Crf

Dr. Abdur Rahman EmooMedical Officer

Department of Cardiology

Dhaka National Medical College Hospital

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Chronic renal failure (CRF) refers to an irreversable deterioration in renal function classically develops over a period of years

Initially it is manifest only as a biochemical abnormality, loss of excretory, metabolic & endocrine function of kidney leads to development of symptoms & signs of CRF.

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Factor 2002 2003 2004 2005

New ESRD cases 86 82 85 93

Incidence (pmp) 150 143 149 163

Age-adjusted incidence (pmp)

232 186 317 181

Sex ratio (male/female)

55/45 63/37 65/35 52/48

Mean age (years), 6SD

46+/-15 50+/-10 47+/-13 46+/-12Diabetic nephropathy (%)

47 43 40 46

ESRD=end-stage renal disease, pmp=per million population, SD = standard deviation. 4

CRF is a permanent, usually progressive, diminution in renal function to a degree that has damaging consequences for the patient.

It is characterized by an increasing inability of the kidney to maintain normal low levels of the products of protein metabolism(such as urea), normal blood pressure and hematocrit, and sodium, water, potassium, and acid-base balance.

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Congenital & inherited : 5% Renal artery stenosis : 5% Hypertension : 5-25% Glomerular disease (IgA nephropathy is common) : 10-

20% Interstitial disease : 5-15% Systemic inflammatory disease : 5% ( SLE, Vasculitis)Diabetes mellitus : 20-40% Unknown : 5-20%

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Hypertension Reduced renal perfusion : Renal artery stenosis

Hypotension due to drug treatment

Na & water depletion

Poor cardiac function Urinary tract obstruction Urinary tract infection Nephrotoxic medication Other infection : increased catabolism & urea production

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Stages Description GFR(ml/min/1.73m2 )

Action

1 Kidney damage with normal or high GFR

> 90 Investigate (Haematuria & proteinurea)

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3

Kidney damage with slightly low GFR

Kidney damage with low GFR

60-89

30-59

Renoprotection- BP control, dietary modification

4 Severe low GFR 15-29 Prepare for renal replacement therapy

5 Kidney failure <15 or dialysis8

HypothesisGlomerular hyperfiltration/hyperperfusionGlomerular hypertension Nephrotoxicity of lipidsSimilarities with atherosclerosisGlomerular hypertrophyNephrotoxicity of proteinuriaGrowth factors Platelet-derived growth factor Transforming growth factor Mesangial/myofibroblast differentiationPodocyte injury 9

hyperperfusion GCP

loss of nephron

adaption of remaining nephrons

glom hypertrophy

mes.proliferation, focal GS, proteinuria

tubu-inters. atrophy

ESRD

glom dis

vasc dis tubu-inters dis

nephroarteriolosclerosis

HBP +hyperlipidemia

atherosclerosis

Renovascular renal failure

Ca P

PTH

Aquired renal cystic disease 10

Early

hypertensionproteinuria,elevated

BUN or sCrnephrotic syndromerecurrent nephritic

syndromegross hematuria

Late(GFR < 15 ml/min, BUN > 60

mg/dL)cardiac failureanemiaserositisconfusion, comaanorexiavomitingperipheral

neuropathyhyperkalemia metabolic acidosis

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Why is chronic renal

failure progressive?

1) Persistence of initial disease process that caused renal injury or presence of additional factors that promote renal injury (mineralization, infection, drugs, toxins, etc.)

2) Hyperfiltration theory: progression of renal disease despite resolution of primary insult.

a. PremiseA reduction in number of nephrons past some critical threshold leads to failure of the remaining nephrons. CRF has been recognized as a progressive disease.

b. MechanismRenal afferent arteriole vasodilation promotes glomerular hypertension which causes further glomerular injury and perpetuation of renal decline.

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Pathogenesis of clinical

syndrome's in CRF

A. Lethargy, fatigue, nausea and depressionThe magnitude of BUN increase is usually proportional

to uremic signs and estimates degree of other retained uremic toxins.

Additional uremic factors: include PTH, by-products of protein catabolism, and other metabolic derangements

B. Polyuria and compensatory polydipsia

1. HyperfiltrationRemnant nephrons are operating under conditions of osmotic diuresis (increased SNGFR).

2. Disruption of renal medullary gradientTubulointerstitial disease as well as high tubular flow rates may prevent maintenance of hypertonic interstitium.

3. Impaired nephron response to ADH

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C. Gastrointestinal signs

1. Uremic stomatitisHigh blood levels of urea diffuse into oral cavity, bacteria convert to ammonia = locally toxic = oral ulceration.

2. Vomiting: more common

a. Central (CNS) causes: uremic toxins stimulate

chemoreceptor trigger zone.

b. Uremic gastroenteritis

i. Local effects: urea and ammonia are locally toxic.

ii. Increased gastrin (reduced renal clearance) results in

increased gastric acid production and gastric mucosal injury.

iii. Other factors: ischemia, altered gastric mucosa turnover, and other likely contribute to gastric injury.

