WEEEK 1: KIDNEY DISEASE: PATHOGENESISI AND RENAL FAILURE

Question 1

What is chronic renal failure?

Answer 1

Chronic Renal Failure refers to as an irreversible deterioration in renal function which classically develops over a period of years.

Question 2

Describe the progress of Chronic kidney failure.
What is uremia?

Answer 2

It starts as a biochemical abnormality, eventually loss of excretory, metabolic and endocrine functions of the kidney leading to the development of the clinical signs and symptoms of renal failure which are referred to as UREMIA.

Uremia is a medical condition that occurs when there is an excess of urea and other waste products in the blood due to the impaired function of the kidneys.

Uremia can lead to a range of symptoms affecting multiple organ systems. Common symptoms include fatigue, weakness, nausea, vomiting, loss of appetite, weight loss, changes in mental status, itching, and fluid retention leading to swelling (edema).

Question 3

What is end stage renal failure (ESRF)?

Answer 3

When death is likely without renal replacement it is referred to as end-stage renal failure (ESRF).

Question 4

What is acute renal failure?

Answer 4

Sudden loss of renal function

Prerenal (dehydration, poor cardiac output sepsis)
Renal intrinsic (GN, IN, drug induced)
Post renal obstructive

Question 5

State the stages of Chronic renal failure.

Answer 5

STAGE 1: Kidney damage with normal or high GFR (> 90).

STAGE 2: Kidney damage with slightly low GFR (60-89).

STAGE 3A & 3B: Moderately low GFR (30-59).

STAGE 4: Severe low GFR (15-29)

STAGE 5: Kidney Failure: < 15 or dialysis

Question 6

State some of the causes of chronic renal failure.

Answer 6

Glomerulonephritis.
Pyelonephritis:
Interstitial nephritis
DM.
Hypertensive nephropathy
Polycystic disease
Analgesic nephropathy
Renal vascular disease
Nephrolithiasis
Prostatic hypertrophy

Glomerulonephritis:

Definition: Inflammation of the glomeruli, the small blood vessels in the kidneys responsible for filtering waste and excess fluids.
Causes: Infections, autoimmune diseases, and other factors can lead to glomerulonephritis.
Pyelonephritis:

Definition: Inflammation of the kidney tissue, usually caused by bacterial infection. It often starts as a urinary tract infection that progresses to involve the kidneys.
Causes: Bacterial infections, commonly Escherichia coli (E. coli).
Interstitial Nephritis:

Definition: Inflammation of the renal interstitium, the tissue between the kidney tubules.
Causes: Drug reactions, infections, autoimmune disorders, and other factors can lead to interstitial nephritis.
Diabetes Mellitus (DM):

Definition: A chronic metabolic disorder characterized by elevated blood sugar levels.
Kidney Involvement: Diabetes is a common cause of kidney disease (diabetic nephropathy) and can lead to progressive damage to the kidneys.
Hypertensive Nephropathy:

Definition: Kidney damage caused by long-term high blood pressure.
Consequence: Chronic hypertension can damage the small blood vessels in the kidneys, leading to kidney dysfunction.
Polycystic Kidney Disease (PKD):

Definition: Genetic disorder leading to the formation of fluid-filled cysts in the kidneys, affecting their structure and function.
Inheritance: Autosomal dominant or autosomal recessive.
Analgesic Nephropathy:

Definition: Kidney damage resulting from the long-term use of certain analgesic medications, especially those containing phenacetin or combinations of aspirin, acetaminophen, and codeine.
Risk: Decreased with the reduction in use of such medications.
Renal Vascular Disease:

Definition: Conditions affecting the blood vessels supplying the kidneys, potentially leading to impaired blood flow.
Causes: Atherosclerosis, renal artery stenosis, and other vascular disorders.
Nephrolithiasis:

Definition: Formation of kidney stones (renal calculi) in the urinary system.
Causes: Various factors, including dehydration, metabolic disorders, and certain medical conditions.
Prostatic Hypertrophy:

Definition: Enlargement of the prostate gland, which can obstruct the flow of urine from the bladder.
Impact: Can lead to urinary retention and, in severe cases, affect kidney function.

Question 7

State some rare causes of Chronic renal failure.

Answer 7

Myeloma
Amylodosis
SLE
Sceloroderma
Vasculitis
Heamolytic Uraemic Syndrome
Nephrocalcinosis.
Gout.
Renal Tumour
Cystinosis.
Oxalosis

Myeloma:

Definition: Multiple myeloma is a cancer of plasma cells that can affect the kidneys, leading to the production of abnormal proteins that may harm kidney function.
Amyloidosis:

Definition: A group of disorders where abnormal proteins (amyloids) build up in tissues and organs, including the kidneys, affecting their structure and function.
SLE (Systemic Lupus Erythematosus):

Definition: An autoimmune disease where the immune system attacks various tissues, including the kidneys. Lupus nephritis is kidney inflammation associated with SLE.
Scleroderma:

Definition: An autoimmune disease causing thickening and hardening of the skin and connective tissues. Renal involvement, known as scleroderma renal crisis, can lead to severe hypertension and kidney damage.
Vasculitis:

