

Urine to plasma osmolality ratio >1.5 < 0.8 – 1.2

Fractional excretion of sodium < 1 > 1

BIOMARKERS FOR EARLY DIAGNOSIS

Biomarkers that indicate renal injury before rise in S.creatinine values would be helpful in pts. at high risk of aki like – children undergoing major surgery or organ transplant, neonates with hypoxia,sepsis or multi organ failure.

Examples are: Neutrophil gelatinase associated lipocalin(NGAL) Interleukin -18 Kidney molecule–1(KIM -1) Cystatin -C

MANAGEMENT

The basic principles of management include Treatment of life-threatening complications Maintenance of fluid and electrolyte balance Supportive care Dialysis & CRRT Specific management of underlying disorder

A. MANAGEMENT OF LIFE THREATENING COMPLICATIONS

Such complications are – Hyperkalemia Fluid overload with heart failure Hypertensive emergencies Profound acidosis Severe anemia

1. Hyperkalemia (>6meq/l): ECG changes- peaked T waves, widening of QRS interval, ST

depression, arrythmia, arrest. Emergency measures(>7meq/l with ECG changes) Calcium gluconate 0.5-1 ml/kg over 5 to 10 mins Salbutamol(5-10mg)nebulization Glucose (50%)0.5-1 gm/kg with 0.1-0.2 unit/kg insulin Less urgent(>6meq/l) deplete body potassium( stop exogenous sources of

potassium, sodium polystyrene sulfonate resin-kayexalate, 1g/kg orally decreases S.K+ by 1meq/L)

2.Fluid overload : fluid restriction Insensible water loss(300ml/m²)+UO+extrarenal

fluid loss Replace insensible loss by 10%D and UO &

extrarenal loss by N/2D5.

3.Pulmonary Edema Oxygen Dopamine (5-10) mcg /kg /min infusion in min

fluid Frusemide (2-4)mg /kg IV

4.Hypertension Symptomatic- Nitroprusside 1-8 mcg/kg/min, Frusemide 2-4

mg/kg IV Asymptomatic- Nifedipine 0.3-0.5 mg/kg PO5.Severe metabolic acidosis pH<7.15, S.bicarbonate<8meq/l Sodium bicarbonate – first IV to ↑pH to 7.2 and S.

bicarbonate to 12meq/l, then orally after correction of S.calcium and phosphorus levels.

Rapid correction can cause tetany.6.Severe anemia Anemia is generally mild (9-10g/dl) If Hb<7g/dl – transfuse PRBCs @10ml/kg slowly over 4-6

hrs.

B.MAINTENANCE OF FLUID AND ELECTROLYTE BALANCE1.Monitor urine output2. Volume resuscitation-• If there is no evidence of fluid overload, then expand

intravascular volume by NS bolus of 20ml/kg over 30min• Repeat boluses may be given in severe hypovolemia• Hypovolemic pts should void within 2hr3.Diuretic challenge-• After volume resuscitation if no urination occurs a single

IVdose of furosemide(2-4mg/kg) and mannitol(0.5g/kg) can be given.

• If still no response occurs stop diuretics and start fluid restriction presuming the pt to be in intrinsic AKI.

4.Hyponatremia(S.Na+<130meq/L) Usually cause d/t excessive IV fluids (dilutional

hyponatemia)-t/t is fluid restriction. Sodium correction is only given if there is-

»symptomatic hyponatremia »S.Na+<120meq/L

Meq of sodium required=0.6xWt(kg)x{125-S.Na+(meq/L)}

Vol. Of 3% N.S. required is twice of above value

12 ml/kg of 3% N.S ↑ses S.Na+ by 10 meq/L 5-10meq/L of S.Na+ should be ↑sed over 30-90mins

5.Hyperphosphatemia,hypermagnesemia, hypocalcemia

• AKI causes phosphate & Mg ions retention.• Hyperphosphatemia in turn causes hypocalcemia.• T/t: low phosph. diet,oral phosph. binders(sevelamer, calcium

carbonate)• Hypocalcemia is usually asymptomatic d/t associated acidosis,

so hypocalcemia should be corrected before correcting acidosis.• Calcium carbonate/gluconate is given at a dose of 30-50 mg/kg

of elemental calcium.• There is risk of metastatic deposition of calcium phosphate when

S.Ca2 + x S.PO43ˉ >70.If fluid is appropriate,then patient should lose 0.5-1% of his wt. daily and S.Na+ should stay normal.

