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Assessment of reversible risk factors
causing
acute-on-chronic renal failure
N Nand*, M Shrama**, H Kumar***
Prity Mehta****
PGIMS, Rohtak - 124 001,
Haryana.
Journal, Indian Academy of Clinical Medicine l Vol. 13, No. 3 l July-September, 2012
By
………. RAMESH NAYAK……… 28/03/2014
for dept of physiology JNMC @ aditya
Contents:
1.Introduction
2.Objectives
3.Material And Methods
4.Results
5.Discussion
6.Conclusion
7.Critical Appraisal
for dept of physiology JNMC @ aditya 2
Functions of kidney
1. Excretory function
2. Regulatory function
3.Endocrine function
4.Metabolic function
H
O
M
E
O
S
T
A
S
I
S
for dept of physiology JNMC @ aditya 3
Renal failure
a)Acute b)Chronic
for dept of physiology JNMC @ aditya 4
a. Acute Renal Failure
- abrupt in onset and reversible
- AZOTEMIA most common
. indicator
- Depending upon the cause
. 3 types:
Prerenal
Postrenal
Renal
for dept of physiology JNMC @ aditya 5
b. Chronic Renal Failure
- progressive and represents irreversible kidney structural damage.
- signs and symptoms occur gradually
kidney has amazing compensatory ability.
- characterized by GFR reduction, reflects
reduction in the number of functional nephrons.
for dept of physiology JNMC @ aditya 6
Stages of progression of CRF:
1. Diminished Renal
Reserve
2. Renal Insufficiency
3. Renal Failure and
4. End-Stage Renal
Disease(ESRD)
CKD
STAGE 1
CKD
STAGE 2
CKD
STAGE 3
CKD
STAGE 4
eGFR
mL/min ≤50% ≤(50-20)% ≤20% ≤5%
serum BUN &
creatinine levels
still normal.
No symptoms
seen.
earliest
symptom
isosthenuria
azotemia,
anemia &
hypertension
begin to
appear.
kidneys cannot
regulate volume &
solute composition
 edema, metabolic
acidosis &
hyperkalemia develop.
 uremia may ensue
with neurologic,
GI and CV
manifestation
Histologically
reduction in
renal
capillaries.
 Atrophy and
fibrosis in
tubules.
 kidney mass
usually reduced.
TO,1. Diminished Renal
Reserve
2. Renal Insufficiency
3. Renal Failure and
4. End-Stage Renal
Disease(ESRD)
CKD
STAGE 1
≤50%
for dept of physiology JNMC @ aditya 7
Manifestations of CRF:
for dept of physiology JNMC @ aditya 8
for dept of physiology JNMC @ aditya 9
ACUTE-ON-CHRONIC RENAL FAILURE
 Any sudden decline in renal functions in patients with known chronic kidney
disease
 Each episode of acute attack - can be attributed to - one or more reversible risk
factors.
 Various reversible risk factor contributing to acute-on-chronic renal failure are:
Volume depletion
Urinary tract obstruction
Infection
Hypotension
Electrolyte imbalance
Accelerated hypertension
Nephrotoxic drugs
for dept of physiology JNMC @ aditya 10
Renal function tests:
1. Urine analysis
(physical, chemical and microscopic examination)
2. Blood analysis
(blood urea, plasma creatinine, serum protein, cholesterol and
. electrolyte)
3. Renal clearance tests
(to measure GFR and RBF)
4. Radiology and renal imaging
5. Renal biopsy
for dept of physiology JNMC @ aditya 11
Management of renal failure:
1) Conservative management
- preventing deterioration of remaining renal function and
- helps the body in compensating for the existing impairment.
2) Renal replacement therapy
- Dialysis and
- Renal transplantation
for dept of physiology JNMC @ aditya 12
Dialysis.
for dept of physiology JNMC @ aditya 13
Assessment of reversible risk factors causing
acute-on-chronic renal failure
1.PREVALENCE:
 ESRD reached epidemic proportions – treatment becoming an
unbearable health care burden.
 conservative estimate of ESRD burden - population of 1.1 billion - around
1,650,000 people develop ESRD in india annually.
 Taking conservative approach, if all patients were to be treated - cost
burden over $6.5 billion annually - health care budget for all of India $3.5
billion.
