CHRONIC RENAL FAILURE

Dr .Naved Akhter

03/09/2013

Chronic kidney disease

• The term chronic kidney disease is defined as renal injury (proteinuria) and/or glomerular filtration rate <60ml/min/1.73m2 for more than 3 months irrespective of the underlying etiology.

Prevalence of CKD in the pediatric population is

approximately 18 per 1 million.

Stages of chronic kidney disease

stages Description GFR(ml/min/1.73m2)

1. Slight kidney damage with normal or increased filtration

>90

2. Mild decrease in kidney function 60-89

3. Moderate decrease in kidney function 30-59

4. Severe decrease in kidney function 5-29

5. Kidney failure :requiring dialysis or transplantation

<15 or on dialysis

• GFR =K*ht in cm/s creatinine

• K infant – 0.45

• children- 0.55

Children < 5 year most commonly result of

Congenital abnormalities such as renal hypoplasia,dysplasia, obstructive uropathy.

After 5 year of age acquired disease(GN,

Common causes of chronic kidney disease

• Glomerulonephritisa) Idiopathic(e.g.focal segmental glomerulosclerosis.b) Secondary to systemic lupus erythematosus.c) IgA nephropathy.d) Microscopic polyarteritis. e) Henoch schonlein purpura.• Reflux nephropathy• Obstructive uropathy.a) Posterior urethral valvesb) Pelviureteric junction obstruction

c)Renal stones.• Developmental anomalies includes bilateral renal

hypoplasia & dysplasia.• Familial nephropathy

a) Alport syndrome

b) Polycystic kidneys

• Others include:

a) Hemolytic uremic syndrome

b) Amyloidosis

c) Renal vein thrombosis

d) Renal cortical nephrosis

PATHOPHYSIOLOGY OF CKD

MANIFESTATIONS MECHANISMS

1. Accumulation of nitrogenous waste products.

•Decrease in GFR.

2.Acidosis •Decreased ammonia synthesis.•Impaired bicarbonate reabsorption.•Decreased net acid excretion.

3.Sodium retention •Excessive renin production.•oliguria

4.Hypertension •Volume overload•Excessive renin production

Cont…5.Urinary concentrating defect.

•Diuresis•Tubular damage

6.Hyperkalemia •Decrease in GFR.•Metabolic acidosis.•Excessive potassium intake.•Hypoaldosteronism.

7.Renal osteodystrophy •Impaired renal production of1,25-dihydroxycholecalciferol•Hyperphosphatemia•Hypocalcemia•Secondary hyperparathyroidism

8.Growth retardation •Inadequate caloric intake•Renal osteodystrophy•Metabolic acidosis•Anemia & GH resistance

9.Bleeding tendency •Defective platelet function.

Cont…10.Anemia •Decreased erythropoietin production

•Iron deficiency•Folate deficiency•Vit B12 deficiency•Decreased erythrocyte survival.

11.Infection •Defective granulocyte function.•Impaired cellular immune function.•Indwelling dialysis catheter.

12.neurologic symptoms such as fatigue ,poor concentration, headache ,drowsiness,memory loss,seizures,peripheral neuropathy.

•Uremic factors•Aluminium toxicity.•hypertension

13.Gastrointestinal symptoms(feeding intolerance,abdominal pain)

•Gastroesophageal reflux.•Decreased GI motility.

Cont…

14.Sodium wasting •Solute diuresis•Tubular damage.

15.Hyperlipidemia •Decreased plasma lipoprotein lipase activity.

16.pericarditis,cardiomyopathy

•Uremic factor•Hypertension•Fluid overload

17.Glucose intolerance •Tissue insulin resistance.

Clinical features

• Children with CKD from chronic glomerulonephritis can present with --edema

--hypertension.

--hematuria.

--proteinuria.• Congenital disorders(renal dysplasia and obstructive

uropathy) can present in neonatal period with-

-- failure to thrive

--polyuria

--UTI

--overt renal insufficiency.

• Uremic Syndrome • Symptomatic azotemia • Fever, Malaise • Anorexia, Nausea • Mild neural dysfunction • Uremic pruritus

Patients with renal osteodystrophy presents with:• Swellings• Muscle weakness• Bone pain• Fractures• Varus and valgus deformities• Neck swan deformity & other deformities.

• Children with familial juvenile nephronophthisis can present with—headache

---fatigue

---lethargy

---anorexia

---vomiting

---polydipsia

---growth failure

Late features with extreme reduction of GFR are:

---itching

---severe acidosis

---hyperkalemia

---left ventricular failure

---Pulmonary edema

---pericarditis

---altered sensorium

The physical examination in patients with CKD can reveal-

---pallor

---sick appearance

---short stature

---bony abnormalities

---edema

---signs of extracellular volume overload

Investigations

• Blood investigations - CBC

-S.urea (13-43mg%)

-S.creatinine (0.8-1.5mg%)

-S.sodium (136-149meq/l)

-S.potassium (3.8-5.2meq/l)

-S.calcium (8.4-11mg%)

-S.phosphate (2.3-4.5mg%)

-Alkaline phosphate (25-250u/l)

-S.ferritin levels: 1-5months (50-200mcg/l)

6months – 15 yrs (7-140mcg/l)

Urine routine/microscopic examination.

a. Urinalysis, microscopic exam, quantitation of protein in urine (protein:creatinine ratio)

b. Calculation of creatinine clearance and protein losses.