C.SUPPORTIVE CARE1. NUTRITION -maximise caloric intake

because of ↑sed met. need -Protein→infant(1.2-2gm/kg),children(0.8-1.2g/kg) -Energy →min 60kcal/kg

-If on dialysis→protein,fluid & electrolyte intake should be ↑sed. -Vit.B-complex & C & micronutrient supplement2. MANAGE INFECTIONS

-↓sed immunity(azotemia,malnutrition) -maintain asepsis, maintain oral hygeine -avoid long term bladder catheterisation

3. DRUGS -Avoid nephrotoxic drugs(esp. aminoglycosides, radiocontrast media,NSAID’S,amphotericin-b) -Dose & dosing interval of other drugs are modified according to severity of AKI. -Dopamine in low dose has no role on outcome of AKI -Fenoldopam(selective peripheral dopamine rec. agonist)-may be helpful in preventing AKI -ANP may be helpful

4. MONITORING -I/O charting,daily wt. measurement, physical exam., S.Electrolytes

D.DIALYSIS & CRRT Indication:Anuria/oliguria Uremia(encephalopathy, pericarditis, neuropathy ) Hyperkalemia: K+ > 6.5 meq/l, K+ 5.5-6.5 meq/l with

ECG changes Hyponatremia: Na+ < 120 meq/l if symptomatic Fluid overload: resistant to diuretics, CCF,HTN Metabolic acidosis: pH< 7.2 despite sodium

bicarbonate therapy. Ca:phosphorus imbalance with hypocalcemic tetany Hypercatabolic states(marked tissue injury, burns,

sepsis, crush syndrome)

Early dialysis is preferred to prevent complication. 3 types of dialysis-a.intermittent hemodialysis(IHD) b.peritoneal dialysis(PD) c.CRRT.

a. IHD: prefferd in patients with relatively stable hemodynamic state. -Highly efficient, 1 session completes in 3-4 hrs -Can be done 3-7 times/week -Complication:hypotension,bleeding,thrombosis,etc

b. P.D: most commonly used in infants & neonates. -For 1 session→1 cycle of 45-60 min needs to be repeated for 8-24 hours/day. -No need for anticoagulation,so ↓sed risk of bleeding,may cause abdominal pain & peritonitis

c. CRRT: Indications-hemodynamic instability, sepsis, extensive trauma, MODS,tumour lysis syndrome -continuos removal of solutes ,fluid & electrolytes -3 types: CVVH, CAVH, CAVHD -CVVH:helpful in management of AKI with severe fluid overload -CAVHD:most effective type pf CRRT.

E.SPECIFIC MANAGEMENT OF UNDERLYING DISORDER

Prerenal AKI: administer crystalloids, stop diuretics, NSAIDs, ACE inhibitors.

ATN: supportive care, discontinue drugs or toxin, treat cause of circulatory failure.

Glomerulonephritis: supportive care, control hypertension, if its due to shunt infection- removal of shunt & appropriate antibiotics are given.

HUS: supportive care, plasma infusion, plasma exchange

Vasculitis: immunosuppressive medication, plasma exchange

Interstital nephritis: discontinue offending drugs, consider steroid therapy.

Renal artery , vein occlusion: anticoagulation, thrombolysis or surgery.

Intrarenal obstruction: discontinue offending drugs, alkaline diuresis for rhabdomyolysis , haemoglobinuria or urate crystal.

Urinary tract obstruction: bladder cathaterization or nephrostomy, surgical treatment of obstruction.

OUTCOME Mortality rates from 30-50% have been reported from

developing countries. But the results have markedly improved at tertiary centers with proper expertise and modern facilities.

Outcome depend upon underlying cause. Prognosis is favourable in ATN from volume depletion,

intravascular hemolysis, acute interstial nephritis and drugs or toxin related AKI especially when complicating factor are absent .

