Complications of chronic renal failure

1. Anaemia:

a. Erythropoietin deficiency

b. Bone marrow toxins retained in renal failure

c. Increased red cell destruction

d. Abnormal red cell membranes causing increased osmotic fragility

e. Increased blood loss due to occult gastrointestinal bleeding, blood sampling, blood loss during haemodialysis or because of platelet dysfunction

f. ACE inhibitors interfere with control of endogenous erythropoietin release.

2. Bone disease: renal osteodystrophy (various bone disease in chronic renal failure). Decreased renal production of 1a-hydoxylase enzyme leads to decreased 1,25-(OH)2D3. This results in gut calcium malabsorption.

a. Hyperparathyroid bone disease: Phosphate retention due to reduced excretion by kidney results in increased PTH synthesis and release. PTH promotes reabsorption of Ca from bone and increase renal tubular reabsorption of Ca.

b. Osteomalacia: 1,25-(OH)2D3 deficiency and hypocalcaemia impairs osteoid mineralization and cause osteomalacia.

c. Osteosclerosis: Sustained excess PTH cause increased bone density and leads to osteosclerosis.

3. Skin disease such as pruritus (itching) mainly due to retention of nitrogenous waste products of protein catabolism.

4. Gastrointestinal complications:

a. Increased risk of peptic ulceration and acute pancreatitis.

b. Constipation

Probably attributable to serum amylase elevation of up to 3 times normal due to retention of high-molecular-weight forms of amylase normally excreted in urine.

5. Metabolic abnormalities:

a. Gout: urea retention due to chronic renal failure may results in gout.

6. Cardiovascular disease

7. Cardiac failure

Management of Chronic Renal Failure

1. Treat underlying cause(s)

2. Renoprotection

Goals of treatment

BP <>

Proteinuria <>

Treatment

Patients with chronic renal failure and proteinuria > 1 g/24 hours:

ACE inhibitor increasing to maximum dose

Add angiotensin receptor antagonist if goals are not achieved

Add diuretic to prevent hyperkalaemia and help to control BP

Add calcium-channel blocker (verapamil or diltiazem) if goals not achieved

Additional measures

Statins to lower cholesterol to <>

Stop smoking (threefold higher rate of deterioration in CRF)

Treat diabetes (HbA1c <>

Normal protein diet (0.8-1 g/kg bodyweight)

3. Correction of complications

Hyperkalaemia

Dietary restriction of potassium intake

Stop drugs causing potassium retention

Ion-exchange resins to remove potassium in gastrointestinal tract (e.g. Sodium polystyrene sulfonate)

Acidosis

Sodium bicarbonate supplements

Hypocalcaemia

Calcium carbonate supplements

Calcitrol or Vitamin D analogue (e.g. alfacalcidol)

Hyperphosphataemia

Oral calcium carbonate / acetate reduces absorption of dietary phosphate

Sevelamar used as gut phosphate binder

Nicotinamide to block intestinal sodium/phosphate cotransporter

Anaemia

Synthetic human erythropoietin

Male erectile dysfunction

Oral phosphodiesterase inhibitor (e.g. sildenafil, tadalafil, vardenafil)

4. Renal replacement therapy

Haemodialysis

Blood from patient pumped through array of semi-permeable membranes

Blood comes in close association with dialysate and substances are filtered down their concentration gradients

Approximately 4-5 hours’ treatment 3 times a week

All patients anticoagulated (e.g. heparin)

Haemofiltration

Removal of plasma water and dissolved constituents across semi-permeable membrane

Replacement with solution of desired biochemical composition

22L exchange 3 times a week

Peritoneal dialysis

Utilizes the peritoneal membrane as a semi-permeable membrane

Tube placed into peritoneal cavity and dialysate run into cavity

Dissolved substances pass into dialysate down concentration gradients

Fluid changed regularly to repeat process

Transplantation

Surgical anastomosis of human kidney on to iliac vessels of recipient

Donor ureter placed into recipient’s bladder

Immunosuppressive treatment needed (e.g. corticosterioids, azathioprine, ciclosporin)

