IM Sheet #12 By Sari Mahasneh

by **Sura** 25/12/2011, 10:43 pm

http://www.mediafire.com/?k8zmo1f6wfclmco

by **Shadi Jarrar** 11/1/2012, 1:46 pm

Today we'll talk about the renal failure.

Renal failure is the loss of function of the kidneys.

Terminology:

In the past it used to be chronic renal failure but recently the term to be used is chronic kidney disease (CKD).

The same thing goes with acute kidney failure and the new term is acute kidney injury (AKI).

The reason for the change in the nomenclature is that not all the renal failure types are similar.

Also, there is a difference between the acute and chronic renal failure which is that the acute renal failure is potentially reversible (because it's injury and not death) even if it includes the complete loss of function of the kidneys while the chronic is irreversible and progressive (because of the death of the nephrons) unless the diagnosis was acute in top of chronic renal failure.

Just to remind you of the anatomy: we have 2 kidney found in the retroperitonially (behind the peritoneum), they contain 2 million nephrons (each kidney has 1 million nephrons)(a nephron is composed of a glomerulus, proximal tubules, collecting ducts, etc.), a big percentage of these nephrons act as a reserve which means that not all the nephrons are active at the same time (as if they work in shifts) and in normal situation the working load is low because there is an excess of the nephrons that are already working.

Kidneys are formed of cortex, medulla and the capsule.

Nephrons are mainly found in the cortex

Acute/chronic renal failure may affect any of these structures:

1. glomeruli: glomerulonephritis

2. Vessels: vasculitis

3. Connective tissue: interstitial nephritis

In case of death to the nephrons, both the number of the active nephrons and the working load increases, because of the increase in the working loads and the continuous active state once the renal failure starts the progression (death of the nephrons) will be faster

Detoxification of the blood is one of the most important functions of the blood as a result accumulation of the toxic metabolic products (creatinine, urea, and potassium) will be seen in case of renal failure.

They secrete erythropoietin which regulates the formation of red blood cells by the bone marrow, so in case of kidney disease the erythropoietin level will fall resulting in decrease in RBC production (anemia) and because of that anemia is one of the most common complications of chronic renal failure (CKD).

Kidney regulates volume, blood pressure and electrolyte balance.

In cases of renal failure the patient may present with volume overload (e.g. Hypertension, edema), electrolyte abnormality (hyperkalemia, calcium (which regulates activation of vitamin D)).

Vitamin D, parathyroid hormone, calcitonin regulates sodium and phosphorus.

In case of renal failure there will be no activation of vitamin D which will lead to hypocalcaemia which will result in osteomalacia. (Osteomalacia is softening of the bones due to a lack of vitamin D or a problem with the body's ability to break down and use this vitamin.)

If further progression of the disease occurred this will result in renal osteoliscopy (not sure of the spelling!)

Renal osteoliscopy is caused by different pathways one of them is the acidosis that happens in the renal failure.

The kidneys usually control the electrolytes in the body; in case of renal failure the kidneys are not capable of controlling the concentration of H ions resulting in acidemia.

Renal failure is classified into 3 major categories:

1) Acute renal failure

a) Pre-renal

b) Renal

c) Post-renal

2) Chronic renal failure

3) Acute in top of chronic renal failure

Pre-renal is a disease affecting the perfusion of the kidneys resulting in diminished activity.

Just to remind u that the kidneys are the most perfused organs of the body (more than the brain, the liver or the muscles).

25% of the cardiac output passes through the kidneys per minute (around 1.25L/min) for the sake of detoxifying/cleaning the blood from the poisonous contents.

So anything that affects the perfusion of the kidneys (e.g. Hypotension, heart failure) is called pre-renal condition.

Post-renal is the disease affecting the anatomic structures that comes after the kidneys such as the ureter (the pelvis of the ureter, bladder, and urethra), so it's mainly blocking of the structures that come after the kidneys.

So pre-renal and post-renal are not associated with the kidney itself, this means that if we discovered that it's post or pre renal then we can treat it easily.

BUT if they were not treated early enough then they will change into renal acute renal failure.

Renal acute renal failure may be caused by inflammation of any anatomic part of the kidneys e.g. Glomerulitis, glomerulonephritis, ATN which stands for acute tubular necrosis, vasculitis or acute/chronic interstitial nephritis.

Acute/chronic interstitial nephritis is the condition involving inflammation of the whole connective tissue.