QUEST india | DaVita’s Clinical Journal for Nephrologists July 2007 Issue 9 By H. Sudarshan Ballal, M.D.
for dept of physiology JNMC @ aditya 14
2.Introduction
 Any sudden decline in renal functions in patients with
known chronic kidney disease (CKD)
 Each episode of acute attack can be attributed to one or
more reversible risk factors.
 Timely management - renal function brought back to basal
level- preventing from ESRD - reducing the cost of renal
replacement therapy.
for dept of physiology JNMC @ aditya 15
3.OBJECTIVE:
- Evaluate risk factors - their degree of reversibility - in cases
of acute-on-chronic renal failure
admitted to a tertiary care hospital, over a period of one
year, i.e., from November, 2006 to October, 2007.
for dept of physiology JNMC @ aditya 16
4.MATERIAL AND METHODS:
MATERIAL:
 The study included 100 cases of acute-on-chronic renal failure
mean age of (48.69 ± 16.02) years.
62 men and 38 women.
 The diagnosis of acute-on-chronic renal failure was based on , patients with CRD
- presenting with sign and symptoms of acute renal failure or
- who presented with
0.5 mg/dl, if baseline serum creatinine was < 3 mg/dl
rise in serum creatinine of
1 mg/dl, if baseline was > 3 mg/dl with in one week period.
for dept of physiology JNMC @ aditya 17
METHODS:
 admitted in the ward - average period of 14.62 days (range: 9 to 24 days)
. - managed conservatively following thorough
clinical evaluation and investigations.
 Specific management of reversible factor(s) and haemodialysis, whereever
needed was also done.
 Observations of various parameters were recorded at baseline and subsequently
at 1 week and 2 week periods which included 24-hour
urine volume, blood urea, serum creatinine, and creatinine clearance.
for dept of physiology JNMC @ aditya 18
 To compare the degree of reversibility, the patients were divided into 4
groups
depending upon their GFR;
GFR (30 - 59 )ml/min group 3
GFR (15 - 29 )ml/min group 4
GFR (5 – 15) ml/min group 5a and
GFR < 5 ml/min group 5b.
 Reversibility of these parameters was then statistically analysed.
for dept of physiology JNMC @ aditya 19
5.RESULTS :
 Majority of patients were found to
have more than one reversible risk
factor
Average being 2.62 (ranging
. from 1to 4)
 however, only one factor was
taken as the major factor depending
upon the clinical situation.
for dept of physiology JNMC @ aditya 20
 Table II depicts degree of reversibility in patients having specific
aggravating factors
for dept of physiology JNMC @ aditya 21
Maximum reversibility was found in patients in stage 4 and
least in stage 5b .
GFR (30 - 59 )ml/min group 3
GFR (15 - 29 )ml/min group 4
GFR (5 – 15) ml/min group 5a
GFR < 5 ml/min group 5b.
for dept of physiology JNMC @ aditya 22
6.DISCUSSION:
 Patients presenting in severe uraemic state - not suffering from end-stage renal
. disease; rather – had significant degree of reversibility of renal function .
study showed, majority of patients were having more than one reversible
risk factor (average 2.62).
 Conservative management + haemodialysis and correction of reversible
risk factor(s) , resulted in significant improvement in mean creatinine clearance
after 2 weeks of follow-up.
proved better chances of reversibility even in patient with stage 3 and
. stage 4 of CRF.
 However, in the earlier studies, the net degree of reversibility was found to be low –
probably because the patients included were of advanced renal
failure (creatinine clearance < 15 ml/min)
for dept of physiology JNMC @ aditya 23
a)Sepsis
 Most common and major factor infecting urinary tract,
identified in the present study.
 Established that patients with CKD - increased risk of sepsis - causes
acute deterioration of renal function.
(which is due to renal vasoconstriction caused by endothelin )
 However the most common site of infection in previous studies was found
to be different by different investigators.
for dept of physiology JNMC @ aditya 24
b)Accelerated Hypertension
 Found to be major factor in 19 patients and had lower degree of
reversibility, although it was statistically significant.
 Causes mucoid intimal proliferation and fibrinoid necrosis in renal
vasculature which is irreversible.
 It was observed by many investigators that patients presenting with
acute-on-chronic renal failure had a poor outcome due to accelerated
hypertension.