Definition: Inflammation of blood vessels, including those in the kidneys. Various forms of vasculitis can affect the kidneys and lead to impaired blood flow.
Hemolytic Uremic Syndrome (HUS):

Definition: A condition involving the breakdown of red blood cells, kidney failure, and low platelet count. Often associated with bacterial infections, especially E. coli.
Nephrocalcinosis:

Definition: Calcium deposits forming in the renal parenchyma, potentially leading to impaired kidney function.
Gout:

Definition: A type of arthritis caused by the buildup of uric acid crystals in the joints. In some cases, uric acid crystals can accumulate in the kidneys, leading to kidney stones and impairment.
Renal Tumor:

Definition: The development of tumors in the kidneys, which can be either benign (non-cancerous) or malignant (cancerous). Renal cell carcinoma is a common type of kidney cancer.
Cystinosis:

Definition: A genetic disorder resulting in the accumulation of cystine crystals in various organs, including the kidneys, leading to kidney dysfunction.
Oxalosis:

Definition: Excessive accumulation of oxalate in the kidneys, often leading to the formation of kidney stones and potential kidney damage.

Question 8

State the signs of chronic renal failure.

Answer 8

Pallor.
Yellow skin pigmentation.
Brown nails.
Purpura.
Bruising.
Excoriation.
Elevated BP
Cardiomegaly.
Pericarditis.
Pleural effusion.
Pulmonary or peripheral edema.
Retinopathy.
Proximal myopathy.
Peripheral neuropathy.
Arrythmias.
Encephalopathy.
Seizures.
Coma
acidosis

Question 9

State blood investigations in Chronic renal failure.

Answer 9

BLOOD:
Decreased Hb( normochromic normocytic).
Increased ESR.
U and E: increased Urea and Creatinine.
Increased glucose in DM.
Decreased calcium, Increased phosphate.
Increased alkaline phosphate ( renal osteodystrophy)
Increased parathyroid hormone.
Increased Uric acid.

Question 10

State urine investigation in Chronic renal failure.

Answer 10

Urine MCS.

24 hour urinary protein.

Creatinine clearance.

Question 11

What is the need for renal ultrasound?

Answer 11

To rule out obstruction( in obstructive uropathy), also to look at renal size. Kidney size is usually small but normal or large in DM, polycystic kidney disease., amyloidosis, myeloma , systemic sclerosis, and asymmetric renal vascular disease.

Question 12

State other investigation for Kidney failure.

Answer 12

CT KUB
CXR: may show Cardiomegaly, pleural effusion/pericardial effusions or pulmonary edema.
Bone x-rays may show renal oestodystrophy.
Renal biopsy

Renal osteodystrophy is a term used to describe a group of bone disorders that occur as a result of chronic kidney disease (CKD). The kidneys play a crucial role in maintaining the balance of minerals in the body, including calcium and phosphorus. When the kidneys are not functioning properly, it can lead to imbalances in these minerals, affecting bone health.

Question 13

Describe the management of chronic renal failure.

Answer 13

Several aspects are considered in management of CRF. These include:

Identifying the underlying renal disease.
Looking for reversible factors which worsen renal function.
Preventing further renal damage

Question 14

State some of the reversible factors in CRF.

Answer 14

1. Hypertension
2. Reduced renal perfusion:
   renal artery stenosis
   Hypotension due to drug treatment
   Sodium and water depletion
   Poor cardiac function
3. Urinary tract obstruction.
4. Urinary tract infection.
5. Other infections: increased catabolism and urea production.
6. Nephrotoxic medications

Question 15

Describe how we can retard the progression of CRF.

Answer 15

CONTROLLING BP: even a small drop in BP can save significant renal function. ACE inhibitors can decrease the rate of loss of function even if BP is normal. Aim for BP of <130/80.

DIET: match dietary and fluid intake with excretory capacity. Protein restriction is sometimes necessary. Na+ restriction may be helpful in controlling BP and prevent edema while K+ restriction is required only in Hyperkaliemia and acidosis. Acidosis can be treated with HCO-3 supplements.

IN DIABETICS ADEQUATE SUGAR CONTROL

Question 16

Describe how the following can be limited in CRF.

ANEMIA

FLUID AND ELECTROLYTE BALANCE

ACIDOSIS

INFECTION:

BLEEDING:
RENAL OSTEODYSTROPHY:

MYOPATHY:

Answer 16

ANEMIA: anemia is very common and it usually correlates with the severity of renal failure. Several mechanisms for anemia include:
Relative deficiency of erythropoeitin.
Diminished erythropoiesis due to toxic effects of uremia on marrow precursor cells.
Reduced red cell survival.

Increased blood loss due to capillary fragility and poor platelet function.
Reduced dietary intake and absorption of iron and other hematinic.
ERYTHROPETIN is given to maintain an HB >11g/dl.

FLUID AND ELECTROLYTE BALANCE: Due to reduced ability of the failing kidney to concentrate urine, a relatively high volume is used to excrete products of metabolism and a fluid intake of around 3 liters/day is desirable.