Using excessive amounts (sometimes one tablet is enough) of analgesics (ibuprofen, diclofenac (voltarin)) or antibiotics may cause acute interstitial nephritis.

Chronic renal failure is classified according to the etiology not the function.

Diabetes mellitus type 1 is more likely to cause renal failure.

Diabetes mellitus type 2 is a more common cause of renal failure.

If we examined 100 patients with DM-type 1 around 40 patients will have nephropathy

If we examined 100 patients with DM-type 2 around 10-20 patients will have nephropathy

If the prevalence of type 2 is 10 times that of type 1 then type 2 is the more common cause even though type 1 has a higher chance to progress to renal failure.

Causes of renal failure (very important) with the normal sized kidneys:

1. Hypertension is another important cause of chronic renal failure.

2. DM and HT usually co-exist with each other.

3. Chronic glomerulonephritis (IGA type),

4. Around 10% have polycystic disease (autosomal dominant genetic disease).

The less important causes are multiple myeloma, amylosis, HIV + ve and ATN acute tubular necrosis.

HTN and DM are the most important causes, their prevalence is increasing with time especially the HTN because of 2 important causes one of which is that the definition of the normal hypertension value keeps decreasing so higher % gets included in the disease state each time this value decreases, the other cause is the quality of diet (junk food) and the decrease in the exercise.

A chronic renal failure patient with DM that is affecting his kidneys has a specific baseline for creatinine level (let's say the baseline is 2), if the patient took 2 tablets of voltarin, in diseased kidneys these tablets may cause acute insult of the kidneys so the creatinine level rises from 2 up to 4 which is a very high rate of increase in the readings.

In these cases we should start thinking of the acute in top of the chronic renal failure, so we shouldn't put the patient on dialysis but investigate for the cause of this abrupt elevation of the levels and treat the cause.

In case we used the ACE or the ARB for the treatment of hypertension and the patient was suffering from renal artery stenosis the patient will develop renal failure, the point is it's very common to treat a renal failure patient with ACE or ARB but if he was having renal artery stenosis and we treated him with these drugs then he will reach the stage of dialysis.

Just to remind u ACE is the angiotensin converting enzyme inhibiter and the ARB is the angiotensin receptor blocker.

So we should stop the ACE/ARB, treat the stenosis and continue with the treatment plan.

Keep in mind that ACE/ARB are strongly indicated in the treatment of renal failure because it slows the progression of the chronic renal failure especially in the absence of renal artery stenosis or atherosclerosis of the renal arteries.

In case of the stenosis the stenosis should be treated then we can put the patient on the ACE/ARB.

Acute in top of chronic renal failure mainly caused by hypovolemia, gastroenteritis, excessive amount of the diuretic, nephrotoxicity (due to NSAIDs, Antibiotics e.g.Gentamycin, Aminoglycosides), obstruction.

Main side effects of these drugs are Hyperkalemia

How to distinguish between Chronic and Acute:

We have to differentiate between them because they differ in prognosis and management.

It's not always easy to distinguish but we have general guidelines that might help such as:

1. Medical history: if we examined the patient last week and now he has renal failure then most probably it's the acute type but if the patient has a previous abnormal baseline and it increased slightly since a longer period of time then it's most probably Chronic.

2. Physical examination the most important test is the blood pressure test.

3. Lab investigation

Sudden onset and rapid depletion in urine output is most probably acute.

T he acute type is potentially reversible with cell death and regeneration but in this case we call it acute kidney injury (AKI).

Chronic is progressive, not reversible and significant real loss of the kidneys (more than 50% of the kidneys are a reserve).

Because of the high reserve we can donate one of the kidneys and live a normal life with only one kidney.

Moreover, recent studies have shown that people who donated one of their kidneys have lower chance for renal failure and health problems, they didn't found a clear explanation but they claimed that it might be due to the increased attention the patients pays to himself especially his health.

One of the most important points in the differential diagnosis is the chronic changes that occur with time in the chronic renal failure patients which mandates imaging such as X-rays, renal ultrasound.

The normal kidney size is around 10-12cm, if during imaging we found that they are e.g.7cm (atrophied) then this indicates that the kidneys are diseased since a long period of time but if the kidneys grew larger then it's most probably acute.

But keep in mind it's not a rule, many patients with normal kidney size suffer from chronic renal failure especially patients with diabetes mellitus.

Usually patients with DM and chronic renal failure have a normal sized kidney.