In cresentic GN, atypical HUS, and AKI associated with sepsis, multi organ failure the prognosis is less satisfactory .

PREVENTION OF AKI

Important measures includes prompt rehydration therapy in acute diarrhea, avoidance or judicious use of nephrotoxic drugs.

Maintenance of proper hydration for patients undergoing diagnostic procedures with radio contrast media.

Forced diuresis along with the use of allopurinol is effective preventing AKI in patient with TLS.

CHRONIC KIDNEY DISEASE

DEFINITON

Irreversible loss of renal function that eventually requires renal replacement therapy

Patient has 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 1 or more of the following features:

• Abnormalities in the composition of the blood or urine• Abnormalities in imaging tests• Abnormalities on kidney biopsy2. GFR <60 mL/min/1.73 m2 for ≥3 mo, with or without the

othersigns of kidney damage described above

GFR

Schwartz formula: GFR = k x height(cm) (ml/min/1.73m²) S.Creatinine(mg/dl)

k= 0.33 for LBW infants 0.45 for term AGA infants 0.55 children & adolescent

female 0.70 adolescent male

New formula by CKD study: uses k= 0.413,Can be used for GFR between 15-75 ml/min/1.73m²In children between 1-16yr.

STAGES OF CKDStage Description GFR

(ml/min/1.73 m²)

1 Kidney damage with normal or ↑ GFR > 90

2 Kidney damage with mild ↓ GFR 60-89

3 Moderate ↓ in GFR 30-59

4 Severe decrease in GFR 5-29

5 Kidney failure <15 or on dialysis

ETIOLOGY:-

1. UNDER 5 YR (most commonly congenital abnormalities) * renal hypoplasia * renal dysplasia * obstructive uropathy * congenital nephrotic syndrome* prune belly syndrome * cortical necrosis * FSGS* polycystic kidney * renal vein thrombosis* hemolytic uremic syndrome

2.AFTER 5 YRS (acquired and inherited disorders)

* glomerulonephritis * nephronophthisis* alport syndrome

3.THROUGHOUT CHILDHOOD YEARS * cystinosis

* hyperoxaluria* polycystic kidney disease

RISK FACTORS FOR CKD H/O AKI H/O V.U.R or recurrent U.T.I Corrected or uncorrected obstructive uropathy H/O A.G.N or N.S Family H/O polycystic kidney disease Past H/O H.S.P k/c/o D.M, HTN,SLE, or vasculitis.

PATHOGENESISHyperfiltration Injury

* final common pathway of glomerular destruction

* hypertrophy of remaining nephrons* increase glomerular blood flow* ↑ glomerular filtration in surviving nephrons * progressive damage to surviving nephrons (due

to elevated hydrostatic pressure/toxic effect of proteins)

* sclerosis of surviving nephrons *leads to a vicious cycle of ↑ glomerular filtration

and hyperfiltration injury.

Proteinuria:* exerts a direct toxic effect* causes infiltration of monocytes / macrophages* enhancing glomerular sclerosis

Hypertension:* exacerbate disease progression * causes arteriolar nephrosclerosis* and hyperfiltration injury

Hyperphosphatemia :* calcium phosphate deposition in renal

interstitium and blood vessels.

Hyperlipidemia:* oxidant mediated injury

PATHOPHYSIOLOGY OF CKD

Accumulation of nitrogenous waste products due to ↓ in GFRAcidosisdue to ↓ed NH3 synthesis.Impaired bicarbonate reabsorption ↓ed net acid excretionSodium retentionexcessive renin production, oliguria Sodium wasting and urinary concentrating defectsolute diuresis,

tubular damage

Hyperkalemia↓ in GFR metabolic acidosis excessive potassium intake hyporeninemic hypoaldosteronism Renal osteodystrophy impaired renal production 1,25-DHCC

hyperphosphatemia hypocalcemia secondary hyperparathyroidism Growth retardation inadequate caloric intake renal osteodystrophy, metabolic acidosis anemia, growth hormone resistance