• Consider complement levels, protein electrophoresis, antinuclear antibodies, ANCA(anti neutrophil cytoplasmic antibody)

• Renal biopsy - particularly in mixed or idiopathic disease

Radiographic Evaluation

a. Renal Ultrasound - evaluate for obstruction, stones, tumor, kideny size, chronic change .

b. Doppler ultrasound or angiography or spiral CT scan to evaluate renal artery stenosis .

c. MRA preferred over contrast agents.

2. Bone Evaluation :a. Severe secondary hyperparathyroidism can lead to

osteoporosis .b. Bone densitometry should be done on patients with CRF

Management of CRF

• Initially, management aims at maintaining nutrition and retarding progression of the renal failure.

• Later ,treatment of complications and replacement therapy in

the form of dialysis or transplantation is required.

DIET• A diet high in polyunsaturated fats,such as corn oil ,

medium chain triglycerides and complex carbohydrates.• Proteins - intake should be 1-2 gm/kg/day• Sodium-needs to be individualized,some requires salt

supplementation,others may require salt restriction.• Potassium: dietary potassium should be avoided.

• Calcium: Ca supplements are given as calcium carbonates,dairy products to avoid to restrict phosphate intake.

• Vitamins B1,B6,B12 and folic acid suppplementation.

• HYPERTENSION• Salt restricted diet (2-3gm/24hr)• Diuretic therapy: thiazide

diuretics(hydrochlorothiazide)2mg/kg/24hr given in children with mild renal dysfunction(CKD stages 1-3)

• In stage 4 CKD,loop diuretics,furosemide(1-2mg/kg/dose bd or tid)

• Hypertension in patients with proteinuria and GFR >30ml/min/1.73m2 to be treated with Angiotensin converting enzyme(ACE)inhibitors-enalapril(0.005-0.01mg/kg/dose) q i/v 8-24hrly,lisinopril.

• Angiotensin II blockers (losartan)is choice of tratment for proteinuric disease and to check the disesase progression to ESRD.

• Ca channel blocker(amlodipine)• Beta blockers(propranolol & atenolol) and centrally acting

agents clonidine may be given to CKD pts. whose B.P does not get controlled by dietary Na restriction,ACE inhibitors & diuretics.

Anemia • Anemia results in patients with CKD 3-4 stages.• Iron(2-4mg of elemental iron/kg/day PO and folic acid

0.1mgiday supplementation.• Patients on hemodialysis shouldv receive i/v iron

supplementation.• Recombinant human erythropoietin(rHuEPO) is to be given

in dosage of 50-150mg/kg/dose subcutaneously 1-3 times weekly ,if Hb <10mg/dl

• Pts resistant to rHuEPO,may be given darbepoetin alfa(Aranesp)at a dose of o.45 mcg/kg/wk.

• PRBC transfusion,if Hb<6mg/dl.

GROWTH• Optimization of caloric and protein intake .• Recombinant human GH(rHuGH) 0.05mg/kg/24hr s/c ,with a

goal of normal height velocity for age & continues until the patient reaches the 50th percentile for midparental height or achieves a final adult height or undergoes renal transplantation.

Renal osteodystrophy• Low phosphorous diet• Infants should be given low phosphorous formula similac

60/40• Phosphate binders-calcium carbonate and calcium acetate.• the starting dose is 30-50 mg/kg/day of calcium.

• Vitamin D therapy• Pts with low 25(OH)D levels should be treated with

ergocalciferol.• Pts with normal 25(OH)D level but elevated PTH leve lshould

be treated with 0.01-0.05mcg/kg/24 hr of calcitriol (rocaltrol,0.25mcg capsules or 1mcg/ml suspension).

• Infections• UTI and other infections should be promptly treated with

effective and least toxic drugs.

• Immunization• Children with CKD should receive complete vaccination in

order to prevent infection associated morbidities.• Vaccination against Hepatitis b is relevant since dialysis and

recurrent hospitalization exposes patients to risks of blood borne pathogens.

• Live vaccines are contraindicated after renal transplant because of immunosuppression.

• Children who have not completed their immunisation schedule prior to transplantation will remain at risk of varicella,measles,mumps and rubella.

END STAGE RENAL DISEASE

• ESRD represents the stage in which a patient’s renal dysfunction has progressed to the point at which homeostasis and survival can no longer be sustained with native kidney function and maximal medical management.

• In ESRD,the GFR corresponds to 5-10ml/min/1.73m2• At this point ,renal replacement therapy(dialysis or renal

trasplantation ) becomes necessary.• Chidren with ESRD required a period of dialysis before

transplantation can be performed.• It is recommended that plans for renal replacement therapy

be initiated when a child reaches stage 4 CKD.

