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Pharmacy Clinic
Cases
Case study
Management of Drug Related Problems in Patient with Chronic Renal Failure
By
MOAYYAD J.A.AL-OMAR; Clinical pharmacist
Introduction
Body organs considered as one unit, all working together and every one is affected
by the other. Diabetes and hypertension is a good example of that by affecting many
organ systems and disturbing its function and the kidney is one of those organs, so
the basic preventive therapy is much more effective than the curative treatment due
to the difficulty in the treatment of kidney failure if already happened.
As kidney failure progressed and damage happened then the result is the increase in
toxins, urea and drugs in the blood which lead to other problems and the series of
disorders will end with patient to die. As far as drug therapy is concern, we
concentrate in the preservation of what is remained from the kidney by close
monitoring of blood pressure and blood glucose level, and trying to prevent anemia
due to such complication and maintaining hemoglobin with in the accepted normal
range as possible as we can.
Patient information and history of present illness
Mr. YT 57.1 years old Japanese male admitted to the medical ward in 15th of
November with a chief complain of Shortness Of Breath for two days worsening in
the admission day, itching of the body, swelling (can't remember how many days),
fever for two days, chills, lethargy, foot ulcers (can't remember how many days),
abdominal pain (Not radiated, nausea, vomiting)
Social history
Mr. YT is married having 3 sons and work as traveling agent. He is non-alcoholic, non-
smoker and lives with his housewife
Past medical and medications history
He has history of diabetes mellitus for 3yrs, hypertension, chronic renal failure and
not known duration of diabetic ulcers. He was on •gliclazide 40 mg od, vitamin b
complex 1/1 tds, ferrous sulphate 200 mg tds, diltiazem 30 mg tds, furosemide 120
mg tds, calcium carbonate 1000 mg tds, isordil 10 mg tds with unknown history of
allergy to any of the drugs
Physical examination
He presented with Shortness Of Breath, mild dyspnea, pale, pedals edema+, Temp.
38°c, fever x 2/7, lethargy, BP 140/80, PR 100
Lungs: Bilateral crepts
CVS: S1, S2
Foot: Swollen, Bloody
Abdomen: Soft, tender, Bs – sluggish, No rigidity
Orthopedic review: Right foot ulcer x 1/12, Increase in size, No pus, Orthopnoea,
Foot gangrene 3rd toe (Sluggy and pale)
Laboratory studies
BUSE (Na+ 127mmol/l, K+ 3.0mmol/l, Urea 24.0mmol/l). Serum Creatinine 301
µmol/l, calculated serum creatinine clearance 24.7ml/min. CBC (WBCs 20.2x103 /µl,
RBCs 2.7x106 /µl, HGB 7.9mg/dl, HCT 0.227l/l , PLT 357 x103 /µl). ABGs (PH 7.432,
PO2 78mmHg, PCO2 3.1mmHg, HCO3-15.2 mEq/l.
Reflomat® chart shows the presence of hyperglycemia despite the use of Actrapid
S/C 8u TDS. Clotting profile (PT 17 sec., INR 1.62, APTT 32.2sec.)
Impression and diagnosis
The patient diagnosed to have acute on chronic renal failure, sepsis (TRO peritonitis),
right foot ulcer (gangrene) in the 3rd toe, hypertension, diabetes mellitus and after
below knee amputation the patient got post surgical infection with Morganella
morganii which is sensitive to cefoperazone and ceftazidime and Klebsiella pneumonia
which is also sensitive to cefoperazone, imipenem and ceftriaxone
The anti human immunodeficiency virus and syphilis was non reactive
Drug therapy
The patient has given intra venous unasyn® 1.5 g starting dose and continue three
times daily for one week, Caps. Ferrous fumarate 200 mg three times daily, Diltiazem
30 mg tds, intra venous Furosemide 80 mg stating dose and then 40 mg three times
daily, actrapid 8 U three times daily (omit if <8), calcium carbonate 100 mg two
tablets three times daily, Isordil 10 mg three times daily, O2 2l/min prn. And also
patient was put on restricted fluid 800 ml/day, intra venous amikacin 1gm (day2,
day6, day10), intra venous vitamin K10 mg stating dose and continue once daily for
five days, and the patient was on hemodialysis, intra venous cefobid 1 gm stating
dose and continue twice daily for seven days was added on day 5 to treat the
bacterial infection of Morganella morganii and Klebsiella pneumonia
Discussion
Long term uncontrolled diabetes mellitus and hypertension lead to many
complications and one of these complications is chronic renal failure and the problem
continue to have more complications related to renal failure including anemia due to
loss of renal activity to produce erythropoetin and also immune disturbance and
platelet dysfunction, increasing BUN concentration in the blood lead to mental
abnormalities and unfiltered toxins in the blood causes itching, renal osteodystrophy
due to the abnormal vitamin D metabolism and secondary hyperparathyroidism which
induces osteoclast effect, electrolyte disturbances (hyponatraemia,
hypomagnesaemia, hyperkalaemia, hypocalcaemia), changes in PT and coagulation
abnormality, acid-base disorders.