Anemia↓ed erythropoietin production iron deficiency, folate deficiency,vit B12

deficiency ,↓ed erythrocyte survival Bleeding tendency defective platelet function Infection defective granulocyte function,

impaired cellular immunity,indwelling dialysis catheters Neurologic symptoms (fatigue, poor

concentration, headache, drowsiness, memory loss, seizures, peripheral neuropathy)

uremic factors, aluminum toxicity, hypertension

Malnutrition anorexia,nausea,vomitting(uremic gastritis) abnormal taste sensation inappropriate dietary restrictions protein loss due to dialysis Gastrointestinal symptoms (feeding intolerance, abdominal pain)

gastroesophageal reflux decreased GI motility

Hypertension volume overload, excessive renin production

Hyperlipidemia decreased plasma lipoprotein lipase activity

Pericarditis / Cardiomyopathy uremic factors, hypertensionfluid overload

Glucose intolerance tissue insulin resistance

CLINICAL MANIFESTATIONFeatures of advanced CKD (stage 3-5)

* lethargy, fatigue,anorexia, vomiting * growth retardation* failure of thrive * anemia* hypertension

* bone diseaseLate features

* itching * severe acidosis* hyperkalemia* LVF, pulmonary edema

* uremic pericarditis * altered sensorium

LABORATORY FINDINGS* elevated BUN and creatinine* ↓ GFR* hyperkalemia * hyponatremia * acidosis* hypocalcemia * hyperphosphatemia * elevated uric acid * hypoproteinemia (if proteinuria)* normocytic, normochromic anemia * elevated serum cholesterol and triglyceride * hematuria & proteinuria(glomerulonephritis)

MANAGEMENT OF CKD AIMS OF TREATMENT* Retarding the progression of renal dysfunction *Replacing absent/diminished renal function

ROUTINE MONITORING TO BE DONE OF…*Blood studies- RFT, S.electrolytes, S.calcium & phosphorus, S.albumin, alk.phosphatase, Hb%,*S.Parathormone and bone X-rays- to detect renal osteodystrophy*ECHO- To detect LVF & cardiac dysfunction early.

STRATEGY TO SLOW THE PROGRESSION * optimal control of hypertension(<75th percentile) * reduce proteinuria(goal<300mg/m²/day) * ACE inhibitors/ ARBs are drugs of choice for both

* maintain serum phosphorus (ca x ph=<55)* prompt treatment of infections and episodes of

dehydration * correction of anemia(erythropoetin/darbepoetin-

alpha)* control of hyperlipidemia * non hypercalcemic doses of vit D analogs * prevention of obesity * avoid use of NSAID and nephrotoxic drugs

NUTRITION Assesment of adequacy of dietary intake(3-day diet record) Assesment of nutritional status(wt, wt/age,ht/age, BMI, HC)-

should be done atleast semi-annually. If there is malnutrition- 125% of RDA of calories should be

given for catch up growth Total calories = 55-60%(carbohydrates),30%(fats), 10%

(proteins)Proteins- low protein diet not recommended-diet should contain 100%RDA of protein-of that >50% should be from high biological value proteins-children on dialysis should take extra 0.4-0.8g/kg/day of protein-excessive proein intake should be avoided in children with

metabolic acidosis and hyperphosphatemia

Fats- there is ↑sed risk of CVD in CKD. -Saturated fats should be <10% of total calories -Diets rich in PUFA,MCT & complex carbs prefered.

Vitamins-100% RDA of Vit A,B1,B2,B6,B12,D,E,K, Folic acid,Cu,Zn should be taken. -Requirements in CKD:B1,B2,F.A→1mg each pyridoxine,pantoyhenic acid→10mg each vit C(50mg),vit B12(5mg),Biotin(300mg). -If GFR<40 then F.A. supplementation is needed in order to prevent hyperhomocycstinemia. -Children on PD need vit C,pyridoxine & F.A supplementation.

Restriction of dietary phosphorous: -In CKD stage 3 to 5 & 5D, 80-100% RDA should

be given. -foods rich in phosphorous should be avoided, but taking care not to cause inadequate protein intake because such foods are also rich source of proteinFood should be attractive & pleasant.Unnecessary restriction should be avoided.Infants needing top feed should receive special formula with high calorie, low sodium & phosph.If oral feeding is not adequate, supplemental NGT feeding can be given.