Another indicating test used in the attempt to diagnose renal failure as chronic is a bone test in which a radiograph is taken for the distal phalanx of the hand and usually in chronic renal failure we can notice bone resorption due the elevated levels of parathyroid hormone.

Anemia, hyperkalemia, hyperphosphatemia, hyperphosphatasia and metabolic acidosis occurs both in acute and chronic but if the readings were farther away from the normal it may indicate that it's chronic but it's not a rule.

Classification depends on the creatinine levels and the estimated Glomerular filtration rate EGFR, creatinine levels are used to measure the GFR by certain equations such as Cockcroft-Gault formula, MDRD Modification of Diet in Renal Disease.

The normal range of the GFR is 90-110 ml/min/1.73m^2. and that for the creatinine is 0.4 mL/min per year (The dr. didn't mention the units).

In cases of pregnancy the reserve nephrons start to work the GFR increases up to 180-200 and the creatinine level decrease (sometimes it increases but if it was within normal range then it's fine)so this is normal in case of pregnancy.

Classification of the stages of the chronic renal failure:

1. Stage 1 GFR above 90mL: The first stage is asymptomatic this means that if we were able to diagnose the disease in the early stages then we can start the prevention of the progression

2. Stage 2 GFR of 60 to 90: there is slightly decrease in the GFR, proteinurea and shrinkage in the size of the kidneys (slight evidence of kidney disease)

3. Stage 3 GFR of 30 to 60: moderately reduced GFR and other evidence of kidney damage.

4. Stage 4 GFR of 15 to 30: (also called predialysis stage) severely reduced GFR and other evidence of kidney damage.

5. Stage 5 GFR less than 15 mL (dialysis or the end-stage renal disease): also called end-stage renal disease, it's defined as the human being will not be able to survive without support or what is called renal replacement therapy.

Stage 1 doesn't appear clinically because of the huge reserve of the kidneys (silent disease), the patient presents with very high readings that indicate renal failure and urgent need for dialysis.

Usually patients that claim a pain from their kidneys is a referred pain from the GI or the muscles of the abdomen but not from the kidneys themselves.

So they present with non-specific presentations such as anemia, hypertension, itching, edema and similar non-specific symptoms.

This means that if the patient was not diagnosed correctly he might end up with dialysis.

The main problem in the diagnosis of the chronic renal failure is that there are no specific symptoms and No hematurea.

Kidney transplantation surgery has one of the highest prognosis of all the other transplantation surgeries.

Stage 5 exists because we have the dialysis and the transplantation otherwise stage 5 won't exist.

This graph is very important and it shows the relation between the function of the kidneys (GFR) and the serum creatinine.

It's important because it shows what happens in the renal failure patients.

We can notice that the graph has 2 components vertical (steep in the early stages) and horizontal (in the final stages).

With time the GFR decreases and the serum creatinine level increases.

If we interpret the relationship then we can see that to a certain point the difference of the creatinine readings stays minimal (even though the disease is progressing) but after this point the difference starts to increase tremendously.

In other words the GFR has to decrease more than 60% for the creatinine level to change from 1 to 1.5 but after that the difference starts increasing tremendously with lower GFR decrease.

Some patients with low readings of the serum creatinine claims that they have MILD renal failure, there is nothing named mild once u have the renal failure it's called renal failure without the mild term.

If the creatinine level reaches 2 then the patient has lost more than 75% of his kidneys.

But if a patient presents with creatinine level of 4 then this patient don't differ from a patient with creatinine level of 10 because both of them already reached stage 5.

To summarize any small change in the serum creatinine level in the early stages is caused by huge loss of the renal function while in the final stages a huge change in serum creatinine is caused by slight decrease in the GFR (a change from 5 to 6 is not the same as that of a change from 1 to 2).

Note: serum creatinine is not a good marker (even if it's the gold standard) for renal failure patients neither do urea.

Recently new markers are used but they are not common yet.

An NSAID tablet can change the creatinine level from 1 to 4 because of the huge decrease in the GFR it might cause but if it was administered to a patient with high serum creatinine level it won't decrease the GFR that much.

As we said before the chronic type have no specific symptoms and it might affect any system in the body.

Acute in top of chronic is caused mainly by:

1. NSAIDs

2. Antibiotics: e.g. gentamycin

3. Contrast for a radiograph

This means that if we didn't intervene and give the patient these certain substances then he wouldn't develop the acute in top of chronic.

The importance of chronic renal failure is that:

1. It's a common cause of mortality (25%); it's the 2^nd most common cause after the lung cancer and before the colorectal cancer.

