1) Acute kidney injury (AKI) frequently develops in patients with sepsis, with an incidence ranging from 30-70%. 2) The development of AKI in sepsis is associated with significantly higher mortality, over 50%. 3) Survivors of sepsis and AKI also have a higher long term risk of developing chronic kidney disease.

1. RIÑON
Dr. Cristian Pedreros Rosales
Médico Internista - Nefrólogo
Jefe Unidad de Paciente Crítico
Hospital Las Higueras de Thno.
Profesor Asistente
Departamento de Medicina Interna
Universidad de Concepción
EL
EN LA
SEPSIS

2. ¿Porque es importante el tema?

3. ¿Porque es importante el tema?
El riñón falla primero
Sepsis + AKI = Mortalidad >50%
Sobrevivientes tiene más riesgo de ERC
Tran DO, et al. Nephrol Dial Transplant 1993; 8: 1079-1084
Bagshaw SM, et al. Clin J Am Soc Nephrol 2007;2:431-439
Rimes-Stigare C, et al. Crit Care 2015;19:221

4. ¿Cuál es la incidencia de AKI en sepsis?
30%… 50%… 70%… más?!

5. –Pereira M, et al. Clinical Kidney Journal. December 2016:sfw107-sfw109.
RIFLE, AKIN and KDIGO classi
fi
cations

6. –Pereira M, et al. Clinical Kidney Journal. December 2016:sfw107-sfw109.
Incidence of AKI according to RIFLE, AKIN and KDIGO criteria
n=457

7. “–Uchino S, et al. JAMA. 2005;294:813-8
La principal causa
de AKI en la UCI es
la sepsis”

8. –Rodrigo E, et al. Nefrologia. 2016;36(5):530-534.
Fallecimiento intrahospitalario con cada estadio de AKI…

9. –Godin M, et al. Semin Nephrol 35:12-22, 2015
Three models of sepsis and AKI classi
fi
ed by sequence of injury

10. Sepsis and AKI pathophysiological interaction in Sepsis-Associated -AKI
–Alobaidi R, et al. YSNEP. 2015;35(1):2-11

11. –Intensive Care Med (2011) 37:241–248.
Sepsis as a cause and consequence of acute kidney injury
“Signi
fi
cant predictors of
sepsis in AKI patients… were
fl
uid accumulation, oliguria, severity
of illness score, non-surgical
procedures, and dialysis”.

12. –Godin M, et al. Semin Nephrol 35:12-22, 2015
Three models of sepsis and AKI classi
fi
ed by sequence of injury

13. Condiciones
previas y FR
Efectos directos
de la sepsis
Intervenciones
médicas

14. Condiciones
previas y FR
Efectos directos
de la sepsis
Intervenciones
médicas

15. Población con mayor riesgo de desarrollar AKI asociada a sepsis
–Alobaide R, et al. Semin Nephrol 2015; 35:12-22.
Edad>65 años
Comorbilidad (ERC, DM2, ICC, Ca, DHC)
Sitio de la infección (No-pulmonar)
Uso previo de IECA/ARAII
Uso previo de diuréticos

16. Risk Factors on the First Day of Sepsis for the Development of AKI
–Hoste E, et al. J Am Soc Nephrol 14: 1022–1030, 2003.
PAM <70 mmhg
PVC >8 cmH2O
BH >2 L /24h
Débito urinario <1500 cc/24h
Necesidad de DVA
PaO2/FiO2 <160
Hto <30%
Scr >1,0 mg/dL
pH <7,35
1

17. Condiciones
previas y FR
Efectos directos
de la sepsis
Intervenciones
médicas

18. –Schrier RW, Wang W. N Eng J Med. 2004;351(2):159-169.
“Arterial Vasodilatation and Renal Vasoconstriction in Patients with Sepsis”

19. Low-dose dopamine in patients with early renal dysfunction:
a placebo-controlled randomised trial
–Bellomo R, et al. Lancet. 2000 Dec 23-30;356(9248):2139-43.

20. Intravenous
Haemodynamic measurements in conscious sheep
Pressure
amplifers
Flow
meter
s
•
•Systolic, diastolic, mean arterial pressure
Systolic, diastolic, mean arterial pressure
•
•Central venous pressure
Central venous pressure
•
•Cardiac output, heart rate, stroke volume,
Cardiac output, heart rate, stroke volume,
maximum aortic flow, dF/dt.
maximum aortic flow, dF/dt.
•
•Regional flows and conductances
Regional flows and conductances
•
•urinary flow
urinary flow

22. Cortical
fl
ow probe
Medullary
fl
ow probe

23. Intrarenal blood
fl
ow distribution in hyperdynamic septic shock:
Effect of norepinephrine.
–Di Giantomasso D, et al. Crit Care Med. 2003 Oct;31(10):2509-13.