ACIDOSIS: Declining renal function is associated with metabolic acidosis which is often asymptomatic. It may contribute to reduced renal function and increased tissue catabolism.

The plasma bicarbonate should be maintained above 22 mmol/l by giving sodium bicarbonate supplements.(starting dose of 1g 8 hourly increasing as required).The increased sodium intake may induce hypertension or oedema; calcium carbonate( up to 3g daily ) is an alternative that is also used to bind dietary phosphate.

INFECTION: both cellular and humoral immunity are impaired and there is increased susceptibility to infection. Infections are the second most common cause of death in dialysis patients, after cardiovascular disease; they must be recognized and treated promptly.

BLEEDING:CRF patients have an increased tendency to bleed and this manifests in patients with advanced disease as cutaneous ecchymoses and mucosal bleeds. There is impaired platelet function and prolonged bleeding time. Adequate dialysis partially corrects the bleeding tendency

RENAL OSTEODYSTROPHY: This metabolic bone disease which accompanies CRF consists of a mixture of osteomalacia, hyperparathyroidism bone disease, osteoporosis and osteosclerosis.

To minimize the effects of CRF on bone, plasma calcium and phosphate should be kept as near to normal as possible. Hypocalcemia is corrected by giving synthetic analogues of Vit D. Hyperphosphatasemia is controlled by dietary restriction of foods with high phosphate content. (milk, cheese, eggs) and the use of phosphate binding drugs administered with food.

MYOPATHY: Generalized myopathy is due to a combination of poor nutrition, hyperparathyroidism, Vitamin D deficiency and disorders of electrolyte metabolism. Muscle cramps are common, and quinine sulphate may be helpful. The “restless leg syndrome

Question 17

Describe RENAL REPLACEMENT THERAPY need.

Answer 17

End stage renal failure is the irreversible loss of kidney function. At the point that the kidneys fail to support life, renal replacement therapy (RRT) is required. For suitable patients, kidney transplants are generally considered the most cost effective approach..

Question 18

Describe INTERMITTENT HAEMODIALYSIS.

Answer 18

This is the standard blood purification therapy in ESRF.

Hemodialysis is started when the patient has symptomatic advanced renal failure but before the development of serious complications, often with a plasma creatinine of 600-800umol/l.

Vascular access is required; an arteriovenous fistula should be formed, usually in the forearm, when the patient reaches stage 4 kidney disease so that the fistula has time to develop.

Haemodialysis is usually carried out for 3-4 hours three times weekly. Most patients notice an improvement in symptoms during the first 6 weeks of treatment.

Plasma urea and creatinine are lowered by each treatment but do not return to normal.
Intermittent hemodialysis can be done at hospital or at home.

Many patients lead normal and active lives, and patient survival for more than 20 years is possible especially among young patients without external disease.

Question 19

Describe CONTINOUS AMBULATORY PERITONEAL DIALYSIS(CAPD).

Answer 19

CAPD is a long-term dialysis involving insertion of permanent Silastic catheter into the peritoneal cavity.
2L of sterile dialysis fluid are introduced and left in place for approximately 6 hours. During this time metabolic waste products diffuse from peritoneal capillaries into the dialysis fluid down a concentration gradient.

The fluid is then drained and fresh dialysis fluid introduced. The inflow fuild is rendered hyperosmolar by the addition of glucose; this results in net removal on each cycle (ultrafiltration).

To minimise the effects of CRF on bone, plasma calcium and phosphate should be kept as near to nomal as possible. Hypocalcaemia is corrected by giving synthetic analogues of Vit D.

Hyperphosphataemia is controlled by dietary restriction of foods with high phosphate content.( milk, cheese, eggs) and the use of phosphate binding drugs administered with food

This cycle is repeated four times daily during which time the patient is mobile and able to undertake normal daily activities.

Question 20

Describe AUTOMATED PERITONEAL DIALYSIS:

Answer 20

This system is similar to CAPD but uses a mechanical device to perform the fluid exchanges during the night, leaving the patient free, or with only a single exchange to perform, during the day.

Question 21

State problems with Continuous ambulatory peritoneal dialysis.

Answer 21

CAPD peritonitis
Catheter exit site infection.
Ultrafiltration failure
Peritoneal membrane failure.

Question 22

DO THE COMPARISON OF HAEMODIALYSIS AND PERITONEAL DIALYSIS

Answer 22

HEMODYIALISIS
*4 HOURS, 3 times per week
*2-3 days between treatments
*Requires hospital visit
*Requires venous circulation for venous access
*Careful compliance with diet and fluid restriction needed between treatments
*Fluid removal compressed into treatment periods; may cause symptoms and haemodynamic instability
*Infections related to vascular access may occur
*Patients are to some extent dependent on others

Peritoneal dialysis
*Four exchanges per day usually required, each taking 30-60 minutes (CAPD) or 8-10 hours each night (automated peritoneal dialysis)
*A few hours between treatment
*Performed at home
*Requires an intact peritoneal cavity without major scarring from previous surgery
*Diet and fluid less restricted
*Slow continuous fluid removal, usually asymptomatic
*Peritonitis and catheter-related infections may occur
*Patients can take full responsibility for their treatment