 While others observed that with long term control of blood pressure,
renal function recovers sufficiently to allow for withdrawal of dialysis.
for dept of physiology JNMC @ aditya 25
c)Volume depletion
 was found to be a major factor in 10 patients with maximum degree of
reversibility,
 whereas patients who had hypotension along with volume depletion
had a lower degree of reversibility.
 Results of heart failure and bleeding were not statistically significant
because number of observation was less than 5.
 Mc Innes observed that patients with pre-renal failure had 60%
recovery, whereas patients with intrinsic renal failure had 48% mortality.
for dept of physiology JNMC @ aditya 26
d)Electrolyte disturbance
• Salt depletion - aggravating factor & found
hyponatraemia - most common electrolyte disturbance
• Burkhard - hyponatraemia was the most common electrolyte imbalance
It was not a strong predictor of renal function decline
Hypernatraemia was found to be a stronger predictor.
• Hyponatraemia - most common electrolyte disturbance in the present study
- found minimum degree of reversibility in patients with electrolyte
disturbance
for dept of physiology JNMC @ aditya 27
e)Obstructive uropathy
 Many investigators have observed
good reversibility of renal function on release of obstruction.
 However, Mc Innes
found poor outcome in these patients
which was probably due to malignant disease in the pelvis.
 In this study, 14 patients had obstructive uropathy as a major cause,
. and it was second most reversible factor.
for dept of physiology JNMC @ aditya 28
7.CONCLUSION
On the basis of results of the present study it can be concluded
that:
- Patients presenting in a severe uraemic state may not be suffering
from ESRD and each patient should be investigated for the presence of
reversible risk factor(s).
so that * renal function can be restored and
* the need of renal replacement therapy can be
. delayed.
- Volume depletion and urinary tract infection were found to be the
most reversible aggravating factors observed by the study.
for dept of physiology JNMC @ aditya 29
8.CRITICAL APPRAISAL
• Type of study not mentioned.
• Place where study done, not mentioned clearly.
• Basis of inclusion criteria not explained.
• Method of statistical analysis not mentioned.
for dept of physiology JNMC @ aditya 30
Refrences:
Medical Physiology by Indu Khurana
Pathophysiology (Concepts of altered health status) by Carol Mattson
for dept of physiology JNMC @ aditya 31
Thank You…………….
for dept of physiology JNMC @ aditya 32

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  • 1. Assessment of reversible risk factors causing acute-on-chronic renal failure N Nand*, M Shrama**, H Kumar*** Prity Mehta**** PGIMS, Rohtak - 124 001, Haryana. Journal, Indian Academy of Clinical Medicine l Vol. 13, No. 3 l July-September, 2012 By ………. RAMESH NAYAK……… 28/03/2014 for dept of physiology JNMC @ aditya
  • 3. Functions of kidney 1. Excretory function 2. Regulatory function 3.Endocrine function 4.Metabolic function H O M E O S T A S I S for dept of physiology JNMC @ aditya 3
  • 4. Renal failure a)Acute b)Chronic for dept of physiology JNMC @ aditya 4
  • 5. a. Acute Renal Failure - abrupt in onset and reversible - AZOTEMIA most common . indicator - Depending upon the cause . 3 types: Prerenal Postrenal Renal for dept of physiology JNMC @ aditya 5
  • 6. b. Chronic Renal Failure - progressive and represents irreversible kidney structural damage. - signs and symptoms occur gradually kidney has amazing compensatory ability. - characterized by GFR reduction, reflects reduction in the number of functional nephrons. for dept of physiology JNMC @ aditya 6
  • 7. Stages of progression of CRF: 1. Diminished Renal Reserve 2. Renal Insufficiency 3. Renal Failure and 4. End-Stage Renal Disease(ESRD) CKD STAGE 1 CKD STAGE 2 CKD STAGE 3 CKD STAGE 4 eGFR mL/min ≤50% ≤(50-20)% ≤20% ≤5% serum BUN & creatinine levels still normal. No symptoms seen. earliest symptom isosthenuria azotemia, anemia & hypertension begin to appear. kidneys cannot regulate volume & solute composition  edema, metabolic acidosis & hyperkalemia develop.  uremia may ensue with neurologic, GI and CV manifestation Histologically reduction in renal capillaries.  Atrophy and fibrosis in tubules.  kidney mass usually reduced. TO,1. Diminished Renal Reserve 2. Renal Insufficiency 3. Renal Failure and 4. End-Stage Renal Disease(ESRD) CKD STAGE 1 ≤50% for dept of physiology JNMC @ aditya 7
