Dr. Jumana Albaramki

Chronic renal failure

Plasma Cr does not rise until renal function has fallen to less than half normal levels

Cr affected by muscle bulk

GRF= height x k /creat in mg/dl ml/min/1.73 m2

Normal progression of GFR with age

Creatinine with age

presentation

AsymptomaticAnorexia,lethargyPolydipsia,polyuriaAnemia,HTNFTT,bone osteodystrophyCauses:

1.Structural congenital malformations2.Hereditary nephropathy

3.Glomerulonephritis

Management

Investigations:FBC,iron studiesEUC, biocarbonte,Ca,PO4,ALP,PTHUrine protein,lipid profileAttention:

Nutrition,fluid.growth,anemia,HTN,renal osteodystrophy

Prevention of progression of CRF

1.Proteinuria:due to hyperfilteration,ACEI,ARB dilate afferent art and reduce intraglomerular pressureACEI cause anemia,high K,Cr, cough

2.HTN3.Dyslipidemia

PTH

Mobilizes Ca from bones

Decrease renal tubular absorption of PO4

Increase renal tubular absorption of Ca

Promote 1 alpha hydroxylase

Disorders of Bone Mineral Metabolism in CKDReduced 1,25 OH vit D impairs intestinal Ca absorption leads to low Ca and increase PTH stimulates 1hydroxylase increase Vit D,Ca.Calcemic response to PTH is reduced CKDCa major regulator of parathyroids High PO4 increase FGF23 increase excretionHigh PO4 stimulte PTH,lowers CaAcidosis impairs bone mineralization

Clinical ManifestationsBone painMyopathy due uremic toxins,carnitine defSkeletal deformities:bowing,genu valgum,ricket changes of widening of metaphyseal regionsSlipped epiphyses,proximal femur,presents as limping,waddling gaitFracturesVascular calcification (maintain PO4 X Ca <65 mg2/dl2)

Biochemistry

Ca low or normal,high in low turn over,tertiary hyperparathyroidism, Tx with calcitriol,volume depletionPO4 high is age dependantPTH high,ALP highXrays detect subperiostal resorption,

Treatment

Optimal control of PO4 by diet ,phosphate binders (Ca carbonate 40%elemental Ca),dialysis not enough,to be taken with meals.

Sevelamer HCL.:lower risk of hypercalcemia,lower lipids,same efficacy as CaCO3 in lowering PO4.

maintain PO4 X Ca <55mg2/dl2 in adults, <65mg2/dl2 in chidren

Vitamin D:10-60ng/kg/day,increase PO4,Ca,given daily or intermittentCalimimetic,parathyroidectomy

Target PTH in children with CKDCKD stageGFR (ml/min

x1.73 m2)Target PTH range

260-8935-70pg/ml

330-5935-70pg/ml

415-2970-110pg/ml

5) PTH resistance

<15200-300pg/ml

Histologic classification of renal osteodystrophy

TYPEEtiologyDescriptionComments

High turn over

Ostitis fibrosa

hyperparathyroidism

High bone formation,resorption,woven bone,marrow fib

Common unTX,skeletal deformitis

Low turn over,adynamic

Low PTH,Ca,vit D,

Low bone formatn,resorptn

Low osteoid

Fractures,calcifications

osteomalaciaAL,acidosisOsteoid,demineralized bone

Anemia in CRDErythropoietin DeficiencyBlood loss (HD lines,GIT losses due to impaired platelet function)Decreased RBC survivalHyperparathyroidism decrease BM production.Aluminum toxicityIron deficiencyVitamin B12,folate deficiencyInflammation,infection

Clinical effects of anemiaSystemic symptoms of fatigue,loss of appetite,decrease exercise toleranceCVD:LVHAnemia increase mortalityEvaluation:FBC,ret,ferritin,iron,TIBCTSAT:Iron/TIBC should be >20%Target Hb levels based on KDOQI guidelines is between 11-13Ferritin be above 100 in predialysis patients

ESArHuEPO s.c. as 100 U/kg/week in two doses in predialysis,PDrHuEPO i.v. as 150 U/kg/week in three doses in HD.S.c. longer half life than ivComplications:HTN,seizures,iron defiency,thrombosis,EPO antibodiesNew darbepoetin-:longer T1/2, every 2 wk

Iron thearpy

iron not to be given with food,phosphate binders3-5mg/kg elemental ironIV iron in HD as iron sucroseVarious oral preparations as ferrous sulphate,ferrous gluconate

nutritionAdequate nutrition to promote growth,prevent complications of uremia,bones.Protein intake 1.1 g/day 1-6 yHigher protein in dialysisLow phosphate,potassium diet

Vitamin but vit A,minerals as folic acidSpecial formula low in K,PO4,increase energy by adding lipid,sugarSalt supplements in tubular losses

Causes of growth failure in CKDGenetic factors:gender,parental height,syndromesAge of onset of CKDResidual renal functionTreatment modalityEnergy malnutritionWater and electrolyte disturbances:renal dysplasia needs salt.

Metabolic acidosisAnemia,renal osteodystrophy

Gonadotropic hormone axis

Growth hormone levels are normal to highGH resistance due to low GH receptor expression or post-receptor signaling defect.

IGF1 levels are high and there is resistance to its action

Treatement of growth failureAdequate caloric intake to 100% of RDATreatment with alkali,saltCalcitriolGrowth hormone:benefit more in pre endsatge CKD,than dialysisPrepubertal start cause a marked pubertal growth spurt.

Treatment of ESRDPeritoneal dialysis:CAPD,NIPDCCPD :Uses an automated machine with 7 night cycles with a long day time dwellAcute intermittent hemodialysis:needs vacular acsess as AV fistula,permcathRequires 3 X 5 hour sessions/weekDiffusion through a semipermeable membrane,ultrafilteration of fluids

Transplantation

Living or cadervic donons,HLA matchingNeeds long immunosuppression with steriods,CNI, mycophenolate acetateProblems :rejection,hypertension,infection,obstruction,chronic allograft nephropathyLRD 1 year graft survival of 91%,5 years of 74 %CRD 1 year graft survival of 80%,5 years of 60 %

Dialysers