1

• Time to initiate dialysis is based on the combination of the biochemical and clinical characteristics of patient including refractory fluid overload, electrolyte imbalance, acidosis, growth failure or uremic symptoms including fatigue, nausea.

• Age is defining factor in dialysis modality selection• 88% of infants and children from birth to five years of age are

treated with peritoneal dialysis and 54% of children >12 years of age are treated with hemodialysis.

Indications for hemodialysis

a. Uremia - azotemia with symptoms and/or signs b. Severe Hyperkalemia c. Volume Overload - usually with congestive heart failure

(pulmonary edema) d. Toxin Removal - ethylene glycol poisoning, theophylline

overdose, etc.

Procedure for Hemodialysis

• For hemodialysis require vascular access either an arteriovenous fistula or graft or a double lumen indwelling catheter in a central vein(internal jugular,subclavianor femoral vein)

• During HD session,blood is circulated through an extracorporeal circuit that includes a hollow fiber dialyzer.

• Anticoagulation of circuit is achieved by systemic heparinization

• The procedure requires high degree of technical expertise and continuous monitoring.

Efficacy of hemodialysisa. Some acids, BUN and creatinine are reduced

b. Phosphate is dialyzed, but quickly released from bone

c. Very effective at reducing intravascular volume/potassium

d. Once dialysis is initiated, kidney function is often reduced

e. Not all uremic toxins are removed and patients generally do not feel "normal"

f. Response of anemia to erythropoietin is often suboptimal with hemodialysis

Renal transplantation• Treatment of choice in children with ESRD.• Children are excellent candidates for renal transplantation

due to lack of comorbidities.• Contrindications :• Acute infection• Untreated malignancy• Chronic hepatitis B infection.

• Pre transplant evaluation of the recipient• Socioeconomic factors to be considered before undertaking

renal transplant.• ABO blood group compatibility and a negative lymphotoxicity

T cell cross match between recipient and donor are required.• Appropriate immunization should be given.• Nutritional status should be optimized.• The cause of ESRD should be investigated since certain

disease can recur in the graft.

• Cross-match• Each recipient is cross matched with the prospective living or

deceased donor prior to transplantation.• Recipient ‘s serum is tested against donor T and B cells to

detect any preformed antibodies.• Conventional cross matching is done by lymphocytotoxicity

assay,pretreatment of serum with dithiotriol(DTT)that breaks s-s bonds in IgM antibodies differentiates between auto and allo antibodies.

• Sensitivity of cross match has increased many fold by antihuman globulin enhanced CDC,ELISA and flow cytometry technique.

• Donor evaluation• Donor work up includes:• Thorough evaluation of medical history,physical examination,• Determination of blood group and HLA typing,liver and kidney

function tests including urinalysis and 24 hr urine protein estimation.

• Screening for infections( HIV,Hep B & C,Tuberculosis and syphillis).

• Screening for malignancy and cardiac status.

Transplant procedure• In children who weighs> or equal to20kgs allograft is placed in

the illiac fossa,renal artery and vein are connected to child’s common or external illiac artery and vein respectively as end to side anastomosis.

• In infants and young children<20 kg the kidney is placed higher up in the abdomen in the retroperitoneum,renal artery and renal vein are connected to the side of the aorta and inferior vena cava close to the bifurcation.

• The ureter is generally anastomosed to the bladder using ureteroneocystostomy.

Complication of transplantation

• Delayed allograft function• DGF refers to transplants that fail to function after blood flow

through the allograft is established.• Causes of DGF: • Hyperacute rejection• Renal artery or venous thrombosis.• Acute tubular necrosis.• Urinary obstruction or leak.

• Surgical complications• Lymhocele• Perirenal serous fluid collection• Hematoma• Urinary leaks and obstruction at UVJ, uretrovesical junction.

Allograft rejection• AR usually occurs in the first 3 months• Indicated by asymptomatic rise in s.creatinine level• Cyclosporine/tacrolimus toxicity,dehydration,urinary

obstruction should be excluded.• The Dx of AR is made by graft biopsy.• Donor specific antibodies should be obtained in case of

suspected AMR.• Delayed rejection are due to non adherence with therapy.

Other complications• Infections• 1 month: wound infection,UTI, pneumonia & fungal infections• Btw 1-6 months infections include CMV,EBV,HSV,varicella

zoster and fungal infections.• Hypertension is the most common complication.• Hematological complications:anemia,erythrocytosis,and

rarely leukopenia & thrombocytopenia.• Metabolic complications:

hypomagnesemia,hypophosphstemia,hypercalcemia,hyperkalemia,tubular acidosis & dyslipidemia.

• Recurrence of primary disease in allograft.• De novo glomerulonephritis• Excessive wt.gain,growth retardation,IDDM,osteopenia &

decreased bone mass.

Long term management of transplant recipient

• Minimum immunosuppression without risking rejection.• Optimize BP control.• Maintain optimal weight,growth and nutrition.• Sreen and manage dyslipidemia.• Maintain age appropriate immunization.• Optimize bone health.• Screen for malignancy.• Optimize child and family’s quality of life.

Thank you