Chronic renal failure

It is the irreversible deterioration in renal function which results from a diminished mass of the excretory, metabolic and endocrine functions of the kidney which leads to the development of the clinical syndrome of uremia.

CRF is a slowly progressive, irreversible cessation of renal function manifesting as biochemical, metabolic, fluid, electrolyte, and acid-base imbalances.

Often a gradual decline in GFR occurs over a period of years, however for diagnosis of chronic renal failure GFR must be reduced for at least 3-6 months.

Normal kidney functions

• Excretory. Excretion of waste products & drugs.

• Regulatory control of body fluid volume and composition (acid-base balance)

• Endocrine production of erythropoietin, renin and prostaglandin

• Metabolic activation of Vitamin D.

STAGES OF CRF

There are 4 stages of functional deterioration in renal failure.

1. Diminished renal reserve

• There is a mild reduction in renal function.

• Creatinine clearance decreases from normal 120 ml/min to approximately 50 ml/min.

• Increase in serum creatinine level

• Renal regulatory, excretory and metabolic functions remain intact and the patient is symptom-free.

2. Renal insufficiency

• Creatinine clearance continues to decrease to about 10 ml/min.

• Serum creatinine rises to the range of 2. 1-5.0 mg/dl.

Initial manifestations of renal insufficiency usually appear.

Further stress due to infection or dehydration intensifies the symptoms requiring therapeutic intervention.

3. Renal failure

Creatinine clearance has decreased to about 5 ml/min

Serum creatinine is greater than 8 mg/dl.

The patient is symptomatic and requires medical management.

4. Uremic syndrome

Creatinine clearance is < 5 ml/min. and o Serum creatinine is > 12 mg/dl.

The patient develops clinical manifestations in every system of the body.

PATHOPHYSIOLOGY

Hyperfiltration

Reduction in renal mass leads to hypertrophy of the remaining nephrons due to adaptive hyperfiltration.

This adaptation places a burden on the remaining nephrons that lead to progressive glomerular sclerosis and interstitial fibrosis.

Uremic toxins

Uremic toxins produce signs and symptoms in CRF

Because insulin is removed from the plasma by renal cells which degrade it intracellularly, circulating insulin levels in plasma are slight to moderately increased in most fasting uremic patients and sugar levels may become normal in previously hyperglycemic patients. Patients have a false impression that their diabetes is cured; unfortunately, now they are developing renal impairment as a complication of diabetes.

Protein metabolism

• Increased catabolism of protein.

• Reduced capacity to eliminate nitrogenous end products of protein catabolism that leads to retention of nitrogenous substances. It is a major cause of organ dysfunction resulting in the development of signs and symptoms of uremia.

Lipid metabolism

• Hypertriglyceridemia – due to increased insulin lipogenic effect and reduced lipoprotein lipase enzyme preventing lipid utilization.

• Low HDL
– Normal cholesterol

Fluid and electrolytes

Sodium retention due to impaired sodium-potassium pump leads to increased intracellular sodium and water causing volume overload, hypertension, and oedema formation.

Hypothermia

It results from retention of some toxins and the impaired sodium-potassium pump

Causes

Diabetes Mellitus

Hypertension

Urinary tract infection

Chronic pyelonephritis

Polycystic kidneys

Glomerulonephritis

Renovascular disease

Interstitial nephritis

Amyloidosis

Multiple Myeloma

Polyarteritis nodosa

CLINICAL FEATURES

Non-specific features: nausea, vomiting, malaise, pruritus-*drowsiness, diarrhoea, fits, and coma.

Features of complications: anaemia, bone pain, etc.

Urinary symptoms: The patient may present with anuria (<50ml), oliguria (<400ml), nocturia, or polyuria.

Asymptomatic: In the early stages of disease patient may be asymptomatic and renal insufficiency is revealed by the discovery of proteinuria, anaemia, hypertension or raised blood urea during a routine examination.

Symptomatic; Symptomatic uremia mostly presents with anorexia, nausea & vomiting, but it may present with symptoms of anaemia, bone disease, hypertension, hypertensive heart disease, endocrine disturbances (amenorrhoea & erectile impotence)

EXAMINATION OF UREMIC PATIENT

GENERAL APPEARANCE

• Mental status-conscious, drowsy, comatose.

• Hyperventilation – indicates metabolic acidosis

• Hiccups

– Complexion – sallow complexion due to impaired excretion of urinary pigments (urochromes) combined with anaemia.

• State of hydration: dehydration or oedema.

• In terminally ill patient: drowsiness, coma, twitching due to myoclonic jerks and epileptic seizures.

HANDS

• Half-and-half nails (Tarry’s nail): brown line of at least 1mm wide at the distal end of the nail, present in 1/3 of CRF patients.

