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Dr Dravid A*,Dr Sadre A.N, Dr, Munshi N, Dr Dhande S.
Ruby Hall Clinic, Pune, India
 Tenofovir based fixed dose combinations have been
increasingly used in India over the last 3 years.
 Tenofovir usage is associated with small but significant
risk of acute kidney injury (AKI) which ranges from 0.5-
2.5%.
 Data from resource limited settings like India is sparse.
 Objective of this study is to determine incidence, risk
factors and outcome of Tenofovir induced Acute kidney
injury (Serum creatinine > 2 mg/dl or Creatinine
clearance decrease by 50 % compared to baseline, Rifle
criteria 2002) in HIV infected patients attending tertiary
level HIV clinic in Pune, Western India.
 In this retrospective observational cohort analysis ,all patients
enrolled at the clinic from March 2009 to July 2012 who were
initiated on Tenofovir based ART and had regular follow up were
included.
 Patients were started on Tenofovir based ART only if Creatinine
clearance was > 50 ml/min. (Cockroft Gault(CG) formula)
 Serum creatinine and creatinine clearance values were measured
at baseline, 1 month after initiation of ART and every 6 months
thereafter.
 Tenofovir was discontinued if Serum Creatinine > 2 mg/dl
(normal value 0.6-1.2 mg/dl) or Measured creatinine clearance
decreased by > 50% on follow-up.
 512 patients were included in analysis
 Mean age of population was 41 yrs (min-14 yrs,max-73 yrs)
 The cohort consisted of 358 males (70%) and 154 females (30%).
 Mean baseline CD4 count was 164 cells/mm3
 35% patients had baseline opportunistic infection(OI) .
 Average weight of cohort was 56 kg and Mean baseline creatinine
clearance was 92.55 ml/min.
 77.7% patients were exposed to Tenofovir with Non nucleoside
reverse transcriptase inhibitors (NNRTI) and 22.3% to
Tenofovir with Protease inhibitors (PI).
 Mean duration of follow up was 19 months(median – 26 months)
with 65% patients having follow-up >=12 months.
 Tenofovir induced AKI developed in 25 patients
(incidence 4.88 %).
 Median time to developing AKI was 6 months(min-
0.5 months,max-49 months).
 13 patients developed AKI within 6 months while 12
patients developed it after 6 months on ART.
 On stopping tenofovir, 15 patients had complete
recovery of renal function.
 Partial recovery was seen in 5 patients and 5 patients
died (mortality rate 20 %).
 Haemodialysis as a treatment option was used in 3
patients but out of them only 1 survived.
Risk Factors for kidney
injury
Total
number of
patients
Number
of patients
with risk
factor
% of total
number
having risk
factor
Number of
patients with
risk factor
who
developed
AKI
% of patients
with risk
factor
developing
AKI
Association
of risk factor
with
Tenofovir
induced AKI
by Pearson’s
chi square test
(p value)
Age >=50 yrs 512 88 17.1% 10 11.3% 0.001
Creatinine clearance
(50-70 ml/min)
512 164 32.03% 19 11.59% 0.0001
Use of protease
inhibitors
512 109 21.29% 13 11.93% 0.001
CD4 =<200 cells/mm3
512 295 57.62% 18 6.1% 0.093
Diabetes mellitus 512 36 7% 9 25% 0.0001
Hypertension 512 49 9.6% 7 14.2% 0.001
Nephrotoxic drugs 512 41 8.07% 7 17.07% 0.001
Renal calculus
disease
512 17 3.32% 4 23.52% 0.0001
Obstructive uropathy 512 7 1.3% 1 14.2% 0.0001
 Incidence of Tenofovir induced AKI in our cohort is higher than
previously reported in Western data.
 It could be attributed to lower body weight, lower baseline
creatinine clearance and higher incidence of co-morbidities in our
patients.
 Tenofovir AKI leads to increased healthcare costs entailing
Intensive care unit admission, haemodialysis in addition to the
increased morbidity and mortality .
 Hence intensive monitoring of creatinine and creatinine clearance
values is needed especially in patients with concomitant risk
factors for kidney disease.
 The main limitation of our study is its retrospective observational
nature and that it was performed at a tertiary level hospital which
could lead to referral bias.