Sources: Kumar and Clark, Clinical Medicine

Prognosis

Chronic Kidney Disease

The prognosis of patients with chronic kidney disease is guarded as epidemiological data has shown that all cause mortality (the overall death rate) increases as kidney function decreases.[6] The leading cause of death in patients with chronic kidney disease is cardiovascular disease, regardless of whether there is progression to stage 5.[6][7][8]

While renal replacement therapies can maintain patients indefinitely and prolong life, the quality of life is severely affected.[9][10] Renal transplantation increases the survival of patients with stage 5 CKD significantly when compared to other therapeutic options;[11][12] however, it is associated with an increased short-term mortality (due to complications of the surgery). Transplantation aside, high intensity home hemodialysis appears to be associated with improved survival and a greater quality of life, when compared to the conventional three times a week hemodialysis and peritoneal dialysis.[13]

NEPHROTIC SYNDROME

The prognosis depends on the cause of nephrotic syndrome. It is usually good in children, because minimal change disease responds very well to steroids and does not cause chronic renal failure. However other causes such as focal segmental glomerulosclerosis frequently lead to end stage renal disease. Factors associated with a poorer prognosis in these cases include level of proteinuria, blood pressure control and kidney function (GFR).

PATHOPHYSIOLOGY

CHRONIC RENAL FAILURE
Pathophysiology
• GFR remains the same initially due to hyperfiltration and nephron hypertrophy
• It is only after total GFR has dropped below 50% that urea and creatinine levels in the blood become to increase due to poor clearance  plasma creatinine value will roughly double in a 50% reduction in GFR
• Hyperfiltration and hypertrophy, while initially beneficial, are thought to be a major cause of progressive renal dysfunction
 increased glomerular capillary pressure  damaged capillaries  segmental glomerulosclerosis  global glomerulosclerosis
• Increased potassium, urea and creatinine in both chronic and acute renal failure
• Chronic can be differentiated as it also associated with
o Anaemia  inadequate EPO
o Bone deficiency low calcium, increased phosphate and overactive PTH
o Key finding in ultrasonography is small kidneys due to atrophy and fibrosis
Disease Processes seen in CRF
o Anaemia – inadequate EPO produced in kidneys
o Vascular disease – this is the major cause of death in chronic renal failure.
o Hypertension – results from hypervolaemia from sodium and water retention. May be associated with excess renin retention
o Dehydration – some patients preserve fluid but loose tubular function so a very dilute urine is excreted which can lead to dehydration
o Skin –
 Uremic frost – high levels of urea see crystals deposited on skin
 Itch – often arises with secondary or tertiary hyperthyroidism
 Pallor (anaemia) or skin pigmentation can occur
o Gastrointestinal – nausea, vomiting, anorexia and heartburn are common
o Endocrine
 Men – loss of libido, impotence, decreased sperm count
 Women – loss of libido, reduced ovulation and infertility
o Neurological and Psychiatric – untreated, renal failure can cause fatigue, diminished consciousness and even coma. Tremor, increased muscle tone and agitation often accompany this. Glove and stocking sensory loss and distal muscle weakness is common.
o Immunological – uremia suppresses the function of immune cells and dialysis can inappropriately activate immune effectors, such as complement.
o Hyperlipidemia – this is common due to decreased catabolism of triglycerides.
o Cardiac disease – pericarditis is more likely if urea or phosphate levels are high, or if there is severe secondary hyperparathyroidism.

Investigation for Chronic Kidney Disease

Urinalysis
Testing of urine is a basic test for the presence and severity of kidney diseases. 24-hour-collection is a general investigation for kidney diseases. The collected urine is then analysed through dipstick, or microscopy.

What to look for?
- Clear / cloudy?
- Colour change
>>>large amount of RBC stains urine pink or red i.e. haematuria
- Urine pH
>>>normal pH between 4.6 – 8
- Urine volume in 24 hours
- Presence of haemoglobin / glucose / protein / leucocyte esterase / nitrites / ketones / creatinine
>>>the above substances is sometimes present in small quantities in the normal population
>>>protein : creatinine ratio is almost as accurate as 24hr urine collection in diagnosing nephrotic syndrome
- Casts / lipids / organisms can be identified through urine microscopy

Any positive findings should be further investigated as they can be transient, of no prognostic importance, or indicative of other diseases. Other evidences of renal disease e.g. abnormal renal function, or clues from patient’s history, examination etc. should be taken into account for the diagnosis.