For all these reasons, the best way is to prevent the progression of renal impairment
as possible by trying to correctly manage the main cause. Here two main things that
we can manage to prevent further renal damage; first is diabetes and second is
hypertension. The diabetes control and complications trial (DCCT) showed that for
every 10% reduction in haemoglobin A1c, a corresponding 40% reduction occurred in
the rate of retinopathy; similar reductions were also found in the rates of
nephropathy and neuropathy.1,3
Even if we cannot get tight control, we can do some good by any degree of control.
The diabetes control and complications trial (DCCT) was a multicentre (1441
patients), randomized study designed with sufficient statistical power to compare
intensive versus standard diabetes therapy with regard to effects on the
development and progression of diabetic nephropathy, retinopathy, and neuropathy.
The results showed that intensive therapy reduced the incidence of microalbuminurea
and albuminurea when compared to conventional therapy in both primary prevention(
n= 726) and secondary pretension( n=715). Intensive insulin therapy composed of
two regimens First Regimen: Two third of the dose in the morning of an intermediate
–to-regular ratio of 2:1, given 30 minutes before breakfast and the second injection
is given 30 minutes before the evening meal; the ratio of intermediate acting-to-
regular is 1:1. Second Regimen: Regular insulin only, the patient total daily insulin
requirement is divided into four equal doses, each given 30 minutes before meals and
at bedtime.1
As regard to hypertension “The NKF is urging physicians to lower the blood pressure
of patients with CRF to <130/80 millimeters of mercury (mmHg).
This is an improvement over the previous standard of 130/85 mmHg, recommended
in 1997 in the Sixth Report of the Joint National Committee”
So for this case I recommend to change Diltiazem to Captopril according to a
multicenter controlled clinical trial showed that Captopril can slow the progression of
renal disease. This effect was independent of blood pressure reduction and of
greatest benefit in those with the lowest renal function”7
If BP is not controlled well by Captopril alone then we add Diltiazem “a study by Pérez-
Maraver and colleagues suggesting an additive benefit of the ACEi/non-
dihydropyridine CCB combination in patients with hypertension and chronic renal
failure. 4
For anemia we should remember that Effective erythropoiesis requires both iron and
erythropoietin. When CRF patients lack an adequate supply of either one or both,
anemia results.5
Target Hematocrit /Hemoglobin for Epoetin Therapy should be 33%(Hgb 11 g/dL) to
36% (Hgb 12 g/dL). (Evidence). My recommendation is to give SC Epoetin 80-120
units/Kg/wk (typically 6,000 units/wk) in two to three doses per week. Supplemental
iron should be administered to prevent iron deficiency and to maintain adequate iron
stores so that CKD patients can achieve and maintain an Hgb 11 to 12 g/dL (Hct
33% to 36%) in conjunction with Epoetin therapy. 5
Conclusion
I just say that WBCs still high so blood culture should be done to make sure of the
absence of microorganisms in the blood. In the other hand insulin intensive therapy
is of importance in the management of diabetes in chronic renal failure patients and
the achievement of BP target in CRF is an essential goal as well in the prevention of
progression of the Kidney diseases and HBG >12mg/dl and HCT >36% is the
determinant parameters in the treatment of anemia in CRF patients.
The possibility of achieving such targets is not that difficult, as for intensive insulin
therapy to be applied instead of actrapid can be done only by at least applying the
second regimen mentioned earlier which is composed of regular insulin only, the
patient total daily insulin requirement is divided into four equal doses, each given 30
minutes before meals and at bedtime, and this attempt is achievable.
Blood pressure control by using ACEIs is possible and captopril is available in the
hospital and also affordable, not considered as an expensive drug.