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Ameet dravid :: Presentation on HIV

  • 1. Dr Dravid A*,Dr Sadre A.N, Dr, Munshi N, Dr Dhande S. Ruby Hall Clinic, Pune, India
  • 2.  Tenofovir based fixed dose combinations have been increasingly used in India over the last 3 years.  Tenofovir usage is associated with small but significant risk of acute kidney injury (AKI) which ranges from 0.5- 2.5%.  Data from resource limited settings like India is sparse.  Objective of this study is to determine incidence, risk factors and outcome of Tenofovir induced Acute kidney injury (Serum creatinine > 2 mg/dl or Creatinine clearance decrease by 50 % compared to baseline, Rifle criteria 2002) in HIV infected patients attending tertiary level HIV clinic in Pune, Western India.
  • 3.  In this retrospective observational cohort analysis ,all patients enrolled at the clinic from March 2009 to July 2012 who were initiated on Tenofovir based ART and had regular follow up were included.  Patients were started on Tenofovir based ART only if Creatinine clearance was > 50 ml/min. (Cockroft Gault(CG) formula)  Serum creatinine and creatinine clearance values were measured at baseline, 1 month after initiation of ART and every 6 months thereafter.  Tenofovir was discontinued if Serum Creatinine > 2 mg/dl (normal value 0.6-1.2 mg/dl) or Measured creatinine clearance decreased by > 50% on follow-up.
  • 4.  512 patients were included in analysis  Mean age of population was 41 yrs (min-14 yrs,max-73 yrs)  The cohort consisted of 358 males (70%) and 154 females (30%).  Mean baseline CD4 count was 164 cells/mm3  35% patients had baseline opportunistic infection(OI) .  Average weight of cohort was 56 kg and Mean baseline creatinine clearance was 92.55 ml/min.  77.7% patients were exposed to Tenofovir with Non nucleoside reverse transcriptase inhibitors (NNRTI) and 22.3% to Tenofovir with Protease inhibitors (PI).  Mean duration of follow up was 19 months(median – 26 months) with 65% patients having follow-up >=12 months.
  • 5.
  • 6.  Tenofovir induced AKI developed in 25 patients (incidence 4.88 %).  Median time to developing AKI was 6 months(min- 0.5 months,max-49 months).  13 patients developed AKI within 6 months while 12 patients developed it after 6 months on ART.  On stopping tenofovir, 15 patients had complete recovery of renal function.  Partial recovery was seen in 5 patients and 5 patients died (mortality rate 20 %).  Haemodialysis as a treatment option was used in 3 patients but out of them only 1 survived.
  • 7.
  • 8. Risk Factors for kidney injury Total number of patients Number of patients with risk factor % of total number having risk factor Number of patients with risk factor who developed AKI % of patients with risk factor developing AKI Association of risk factor with Tenofovir induced AKI by Pearson’s chi square test (p value) Age >=50 yrs 512 88 17.1% 10 11.3% 0.001 Creatinine clearance (50-70 ml/min) 512 164 32.03% 19 11.59% 0.0001 Use of protease inhibitors 512 109 21.29% 13 11.93% 0.001 CD4 =<200 cells/mm3 512 295 57.62% 18 6.1% 0.093 Diabetes mellitus 512 36 7% 9 25% 0.0001 Hypertension 512 49 9.6% 7 14.2% 0.001 Nephrotoxic drugs 512 41 8.07% 7 17.07% 0.001 Renal calculus disease 512 17 3.32% 4 23.52% 0.0001 Obstructive uropathy 512 7 1.3% 1 14.2% 0.0001
  • 9.
  • 10.  Incidence of Tenofovir induced AKI in our cohort is higher than previously reported in Western data.  It could be attributed to lower body weight, lower baseline creatinine clearance and higher incidence of co-morbidities in our patients.  Tenofovir AKI leads to increased healthcare costs entailing Intensive care unit admission, haemodialysis in addition to the increased morbidity and mortality .  Hence intensive monitoring of creatinine and creatinine clearance values is needed especially in patients with concomitant risk factors for kidney disease.  The main limitation of our study is its retrospective observational nature and that it was performed at a tertiary level hospital which could lead to referral bias.

Notas del editor

  1. 11.