  • 8. Manifestations of CRF: for dept of physiology JNMC @ aditya 8
  • 9. for dept of physiology JNMC @ aditya 9
  • 10. ACUTE-ON-CHRONIC RENAL FAILURE  Any sudden decline in renal functions in patients with known chronic kidney disease  Each episode of acute attack - can be attributed to - one or more reversible risk factors.  Various reversible risk factor contributing to acute-on-chronic renal failure are: Volume depletion Urinary tract obstruction Infection Hypotension Electrolyte imbalance Accelerated hypertension Nephrotoxic drugs for dept of physiology JNMC @ aditya 10
  • 11. Renal function tests: 1. Urine analysis (physical, chemical and microscopic examination) 2. Blood analysis (blood urea, plasma creatinine, serum protein, cholesterol and . electrolyte) 3. Renal clearance tests (to measure GFR and RBF) 4. Radiology and renal imaging 5. Renal biopsy for dept of physiology JNMC @ aditya 11
  • 12. Management of renal failure: 1) Conservative management - preventing deterioration of remaining renal function and - helps the body in compensating for the existing impairment. 2) Renal replacement therapy - Dialysis and - Renal transplantation for dept of physiology JNMC @ aditya 12
  • 13. Dialysis. for dept of physiology JNMC @ aditya 13
  • 14. Assessment of reversible risk factors causing acute-on-chronic renal failure 1.PREVALENCE:  ESRD reached epidemic proportions – treatment becoming an unbearable health care burden.  conservative estimate of ESRD burden - population of 1.1 billion - around 1,650,000 people develop ESRD in india annually.  Taking conservative approach, if all patients were to be treated - cost burden over $6.5 billion annually - health care budget for all of India $3.5 billion. QUEST india | DaVita’s Clinical Journal for Nephrologists July 2007 Issue 9 By H. Sudarshan Ballal, M.D. for dept of physiology JNMC @ aditya 14
  • 15. 2.Introduction  Any sudden decline in renal functions in patients with known chronic kidney disease (CKD)  Each episode of acute attack can be attributed to one or more reversible risk factors.  Timely management - renal function brought back to basal level- preventing from ESRD - reducing the cost of renal replacement therapy. for dept of physiology JNMC @ aditya 15
  • 16. 3.OBJECTIVE: - Evaluate risk factors - their degree of reversibility - in cases of acute-on-chronic renal failure admitted to a tertiary care hospital, over a period of one year, i.e., from November, 2006 to October, 2007. for dept of physiology JNMC @ aditya 16
  • 17. 4.MATERIAL AND METHODS: MATERIAL:  The study included 100 cases of acute-on-chronic renal failure mean age of (48.69 ± 16.02) years. 62 men and 38 women.  The diagnosis of acute-on-chronic renal failure was based on , patients with CRD - presenting with sign and symptoms of acute renal failure or - who presented with 0.5 mg/dl, if baseline serum creatinine was < 3 mg/dl rise in serum creatinine of 1 mg/dl, if baseline was > 3 mg/dl with in one week period. for dept of physiology JNMC @ aditya 17
  • 18. METHODS:  admitted in the ward - average period of 14.62 days (range: 9 to 24 days) . - managed conservatively following thorough clinical evaluation and investigations.  Specific management of reversible factor(s) and haemodialysis, whereever needed was also done.  Observations of various parameters were recorded at baseline and subsequently at 1 week and 2 week periods which included 24-hour urine volume, blood urea, serum creatinine, and creatinine clearance. for dept of physiology JNMC @ aditya 18
  • 19.  To compare the degree of reversibility, the patients were divided into 4 groups depending upon their GFR; GFR (30 - 59 )ml/min group 3 GFR (15 - 29 )ml/min group 4 GFR (5 – 15) ml/min group 5a and GFR < 5 ml/min group 5b.  Reversibility of these parameters was then statistically analysed. for dept of physiology JNMC @ aditya 19
  • 20. 5.RESULTS :  Majority of patients were found to have more than one reversible risk factor Average being 2.62 (ranging . from 1to 4)  however, only one factor was taken as the major factor depending upon the clinical situation. for dept of physiology JNMC @ aditya 20
  • 21.  Table II depicts degree of reversibility in patients having specific aggravating factors for dept of physiology JNMC @ aditya 21