FLUID & ELECTROLYTE

* most patients maintain normal sodium & water balance*Usual sodium intake is allowed*2g of salt is allowed daily,no extra salt*if BP is high- restrict to 0.8-1g/day*if there is polyuria with urinary sodium loss: give high volume, low caloric density feeding with sodium supplements* high BP, edema or heart failure: require sodium restriction & diuretic therapy * fluid restriction is rarely necessary untill ESRD* hyperkalemia: restriction of dietary K+ intake

oral alkalinizing agent kayexalate

*hypokalemia- due to excessive diuretics- <3meq/l -supplements rich in potassium given*potassium intake is restricted if GFR<10 ml/min/1.73m²

GROWTH*Growth impairment occurs when GFR<50%

*Firstly t/t Nutritional deficiencies,acid-base imbalance,correct salt depletion and calcium and vit D deficiency *Short stature is long term sequelae

* growth hormone resistant state (GH ↑, IGF ↓)* abnormality of IGF binding protein

*children who remain<-2SD for ht despite adequate medical support can be given recombinant human GH (0.05mg/kg/24hrs),SC daily

* continue until the pt reaches50th percentile for MPH or achieves a final adult height or undergoes renal transplantation

CHRONIC KIDNEY DISEASE-MINERAL BONE DISEASE

The syndrome of clinical,metabolic and imaging deformities in CKD is termed as CKD-MBD.

The term osteodystrophy should be restricted to description of histological features on bone biopsy.

Most common condition seen in children is a high turnover bone disease caused by secondary hyperparathyroidism

The skeletal finding in this condition is Osteitis fibrosa cystica

Pathophysiology of CKD-MBD

* When GFR decline to 50% of normal* Decline in 1 hydroxylase activity* Decreased production of activated vit. D* ↓ intestinal absorption of calcium* Hypocalcaemia * Secondary hyperparathyroidism(to correct hypocalcemia) * Increased bone resorption * When GFR declines to 25% of normal * Hyperphosphatemia – further promotes hypocalcemia and increased PTH production

Clinical manifestations of CKD-MBD * Muscle weakness, Bone pain * Fractures with minor trauma

* Rachitic changes, varus or valgus deformity slipped capital femoral epiphysis.

* s.Ca↓, s. Ph↑, ↑alkaline phosphate, ↑PTH * Subperiosteal resorption of bone with widening of metaphysis

Treatment of CKD-MBD

* T/t goals-prevent bone deformity and normalize growth velocity *Target phosphorus levels- adolescent(3.5-5.5mg/dl) children(4-6mg/dl) *Low phosphorus diet(similac PM 60/40)

* Phosphate binders- Calcium carbonate & calcium acetate Sevelamer (Renagel) non calcium binder Avoid aluminum based binder * Vitamin D therapy-(Vit D levels

<30ng/ml(insufficiency) <15ng/ml(deficiency) - oral vit D3- 2lakh -4lakhs unit over 2-3 mnths - in CKD stg 5 active vit D analogs are used- paricalcitol,doxercalciferol * Maintain calcium / phosphorus product (Ca x PO4) at < 55

ANEMIA

* Inadequate erythropoeitin production * Iron deficiency * Folic acid , Vitamin B12 deficiency * Decreased erythrocyte survival * Erythropoeitin if Hb < 10g/dl dose 50-150 mg/kg/dose S/C 1-3

times/wk* Keep Hb between 11-12g/dl* Darbopoeitin alfa (longer acting) dose 0.45μg/kg/wk

HYPERTENSION

* Salt-restriction * Diuretic therapy * Hydrochlorothiazide 2 mg/kg/24hrs* Furosemide 1-2 mg/kg/dose * ACE inhibitors - angiotensin II blockers (Enalapril, lisiopril, losartin) for proteinuric renal disease * Calcium channel blockers (Amlodipin) * B-Blockers (propranolol, atenolol)

IMMUNIZATIONS

* Immunization according to the schedule * Avoid live vaccine if on immunosuppressive drugs* Give live vaccine(MMR& Varicella vaccine) before renal transplantation * Yearly influenza vaccine * Suboptimal response