Blood test
- Blood urea nitrogen (BUN) & serum potassium increase in kidney diseases
- Serum creatinine increases due to decrease excretion via urine in kidney diseases

Glomerular Filtration Rate
The functional unit of kidneys, nephrons, is responsible for the controlling the amount of substances that stay in plasma or excreted via urine. To assess the renal excretory capacity, the ideal substance should be freely filtrated across the glomerulus, neither reabsorbed nor excreted into renal tubules, in a steady state concentration in plasma, and easily and reliably measured – which, does not exist.
Creatinine is universally used for the test, despite its varying concentration with diet, gender, muscle mass etc. With an impaired renal function there is correspondingly more tubular creatinine secretion, while a fall in GFR.

Renal imaging
Ultrasound is by far the most commonly used technique for screening and investigation. The imaging provides information of:
- Renal size, which is usually in proportion to body weight, between 9 - 12cm
- Shape, symmetry of kidneys
- Renal cysts, tumour, stone, obstruction
Small kidneys are noted in person with chronic renal disease.

Contrast study of kidneys is less common as person with pre-existing renal impairment, advanced age, diabetes etc. have an increased risk of contrast-induced nephropathy.

Renal biopsy
This is a highly specialized investigation to diagnose renal disease, especially when person presents with unexplained reduction in renal function. The test however, should only be performed after careful consideration of the risk to benefit ratio.

signs/differention with Cardiac Failure

A rise in hydrostatic pressure occurs in cardiac failure. A fall in oncotic pressure occurs in nephrotic syndrome syndrome and liver failure (more complicated than that, but one of the key distinctions).

Oncotic pressure, or colloid osmotic pressure, is a form of osmotic pressure exerted by proteins in blood plasma that usually tends to pull water into the circulatory system.
Throughout the body, dissolved compounds have an osmotic pressure. Because large plasma proteins cannot easily cross through the capillary walls, their effect on the osmotic pressure of the capillary interiors will, to some extent, balance out the tendency for fluid to leak out of the capillaries. In other words, the oncotic pressure tends to pull fluid into the capillaries. In conditions where plasma proteins are reduced, e.g. from being lost in the urine (proteinuria) or from malnutrition, the result of low oncotic pressure can be excess fluid buildup in the tissues

Hydrostatic pressure within blood vessels tends to cause water to filter out into the tissue. This leads to a difference in oncotic pressure… etc

*Starling equation

Starling's equation states that the rate of leakage of fluid is determined by the difference between the two forces and also by the permeability of the vessel wall to water, which determines the rate of flow for a given force imbalance.

In terms of differences in signs of the disease, they’re hard to separate, as often chronic renal failure leads to cardiac failure, but the key distinctions can be found in the contents of the blood – tests demonstrating accumulation of sulfates, phosphates, uric acid, etc. being indicative of renal failure.

Nephrotic Syndrome

Glomerular filtration rate

• Measures the volume of filtrate formed per minute
• Is usually constant – normally is about 90-120 ml/min (is lower in the elderly)
o Autoregulation between 70-150 mmHg keeps it constant
 Myogenic mechanism (increased blood pressure causes arteriole to constrict, and vice versa)
 Macula densa (acts according to [NaCl]
• GFR = NFP (net filtration pressure) x Kf
o NFP = P (gc) – P (bs) – π (gc)
 Gc = glomerular capillary
 Bs = bowman’s space
o Kf = glomerular filtration co-efficient = hydraulic conductivity x glomerular capillary surface area
• GFR falls with:
o Decrease in intrarenal blood flow
o Damage to or loss of glomeruli
o Obstruction to the filtrate through the tubule


Creatinine clearance
• Is used to measure the GFR – once the serum creatinine is elevated, it is a good guide to GFR, and can measure further deterioration
o Serum creatinine does not rise above normal until there is a 50-60% reduction of the GFR
• The level of creatinine in the blood is dependent on age, sex and muscle mass – not affected much by protein intake, unlike urea
• Inulin is the standard
o not used in clinical practise because it is not practical, even though it is only excreted through glomerular filtration
• Creatinine is excreted by both glomerular filtration and tubular secretion
o However, very little is excreted by tubular secretion, so it is basically like inulin
• urine is collected over a period of 24 hours
o plasma level measured within this 24-hour period
o U (urine clearance of creatinine) = V (rate of urine flow) / P (plasma creatinine concentration)