2. It's a very common disease: 7.5 million of the US population suffer from stage 3 renal failure and 0.5 million suffer from stage 4 so overall around 8 million of the US population suffer from chronic renal failure, they call this phenomena the iceberg phenomena because only a small part of the iceberg is visible above the level of the ocean surface while the most important and the bigger percentage is not visible and found below the ocean surface.

3. It's a very expensive disease; its treatment (dialysis/transplantation) requires too much money.

There is an association in the US called NIH, this association main concern is the medical field and the research field, it's a huge association in which its budget is $23 billion (4 times the HKJ budget), and more than 90% of their budget is spent on the chronic renal failure patients.

In the past the main concern in the treatment of the chronic renal failure patient was to slow the progression of the disease but recently it became the 2^nd concern and the main concern is to try to prevent the death of patients in each stage because the % of patients who die before progressing to the next stage is much higher than the % of patient who progress to the next stage.

In other word, most of the patients with stage 1 or 2 will die before they reach the dialysis stage because of the cardiovascular complications such as CVA, stroke, MI, etc.

The best management for these patients is to lower the hyperlipidemia, lower BP for a hypertensive patient, stop the smoking and control the DM and stuff like that.

The mortality of a patient with early stage renal failure and cardiovascular problems is very high.

Studies showed that its high (about twice) even in the very early stage of renal failure in the stage of microalbuminurea which occurs before the proteinurea can be detected.

So the renal failure is a more important risk factor than smoking, DM or hypertension in the development of cardiovascular diseases or death.

Azotemia: both the urea and the creatinine levels are elevated, might be elevated by causes other that renal failure such as steroids intake, GI bleeding, tetracycline medication, dehydration, etc. In these cases it's not called renal failure but azotemia.

If renal failure is present (loss of function) and accumulation of toxic waste products in the body and the patient starts showing symptoms of urea accumulation then this is called renal failure.

Uremia is advanced chronic renal failure in which clinical symptoms are present (systemic symptoms and not renal).

So azotemia is elevated levels without symptoms while the uremia is elevated levels with systemic symptoms.

The uremia is associated more with the symptoms more than that with the numbers of the elevated levels of the creatinine.

Our role is to decrease the medication intake especially the NSAIDs by the patient so we have to give proper instructions to the patient about when to use the drug and how much.

The dr. is talking about a comparison between 2 patients one with renal failure that is quickly progressing and the other patient with renal failure but undergoing treatment in which we postponed the need for the dialysis from 4 years to six years which is a very good marker and our 2^nd concern in the treatment.

The 1^st concern is to do our best to prevent the cardiovascular complications to decrease the high mortality rate.

A patient with early stage chronic kidney disease has 5-10 times higher mortality rate (die from cardiovascular impairment) than to progress to end-stage renal disease.

The patients we deal with are usually the patients who undergo dialysis or undergone renal transplantation.

Patients with kidneys transplantation are usually immunocompromised due to the drugs they take (e.g. cyclosporine) so if we are going to do an invasive procedure then we should prescribe a prophylaxis antibiotic (e.g. amoxicillin, clindamycin), we should prescribe 2 tablets before the procedure and 2 tablets after the procedure.

However, we should pay attention to the drug-drug interaction e.g. erythromycin depress the effect of the cyclosporine and the patient will end up with renal failure, so the best way is to call the patient physician and ask him what drug shall u prescribe.

The best replacement and treatment for the kidney failure patient is the transplantation, and then there are the hemodialysis and the peritoneal dialysis.

The 2 types of the dialysis has their specific indications

The patient who undergoes dialysis take heparin (causes bleeding) just before the dialysis, the half-life of heparin is 3 hours so the best time to treat these patients after few hours from the dialysis (e.g. if the patient did the dialysis at the morning then we can perform the operation afternoon).

The best time to treat these patients at our clinics is after the dialysis just after the heparin is removed from the body.

We can't perform the operation before the dialysis because there are too many metabolic waste products in the blood which is dangerous.

Also, patients in the initial stages of the renal failure should not be given NSAIDs because they might end up with dialysis.

Finally some drugs half-life increases with renal failure patients so we should be careful about the dose adjustment.

DONE BY: SARI ADEL MAHASNEH

DATE OF LECT.:20-12-2011

IM Sheet #12 By Sari Mahasneh

IM Sheet #12 By Sari Mahasneh

Re: IM Sheet #12 By Sari Mahasneh