But the problem is in achieving hemoglobin target and also hematocrit, because we
need to use erythropoietin, and I’m not sure about the availability and the cost of
this drug, and patient financial status is not that good, he can’t afford hemodialysis,
how about erythropoietin. It is now a financial and availability problem, for me as a
pharmacist, I mainly look to the patient as a human being and not as a material can
sell and buy, so even if the drug is expensive, the government should provide it
otherwise why we have government, to request for money only, and we should not
consider the cost of therapy if the cost affects the status of the disease especially
when the patient is critically ill, and changing drugs in the sense of saving money will
affect patient’s clinical status negatively.
If we can’t provide the complete therapy, at least we should tell the patient or his
relatives and explain to them the usefulness and the importance of this drug and ask
them to go to welfare or any other associations trying to solve their problem and
save their patient’s life, otherwise the patient will gradually die and our aim as clinical
pharmacist will not accomplished.
References
1) Diabetes Control and Complication Trial Research (DCCT), the effect of intensive
treatment of diabetes on the development and progression of long term
complications in insulin dependent diabetes mellitus. N Engl J Med. 1993;329:977-86
2) (New York, NY) August 29, 2000 – The National Kidney Foundation (NKF)
3) Santiago JV. Perspectives in diabetes-lessons from the diabetes control and
complications trial. Diabetes 1993; 42:1549-1554
4) Pérez-Maraver M, Carrera M, et al. Beneficial effect of captopril-diltiazem vs
captopril in type 2 diabetic, hypertensive, microalbuminuric patients. Program and
abstracts of the 36th Annual Meeting of the European Association for the Study of
Diabetes; September 17-21, 2000; Jerusalem, Israel. Abstract 1006.
5) GUIDELINES FOR ANEMIA OF CHRONIC KIDNEY DISEASE; 2001 National Kidney
Foundation, Inc
6) Maki DD. Ma JZ. Louis TA. Kasiske BL. Long term effects of antihypertensive
agents on proteinureaand renal function. Arch Inter Med 1995; 155:1073-1080
7) Lewis EJ. Hunsicker LG. Bain RP. Rohde RD. the effect of an angiotensin
converting enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456-
1462
8).Diabetes Control and Complication Trial Research Group. The effect of intensive
treatment of diabetes on the development and progression of long term
complications in insulin dependent diabetes mellitus; N Engl J Med 1993;329:977-986
9). Pastan S, Bailey J: Dialysis therapy. N Engl J Med 1998 May 14; 338(20): 1428-37
Management of Drug Related Problems in Patient with Chronic Renal Failure
By
MOAYYAD J.A.AL-OMAR; Clinical pharmacist
Introduction
Body organs considered as one unit, all working together and every one is affected
by the other. Diabetes and hypertension is a good example of that by affecting many
organ systems and disturbing its function and the kidney is one of those organs, so
the basic preventive therapy is much more effective than the curative treatment due
to the difficulty in the treatment of kidney failure if already happened.
As kidney failure progressed and damage happened then the result is the increase in
toxins, urea and drugs in the blood which lead to other problems and the series of
disorders will end with patient to die. As far as drug therapy is concern, we
concentrate in the preservation of what is remained from the kidney by close
monitoring of blood pressure and blood glucose level, and trying to prevent anemia
due to such complication and maintaining hemoglobin with in the accepted normal
range as possible as we can.
Patient information and history of present illness
Mr. YT 57.1 years old Japanese male admitted to the medical ward in 15th of
November with a chief complain of Shortness Of Breath for two days worsening in
the admission day, itching of the body, swelling (can't remember how many days),
fever for two days, chills, lethargy, foot ulcers (can't remember how many days),
abdominal pain (Not radiated, nausea, vomiting)
Social history
Mr. YT is married having 3 sons and work as traveling agent. He is non-alcoholic, non-
smoker and lives with his housewife
Past medical and medications history
He has history of diabetes mellitus for 3yrs, hypertension, chronic renal failure and
not known duration of diabetic ulcers. He was on •gliclazide 40 mg od, vitamin b
complex 1/1 tds, ferrous sulphate 200 mg tds, diltiazem 30 mg tds, furosemide 120
mg tds, calcium carbonate 1000 mg tds, isordil 10 mg tds with unknown history of
allergy to any of the drugs
Physical examination
He presented with Shortness Of Breath, mild dyspnea, pale, pedals edema+, Temp.