Albumin
• A blood protein – provides the plasma oncotic force
• As the blood passes through the glomerulus, plasma is filtered into Bowman’s space
o Thus, the concentration of albumin rises within the glomerulus
o This draws fluid back into the glomerulus as it exits Bowman’s capsule


Nephrotic syndrome - glomerulopathy
• Hypoalbuminaemia
o Urinary loss of more than 3.5 g daily in adults
o Albumin synthesis rate is increased HOWEVER
 Increased catabolism of reabsorbed albumin in the proximal tubules
 High dietary intake of protein = decreased plasma albumin concentration
• Can be prevented by ACE inhibitors – prevents the increase in urinary albumin excretion due to high protein diet
• Proteinuria
o Partly due to structural damage of the glomerular basement membrane
 Increase in the size and number of pores – passage of more and larger molecules
o Partly due to the reduction of the negative charge components in the glomerular capillary wall
 Proteins not repelled = heavy proteinuria
• Hyperlipidaemia
o Increase in LDLs, VLDLs and intermediate –density lipoproteins (IDLs)
o No change in HDLs
o Is due to increased synthesis of lipoproteins and is also a direct result of low plasma albumin
o Reduced clearance of triglycerides with lipoproteins (VLDLs and chylomicrons) due to albuniuria
• Oedema due to hypoalbuminaemia
o Lower plasma oncotic pressure  less plasma is reabsorbed once is passes across the capillary wall

Causes of chronic renal failure

Causes of chronic renal failure
* Diabetes. Diabetes mellitus is a leading cause of chronic kidney failure in the United States.
* High blood pressure (hypertension). Elevated blood pressure can damage the glomeruli and ultimately cause the nephrons containing damaged glomeruli to lose their ability to filter waste from your blood.
* Obstruction of urine flow. An enlarged prostate, kidney stones or tumors, or vesicoureteral reflux — a condition that results when urine backs up into your kidneys from your bladder — can block urine flow, increasing pressure in your kidneys and reducing their function.
* Kidney diseases. These include clusters of cysts in the kidneys (polycystic kidney disease), kidney infection (pyelonephritis) and inflammation of the glomeruli (glomerulonephritis), a condition that causes your kidneys to leak protein into your urine and damages nephrons.
* Kidney artery stenosis. This is a narrowing or blockage of the kidney (renal) artery before it enters your kidney, which impairs blood flow and leads to kidney damage.
* Toxins. Ongoing exposure to fuels and solvents, such as carbon tetrachloride, and lead — in lead-based paint, lead pipes, soldering materials, jewelry and even alcohol distilled in old car radiators — can lead to chronic kidney failure.

References
• Mayoclinic.com

Diagnosis of Chronic Renal Failure

Some signs of chronic renal failure are more obvious than others. These are:

* increased urination, especially at night
* decreased urination
* blood in the urine (not a common symptom of chronic renal failure)

Other symptoms aren't as obvious, but are a direct result of the kidneys' inability to eliminate waste and excess fluid from the body:

* puffy eyes, hands, and feet (called edema)
* high blood pressure
* fatigue
* loss of appetite
* nausea and vomiting (this is a common symptom)
* thirst
* bad taste in the mouth or bad breath (ammonia)
* weight loss
* generalized, persistent itchy skin
* muscle twitching or cramping
* a yellowish-brown tint to the skin

As the kidney failure gets worse and the toxins continue to build up in the body, seizures and mental confusion can result.

Being diagnosed with chronic renal failure can be very frightening. The future of the condition, however, depends on the medical problem that caused the kidney failure, how much kidney damage has occurred, and what, if any, complications are present.

Some of these complications include:

* anemia
* increased risk of bleeding
* hypertension (high blood pressure)
* increased risk of infection
* dehydration
* seizures
* brittle bones
* malnutrition