3. Diarrhea: uremic enterocolitis (less common) - may occur in part due to high ammonia levels. 18

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D. Anemia: normocytic, normochromic, non-regenerative.

1. Decreased erythropoietin (EPO) production: predominant cause of anemia in CRF.Intrinsic renal disease = decreased synthesis of EPO = decreased BM production of RBC's.Unidentified circulating uremic inhibitors may also play a role in inhibiting erythropoiesis.

2. Reduced RBC survival: uremic toxins decrease lifespan of circulating RBC's.

3. Blood lossa. Bleeding tendency: often noted in uremic patients.

Characterized by prolonged mucosal bleeding time. Circulating uremic toxins may cause platelet defects.

b. Gastrointestinal bleeding: may occur in association with GI ulceration and platelet defects.

E. Hypertension

1. Common complication: with chronic renal disease the incidence of HT is 50 – 93%

2. Etiology: pathogenesis not fully understood - likely multifactorial

a. BP = cardiac output X peripheral resistance

b. Possible contributory factors

i. Sodium retention from decreased renal excretion (= increased ECF)

ii. Activation of RAS (= vasoconstriction and ECF expansion)

iii. Sympathetic activation and endothelial factors

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3. Clinical signs: often clinically silent.

a. Vasculature: sustained arterial HT = muscular occlusion of small arteries = decreased perfusion (especially heart, eyes, kidneys, and brain).

b. Heart: sustained HT may result in LVH (usually subclinical).

c. Ocular lesions: dilated, tortuous retinal vessels, retinal hemorrhage, detachments, and blindness.

1. RSHP develops in patients with CRF as a result of the body's attempt to maintain calcium and phosphorus homeostasis.

2. Sequela of RSHP

a. Phosphorus: compensatory increases in PTH act to decrease Pi and increase serum Ca levels. When GFR declines to < 20%, renal adaptive mechanisms have been maximized and hyperphosphatemia occurs.

b. Calcitriol (vitamin D3)

i. Early in CRF, retained Pi = increased PTH = increased calcitriol production.

ii. Later in CRF, loss of ability to make calcitriol = elevated set-pt for Ca-induced suppression of PTH = PTH secretion despite normal to high iCa.

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c. Renal osteodystrophy

i. Increased PTH = mobilization of Ca/Pi from bone; if prolonged = ROD (demineralization and replacement with fibrous tissue)

ii. Clinically evident ROD is uncommon - occurs most often in the immature animal due to metabolically more active bone.

d. Soft tissue mineralization: most often affects the lungs, kidneys, heart, arteries, and stomach. Common in cases of advanced CRF. When Ca X Pi > 70 = soft tissue mineralization may occur.

e. Other sequela of RSHPPTH has been implicated as a "uremic toxin": malaise, anemia, neurologic signs. Mechanism of toxicity: increase PTH = increased Ca into cells = cell dysfunction or death.

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1. Normal function of the kidney in acid - base regulation.The kidney works in concert with the lungs and the blood buffer system to maintain normal acid-base homeostasis within the body.

a. The proximal renal tubule excretes majority of acid (reabsorbs HCO3, makes NH3).

b. The distal renal tubule excretes H+ (under influence of aldosterone), and also makes NH3.

2. The kidney in CRF

a. Development of acidosisCompensatory mechanisms maintain acid - base status until GFR has decreased to < 5 - 20% of normal.

b. Role of ammonia

i. H+ excretion is sustained mostly by increasing production of NH3 (H+ trapped in urine as NH4+).

ii. Even with compensatory increase in NH3 production/nephron there is a total decrease in NH3 production due to the overall loss of functional nephrons in advanced RF.

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H. Hypokalemia: serum K+ < 3.5 mEq/L.

Chronic acidosis promotes hypokalemia (increase H+ = increase aldosterone = increase K+/H+ excretion).

I. Proteinuria

Urinary protein excretion typically is increased (1.5 - 2X normal) with CRF.

Proteinuria in CRF is likely due to changes in glomerular hemodynamics rather than structural glomerular lesions.

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1. InfectionUremia is associated with impaired CMI and neutrophil function - bacterial infections are common complications of the patient with CRF.

2. Dyslipoproteinemias: common in people with CRF.

a. Pathogenesis: not completely understoodMay be associated with increased PTH levels (suppresses insulin release = decreased lipoprotein lipase = increased lipoproteins).

b. Clinical consequencesLipoproteins are entrapped in mesangium of glomeruli = taken up by macrophages = foam cells = increased production of PG's and toxic by-products = glomerular injury = glomerulosclerosis.

3. Neurological abnormalities

May note mental dullness, lethargy, tremors, peripheral neuropathies and uremic encephalopathy. Likely due to effects of PTH, hypertension, electrolyte disturbances or other uremic toxins.