• Anemia – pallor palmar creases

• Flapping tremors

-Look for an A/V fistula for dialysis.

ARMS

• Bruising: resulting from nitrogen retention that causes impaired prothrombin consumption, defects in platelet factor, and abnormal platelet aggregation.

• Scratch marks: due to pruritus as a result of deposition of calcium or phosphate in the skin or stimulation of nerve endings due to some retained toxin.

-Uremic frost: fine white powder present on the skin due to precipitation of high concentration of urea in sweat.

FACE

• Anemia

• Uremic fetor – the smell from the mouth due to the breakdown of urea to ammonia.

-Mucosal ulcers: due to dryness as a result of decreased saliva, thrush.

CHEST

• Auscultate heart for pericardial rub

• Auscultate lungs for pulmonary oedema, pneumonia as the patient is prone to have an infection due to immunosuppression.

ABDOMEN

• Palpate kidney for enlargement, mass, polycystic kidney.

• Auscultate renal bruit.

BACK

• Strike vertebral column with a base of fist gently to elicit tenderness due to osteodystrophy.

• Renal punch: to elicit tenderness in renal angle as a manifestation of renal infection.

• Examine for sacral oedema

LEGS

• Examine for oedema, scratch marks

• Neuropathy manifesting as loss of sensation and absent reflexes.

FUNDI

Look for retinal changes of diabetes and hypertension.

INVESTIGATIONS IN CRF

Blood Urea

• Urea is raised in CRF and is helpful in assessing renal function.

• It is synthesized mainly in the liver and is the end product of protein catabolism. About 30- 70% of urea is reabsorbed after filtration.
– Dehydration causes increased urea absorption and the GFR is underestimated.

Serum creatinine

• Creatinine is the most useful clinical test in assessing the progression of renal failure. However, at least 50% of renal function is lost before serum creatinine begins to rise. Therefore the normal level of creatinine does not rule out
impairment of renal function.

• Serial estimation of serum creatinine provides the best indication of the state of renal function in patients with CRF.

• Creatinine is the product of muscle metabolism. It is freely filtered and not reabsorbed, however, a small amount is
eliminated by tubular secretion that increases with dehydration overestimating the GFR.

Electrolytes

• Hyponatremia is common

• Potassium is normal until end-stage.

• Calcium is low and phosphate high

-Low GFR

Ultrasound kidneys

It is useful in detecting:

• Renal size; kidneys less than 10 cm are considered small.

• Hydronephrosis

• Renal mass

• Polycystic kidney

Renal biopsy

Renal biopsy is indicated when it is an unexplained renal failure with normal-sized kidneys.

Urine analysis

Proteinuria, hematuria, cast

Others

LFT, Glucose, FBE, cholesterol

MANAGEMENT

• Dietary modifications

• Treatment of complications

• Dialysis

• Renal transplantation

DIET

Protein restriction

Early protein restriction slows the progression to end-stage renal disease. Daily protein intake should be 0.6-1 g/kg.

Potassium restriction

Required when GFR falls below 10-20 ml/min. Intake less than 60 mEq/d is recommended. Advise the patient to avoid high potassium foods (e.g. bananas, coffee, tomatoes etc.)

Phosphorous restriction

The phosphorous level should be kept below 4.5 mg/dl. Avoid phosphorous rich food such as eggs, dairy
products and meat.

Carbohydrates & fat should be adequate to provide energy to the body.

Salt and water restriction

– Patient of CRF should be volume expanded as suggested by a small amount of pedal oedema. The patient should take 2-3 L/d to excrete waste products as effectively as possible by remaining intact nephrons.

– Sodium:  In the absence of oedema, cardiac failure, or hypertension, sodium restriction is contraindicated & the patient should take no added salt diet.

COMPLICATIONS IN CRF

ANAEMIA

Clinically significant anaemia develops when GFR falls below 20-25 ml/min.

It is usually normocytic normochromic anaemia caused by:

• Reduced erythropoietin production by the kidney

• Reduced red cell survival due to uremia

• Bone marrow depression due to toxic effect of uremia

. Clinical features of anaemia: dyspnoea on exertion, fatigue

Hypertension

Hypertension in CRF results from multiple factors such as:

– Salt and water retention causing volume overload

–  Hyper-reninemia

• Sympathetic stimulation causing peripheral and renal vasoconstriction.

Hypertension may develop any time in the course of renal failure even before the serum creatinine is raised.

Control of hypertension delays the progression of renal failure.

Cardiac manifestations secondary to hyperkalemia

Bradycardia, AV block, ventricular arrhythmias, and cardiac arrest.

Others

• Gout.
• Metabolic acidosis.
• Secondary hyperparathyroidism.
• Bone disease and high phosphorus (hyperphosphatemia)
• Fluid buildup.