38°c, fever x 2/7, lethargy, BP 140/80, PR 100
Lungs: Bilateral crepts
CVS: S1, S2
Foot: Swollen, Bloody
Abdomen: Soft, tender, Bs – sluggish, No rigidity
Orthopedic review: Right foot ulcer x 1/12, Increase in size, No pus, Orthopnoea,
Foot gangrene 3rd toe (Sluggy and pale)
Laboratory studies
BUSE (Na+ 127mmol/l, K+ 3.0mmol/l, Urea 24.0mmol/l). Serum Creatinine 301
µmol/l, calculated serum creatinine clearance 24.7ml/min. CBC (WBCs 20.2x103 /µl,
RBCs 2.7x106 /µl, HGB 7.9mg/dl, HCT 0.227l/l , PLT 357 x103 /µl). ABGs (PH 7.432,
PO2 78mmHg, PCO2 3.1mmHg, HCO3-15.2 mEq/l.
Reflomat® chart shows the presence of hyperglycemia despite the use of Actrapid
S/C 8u TDS. Clotting profile (PT 17 sec., INR 1.62, APTT 32.2sec.)
Impression and diagnosis
The patient diagnosed to have acute on chronic renal failure, sepsis (TRO peritonitis),
right foot ulcer (gangrene) in the 3rd toe, hypertension, diabetes mellitus and after
below knee amputation the patient got post surgical infection with Morganella
morganii which is sensitive to cefoperazone and ceftazidime and Klebsiella pneumonia
which is also sensitive to cefoperazone, imipenem and ceftriaxone
The anti human immunodeficiency virus and syphilis was non reactive
Drug therapy
The patient has given intra venous unasyn® 1.5 g starting dose and continue three
times daily for one week, Caps. Ferrous fumarate 200 mg three times daily, Diltiazem
30 mg tds, intra venous Furosemide 80 mg stating dose and then 40 mg three times
daily, actrapid 8 U three times daily (omit if <8), calcium carbonate 100 mg two
tablets three times daily, Isordil 10 mg three times daily, O2 2l/min prn. And also
patient was put on restricted fluid 800 ml/day, intra venous amikacin 1gm (day2,
day6, day10), intra venous vitamin K10 mg stating dose and continue once daily for
five days, and the patient was on hemodialysis, intra venous cefobid 1 gm stating
dose and continue twice daily for seven days was added on day 5 to treat the
bacterial infection of Morganella morganii and Klebsiella pneumonia
Discussion
Long term uncontrolled diabetes mellitus and hypertension lead to many
complications and one of these complications is chronic renal failure and the problem
continue to have more complications related to renal failure including anemia due to
loss of renal activity to produce erythropoetin and also immune disturbance and
platelet dysfunction, increasing BUN concentration in the blood lead to mental
abnormalities and unfiltered toxins in the blood causes itching, renal osteodystrophy
due to the abnormal vitamin D metabolism and secondary hyperparathyroidism which
induces osteoclast effect, electrolyte disturbances (hyponatraemia,
hypomagnesaemia, hyperkalaemia, hypocalcaemia), changes in PT and coagulation
abnormality, acid-base disorders.
For all these reasons, the best way is to prevent the progression of renal impairment
as possible by trying to correctly manage the main cause. Here two main things that
we can manage to prevent further renal damage; first is diabetes and second is
hypertension. The diabetes control and complications trial (DCCT) showed that for
every 10% reduction in haemoglobin A1c, a corresponding 40% reduction occurred in
the rate of retinopathy; similar reductions were also found in the rates of
nephropathy and neuropathy.1,3
Even if we cannot get tight control, we can do some good by any degree of control.
The diabetes control and complications trial (DCCT) was a multicentre (1441
patients), randomized study designed with sufficient statistical power to compare
intensive versus standard diabetes therapy with regard to effects on the
development and progression of diabetic nephropathy, retinopathy, and neuropathy.
The results showed that intensive therapy reduced the incidence of microalbuminurea
and albuminurea when compared to conventional therapy in both primary prevention(
n= 726) and secondary pretension( n=715). Intensive insulin therapy composed of
two regimens First Regimen: Two third of the dose in the morning of an intermediate
–to-regular ratio of 2:1, given 30 minutes before breakfast and the second injection
is given 30 minutes before the evening meal; the ratio of intermediate acting-to-
regular is 1:1. Second Regimen: Regular insulin only, the patient total daily insulin
requirement is divided into four equal doses, each given 30 minutes before meals and
at bedtime.1
As regard to hypertension “The NKF is urging physicians to lower the blood pressure
of patients with CRF to <130/80 millimeters of mercury (mmHg).
This is an improvement over the previous standard of 130/85 mmHg, recommended
in 1997 in the Sixth Report of the Joint National Committee”
So for this case I recommend to change Diltiazem to Captopril according to a
multicenter controlled clinical trial showed that Captopril can slow the progression of
renal disease. This effect was independent of blood pressure reduction and of
greatest benefit in those with the lowest renal function”7
If BP is not controlled well by Captopril alone then we add Diltiazem “a study by Pérez-
Maraver and colleagues suggesting an additive benefit of the ACEi/non-
dihydropyridine CCB combination in patients with hypertension and chronic renal
failure. 4
For anemia we should remember that Effective erythropoiesis requires both iron and
erythropoietin. When CRF patients lack an adequate supply of either one or both,
anemia results.5
Target Hematocrit /Hemoglobin for Epoetin Therapy should be 33%(Hgb 11 g/dL) to
36% (Hgb 12 g/dL). (Evidence). My recommendation is to give SC Epoetin 80-120
units/Kg/wk (typically 6,000 units/wk) in two to three doses per week. Supplemental
iron should be administered to prevent iron deficiency and to maintain adequate iron
stores so that CKD patients can achieve and maintain an Hgb 11 to 12 g/dL (Hct
33% to 36%) in conjunction with Epoetin therapy. 5
Conclusion
I just say that WBCs still high so blood culture should be done to make sure of the
absence of microorganisms in the blood. In the other hand insulin intensive therapy
is of importance in the management of diabetes in chronic renal failure patients and
the achievement of BP target in CRF is an essential goal as well in the prevention of
progression of the Kidney diseases and HBG >12mg/dl and HCT >36% is the
determinant parameters in the treatment of anemia in CRF patients.
The possibility of achieving such targets is not that difficult, as for intensive insulin
therapy to be applied instead of actrapid can be done only by at least applying the
second regimen mentioned earlier which is composed of regular insulin only, the
patient total daily insulin requirement is divided into four equal doses, each given 30
minutes before meals and at bedtime, and this attempt is achievable.
Blood pressure control by using ACEIs is possible and captopril is available in the
hospital and also affordable, not considered as an expensive drug.
But the problem is in achieving hemoglobin target and also hematocrit, because we
need to use erythropoietin, and I’m not sure about the availability and the cost of
this drug, and patient financial status is not that good, he can’t afford hemodialysis,
how about erythropoietin. It is now a financial and availability problem, for me as a
pharmacist, I mainly look to the patient as a human being and not as a material can
sell and buy, so even if the drug is expensive, the government should provide it
otherwise why we have government, to request for money only, and we should not
consider the cost of therapy if the cost affects the status of the disease especially
when the patient is critically ill, and changing drugs in the sense of saving money will
affect patient’s clinical status negatively.
If we can’t provide the complete therapy, at least we should tell the patient or his
relatives and explain to them the usefulness and the importance of this drug and ask
them to go to welfare or any other associations trying to solve their problem and
save their patient’s life, otherwise the patient will gradually die and our aim as clinical
pharmacist will not accomplished.
References
1) Diabetes Control and Complication Trial Research (DCCT), the effect of intensive
treatment of diabetes on the development and progression of long term
complications in insulin dependent diabetes mellitus. N Engl J Med. 1993;329:977-86
2) (New York, NY) August 29, 2000 – The National Kidney Foundation (NKF)
3) Santiago JV. Perspectives in diabetes-lessons from the diabetes control and
complications trial. Diabetes 1993; 42:1549-1554
4) Pérez-Maraver M, Carrera M, et al. Beneficial effect of captopril-diltiazem vs
captopril in type 2 diabetic, hypertensive, microalbuminuric patients. Program and
abstracts of the 36th Annual Meeting of the European Association for the Study of
Diabetes; September 17-21, 2000; Jerusalem, Israel. Abstract 1006.
5) GUIDELINES FOR ANEMIA OF CHRONIC KIDNEY DISEASE; 2001 National Kidney
Foundation, Inc
6) Maki DD. Ma JZ. Louis TA. Kasiske BL. Long term effects of antihypertensive
agents on proteinureaand renal function. Arch Inter Med 1995; 155:1073-1080
7) Lewis EJ. Hunsicker LG. Bain RP. Rohde RD. the effect of an angiotensin
converting enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456-
1462
8).Diabetes Control and Complication Trial Research Group. The effect of intensive
treatment of diabetes on the development and progression of long term
complications in insulin dependent diabetes mellitus; N Engl J Med 1993;329:977-986
9). Pastan S, Bailey J: Dialysis therapy. N Engl J Med 1998 May 14; 338(20): 1428-37