24. Detection of renal blood
fl
ow abnormalities in septic and critically ill patients
using a newly designed indwelling thermodilution renal vein catheter.
–Brenner M, et al. Chest. 1990 Jul;98(1):170-9.
n= 8
El FSR depende del GC.
El FSR se mantiene o aumenta.
Pero la VFG cae igual…

25. Sepsis-Associated Acute Kidney Injury: Macrohemodynamic and
Microhemodynamic Alterations in the Renal Circulation
–Prowle JR, Bellomo R.YSNEP. 2015;35(1):64-74

26. Sepsis-Associated Acute Kidney Injury: Macrohemodynamic and
Microhemodynamic Alterations in the Renal Circulation
–Prowle JR, Bellomo R.YSNEP. 2015;35(1):64-74

27. AII, AVP
SEPSIS

28. Intravenous angiotensin II for the treatment of high-output shock
(ATHOS trial): a pilot study
–Chawala L, et al. Critical Care 2014, 18:534
n=20

29. Intravenous angiotensin II for the treatment of high-output shock
(ATHOS trial): a pilot study
–Chawala L, et al. Critical Care 2014, 18:534

30. The effects of vasopressin on acute kidney injury in septic shock
–Gordon AC, et al. Intensive Care Med. 2010 Jan;36(1):83-91.
RIFLE-R
RIFLE-I
RIFLE-F
Sin cambios en
la función renal…

31. ¿Qué explica esta disociación
entre
fl
ujo y función?

32. Debe ser NTA…

33. –Alobaidi R, et al. YSNEP. 2015;35(1):2-11.
Porcine sepsis model does not show renal tubular necrosis…

34. Cellular mechanisms involved in septic AKI:
cellular activation, hibernation, and suicide.
–Martensson J, et al. Contrib Nephrol 2016, 187:36–46

35. –Mårtensson J, Bellomo R. Critical Care Clinics. 2015;31(4):1-12.

36. Connection between Tubular Injury and Impaired Glomerular Filtration
Hibernación
celular ↑Na
a la mácula
densa
Vasocontracción
–Martensson J, et al. Contrib Nephrol 2016, 187:36–46

37. Condiciones
previas y FR
Efectos directos
de la sepsis
Intervenciones
médicas

38. Daño inducido por VM
Fluidos

39. Injurious mechanical ventilation and end-organ epithelial cell apoptosis and
organ dysfunction in an experimental model of ARDS
–Martensson J, et al. Contrib Nephrol 2016, 187:36–46
mayor tasa de apoptosis

40. “
Positive
fl
uid balance as a prognostic factor for mortality and acute kidney
injury in severe sepsis and septic shock
–de Oliveira FS, et al. J Crit Care. 2015 Feb;30(1):97-101.
EL BH positivo tardío es un
factor independiente de
mortalidad en sepsis y no
asocian a mejoría renal”.

41. Pathophysiology of
fl
uid-induced acute kidney injury
–Mårtensson J, Bellomo R. Current Opinion in Critical Care. 2015;21(4):292-301.

42. Evolución del conocimiento de AKI en relación a
fl
uidos…
2008;
VISEP
A crossover study of
pentastarch and intensive
insulin therapy
HES was associated
with increasing AKI
and RRT.
N Engl J Med.
2008;358(2):125–
139
2011; SAFE
substudy
Possible improved mortality
outcome with albumin
No change.
Intensive Care Med.
2011;37(1):86–96.
2012; 6S
study
HES 130/0.4 versus Ringer’s
lactate in severe sepsis
HES had an increased
risk of death and RRT.
N Engl J Med.
2012;367(2): 124–
134
2012;
CHEST
Trend toward increased
mortality with 6% HES
Increased
requirement of RRT
with HES.
N Engl J Med.
2012;367(20): 1901–
1911
2015; Split
Trial
Determine the e
ff
ect of a
bu
ff
ered crystalloid compared
vs saline AKI in ICU.
No di
ff
erence
between saline and
balanced solutions in
AKI.
JAMA.
2015;314(16):1701–
1710

43. Cloro…

44. Cl-
Schnermann J, et al.
Activation of tubulo-
glomerular feedback by
chloride transport.
P
fl
ugers Arch. 1976
Bullivant EMA, et al.
Intrarenal vasoconstriction
during hyperchloremia: role
of thromboxane.
Am J Physiol. 1989
Tx
A-II Quilley CP, et al.
Chloride anion concentration
as a determinant of renal
vascular responsiveness to
vasoconstrictor agents.
Br J Pharmacol. 1993
“Explanation for putative chloride-associated
detrimental renal outcomes”

45. Relationship between renin secretion and chloride
concentration [Cl-] at macula densa.

46. Vallon V, et al. Eur J Heart Fail 10 (2008) 176–187

47. Cl-

48. ¿Hay alguna terapia
que sirva?

49. –Mårtensson J, Bellomo R. Critical Care Clinics. 2015;31(4):1-12.
Therapeutic targets in patients with or at risk of septic AKI

50. –Mårtensson J, Bellomo R. Contrib Nephrol. 2016;187:36-46.
Future Therapies: Potential therapeutic targets in septic AKI

51. –Doyle J, Forni L. BTT. 2016;Volume 10:149-156.
Update on sepsis-associated acute kidney injury:
emerging targeted therapies

52. –Forni LG, Ricci Z, Ronco C.YSNEP. 2015;35(1):55-63.
Extracorporeal Renal Replacement Therapies in the Treatment of Sepsis:
Where Are We?

53. El Riñón en la Sepsis:
Mensajes para la casa
Es muy frecuente el compromiso renal en sepsis
La asociación es muy letal
AKI favorece la sepsis y visceversa
El
fl
ujo renal casi siempre es normal
La etiología es compleja
El mejor tratamiento es la prevención
Tratamientos especí
fi
cos están en curso
La TRR es de soporte