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Acute Renal Failure Chronic Renal Failure

1. Hematocrit to increased (dehydration) Decreased (chronic anemia)

2. Azotemia/PO4 Elevated Elevated

3. Potassium Usually increased to decreased

4. Calcium Low to normal Low, normal, or high

5. Urinalysis Active sediment Inactive sediment

6. Urination Oliguria, anuria Polyuria

7. Weight Good nutritional status Weight loss

8. Kidneys to increased size Small, irregular

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1. CBC :

May note a normocytic, normochromic, non-regenerative anemia and variable leukocytosis (secondary to associated stress, infection or inflammation).

2. Haematinics : supplementation if deficient to optimise response to erythropoietin.

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Serum biochemistry profile :Characteristic findings may include *azotemia,

*hyperphosphatemia, *metabolic acidosis, *hypokalemia, variable calcium levels, and elevations in serum amylase and lipase (usually not greater than 2 - 4X normal). *Indicates the four most common findings on serum biochemistry profile.

Parathyroid hormone Lipid profile S. Glucose level

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Ultrasonography : to confirm/refute two equal-sized unobstructed kidneys.

Chest X-ray : heart size, pulmonary oedema. ECG : if >40 yrs or risk factors for cardiac disease Renal artery imaging

Microbiology :Hepatitis & HIV serology—if dialysis is needed.

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Group & save

Tissue typing

Cytomegalovirus if transplantation is needed

Epstein-Barr virus

Varicella zoster virus

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TreatmenTreatmentt

Aim of treatment :-

Primary disease and reversible factors

treatment

Conservative treatment

Treatment of complications of uremia

Blood purification

Renal transplantation

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Enough calorie intake: 126-147KJ

Low protein diet: 0.6-0.8g/kg/d,60% high quality protein

Essential amino acid supplement

-ketoacid supplement

Vitamin supplement: folic acid, Vit C, Vit B6, Vit D

Fluid intake—3 lt/day associated with 5-10 g/day of NaCl

& 70 mmol/day.

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Control of Blood Pressure :-ACE inhibitor is more effective than other therapies. Angiotensin-II receptor antagonists also reduce glomerular perfusion pressure.

Correction of Anaemia :- Recombinant human erythropoietin is effective in correcting anaemia .

Atherosclerosis :- Atherosclerosis is common & treated by anti-lipidemic drugs.

Hypocalcaemia :- is corrected by 1α hydroxylated synthetic analogues of vitamin-D.

Hyperphosphataemia :- is controlled by dietary restriction of foods (milk, cheese, eggs etc).

Acidosis :- is controlled by calcium carbonate (upto 3gm/day).

Infection :- it must be recognised & treated promptly.45

GI manifestation :- to reduced by using H2 receptor or proton-pump inhibitor.

Neuropathy :- results from demyelination of medulated fibres. Amitriptyline & Gabapentine used to symptom relief.

Myopathy :- Generalised myopathy due to combination of poor nutrition , hyperparathyroidism , vit-D deficiency.Muscle cramp are common & quinine-sulphate may be helpful. Patient ‘s legs are jumpy during night & is often improved by clonazepam.

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Hemodialysis

Peritoneal dialysis

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Healthy Kidney Renal ReplacementPhysical Basis

Left KidneyRight Kidney

Right Ureter

Large Intestine

Liver

Lung

Superior Vena Cava

Heart

Aorta

Spleen

Small Intestine

Left Ureter

Bladder

Diseased Kidney 48

Bacteria

Medium sizedMolecules, e.g.2-Microglobulin

Water Flow isEasily Possible

Erythrocyte,Red Blood Cell

Albumin, asExample of a BigProtein Molecule

Electrolytes

The semipermeable membrane functions similar to a fine sieve, only molecules that are small enough can pass.

Healthy Kidney Renal ReplacementPhysical BasisDiseased Kidney 49

Blood PumpAnti-Coagulation

Blood tothe Patient

Blood fromthe Patient

Dialyzer

Fresh Dialysate

UsedDialysate


BloodInflow

DialysateOutflow

Bundle ofCapillaries inthe Housing

DialysateInflow

BloodOutflow

The dialysate flows outside of the capillaries,blood within the capillaries countercurrently.

Solute Transferacross the Capillary Walls


Peritoneum

PeritonealDialysis Solution

Bag with Fresh Solution

ImplantedCatheter

Bag for Used Solution

Peritoneal dialysis is done by filling

specially composed peritoneal dialysis

solution into the abdominal cavity.

The solute transfer between blood and

the solution happens by diffusion.

The water removal from the patient is

an osmotic process.


Aorta

Connection ofRenal Artery and Vein to the PelvicVessels

Liver

Kidney Transplantin the Fossa Iliaca, Not at the Position of Healthy Kidneys

Connection ofthe Ureter to the

Bladder of theRecipient


Crf

Health & Medicine

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