  • 22. Maximum reversibility was found in patients in stage 4 and least in stage 5b . GFR (30 - 59 )ml/min group 3 GFR (15 - 29 )ml/min group 4 GFR (5 – 15) ml/min group 5a GFR < 5 ml/min group 5b. for dept of physiology JNMC @ aditya 22
  • 23. 6.DISCUSSION:  Patients presenting in severe uraemic state - not suffering from end-stage renal . disease; rather – had significant degree of reversibility of renal function . study showed, majority of patients were having more than one reversible risk factor (average 2.62).  Conservative management + haemodialysis and correction of reversible risk factor(s) , resulted in significant improvement in mean creatinine clearance after 2 weeks of follow-up. proved better chances of reversibility even in patient with stage 3 and . stage 4 of CRF.  However, in the earlier studies, the net degree of reversibility was found to be low – probably because the patients included were of advanced renal failure (creatinine clearance < 15 ml/min) for dept of physiology JNMC @ aditya 23
  • 24. a)Sepsis  Most common and major factor infecting urinary tract, identified in the present study.  Established that patients with CKD - increased risk of sepsis - causes acute deterioration of renal function. (which is due to renal vasoconstriction caused by endothelin )  However the most common site of infection in previous studies was found to be different by different investigators. for dept of physiology JNMC @ aditya 24
  • 25. b)Accelerated Hypertension  Found to be major factor in 19 patients and had lower degree of reversibility, although it was statistically significant.  Causes mucoid intimal proliferation and fibrinoid necrosis in renal vasculature which is irreversible.  It was observed by many investigators that patients presenting with acute-on-chronic renal failure had a poor outcome due to accelerated hypertension.  While others observed that with long term control of blood pressure, renal function recovers sufficiently to allow for withdrawal of dialysis. for dept of physiology JNMC @ aditya 25
  • 26. c)Volume depletion  was found to be a major factor in 10 patients with maximum degree of reversibility,  whereas patients who had hypotension along with volume depletion had a lower degree of reversibility.  Results of heart failure and bleeding were not statistically significant because number of observation was less than 5.  Mc Innes observed that patients with pre-renal failure had 60% recovery, whereas patients with intrinsic renal failure had 48% mortality. for dept of physiology JNMC @ aditya 26
  • 27. d)Electrolyte disturbance • Salt depletion - aggravating factor & found hyponatraemia - most common electrolyte disturbance • Burkhard - hyponatraemia was the most common electrolyte imbalance It was not a strong predictor of renal function decline Hypernatraemia was found to be a stronger predictor. • Hyponatraemia - most common electrolyte disturbance in the present study - found minimum degree of reversibility in patients with electrolyte disturbance for dept of physiology JNMC @ aditya 27
  • 28. e)Obstructive uropathy  Many investigators have observed good reversibility of renal function on release of obstruction.  However, Mc Innes found poor outcome in these patients which was probably due to malignant disease in the pelvis.  In this study, 14 patients had obstructive uropathy as a major cause, . and it was second most reversible factor. for dept of physiology JNMC @ aditya 28
  • 29. 7.CONCLUSION On the basis of results of the present study it can be concluded that: - Patients presenting in a severe uraemic state may not be suffering from ESRD and each patient should be investigated for the presence of reversible risk factor(s). so that * renal function can be restored and * the need of renal replacement therapy can be . delayed. - Volume depletion and urinary tract infection were found to be the most reversible aggravating factors observed by the study. for dept of physiology JNMC @ aditya 29
  • 30. 8.CRITICAL APPRAISAL • Type of study not mentioned. • Place where study done, not mentioned clearly. • Basis of inclusion criteria not explained. • Method of statistical analysis not mentioned. for dept of physiology JNMC @ aditya 30
  • 31. Refrences: Medical Physiology by Indu Khurana Pathophysiology (Concepts of altered health status) by Carol Mattson for dept of physiology JNMC @ aditya 31
  • 32. Thank You……………. for dept of physiology JNMC @ aditya 32