HD Academy 2024 - Hybrid Therapies (Francey) PDF

NEPHROBERN Principles of Hybrid Therapies Thierry Francey Dr. med. vet., Dipl. ACVIM (SAIM), ECVIM-CA Founding member ACVNU Small Animal Internal Medicine - Nephrology Department of Clinical Veterinary Medicine...

NEPHROBERN Principles of Hybrid Therapies Thierry Francey Dr. med. vet., Dipl. ACVIM (SAIM), ECVIM-CA Founding member ACVNU Small Animal Internal Medicine - Nephrology Department of Clinical Veterinary Medicine Vetsuisse Faculty University of Bern tf - 10/21/2024 Hybrid therapies Share the characteristics of both intermittent and continuous techniques in terms of treatment frequency, duration, and modality Attempt to optimize the pros and cons of both modalities efficient solute removal slower ultrafiltration rates for hemodynamic stability less anti-coagulant exposure Kellum JA, Bellomo R, Ronco C. Continuous renal replacement therapy (2016) lower costs decreased "nurse" workload improved ICU workflow Name also used for the combination of hemodialysis and peritoneal dialysis Blood purification strategies IHD Intermittent Intermittent hemodialysis Diffusive Hybrid therapies Convective (Hemodialyisis, HD) (PIRRT, iHDF...) (Hemofiltration, HF) CVVHF Continuous Continuous hemofiltration Hybrid therapies: one concept many names Sustained low-efficiency dialysis (SLED) Slow low-efficiency extended daily dialysis (SLEDD) Prolonged intermittent daily renal replacement therapy (PIRRT) Extended dialysis (ED) Extended daily dialysis (EDD) Extended daily dialysis with filtration (EDDf) Go-slow dialysis Accelerated veno-venous hemofiltration (AVVH)... Kellum JA, Bellomo R, Ronco C. Continuous renal replacement therapy (2016) Villa G et al. Nomenclature for renal replacement therapy and blood purification techniques in critically ill patients: practical applications (Crit Care, 2016) Hybrid therapies Diffusion Convection Short tx Long tx Discontinuous tx Continuous tx Dialysate generation Dialysate in bags Water treatment No water treatment Baxter Prismaflex Fresenius 5008 Fixed machine Mobile machine Qb > Qd Intermittent Hemodialysis (IHD) Continuous Renal Replacement Therapy (CRRT) Blood purification strategies Intermittent Diffusive Convective (HD) (HF) Continuous Hemodialysis (HD) Treatment based on diffusion and removal of low molecular weight solutes across a semi-permeable membrane. Removal efficacy depends on the concentration gradient across the membrane and on the molecular weight of the solute to be removed. Cutoff approximately 500 - 1’000 Da. Urea (60 Da) Creatinine (113 Da) Blood Dialysate  Blood purification strategies IHD Intermittent Diffusive Convective (HD) (HF) Fresenius 5008 Continuous Hemofiltration (HF) Treatment based on convective removal of solutes across a semi-permeable membrane. Removal efficacy extended to larger molecules. Cutoff approximately 10’000 – 50’000 Da. β2-microglobulin (11’800 Da) Leptin (16’000 Da) IL6 (24’500 Da) Blood Filtrate Blood purification strategies Intermittent Diffusive Convective (HD) (HF) Baxter Prismaflex Continuous CRRT CVVHF Blood purification strategies Intermittent Diffusive Convective (HD) (HF) CVVHDF Add diffusive clearance CRRT Continuous CVVHF Blood purification strategies Intermittent PIRRT Diffusive Convective (HD) (HF) CRRT Continuous CVVHF Hemodiafiltration (HDF) Treatment based on both diffusive and convective removal of solutes across a semi-permeable membrane. Low MW solutes removed mostly by diffusion and larger MW solutes by convection. Urea (60 Da) IL6 (24’500 Da) Blood Dialysate + Filtrate Why should we do that? - in CRRT Add diffusive clearance? Increase small solute removal (e.g. post-acute) Add intermittence and discontinuity? Convenience (especially after first days) Facilitate other interventions (diagnostic / therapeutic) Improve hospital / ICU workflow Caseload (1 machine for >1 patient) Decrease side-effects of therapy (e.g. continuous anticoagulation) I know why... Blood purification strategies IHD Intermittent Add convective clearance I-HDF Diffusive Convective (HD) (HF) Continuous Blood purification strategies Intermittent IHD Diffusive Convective (HD) (HF) HV-HDF PIRRT Continuous Why should we do that? - in IHD Add convective clearance? Increase middle molecule removal (AKI: inflammatory mediators, cytokines; CKD: residual syndrome) ± Dilution of coagulation factors (with pre-dilution) Go long treatments? Improve removal of solutes with slow intercompartmental equilibration ("non-urea-like") Less aggressive fluid removal (e.g. in severe fluid overload) More physiologic Add convective clearance Golper TA. Is hemodiafiltration ready for broader use? (KI, 2016) The middle molecules ? European Uremic Toxin Work Group middle molecules: 500 Daltons - 60 kD Vitamin B12 (1.355 kD). A middle molecule of lower MW; cleared by most modern dialyzers. β2-microglobulin (11.8 kD). Accumulation associated with a real medical condition: β2-amyloidosis. Newer dialyzers provide good clearance. light chain (25 kD). Small enough to get dialyzed. Ronco C, et al. Expanded haemodialysis: from operational mechanism to clinical results. NDT (2018) Add convective clearance Imamovic G. Principles of Haemodiafiltration: rationale for improved patients’ survival (Adv HDF, 2016) Blood purification Convection Gambro Blood flow : Dialysate flow Qb : Qd (blood flow : dialysate flow) 1:3 1:1 3:1 Qd in excess Qb in excess (blood de-saturated) (dialysate saturated) "Qb limiting" "Qd limiting" Best use of your Best use of your blood flow expensive therapy fluid Main strategy used in IHD Main strategy used in CRRT Duke, 10 kg dog, 1st treatment goals tx: URR 40%, fluid removal 500ml in 5h Choice of modality? Qb (blood flow) limiting efficacy Qd (dialysate flow) in excess Qb 30-50 ml/min iHD 0 60 120 180 240 300 ~CL Td (min) CRRT HD: Hemodialysis 40 Pv 40 AV-reduction (200 – 40) / 200 = 80% Qd 500 ml/min Clearance 20 kg 100 * 0.8 = 80 ml/min 200 Qb Urea 200 mg/dl Pa Qb 100 ml/min What can we expect from this tx? Dog 20 kg Endogenous CL with normal renal function creatinine: 3 ml/kg/min = 3 x 20 x 300 = 18 L urea: ~9 L IHD: Qb 100 ml/min Cowgill LD, Francey T (2012) Td 5 h 100 Qp (Qbacc, blood processed) : 90 80 = 100 ml/min x 300 min = 30 L 70 BUN (mg/dL) = 1.5 L/kg 60 50 Clearance: = 80 ml/min x 300 min = 24 L 40 30 = 4 ml/kg/min 20 URR 86% 10 Expected URR: ~80% 0 0 1 2 3 4 5 Tx duration (h) HF: Hemofiltration (pre) (100 ml/min) 100 Pv 100 AV-reduction (200 – 100) / 200 = 50% Clearance 100 * 0.5 = 50 ml/min 100 100 ml/min Qb Urea 200 mg/dl 100 (200 ml/min) 200 Pa Qb 100 ml/min Qinf 100 ml/min What can we expect from this tx? 100 90 80 70 BUN (mg/dL) 60 Dog 20 kg 50 40 Endogenous CL with normal renal function 30 20 URR 71% creatinine: 3 ml/kg/min = 3 x 20 x 300 = 18 L 10 urea: ~9 L 0 0 1 2 3 4 5 Tx duration (h) IHF (pre): Qb 100 ml/min Qinf 100 ml/min Td 5 h Qp (Qbacc, blood processed) : = 100 ml/min x 300 min = 30 L = 1.5 L/kg Clearance: = 50 ml/min x 300 min = 15 L = 2.5 ml/kg/min Expected URR: ~60% HF: Hemofiltration (post) Qinf 20 ml/min (100 ml/min) 160 200 Pv (80 ml/min) 160 AV-reduction (200 – 160) / 200 = 20% Clearance 100 * 0.2 = 20 ml/min 200 20 ml/min [FF 20%] Qb Urea 200 mg/dl 200 (100 ml/min) 200 Pa Qb 100 ml/min What can we expect from this tx? Dog 20 kg Endogenous CL with normal renal function creatinine: 3 ml/kg/min = 3 x 20 x 300 = 18 L urea: ~9 L IHF (post): Qb 100 ml/min Qinf 20 ml/min Td 5 h Qp (Qbacc, blood processed) : = 100 ml/min x 300 min = 30 L = 1.5 L/kg Clearance: = 20 ml/min x 300 min = 6 L = 1 ml/kg/min Expected URR: ~30% HDF: Hemodiafiltration (pre) (100 ml/min) 20 Pv 20 AV-reduction Qd 500 ml/min (200 – 20) / 200 = 90% Clearance 100 * 0.9 = 90 ml/min 100 ml/min Qb Urea 200 mg/dl 100 (200 ml/min) 200 Pa Qb 100 ml/min Qinf 100 ml/min HDF: Hemodiafiltration (post) Qinf 20 ml/min (100 ml/min) 32 40 Pv (80 ml/min) 32 AV-reduction Qd 500 ml/min (200 – 32) / 200 = 84% Clearance 100 * 0.84 = 84 ml/min 20 ml/min [FF 20%] Qb Urea 200 mg/dl 200 (100 ml/min) 200 Pa Qb 100 ml/min  Qb Qd Qinf Conv Urea in Urea out ΔA-V CL (ml/min) (ml/min) (ml/min) (L/Tx) (mg/dl) (mg/dl) (%) (L/Tx) HD 100 500 - 200 40 80% 24 HF 100 - 20 6 200 160 20% 6 post HF 100 - 20 6 200 167 16% 4.9 pre HF 100 - 100 30 200 100 50% 15 pre high HDF 100 500 20 6 200 32 84% 25 post HDF 100 500 20 6 200 33 83% 24.9 pre HDF 100 500 100 30 200 20 90% 27 pre high Dog 20 kg, tx 5h  200 160 HF pre 120 HF post BUN (mg/dl) 80 HF pre (high) 40 HD HDF pre HDF post HDF pre (high) 0 0 1 2 3 4 5 Td (h) Online-HDF and water quality Water for dialysis: USA: